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Post Info TOPIC: About contracting HBV and HCV at the same time


Guru

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From Helio News, further info coming out at the recent Paris Liver Meeting about continuing trials on better controls of HBV.  I hope we get to see more of the results from these trials. Nice to know they are still hard at it trying to make better B drugs.

Assembly Biosciences initiates phase 2a trial for HBV core inhibitor - July 10, 2018

Assembly Bioscience announced the initiation of two randomized control phase 2a trials for ABI-H0731, the company's lead hepatitis B core inhibitor, according to a press release.

ABI-H0731 previously demonstrated potent antiviral activity in a phase 1b trial, the results of which were presented at the International Liver Congress 2018 in Paris.

"These studies will provide data on the potential of ABI-H0731 to increase cure rates by suppressing viral replication to a greater degree than is currently achieved with standard nucleos(t)ide therapy alone," Uri Lopatin, MD, chief medical officer of Assembly Biosciences, said in the release. "Such a result would support that clinical cure of chronic HBV may be possible with a finite course of direct acting combination therapy."

The first phase 2a trial will comprise approximately 45 patients positive for HBV e-antigen whose viral load has already been suppressed by nucleos(t)ide therapy. Patients will receive ABI-H0731 or placebo for 6 months. Researchers will follow the patients for HBeAg and HBV surface antigen levels.

The second trial will comprise approximately 24 patients without previous nucleos(t)ide therapy. Similar to the first trial, patients will receive ABI-H0731 or placebo for 6 weeks and have their HBeAg and HBsAg levels tested.

Assembly Bioscience expects results in the first half of 2019.

Reference: www.assemblybio.com

 



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

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More about that new HBV vaccine - (lengthy article, so will only post the abstract here) - this is just the latest I have read about the "Heplisav-B" vaccine ( versus the old usual "Engerix B" vaccine), but I am sure we will be hearing more and more from our docs about "Heplisav" in use in the near future. 

Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B Vaccine With a Novel Adjuvant

Sarah Schillie, MD; Aaron Harris, MD; Ruth Link-Gelles, PhD; José Romero, MD; John Ward, MD; Noele Nelson, MD

DISCLOSURES 

Morbidity and Mortality Weekly Report. 2018;67(15):455-458. 

 

 

 

(Excerpt): Abstract and Introduction

Abstract

Hepatitis B (HepB) vaccination is the primary means of preventing infections and complications caused by hepatitis B virus (HBV). On February 21, 2018, the Advisory Committee on Immunization Practices (ACIP) recommended Heplisav-B (HepB-CpG), a yeast-derived vaccine prepared with a novel adjuvant, administered as a 2-dose series (0, 1 month) for use in persons aged >18 years. The ACIP Hepatitis Vaccines Work Group conducted a systematic review of the evidence, including data from four randomized controlled trials assessing prevention of HBV infection and six randomized controlled trials assessing adverse events in adults. Seroprotective antibody to hepatitis B surface antigen (anti-HBs) levels were achieved in 90.0%-100.0% of subjects receiving HepB-CpG (Dynavax Technologies Corporation), compared with 70.5%-90.2% of subjects receiving Engerix-B (GlaxoSmithKline Biologicals). The benefits of protection with 2 doses administered over 1 month make HepB-CpG an important option for prevention of HBV...

 



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

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Guru

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From Medscape:

Almost 300 Million Worldwide May Be Infected With HBV By Anne Harding - April 04, 2018

NEW YORK (Reuters Health) - About 292 million people worldwide may be infected with hepatitis B virus (HBV), a new modeling study shows.

Just 10% have been diagnosed, however, and only 5% of those eligible for treatment are receiving it, according to Dr. Homie Razavi and colleagues from the Center for Disease Analysis Foundation, a research firm in Lafayette, Colorado. The findings appeared online March 26 in The Lancet Gastroenterology & Hepatology.

"One of the key objectives of this analysis is to say look, we have a serious problem," Dr. Razavi told Reuters Health by phone. "We should have eradicated this a long time ago."

Previous studies based largely on meta-analyses and reviews had pegged global HBV prevalence at 248 million to 257 individuals, Dr. Razavi and his team note in their report.

 

HBV is most common in sub-Saharan Africa and Asia, and mother-child transmission is the main source of new infections. While most adults who contract the virus will clear it, most infected children go on to have chronic HBV infection, leading to cirrhosis and liver cancer.

As with HIV, people with chronic infection must take medication for the rest of their lives to keep the infection under control, typically tenofovir and entecavir.

An HBV vaccine became available in 1981, and has been more widely accessible since 2001, when Gavi, the Vaccine Alliance began supporting HBV vaccination programs. In 2015, the World Health Assembly set HBV goals of 90% childhood vaccine coverage, 0.1% prevalence in 5-year-olds and 80% treatment coverage by 2030.

In the new study, the researchers used a Delphi process with a literature review and expert interviews to develop models of HBV surface antigen (HBVsA) prevalence, prophylaxis, diagnosis and treatment in 120 countries.

A total of 291,992,000 people worldwide had HBV infection in 2016, the authors estimate, or about 3.9% of the global population.

The number includes 1.8 million 5-year-olds, for a prevalence of 1.4%. About 29 million, or 10%, of people with HBV had been diagnosed. Among the 94 million eligible for treatment, based on having cirrhosis and a high viral load, only 4.8 million were on antivirals.

About 46% of infants received a birth-dose vaccination within 24 hours, and 89% of children under age one had received all three doses of the HBV vaccine.

Thirteen percent of babies born to HbsAg-positive mothers had received the full prophylactic treatment of timely birth-dose and follow-up vaccination, along with hepatitis B immunoglobulin. The authors estimate that just 1% of mothers with high viral loads had received antiviral treatment.

 

Currently, Dr. Razavi noted, Gavi does not pay for birth-dose vaccination, so in many countries it is only available to women who can pay out of pocket.

 

Dr. Geoffrey Dusheiko of Kings Hospital and Royal Free Hospital in London co-authored an editorial accompanying the study. "I think that there's enough data in this paper to indicate the prevalence is high in a number of regions, and that we should not procrastinate and undertake expensive seroprevalence studies, but that we should start screening" for HBV, he told Reuters Health by phone.

 

The study "should focus the minds of governments and doctors working in regions of high prevalence, that in order to meet elimination targets we have a long way to go," he added. "We did quite well with overall universal vaccination, but the rest of the picture is somewhat bleak."

 

SOURCE: https://bit.ly/2GO3Byx and https://bit.ly/2q5IJbY

 

Lancet Gastroenterol Hepatol 2018.

 
 

Reuters Health Information © 2018 Cite this article: Almost 300 Million Worldwide May Be Infected With HBV - Medscape - Apr 03, 2018.



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

(SEE UPDATES IN BIO)



Guru

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OK, here's another nerdy thing, just because I have an interest in all things Hep B (and C), oh what the heck, really, in all the heps a,b,c,d,e,f,g! 

This had to do with biopsying Hep B patients versus using "fibroscan" (sorta) but I copy and paste only the "discussion" part of it - as there, it best highlights the bits that are of particular interest to me ... namely, that their data came up with their very well detailed "ratio" of kPa drops in liver stiffness in relation to certain parallels in the ALT drops (over specific time periods) while being treated longer-term for chronic hepB, and, their theories on what may be best seen (in regard to regression and regeneration)!!

Sorry, I just find these things riveting!

 

Excerpt from "Medscape":

Interpretation of Liver Stiffness Measurement-Based Approach for the Monitoring of Hepatitis B Patients With Antiviral Therapy

A 2-Year Prospective Study

X. Liang; Q. Xie; D. Tan; Q. Ning; J. Niu; X. Bai; S. Chen; J. Cheng; Y. Yu; H. Wang; M. Xu; G. Shi; M. Wan; X. Chen; H. Tang; J. Sheng; X. Dou; J. Shi; H. Ren; M. Wang; H. Zhang; Z. Gao; C. Chen; H. Ma; Y. Chen; R. Fan; J. Sun; J. Jia; J. Hou

DISCLOSURES 

J Viral Hepat. 2018;25(3):296-305. 

 

... 

Discussion

We herein evaluated for the first time the dynamic changes in LSM in a large cohort of CHB patients with paired liver biopsies. The kinetics of LSM during 2-year antiviral therapy showed a rapid-to-slow pattern in the present study, which may reflect the remission of both liver inflammation and fibrosis during the first 24 weeks and fibrosis regression during long-term antiviral therapy, in particular, after ALT normalization. Early decline of LSM from baseline to week 52, could be useful for further evaluation of fibrosis reversion after antiviral therapy.

It has been reported that LSM declined during antiviral therapy in 1~3 years longitudinal studies,[13,22] while Ogawa et al[23] described a rapid decline in LSM during the first 3 years of treatment in 22 patients, followed by a transition to a steady-state from 3 to 5 years. In our study with 534 patients, LSM was performed in a 24 (or 28)-week interval, which made it possible to further depict the pattern of LSM kinetics during long-term antiviral treatment. The decline of LSM was in parallel with that of ALT during the first 24 weeks of treatment in a rapid pattern (-2.2 kPa per 24-week). Thereafter, slow (-0.3 kPa per 24-week) but still significant decline in LSM was observed from week 24 to week 104. The overestimating influence of a high ALT level on LSM has been reported previously.[21,24] Similarly, the present study also demonstrated the correlation between the decline in ALT and LSM in the first 24 weeks. However, there was no association between the decline of LSM and ALT from week 24 to week 104. More interestingly, median ALT maintained stable and below 1 x ULN from week 24 to week 104, while LSM declined continuously through 104 weeks. Acknowledging this rapid-to-slow pattern of LSM kinetics during antiviral therapy may help to further explore a time and LSM-based assessment of liver fibrosis in treated patients with CHB.

To further interpret the clinical implication of decline in LSM, we stratified the patients into various subgroups. It is not surprising that the decline in LSM was greater in patients with more severe necro-inflammation and liver fibrosis at baseline as well as with better virological response. These results are consistent with previous LSM observation in patients with chronic hepatitis C (CHC) and CHB during therapy.[22,25] Assuming that LSM changes are pertinent to liver fibrosis changes, it can be explained that sustained viral suppression and inflammation remission are associated with fibrosis regression, and that patients with more severe fibrosis have more prominent beneficial effect of antiviral treatment.[26] Interestingly, LSM declined in all subgroups stratified according to baseline ALT levels and baseline necro-inflammation grades. This might mean that a mixed improvement of necro-inflammation and fibrosis can be achieved through antiviral therapy, irrespective of initial ALT levels and inflammation grades. Liver stiffness measurement changes might reflect both inflammation remission and fibrosis regression especially in the first 24 weeks, as difference in absolute LSM in these subgroups were significant at baseline and week 24, but not at week 52 and thereafter (Figure 2B, Figure 2C). Finally, in multivariate analysis, fibrosis changes were independently associated with decline in LSM through 104-week therapy, which partially revealed the clinical implication of continuous decline in LSM after week 24.

 

The decline of LSM in our study, to a certain extent, reflected the typical course of histological improvement of the liver as showed in the schematic diagram of Figure 5. A higher LSM at baseline may reflect not only more severe liver disease, but also more recent fibrogenesis resulting from unregulated wound-healing induced by necro-inflammation of the liver. For regeneration to occur to replace fibrous tissue, inflammatory reaction must be halted.[27] Accordingly, during the first 24 weeks of antiviral treatment, decline in LSM may reflect both the remission of liver inflammation and the consecutive regression of fibrosis. However, even if inflammation resolves, potential regeneration is not the same for all cases of fibrosis. Generally fibrosis is more likely to regress if it is recent and there is an internal capacity to regenerate.[28] The early decline in LSM at week 52 may reflect the capacity for fibrosis regression, thus was proved to be associated with >1-point decrease in Ishak score in the present study. Further validation study with intensive paralleled liver biopsy is warranted to prove our hypothesis.

Although the percentage decline of LSM was predictive of fibrosis regression in the present study, the absolute LSM value at week 104 should be interpreted with caution. Dual cut-offs of LSM (6.0 kPa and 9.0 kPa for excluding advanced fibrosis and cirrhosis, respectively; 9.0 kPa and 12.0 kPa for confirming advanced fibrosis and cirrhosis, respectively)[21,29] derived from patients with viremia were tested after antiviral therapy in the present study. None of the patients with LSM higher than 9.0 kPa (n = 5) and 12.0 kPa (n = 4) had advanced fibrosis and cirrhosis (showing low positive predictive value). However, patients with LSM lower than excluding cut-offs 6.0 kPa and 9.0 kPa at week 104 all had consistent histological results showing nonadvanced fibrosis and noncirrhosis (negative predictive value, 100%). Nevertheless, the instinct of sample error of liver biopsy should not be ignored, which might underestimate the liver fibrosis stage resulting in missed diagnosis of severe disease by LSM <9.0 kPa or "misdiagnosis" of severe disease by LSM >9.0 kPa/12.0 kPa in the patients after therapy. Accordingly, the excluding cut-off of LSM in HBV suppressed patients actually need to be lowered. In line with our concern, a study of patients with CHC also reported reduced sensitivity (61% vs 82-98%) of the cirrhotic cut-off 12.0 kPa after antiviral therapy and suggested the identification of a lower LSM threshold or a dual cut-off approach for further validation.[30] In case of false negative diagnosis by liver biopsy, noninvasive method for fibrosis dynamic assessment would be effective to supplement liver biopsy during antiviral therapy. Standardization of cut-off values for noninvasive test, especially for the promising LSM, in clinical practice/studies is urgently needed.

There were a few limitations in the present study. First, majority of patients recruited in the initial randomized, controlled trial had mild fibrosis (Ishak <2), accounting for 74.4% at baseline and 93.9% at week 104. This might overestimate the negative predictive value of LSM cut-offs at week 104 for fibrosis assessment in the present study. Therefore, pretreatment cut-offs of LSM should be validated or redefined in further CHB cohorts with antiviral therapy. In addition, the qualified length of liver specimen in our study was >10 mm, with only 30.7% (164 of 534) of the analyzed population with qualified paired biopsies enroled in histological analysis, which was susceptible to patient selection bias. The initial study designed reservation of liver biopsy specimen for a cccDNA study, resulting in inadequate sample length for histological fibrosis assessment. Nevertheless, there were still a large number of patients (164 cases) with qualified paired biopsies; the characteristics of the qualified biopsied patients were comparable to those of analyzed population (n = 534) and patients without adequate liver biopsy (n = 370); biopsy specimens were centrally analyzed and pathologists were blinded to the clinical data and timing of biopsy. Taking all these into consideration, the present results are still convincing to represent the histological changes in the liver.

In conclusion, the present study described a rapid-to-slow decline pattern of the dynamic changes of LSM during long-term antiviral therapy in patients with CHB which was representative of the course of histological improvement of the liver. The cut-offs of LSM for liver fibrosis diagnosis before antiviral treatment should be lowered after long-term treatment. Relative decline of week-52 LSM could serve as a valuable predictor for liver fibrosis regression after 104-week treatment whereas its application after antiviral therapy needs further validation...

 

 

 



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

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Tig


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It's alimentary, my dear Canuck.... no



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Well, finally! - something substantial they have to say on the topic of B core antigens! Interesting (to me anyway) being that I have been addicted to studying up on all things HBV (kind of in relation to having HCV at the same time).

There is so much to read about HBV "surface antigen" and "surface antibodies", AND, HBV "core antibodies", and the use of B DNA testing (or ALT flares or the problem of the absence of signaling ALT flares) to reveal chronic, occult B, and/or B reactivations,  but all the while I have found so little to read about the HBV core antigen itself.

Nice to see "continued thinking/study" about what tests/what "markers" might best reveal chronic/occult/ or reactivated HBV, and/or the potential risk of reactivation of B in response to being under the influence of potent immunosuppressants.

For quite some time, much study could be found the topic of B core antibodies (and  B surface antigens and antibodies), but I have found quite an absence of reading material about core B antigens, which has always been kind of unexplainable and quite perplexing to me, as to why this was so! So, it's was nice (for me) to see some further thought (today) on the potential importance of the B core antigen as a marker.

 

(Excerpt):

Alimentary Pharmacology & Therapeutics

Review Article

Hepatitis B Core-related Antigen (HBcrAg): An Emerging Marker for Chronic Hepatitis B Virus Infection

L.-Y. Mak; D. K.-H. Wong; K.-S. Cheung; W.-K. Seto; C.-L. Lai; M.-F. Yuen

DISCLOSURES 

Aliment Pharmacol Ther. 2018;47(1):43-54. 

 

Abstract and Introduction

Abstract

 

Background:  Chronic hepatitis B (CHB) cannot be completely eradicated due to the presence of covalently closed circular DNA (cccDNA) in the nuclei of infected hepatocytes. While quantification of intrahepatic cccDNA requires liver biopsies, serological markers can be non-invasive alternatives to reflect intrahepatic viral replicative activity. Recently, hepatitis B core-related antigen (HBcrAg) has been advocated as a novel serum marker for disease monitoring and prognostication of CHB.

 

Aim:  To examine the virological aspect and clinical application of HBcrAg with respect to the natural history and treatment of CHB.

 

Methods:  We reviewed all papers published in the PubMed journal list and abstracts from major international meetings that included the keyword "HBcrAg" or "hepatitis B core-related antigen" until March 2017. Selected studies were compared and summarised on the basis of existing theories, as well as the authors' experience.

 

Results:  HBcrAg exhibited good correlation with intrahepatic (ih) cccDNA, ih total hepatitis B virus (HBV) DNA, serum HBV DNA and to a lesser extent HBV surface antigen (HBsAg). In situations where serum HBV DNA levels become undetectable or HBsAg loss is achieved, HBcrAg can still be detectable. This marker is helpful in differentiation of HBeAg-negative chronic hepatitis from HBeAg-negative chronic infection, predicting spontaneous or treatment-induced HBeAg seroconversion, sustained response to nucleos(t)ide analogue (NA), risk of HBV reactivation in occult HBV infection under immunosuppressive therapies, and risk of hepatocellular carcinoma (HCC) development as well as post-operative HCC recurrence.

 

Conclusions: HBcrAg is a potential surrogate marker of cccDNA. It may soon become a useful marker for disease monitoring, predicting treatment response and disease outcome of chronic hepatitis B ...

 

 ... Conclusions

In summary, HBcrAg is a good surrogate marker of intrahepatic cccDNA. It correlates with HBV DNA in all disease states. HBcrAg is helpful in differentiation of HBeAg-negative chronic hepatitis from inactive carrier state as shown by 2 large-scale studies. These 2 disease states carry entirely different clinical implications and prognosis, and the role of HBcrAg in here should be further elaborated in particular for HBeAg-negative patients with apparently normal ALT. In patients with undetectable serum HBV DNA and HBsAg, ie achieving "functional cure," complications would still occur. Certain proportion of patients achieving "functional cure" still have detectable HBcrAg and this warrants prospective studies comparing the long-term outcome between HBcrAg-positive and HBcrAg-negative patients. HBcrAg, similar to HBsAg titre, is potentially useful in predicting HBsAg loss under NA therapy, although the cumulative rates of HBsAg loss is still disappointing. On the other hand, sustained off-therapy response to NA is a more attractive outcome to investigate, as most NA is continued indefinitely and the role of HBcrAg in selecting low-risk patients for NA cessation should be further explored.

Finally, use of HBcrAg needs further exploration in 2 special populations. First, as HBcrAg demonstrated good predictive value for risk of HBV reactivation in occult HBV, and more studies should be performed on moderate-risk and low-risk group for risk stratification, as well as for determining the optimal duration of NA after cessation of rituximab or immunosuppressive therapy for HSCT. Second, predicting HCC by HBcrAg for both treatment-naďve and treatment-experienced group is an exciting area.

However, as remarked in the EASL guideline, most studies were performed in Japan and other Asia countries and large correlation studies derived from Caucasian patients are lacking. As such, in spite of being a very promising new viral marker, more extensive clinical validation is needed before routine use in clinical practice.

 

 

 



-- Edited by Canuck on Saturday 24th of February 2018 10:32:51 PM

__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

(SEE UPDATES IN BIO)



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A very long involved study, but recent, and North American, to compliment other countries' HBV reactivation studies (Japan/Italy/China etc.) A very long read and interesting in itself. All these kinds of retrospective studies NEED to be done, BUT, in the reading, I take away more salient points, such as noticing how abysmal (not so long ago) pre-assessment testing (even the most basic HBV status screenings) were NOT getting done prior to starting HCV treatment, nor checks done during HCV treatment, nor after. I note many were excluded from this study for that very reason, of not having the before/during and after data on them! And my pet peeve arises yet again, in that they are not being more aggressively proactive in testing HBV "core-antibody-only" positive people with HBV DNA testing prior to HCV treatment. No matter how few "core positive only" folk there are, no matter how few of them "might" reactivate (or have reactivated), until the data is in, the last sentence in red below (abstract) pales in safety for these few. Some folk do not ALT flare signal during HCV treatment, not everyone (who should get good follow-up) gets good follow-up. This study ends with recommendations (discussion) that are cost-saving, but (In my thinking) do not go far enough to be protective for some HCV patients.

 

Journal of Viral Hepatitis

Rare Clinically Significant Hepatic Events and Hepatitis B Reactivation Occur More Frequently Following Rather Than During Direct-acting Antiviral Therapy for Chronic Hepatitis C

Data From a National US Cohort

M. Serper; K. A. Forde; D. E. Kaplan

DISCLOSURES 

J Viral Hepat. 2018;25(2):187-197. 

 

Abstract

Recently, cases of hepatitis B virus reactivation (HBVr) with direct-acting antiviral therapy (DAAs) for HCV have been reported. However, few data exist from large, Western cohorts. The study objectives were to evaluate the incidence of alanine aminotransferase (ALT) flares, clinically significant hepatic events, and HBVr among a national cohort of US veterans with prior exposure to HBV (anti-HBc+) treated with DAAs. We used a national administrative database to identify patients treated with DAAs from January 2014 through November 2016 and obtained clinical and demographic as well as HBV and HCV treatment data. HBVr was defined as an at least 1-log increase in HBV DNA titre. Among 17 779 anti-HBc+ patients, 17 400 were HIV- and 379 were HIV+. Among the HIV- patients, 17 266 (99%) were HBsAg- prior to DAA therapy and 134 were HBsAg+. Among HIV-, HBsAg- patients, ALT elevations greater than 10 times the upper limit of normal (ULN; >300 IU/mL) were rare and occurred more frequently after treatment completion: 31 cases (<0.1%) during vs 85 (0.6%) following treatment. Clinically significant hepatic events defined as ALT increases >100 IU/L with total bilirubin >2.5 mg/dL occurred in 39 cases (0.3%), most often following DAA completion (n = 35 cases, 3/35 in setting of HCV relapse). Among 31 patients with post-DAA hepatic events without HCV relapse, 10 (32%) were confirmed unrelated to HBVr by HBsAg and/or HBV DNA testing, 1 (3%) confirmed due to HBVr, and 20 (65%) did not have documented HBV-related testing. One additional case of HBsAg- to + seroreversion was identified. Among HBsAg+ DAA recipients, 2/97 (2%), both with cirrhosis, experienced ALT elevations >300 IU/mL in the setting of HBVr. In conclusion, clinically significant hepatic events and HBVr were rare and much more likely among HBsAg-positive individuals. Anti-HBc + patients should be monitored for ALT flares and HBVr during and possibly for up to 6 months post-DAA therapy ...

 

Discussion

In evaluating a large cohort of anti-HBc+ individuals with chronic HCV undergoing DAA therapy, we identified that the risk of HBVr defined by any increase of HBV DNA was extremely small (<0.1%) and occurred much more frequently, but not exclusively, in HBsAg+ individuals. For HBsAg- patients started on HCV DAA therapy, clinically significant hepatic events were extremely rare, occurring in 35 (0.3%) patients, of whom only 1 had confirmed HBVr but an additional 24 cases could not be excluded due to inadequate testing; thus, the maximal rate of HBVr associated with clinical hepatic events could approximate 0.2% of cases. Among HBsAg+ patients, the risk of HBVr was approximately 10% and was associated with 1 clinically significant hepatic events event in a patient with cirrhosis. In general, clinically significant hepatic events whether confirmed HBVr or not were much more common in cirrhotic patients.

Notably, anti-HBs were not protective against HBVr, and HBVr occurred significantly more often after completion of the HCV DAA course than during active therapy. The median time to HBVr was 112 days, more frequently occurring after the typical 84-day DAA therapy course. Seroreversions from HBsAg- to HBsAg+ status were also quite rare (documented in only 2 cases overall), were associated with ALT elevation in only 1 or the 2 cases and were not confirmed up until SVR12 follow-up. These data suggest that anti-HBc+ patients undergoing HCV DAA therapy should undergo a measurement of ALT and reassessment of HBsAg status at the time of SVR12 determination to exclude rare but possible subclinical seroreversion events.

We describe 6 patients with 4-log or greater HBV DNA increases, all but one of whom were HBsAg+ at the start of DAA therapy. Only 1 patient had concomitant clinically significant hepatic events and among the 5 patients with follow-up data, all responded to HBV therapy with decreases in HBV DNA, ALT and total serum bilirubin. When recognized, HBVr was highly responsive to nucleos(t)ide treatment and no serious sequelae could be identified from administrative data.

Overall, the low rates of adverse events we identify in this large Western cohort are comparable previously published data from China.[12] Although derived from a similar dataset as the previously published data from the VA on HBV reactivation,[13] there are critical differences in our analysis that should be highlighted: (i) the previous analysis only evaluated patients during HCV DAA therapy until 7 days after therapy, likely missing many of the events we identified in longer follow-up of patients; (ii) relied on HBV DNA results which were missing in many patients with hepatitis flares who were not appropriately tested and therefore were unable to estimate the number of possibly undiagnosed HBVr events in the population; and (iii) used a different definition of HBVr requiring a 3-log change in HBV DNA titre. Similar to their findings, we found that most HBVr was associated with relatively modest increases in ALT.

As in all large, real-world observational datasets, most patients had incomplete HBV testing before, during and after HCV DAA initiation as well as infrequent initial/repeat testing at the time of clinical hepatitis events. Approximately 18% of veterans treated with HCV DAAs had no HBV testing results available within 5 years of HCV DAA treatment potentially leading us to underestimate the true incidence of HBV-related adverse events. Serial HBeAg data were not generally available and thus were not reported. Adverse events such as death and transplantation were not globally assessed for the cohort; however, among the patients with significant hepatic events and HBVr, serial assessment of pharmacy records and laboratory testing confirmed successful treatment with HBV therapy in all but 1 case that had no follow-up. SVR12 data were unknown for about one-third of patients at the time of data analysis, including among 10 patients with significant hepatic events; this could falsely overestimate attribution of hepatotoxicity to possible HBVr in the setting of undiagnosed HCV relapse. Lastly, we do not compare outcomes of anti-HBc+ to anti-HBc- patients, however, hepatotoxicity with DAAs is infrequently reported and more common in decompensated cirrhosis, which represents a minority of our cohort.[21,22]

Based on the infrequency of clinically significant hepatic events in this large and diverse Western cohort of anti-HBc+ individuals, we propose several recommendations. First, we strongly concur with current recommendations for universal testing of HBsAg and anti-HBc prior to DAA initiation. Second, we recommend serial ALT determinations during HCV therapy and for at least 6 months after completion of therapy for all anti-HBc+ patients. Third, for HBsAg+ patients without cirrhosis and not currently on nucleos(t)ide therapy due to inactive chronic or immune-tolerant HBV, it is reasonable to follow serial ALT during and after DAA therapy and to continue HBV DNA and ALT testing indefinitely every 6 months as per the current AASLD HBV guidelines.[23] Fourth, HBsAg+ patients with cirrhosis should be pre-emptively treated with nucleos(t)ide analogues concomitant with HCV DAA therapy. Fifth, for HBsAg- individuals with resolved HBV, interval retesting for HBsAg and HBV DNA should be triggered by elevations of ALT during or after DAA therapy; furthermore, we recommend testing HBsAg status once more at the time of SVR12 determination to exclude subclinical seroreversion. We postulate that the above strategies may maximize identification of clinically significant HBVr without excessive testing burden, although the specific recommendations regarding the frequency and duration of post-DAA follow-up among those with resolved HBV should be informed by future studies.

 

 



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

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Excerpt from study (link) of 2017 - ( http://onlinelibrary.wiley.com/doi/10.1111/jvh.12754/full  ) - the conclusion excerpt shown from this study shown below only solidifies my "better safe than sorry stance", that as hard as it may be to show that HBV positive "isolated core antibody only" patients may be in fact "occult" B patients, who might have their B reactivated as a consequence of being put on DAA therapy for HCV, that small sector (as opposed to only at higher risk sectors) does justify special precautions, such a HBV DNA testing before, during and after DAA therapy, as seen done electively by a well-known doc in the USA (see my post/his statement - in my prior post further below dated Feb 4).

 

 HBV reactivation in patients with HCV/HBV cirrhosis on treatment with direct-acting antivirals

Authors - V. Calvaruso, D. Ferraro, L. Licata, M. G. Bavetta, S. Petta, F. Bronte, G. Colomba, A. Craxě, V. Di Marco

 

... In conclusion, as stated by current HCV guidelines,[35] HBV status should be appropriately evaluated by testing for HBsAg, anti-HBc and anti-HBs in all patients before starting a DAA regimen for HCV. For HBsAg-positive patients with cirrhosis, if not already on treatment with Entecavir or Tenofovir, should be considered the prophylactic therapy with a NUC before DAA. HBsAg-negative patients with isolated anti-HBc positivity can also reactivate HBV even if this seems a rare event without clinical and virological outcomes. These patients should however be followed closely when undergoing DAA treatment

These data are not conclusive to indicate prophylaxis with NUCs during therapy with DAAs in all patients with HBV and HCV coinfection, but suggest special attention and precautions in this subset of patients. Further studies, especially in Asian patients, are definitely warranted ... 

 

 

 



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

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Don't pick up hep B if you have hep C!

A new 2 dose HBV vaccine, versus 3 doses (that they have been talking about, for a while now) now recently available in USA.

 

 

Helio - January 12, 2018

Heplisav-B HBV vaccine for adults available in US

 

Dynavax announced in a recent press release its hepatitis B vaccine, Heplisav-B, is now available in the U.S.

"Dynavax is prepared and proud to launch our first product, Heplisav-B, in the United States," Eddie Gray, CEO of Dynavax, said in the press release. "We believe the increase in the rate of infections and poor compliance with current three-shot regimens has the medical community eager for access to Heplisav-B for adults."

Heplisav-B is the first new HBV vaccine for adults in the United Sates in more than 25 years, approved by the FDA on 9, 2017.

The vaccine can now be ordered through a network of distributors, which will continue to broaden. to the press release, Dynavax is currently working with an extensive network of group purchasing organizations and government entities to ensure all patients have access to Heplisav-B and has begun activities to support broad reimbursement through insurance plans.

Heplisav-B is a combination of HBV surface antigen with Dynavax's proprietary Toll-like receptor 9 (TLR9) agonist, designed to enhance immune response. The treatment comprises two doses, with the second dose provided at 1 month.

 

Reference: www.dynavax.com



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

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Just goes to confirm that "prevention" IS the best medicine, the next best thing IS "early" treatment.

 

Medscape - Perspective > Journal of Viral Hepatitis

Higher Risk of Hepatocellular Carcinoma in Chronic Hepatitis B vs Chronic Hepatitis C After Achievement of Virologic Response

G. A. Kim;  DISCLOSURES - J Viral Hepat. 2017;24(11):990-997.

 

Abstract

It is unclear whether the achievement of virologic response modifies the risk of hepatocellular carcinoma (HCC) differently in chronic hepatitis B (CHB) and chronic hepatitis C (CHC). Our aim was to compare the risk of HCC between patients with CHB and CHC who achieved virological response. We analysed data from patients with CHB treated with entecavir (n=2000) or CHC treated with peg-interferon and ribavirin (n=733) at a tertiary hospital from 2004 to 2011. Virological response was defined as serum HBV DNA<15 IU/mL at 1 year of treatment for CHB or the achievement of sustained virologic response for CHC. Virological response was achieved in 1520 patients with CHB (76.0%) and 475 patients with CHC (64.8%). During the median follow-up period of 6 years, 228 patients with CHB (11.4%) and 59 patients with CHC (8.0%) developed HCC. Among patients with virological response, CHB was independently associated with a significantly higher incidence of HCC (hazard ratio, 2.17; 95% CI, 1.30-3.63; P=.003) than CHC. Among patients without virological response, there were no differences in HCC incidence between the two cohorts (P=.52). In patients with cirrhosis at baseline, the incidence of HCC did not differ between the two cohorts even after achieving virological response (P>.99). In conclusion, patients with CHB treated with entecavir were associated with a higher risk of HCC compared to patients with CHC treated with peg-interferon and ribavirin after achieving virological response. However, the risk of HCC did not differ between the two cohorts if the patients had cirrhosis at baseline, even if virological response was achieved.

 

Introduction

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most frequent cause of cancer mortality in the world, accounting for more than 600 000 deaths each year.[1] HCC has been the fastest rising cause of cancer-related deaths in developed countries during the past two decades and is expected to increase further in the next decade.[2,3] Chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) is the most frequent causes of HCC.[2-4] Worldwide, it is estimated that 400 millions and 170 millions people are chronically infected with HBV and HCV, respectively, and approximately 54% and 31% of HCC cases are attributed to HBV and HCV infections.[5,6]

The ultimate goal of treating chronic hepatitis B (CHB) or chronic hepatitis C (CHC) is an improvement in patients' survival by preventing, or at least reducing, the development of cirrhosis, liver failure and HCC. Despite remarkable advances in the antiviral treatments for HBV and HCV during the last two decades, sparse data are available on whether the incidence of HCC is decreasing.[1-3] In fact, a recent systematic review demonstrated that HBV and HCV still are the predominant causes of HCC.[4] A possible explanation would be that some precedent risk factors that are not amenable to antiviral therapy might contribute to the development of HCC. Furthermore, few data are available to determine on whether achieving a virologic response (VR) by treatment of CHB modifies the risk of HCC differently compared with achieving a sustained virologic response (SVR) by treatment of CHC.

The primary aim of this cohort study was to compare the risk of HCC between patients with CHB and CHC who achieved VR and SVR, respectively. In addition, we sought to identify the factors that modify the risk of HCC between patient groups.

 

Discussion

In this observational study, we assessed whether the achievement of VR modifies the risk of HCC differently between patients with CHB and CHC. We found that patients with CHB treated with entecavir had a significantly higher incidence of HCC than patients with CHC treated with PEG-IFN and ribavirin after achieving VR. However, the CHB and CHC cohorts did not differ in incidence of HCC when VR was not achieved or when the patient had cirrhosis at baseline even if VR was achieved. The results were consistently observed by univariate, multivariable, inverse probability weighting and propensity score-matched analyses.

To our knowledge, this is the first study that has directly compared the risk of HCC between patients with CHB and CHC who have achieved VR. VR, which is defined as suppression of the viruses to undetectable serum level by a sensitive polymerase chain reaction assay, has been shown to be associated with reduced risks of mortality and HCC in patients with either CHB or CHC.[12-15] However, the biological significance of VR would differ between CHB and CHC. Achieving SVR after treatment of CHC indicates viral eradication, whereas achieving VR during treatment of CHB suggests suppression of viral replication with HBV remaining in the liver, either integrated into the host genomic DNA or as covalently closed circular DNA.[16] These biological differences of VR between CHB and CHC may explain our findings. The mechanism for the development of HCC is also different between patients with HBV and those with HCV. In patients with CHB, although VR leads to alleviation of hepatic inflammation and can reverse hepatic fibrosis, it may not suffice to prevent HCC development.[17] In contrast, the permanent clearance of HCV by achieving SVR prior to cirrhosis may greatly reduce the risk of HCC.[18] In fact, HBsAg seroclearance after NUC treatment can serve as a sole reliable surrogate marker that is associated with a minimized risk of HCC.[19] It might be worthy to compare the risk of HCC in HCV patients with SVR and HBV patients achieving HBsAg seroclearance. However, not only HBsAg seroclearance after NUC treatment but also the development of HCC after HBsAg seroclearance is so scarce that it might not be appropriate to compare HBsAg seroclearance in CHB with SVR in CHC. Thus, this study compared the risk of HCC between patients who achieved VR in both CHB and CHC.

Our findings are in agreement with the results of previous randomized trials and systematic reviews, which consistently showed that HCC risk can be reduced but not eliminated in CHB patients treated with current potent NUC,[12,14,20,21] while marked reduction in HCC incidence can be observed after treatment that achieves SVR among HCV-infected persons.[12,15] Recent cohort studies have shown that entecavir treatment reduced the risk of HCC and death in CHB patients with cirrhosis compared with no treatment.[22,23]Nonetheless, we found that the risk of HCC persisted to a similar degree in patients with CHB or CHC who had cirrhosis at the time treatment was started. These findings are in line with the fact that cirrhosis is an independent risk factor of HCC for both CHB and CHC, irrespective of VR achievement.[14,24,25] In patients who already have cirrhosis, hepatocytes carrying genetic abnormalities that predispose cancer may be present before the initiation of antiviral treatment. The decision to start HCV treatment early had been hampered by the low efficacy and tolerability of PEG-IFN and ribavirin treatment. This might no longer be the case with the current all-oral direct-acting antiviral agents (DAA) for HCV, which dramatically increase the rate of SVR with minimal adverse effects.

As our patients in different cohorts received different treatments, that is entecavir and PEG-IFN in patients with CHB and CHC, respectively, an intriguing question arises about the effect of treatments on HCC incidence between the two groups. IFN may have an antitumor effect as well as an antiviral effect. Systematic reviews of studies of IFN therapy for patients with CHB have provided conflicting evidence for HBV-related HCC chemoprevention.[12] In contrast, meta-analyses of studies in CHC patients treated with IFN consistently demonstrated a more than 70% reduction in HCC risk occurring independent of the severity of underlying liver fibrosis.[12,15] Because very few patients with CHB are being treated by IFN due to its low efficacy and tolerability and DAAs for CHC only became available as of late 2015 in the country where this study was conducted, this study was not able to compare the two study groups under the same treatment condition. Patients with CHB received IFN-based treatment and patients with CHC received DAA-based treatment are currently attracting attention, the former has the potential beneficial effect of IFN on HCC development, and the latter has the potentially higher risk of HCC development compared with IFN-based treatment.[26] Moreover, the preventive effects of the eradication of HCV on HCC development between IFN-based and DAA-based treatment are still uncertain. Further studies comparing the risks of HCC between patients with CHB and CHC treated by the same regimen are warranted.

The major limitation of this study is that it was based on observational data. Thus, our findings are potentially subject to selection bias and confounding. The unadjusted and adjusted analyses consistently demonstrated a higher risk of HCC in the CHB cohort than in the CHC cohort after VR. However, there may still be some hidden bias due to unmeasured confounders. Despite these limitations, the present observational study is arguably the most reasonable and feasible way to compare the two cohorts because a large sample size and a long-term follow-up period are needed to observe HCC incidence. Secondarily, our study may have limitations for generalization of the results. The predominant population included in this study had genotype C HBV that was acquired through the vertical mode of transmission with a long-duration of infection,[8] and our CHB population had a high prevalence of cirrhosis. These factors might have contributed to the particularly high incidence of HCC in the patients with CHB.[27,28] Third, the data regarding comorbidities such as metabolic syndrome, alcohol abuse and smoking status which might serve as important cofactors for HCC development were not taken into account in the current analysis. Fourth, because we used clinical and radiological criteria for the diagnosis of cirrhosis, some patients with advanced fibrosis or early cirrhosis may be misclassified into noncirrhosis group. Lastly, the number of CHC patients with cirrhosis who achieved VR was relatively small, and the subgroup analysis of them might have insufficient statistical power to demonstrate a significant difference in HCC incidence compared with CHB cohort with cirrhosis.

In conclusion, the present cohort study showed that CHB patients treated with entecavir had a higher risk of HCC than CHC patients treated with PEG-IFN and ribavirin when they achieved VR. However, the risk of HCC was high and did not differ between CHB and CHC patients in the presence of pre-existing cirrhosis. These results suggest that antiviral treatment should be started before the development of cirrhosis in patients with viral hepatitis. Our findings also suggest that HCC surveillance should be continued for CHB patients and cirrhotic CHC patients, regardless of the achievement of VR.

 

Acknowledgements 
We are indebted to Drs. Danbi Lee, Ju Hyun Shim, Kang Mo Kim, Han Chu Lee, Young-Hwa Chung, and Yung Sang Lee; and Information Technology Service Management Team of Asan Medical Center for help in data collection. We also thank Dr. So-Young Park, Ms. HaYeong Koo, and Ms. Kathryn B. Carnes, Director, Scientific Publications, MD Anderson Cancer Center, for critically editing the paper. None received compensation for their work.

J Viral Hepat. 2017;24(11):990-997. © 2017 Blackwell Publishing

 

 

 



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

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Medscape - News > Reuters Health Information

Elevated Liver Cancer, Death Rates With Immune-Tolerant-Phase Chronic HBV

By Will Boggs MD - November 22, 2017

 

NEW YORK (Reuters Health) - Patients with immune-tolerant-phase chronic hepatitis B virus (HBV) infection, who are usually not considered for treatment, face an increased risk of hepatocellular carcinoma (HCC) and death, compared with treated immune-active-phase patients, researchers from Korea report.

 

"Serum liver enzyme (ALT) levels have been used as the criteria to initiate treatment in chronic hepatitis B patients," Dr. Young-Suk Lim from Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea, told Reuters Health by email. "However, the elevation of alanine aminotransferase (ALT) may occur at later phase of liver damage by HBV. Thus, earlier treatment guided by age and serum HBV DNA levels may prevent unnecessary cancers and deaths in chronic hepatitis B patients."

 

The immune-tolerant (IT) phase of chronic HBV infection is characterized by high circulating HBV DNA and normal ALT levels, where histological activity is presumed to be dormant and the risk of disease progression is presumed to be low. Recent studies, however, suggest otherwise.

In a historical cohort study, Dr. Lim's team analyzed data from 3,051 adults with chronic HBV infection to compare long-term outcomes between untreated IT-phase patients and immune-active (IA)-phase patients treated with nucleoside/nucleotide analogs. Median follow-up was 6.3 years.

 

The annual incidence of HCC was significantly higher in the IT-phase group (1.05%) than in the IA-phase group (0.51%), as was the annual rate of death or transplantation (0.76% vs. 0.32%), according to the November 9 Gut online report.

 

In multivariable analysis, the IT group had a 2.54-fold higher risk of HCC and a 3.38-fold higher risk of death or transplantation, compared with the IA group. The findings persisted in inverse-probability treatment weighting and propensity-score-matching analyses.

 

Patients with mildly active disease also had higher risks compared with the IA group - a 3.23-fold higher cumulative incidence of HCC and a 3.21-fold higher incidence of death or transplantation.

 

Factors independently associated with a significantly higher risk of clinical events included older age, male sex, lower HBV DNA levels, and lower platelet counts.

 

"Thus, we think that at least those who have older age >40 years and/or serum HBV DNA levels >4.0 log10 IU/mL and <8.0 log10 IU/mL may have to be treated to reduce the risks of liver cancer and death, even with normal serum liver enzyme (ALT) levels," Dr. Lim said.

 

"Further studies taking new emerging biomarkers for HBV infection into account would be warranted to further stratify the patients for the risk of clinical events," the researchers write. "Randomized controlled trials evaluating the long-term clinical outcomes of the IT-phase patients with or without antiviral treatment may be worthwhile."

 

SOURCE: http://bit.ly/2ATZco5

Gut 2017.

 

 



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HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

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A new HBV immunization.

 

 Helio -  FDA NEWS - November 10, 2017

FDA approves HBV vaccine Heplisav-B for adults

Dynavax announced that the FDA approved Heplisav-B, a recombinant hepatitis B vaccine, for all known subtypes of HBV in adults aged 18 years or older, according to a press release.

"Once physicians and public health institutions become aware of Heplisav-B, it will be an attractive option to use for all those individuals who are indicated to receive hepatitis B vaccines as adults who haven't been vaccinated as children," William Schaffner, MD, professor of preventive medicine at the Vanderbilt University Medical Center, and a public health advisor during Dynavax]s presentations to the FDA, told Healio.com/Hepatology. "Given the performance characteristics of the vaccine, I think it will restimulate people to actually go after those patients more vigorously."

Heplisav-B is a combination of HBV surface antigen with Dynavax's proprietary Toll-like receptor 9 (TLR9) agonist, designed to enhance immune response. The treatment consists of two doses, with the second dose provided at 1 month.

"I think what's remarkable about Heplisav is that it's the first new hepatitis B vaccine in 25 years," Robert Janssen, MD, chief medical officer of Dynavax, told Healio.com/Hepatology. "Really, the most important thing is that two doses of Heplisav induces significantly higher and earlier seroprotection rates than three doses of the other approved vaccines. I think this is important in a time when we're seeing increases in hepatitis B transmissions in the United States."

The vaccine's approval was based on data from three phase 3 noninferiority trials of approximately 10,000 adult patients with HBV who received Heplisav-B.

In the largest phase 3 trial, which included 6,665 patients, Heplisav-B demonstrated a significantly higher rate of protection compared with GSK Source's Engerix-B (95% vs. 81%). Similarly, in a subgroup analysis of 961 patients with type 2 diabetes, Heplisav-B resulted in a significantly higher rate of protection compared with Engerix-B (90% vs. 65%)

The most common local reaction throughout the phase 3 trials was injection site pain (23% to 39%), and the most common systemic reactions included fatigue (11% to 17%) and headache (8% to 17%).

According to Schaffner, although there are HBV vaccines that work effectively in infants, children and adolescents - with protection rates of over 90% - the protection rates of those vaccines are between 40% and 70% in adults. Schaffner noted that the three-dose process of other vaccines over 6 months can often lead to patients not completing the series and leaves patients at risk until the series is complete.

"What we saw in all the groups we looked at, we saw significantly higher rates of protection in the Heplisav group but particularly in those groups who don't respond to the other vaccines," Janssen said in reference to specific populations that often have lower rates of success with the other vaccines, including older patients, those with diabetes, those with obesity and those who smoke."

"For hepatitis B, we now have three very effective vaccines that can be used in populations," Schaffner concluded. "I think if we can get our acts together and get much more aggressive and comprehensive in the delivery of those vaccines, use them all to good effect in the populations indicated, we can reverse that increase in rates of hepatitis B in this country and drive hepatitis B rates down much further."

Dynavax expects to commercially launch Heplisav-B in the U.S. during the first quarter of 2018. -  by Talitha Bennett

Reference: www.dynavax.com

Disclosures: Schaffner reports no relevant financial disclosures. Janssen reports he is an employee of Dynavax.

 

 



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HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

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Just a small snippet, from a very much larger, more involved study regarding the effects of preventing HBV via HBV immunization on world populous in relation to noting a positive decreasing incidence of developing non-hodgkin lymphoma (NHL) as well as helping to prevent HCC. (NHL and HCC thought to be associated as possible later long-term negative outcomes of being HBV infected). There is a need to demonstrate the benefits of HBV vaccination.

 

Medscape - Perspective > Journal of Viral Hepatitis

The Impact of Hepatitis B Virus Infection and Vaccination on the Development of Non-hodgkin Lymphoma

C.-E. Huang; Y.-H. Yang; Y.-Y. Chen; J.-J. Chang; K.-J. Chen; C.-H. Lu; K.-D. Lee; P.-C. Chen; C.-C. Chen - J Viral Hepat. 2017;24(10):885-894. 

 

... In conclusion, this large cohort study confirms the risk of HBV infection for developing NHL and CD20+ aggressive lymphoma. Our study demonstrates, for the first time, universal HBV vaccination reduces the incidence of NHL in adolescent and young adults less than 20 years. It suggests that cancer prevention through HBV vaccination is not only for hepatocellular carcinoma but also NHL in endemic areas of HBV infection. However, this needs a longer period of follow-up for confirmation in older populations. These evidences suggest that HBV could be an etiologic factor for NHL and CD20+aggressive lymphoma, although confirmation of the mechanism needs further study ...

 

 



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HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

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Trial study data presented on one treatment protocol for HBV.

Helio - From the Liver Meeting

Most patients achieve control of HBV with combined interferon therapy

October 24, 2017

WASHINGTON - Replicor announced interim follow-up data from the REP 401 protocol, an ongoing evaluation of the company's REP 2139 combined with tenofovir disoproxil fumarate with pegylated interferon alpha 2a as a treatment for patients with hepatitis B, according data presented at The Liver Meeting 2017.

REP 2139-based combination has for the first time achieved functional control or cure in a very high proportion of patients. Equally as important is the normalization of liver function in the absence of therapy, even in patients with significant liver enzyme elevation before treatment began. Andrew Vaillant, PhD, chief scientific officer at Replicor, told Healio Gastroenterology and Liver Disease. "Replicor believes this interim follow-up data from the REP 401 trial clearly demonstrates that REP 2139 will become the indispensable backbone of future combination therapies."

Early data from the REP 401 protocol showed that eight of 10 patients with HBV achieved functional control of infection at the end of treatment with combined REP 2139, tenofovir disoproxil fumarate and pegylated interferon alpha 2a. Specifically, these eight patients had HBsAg below 1 IU/mL and HBV DNA below 10 IU/mL.

Therapeutic liver flares and anti-HBsAg antibody levelsup to 223,055 mIU/mL accompanied functional control.

Functional control persisted after removal of all parts of therapy with data from 24 weeks in four patients and 12 weeks in four patients. The most recent data showed that four patients achieved HBsAg loss and HBV DNA below 1,000 copies per mL for 6 months after treatment ended.

"Replicor's current REP 401 protocol will continue to track the functional control of patients for 48 weeks after removal of therapy," Vaillant said. "After this follow-up, patients will be enrolled in a long term surveillance trial similar to the one currently underway following completion of our REP 301 trial in HBV/HDV coinfection."

 

Reference: www.replicor.com



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HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

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Just another tidbit about how we hope HBV immunization vaccination rates will continue to rise worldwide.

Helio - IN THE JOURNALS

Low-income nations need greater health investments to eliminate HBV

GBD 2016 SDG Collaborators. The Lancet. 2017;doi:10.106/S0140-6736(17)32336-X.

September 15, 2017

Higher-income northern and western European countries ranked the highest on the United Nation's health-related Sustainable Development Goals index in 2016 regarding the elimination of hepatitis B, according to an analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, or GBD. Countries that ranked the lowest were in sub-Saharan Africa.

"Leaving no one behind is the cornerstone of the Sustainable Development Goals (SDGs), the international development agenda formally adopted by the UN and its member states in September 2015. To deliver on this aim, it is essential to measure where advances have been achieved - and where challenges or new threats are occurring - through routinely updated, comparable monitoring and evaluation," the researchers wrote.

The researchers ranked 188 countries according to estimated trends toward individual SDG indices, including vaccine-preventable diseases, from 1990 to 2030.

In 2016, the countries with the lowest rates of HBV incidence included Andorra, Belgium, Chile, Cuba, Cyprus, Denmark, France, Germany, Israel, Luxembourg, Malta, the Netherlands, Poland, Slovenia, Spain, the United Kingdom and Uruguay. Meanwhile, Austria, Finland, Iceland, Norway and Sweden ranked the highest.

The countries ranked in the bottom 15 percentile with the highest rates of HBV incidence included Benin, Burkina Faso, Cambodia, Cameroon, Chad, Côte d'Ivoire, Guinea, Guinea-Bissau, India, Malawi, Mozambique, Niger, Senegal, Sierra Leone, Somalia, Tanzania, Togo and Zambia. Central African Republic and Tonga ranked in the bottom 5 percentile.

Regarding vaccine coverage, 63% of the 188 countries achieved vaccine access or coverage for 90% or more of their respective populations in 2016. By 2030, researchers project that 78% of the countries will reach vaccine access or coverage for 90% or more of their respective populations.

"Notably, performance on vaccine coverage, a new indicator as part of the GBD SDG assessment, was generally high across the development spectrum with the exception of the lowest [socio-demographic index (SDI)] countries; in fact, several middle-SDI countries such as Brazil had among the highest scores," the researchers wrote.

Projected attainment of SDG targets by 2030, including the elimination of HBV, correlated with the defined socio-demographic index. Countries higher on the socio-demographic index had the highest levels of target achievement.

The researchers projected that absolute levels of overall health spending are likely to remain low among lower-income countries and emphasized that increased development assistance for health and larger allocations toward health to the extent possible will be critical to achieve SDG goals such as HBV elimination. "It is increasingly clear that the health-related SDG agenda hinges upon markedly accelerating progress, particularly among the world's poorest populations. Succeeding in this endeavor is not yet an impossibility - nonetheless, it will demand extraordinary financial and political commitment by national and international agencies alike to ensure that truly no one is left behind in 2030," the researchers concluded. - by Talitha Bennett

 

 

 



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HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

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An interesting "global" look at HCC. One of the bottom lines, is that Hep B immunization (among other things!) can go a long way in helping to prevent HCC:

Incidence of Liver Cancer Rising in Most Areas of the World 

Pam Harrison - October 06, 2017 - Medscape Article

 

The incidence of liver cancer has increased over the past 25 years in much of the world, but the cause of that cancer varies greatly depending on the geographic region and, to a certain extent, also varies according to income. These are the conclusions from the  Global Burden of Disease (GBD) 2015 study, which was published online October 5 in JAMA Oncology.

"Liver cancer remains a major public health burden globally," senior author, Christina Fitzmaurice, MD, MPH, University of Washington, Seattle, and colleagues write.

"Liver cancer was the fourth leading cause of cancer death in 2015 (Fitzmaurice et al) after lung, colorectal, and stomach cancer," the authors report. In actual numbers, a total of 854,000 incident liver cancer cases occurred around the world in 2015, along with 810,000 deaths.

This added up to 20,578,000 disability-adjusted life-years (DALYs) around the world. As the authors explain, 1 DALY represents 1 lost year of healthy life.

The report also notes that between 1990 and 2015, liver cancer incident cases increased by 75%.

In addition, "between 1990 and 2015, cases of liver cancer, deaths, and DALYs increased for all cause groups globally. The highest increase in incident cases was due to HCV [hepatitis C virus], followed by alcohol," the investigators observe.

"The highest burden of liver cancer incident cases, deaths, and DALYs was observed in East Asia," they report.

Analysis of only high-income countries in the Asia Pacific revealed that Japan had 75% of incident liver cancer cases, two thirds of which were caused by HCV infection.

Between 1990 and 2015, age-standardized incidence rates of liver cancer also showed that incidence rates increased by over 100% in many high-income countries, including the United States, Canada, Australia, New Zealand, and most European countries.

On the other hand, age-standardized mortality rates (ASMRs) declined substantially in regions such as East Asia and western sub-Saharan Africa, where liver cancer rates have traditionally been high.

For example, ASMRs in China dropped by one third between 1990 and 2015, possibly because of reduced exposure to aflatoxins and to some extent national hepatitis B virus (HBV) vaccination programs. Aflatoxins are a family of toxins produced by certain fungi that are found on agricultural crops, such as maize (corn), peanuts, cottonseed, and tree nuts.

 Sex Differences

"Marked differences at the global level exist by sex for HBV-related and alcohol-related liver cancer," the investigators continue. For example, HBV caused 203,000 liver cancer cases in men in 2015 but far less than half that number, at 70,000 cases, in women.

Alcohol in turn caused almost the same number of liver cancers in men, at 204,000, in the same year but even fewer than HBV infection caused in women, at only 45,000 cases, again in 2015.

"The contribution of different etiologies to total liver cancer deaths varies markedly between countries and regions," the researchers write.

Overall, HBV and alcohol were the most common causes of death from liver cancer in 2015, causing 33% and 30%, respectively, of global mortality from the disease.

HCV infection caused 21% of liver cancer deaths in the same year, while 16% of deaths were from other causes.

However, the cause of death from liver cancer varied significantly across different geographic regions.

 

For example, HBV infection was least likely to cause death from liver cancer in places such as southern Latin America and most likely to cause death in western Saharan Africa and in Andean Latin America.

HCV infection in turn was the least common cause of death from liver cancer in East Asia but the most common cause of death from liver cancer in high-income countries in the Asia Pacific region.

Alcohol, perhaps not surprisingly, made the smallest contribution to death from liver cancer in North Africa and the Middle East but was the greatest contributor to liver cancer death in Eastern Europe, where it caused over half of all deaths from the disease in 2015.

Alcohol was also the biggest player behind mortality from liver cancer in Belarus.

"Our results show that most cases of liver cancer can be prevented through vaccination, antiviral treatment, safe blood transfusion and injection practices, as well as interventions to reduce excessive alcohol use," the researchers state.

The fact that liver cancer caused by HBV would have decreased had the population remained the same between 1990 and 2015 suggests that global vaccination against HBV infection is starting to be successful.

Indeed, "assuming that present HBV vaccination trends continue, between 2020 and 2050, the number of new HBV infection is estimated to drop by 70%," the study authors suggest.

The overall increase in incidence rates of liver cancer caused by HCV infection also highlights the importance of both prevention and the need to make HCV antiviral medications more affordable to control the infection when present.

Dr Fitzmaurice has disclosed no relevant financial relationships. Disclosures of other coinvestigators are listed in the publication.

JAMA Oncol. Published online October 5, 2017.

 

 

 

 



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

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Yup, easy peasy stuff eh! All ya gotta do is read it and re-read it about a million times just to begin to firmly or loosely entrench difs between antigens and antibodies! And then learn to ignore all acute hep info when all you need to know about is chronic hep, or vise versa!! And then go off and search for and find about a million other studies to read, to try and fill in all the missing blanks that skimming this stuff invariably leaves you with! hee hee C.



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HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

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No matter how many times I read this stuff, I always have to refer back to it when I have a question. There are so many variables and small nuances with HBV. It's good to have these resources when the questions arise. Until recently they weren't aware of the reactivation possibilities, so again, we add a little more to the HBV equation.

No quizzes allowed...  wink



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Pulled this up from where is was buried below. Hard stuff to fathom, but this older CDC thing covers the basics. C.

 

Just more review about HBV:

Hepatitis B

Like hepatitis A, hepatitis B in adults produces hepatocellular enzyme level elevations (AST and ALT predominate). In adults who acquire hepatitis B, the infection almost always clears, but antibodies persist. In a few, the disease does not resolve but becomes chronic. These patients retain serum markers of viral infection. Many blood tests are available for hepatitis B antigenic determinants and their antibodies. It is best to separate testing appropriate for the acute hepatitis situation from testing for chronic liver disease caused by hepatitis B. Only a few tests need to be considered by the generalist to determine the status of a patient with possible hepatitis B. A full discussion of hepatitis B can be seen in the Disease Management chapter on Hepatitis B.

Acute Hepatitis B

Hepatitis B surface antigen (HBsAg) emerges within 2 weeks of exposure but can often be delayed for weeks or months. This antigen is present in the blood for a variable period, usually encompassing the time during which the patient is clinically ill and most likely to seek medical attention. In patients with mild symptoms whose testing may be delayed, the HBsAg level may have already declined. In this case, a second chance to make the diagnosis comes from detection of the IgM antibody directed against the hepatitis B core (HBc) antigen, anti HBc-IgM (Table 6). Similar to the testing for acute hepatitis A, selective testing of serum IgM anti-HBc is required to establish a diagnosis of acute hepatitis B in patients whose HBsAg levels have already declined. The total anti-HBc antibody test will be positive in the presence of either anti-HBc IgG or IgM.

Table 6. Common Hepatitis B Testing Results
TestResultInterpretation
HBsAgNegativeSusceptible
Anti-HBcNegative 
Anti-HBsNegative 
HBsAgNegativeImmune due to natural infection
Anti-HBcPositive 
Anti-HBsPositive 
HBsAgNegativeImmune due to hepatitis B vaccination
Anti-HBcNegative 
Anti-HBsPositive 
HBsAgPositiveAcutely infected
Anti-HBcPositive 
IgM anti-HBcPositive 
Anti-HBsNegative 
HBsAgPositiveChronically infected
Anti-HBcPositive 
IgM anti-HBcNegative 
Anti-HBsNegative 
HBsAgNegativeInterpretation unclear 4 possibilities:
Anti-HBcPositive1. Resolved infection (most common)
Anti-HBsNegative2. False positive
  3. "Low level" chronic infection
  4. Resolving acute infection

From: Interpretation of hepatitis B serologic test results. Centers for Disease Control and Prevention website. www.cdc.gov. Accessed June 27, 2013.

In acute hepatitis B, medical attention is not sought early. In such cases the HBsAg may have already disappeared. The anti-HBs will not yet have emerged. Thus the sole viral marker may be anti-HBc. This same serologic pattern may be seen years after infection when the titer of anti-HBs is low. Sorting out the difference between late resolved hepatitis B and the period in acute hepatitis B described above can be achieved by testing for anti-HBc IgM which will be positive during this so-called "window period" of acute hepatitis B.

Chronic Hepatitis B

Chronic hepatitis B is characterized by persistence of HBsAg for a period longer than 6 months with positive anti-HBc (IgG), and negative anti-HBs. An additional antigen-antibody system plays a role in patients with chronic hepatitis B and requires mention: the hepatitis B e antigen (HBeAg) and its antibody (anti-HBe). HBeAg positivity in chronic hepatitis B usually indicates active viral replication and significant liver injury. In time, HBeAg may be lost, replaced by its antibody, anti-HBe. This transformation is often associated with lower level infection (less viral replication) or HBV DNA, lower AST and ALT values, and less (or no) hepatic inflammation.

Reactivation Hepatitis B

Hepatitis B reactivation is a sudden increase in hepatitis B virus (HBV) replication or the reappearance of active inflammatory disease of the liver in a patient with previously documented resolved HBV, or with the inactive HBsAg carrier state. Reactivation is usually triggered by immunosuppression in the host, which can occur following the use of chemotherapeutic agents for malignancy and following therapy for autoimmune diseases or organ transplantation.

Reactivation can also occur spontaneously. The extent of clinical manifestation from reactivation HBV can vary from a transient, clinically silent disease to severe or acute liver failure. A chronic infectious state can also be seen following HBV reactivation. Diagnosis of HBV reactivation depends on the HBV disease state before activation. In a patient with resolved infection (negative HBsAg and positive anti-HBs), reactivation is indicated by the decline in anti-HBs and the reappearance of HBsAg. In patients with quiescent HBV with positive HBsAg, reactivation is diagnosed by a rise in the serum HBV DNA (>1 log10 IU/mL) or a rise in the serum ALT levels (>3 times baseline). Reappearance of HBeAg in a patient with previous negative HBeAg also indicates HBV reactivation.

Role of HBV DNA Assays, HBV Genotypes and Liver Biopsy in Chronic Hepatitis B

HBV DNA level plays several important roles in chronic hepatitis B. It is the most important factor for predicting the progression to cirrhosis, helps to determine the need for treatment in HBeAg negative patients, and also plays a crucial role in estimating the response to treatment. Up to 8 HBV genotypes, labeled from A to H, have been identified. Recent studies have shown that some genotypes are associated with early HBeAg seroconversion, less progression to cirrhosis and hepatocellular carcinoma, and may also predict the response to treatment with interferon. These concepts and exceptions are discussed more fully in the Hepatitis B chapter. A clinical practice guideline on viral hepatitis B has provided additional information on laboratory testing in various contexts of hepatitis B infection.7

Resolved Hepatitis B and Immunization Status

As indicated in Table 6, an individual with resolved hepatitis B infection almost always has anti-HBc and anti-HBs. An individual successfully immunized against hepatitis B expresses only anti-HBs. Confusion may occasionally arise in the interpretation of hepatitis B tests in a patient who has recovered from hepatitis B many years ago and who has a low or absent level of measurable anti-HBc.

 



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

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Quicker HBV immunizations may (some day soon) be possible, quicker protection for us, should immunization be ordered prior to starting our hep c treatment.

 

 Medscape -  News & Perspective - Marcia Frellick - July 30, 2017

 FDA Panel Supports Licensing Two-Dose Hep B Vaccine

 

(excerpts)

 

... Heplisav-B, Dynavax Technology's experimental hepatitis B vaccine, was recommended for licensing at a meeting Friday of the US Food and Drug Administration's (FDA's) Vaccines and Related Biological Products Advisory Committee.

 

The committee voted 11-1 (with 3 abstentions) that the available data support administration of Heplisav-B to adults aged 18 years and older.

 

Much of the praise was for Hepislav's shorter schedule: it is given twice over 1 month instead of rivals' three doses over 6 months, important because of the low percentage of patients who currently complete all three doses.

 

The FDA does not have to follow the advice of its advisory panels but typically does.

Last November, the FDA rejected Dynavax's marketing application for the vaccine for the second time in 3 years.

 

Although pivotal trials have shown that Heplisav-B is effective, its safety profile is not as clear, according to an FDA review released before Friday's discussion.

Darcie Everett, MD, PhD, with the Division of Viral Products in the FDA, reported that Dynavax has proposed that Kaiser Permanente in northern and southern California use electronic health record databases to conduct the postmarketing study, for which Dynavax will supply Heplisav-B free of cost.

 

Benefit vs Risk

Gregory Poland, MD, professor of medicine and director of the Vaccine Research Group at the Mayo Clinic, chaired the safety evaluation and adjudication committee for two of the three pivotal trials for Heplisav-B.

 

He told the committee, "I believe Heplisav provides me as a clinician with a critical tool that will move to the protection of more adults in the US.

 

"While the impressive success of the hepatitis B vaccine in children could create the perception that a new hepatitis B vaccine isn't needed, it's a far different story in adult medicine," he said. "Acute cases are increasing in adults."

 

Heplisav has several advantages. These include rapid induction of "almost 90% by 8 weeks and nearly all by 12-plus weeks," which will help protect those at higher risk as well as healthcare workers; reliable induction of immunity; and a shortened immunization schedule.

 

Common sense suggests that people are more likely to follow the two-dose, 1 month schedule, he noted, which is crucial for full protection.

 

"From my perspective, the safety profile of Heplisav is similar to Endrix, which is reassuring. The results from a clinical trial showed similar rates of local and systemic postinjection reactions, adverse events, and serious adverse events. Rates of death were similar when excluding drug overdose."

 

"Nonetheless, we all know that rare events, coincidental or not, may occur with wider use," he said, and added his support for a rigorous postmarketing study, as proposed.

 

The US Centers for Disease Control and Prevention estimates that up to 2.2 million people in the United States have chronic hepatitis B virus infection and that about 786,000 people worldwide die each year from hepatitis B virus-related liver disease. There is no cure for hepatitis B, and disease prevention through more effective vaccines is critical to reducing the spread of the disease ... 

 

 

 



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

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Just more support on my unpopular expensive "more safe than sorry" theory, that all HCV pts. being readied for HCV treatment should have HBV DNA testing prior to treatment (and perhaps after!), even if there are only a few of us who might be a dormant "occult" B, or even if there are only a few of us who possess core B antibody/with no surface antigen (deemed a resolved B).

Even tho this study is small and limited, with some "null" outcomes, it, like many other studies and articles on B reactivation risks, leaves important unanswered questions. What remains is that we may not be able to safely rely (soley) on neg B surface antigen tests alone.

DAA treatment for HCV raises risk for potential HBV reactivation

Yeh ML, et al. J Gastroenterol Hepatol. 2017;doi:10.1111/jgh.13771.

 Helio - March 13, 2017

Patients with chronic hepatitis C and a current hepatitis B infection have a potential risk for HBV reactivation during direct-acting antiviral therapy, according to the results of a prospective study.

"There is increasing concern regarding hepatitis flare related to HBV reactivation during DAA therapy in [chronic HCV] patients with current or past HCV infections," the researchers wrote."The current study demonstrated that there is no impact of HBV exposure on [chronic HCV] treatment with pan-oral DAA in high HBV endemic areas, such as Taiwan, in terms of HCV efficacy. However, we also found that patients still carried the risk of HBV virological reactivation with a clinical hepatitis flare-up during therapy."

Researchers conducted the study in one tertiary hospital in Taiwan between December 2013 and August 2016 and evaluated 64 chronic HCV patients treated with DAA therapy. Seven patients had current HBV infections (positive hepatitis B surface antigen, or HBsAg) and 57 had past HBV infections (negative HBsAg/positive hepatitis B core antibody, or Anti-HBc). Mean patient age was 63 years and 26.6% were men. Twenty-two patients had liver cirrhosis and four had hepatocellular carcinoma.

Twenty-three patients received Harvoni (ledipasvir/sofosbuvir, Gilead Sciences), 17 received Sovaldi (sofosbuvir, Gilead Sciences) plus ribavirin, 15 received Daklinza (daclatasvir, Bristol-Myers Squibb) and nine received Viekira Pak (paritaprevir/ritonavir/ombitasvir/dasabuvir, AbbVie).

Regarding patients with past HBV infections, two had clinical reactivation at week 4, one at week 8 and one at end of treatment, but no patients had virological reactivation during treatment.

Of the seven patients with a current HBV infection, three patients had detectable pre-treatment HBV DNA levels of 127,998 IU/mL and 16,600 IU/mL and four had no detectable HBV DNA. The patient with detectable HBV DNA of 16,600 IU/mL had a virological and clinical reactivation. Three of the patients without detectable HBV DNA at baseline had virological reactivation. One had HBV DNA reappearance at week 1 and one had reappearance at week 4, while there was an HBV DNA surge in the third patient at week 8 that spontaneously declined to an undetectable level by the end of treatment.

No mortality, liver transplantation or obvious fluctuation of the HBsAg level was observed in any patient. Due to the small sample size, the researchers were unable to analyze the factors associated with HBV reactivation.

"The mechanism through which HBV reactivation occurs remains unknown. Prior studies have demonstrated that hepatitis C virus might suppress hepatitis B virus, but the mechanism remains uncertain," the researchers wrote. "Although [interferon]-based therapy was effective in the treatment of HBV/HCV dually infected patients, HBV reactivation after HCV eradication has also been reported with IFN-based therapy for HBV/HCV dually infected patients. Interestingly, HBV reactivation was not reported in patients with an occult HBV infection with [pegylated-interferon]-based therapy but was reported in those with pan-oral DAA therapy. The distinct mechanism that was involved was considered but requires further investigation." -  by Talitha Bennett

Disclosure: The researchers report no relevant financial disclosures.

 

 



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

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Now, I love this person's thinking!! (He was making a comment, in regard to a article, on how to handle HBV testing prior to treating for HCV). Not only does he cut to the chase and recognize the risk (to those few of us who appear to be spontaneously resolved HBVers with only Positive core antibodies), he actually goes further in his practise, and walks the walk, independently adopting and employing (wisely, in my opinion) the expensive and safest way to rule out whether he needs to treat us for B prior to treating us for C!!! B DNA testing!!!  My long-time bone of contention, that the few people with occult B or showing only B core positve antibody, are at more risk/can be more easily be missed as a B, without a B DNA being done. Breath of fresh air this guy! 

biggrin C.

... This Clinical Thought provides timely awareness in the face of more and more reports of HBV reactivation/flares in the setting of HCV/HBV co-infection and HCV treatment. Basing HBV treatment on changes in HBV DNA level represents a practical approach to how and when to intervene, recognizing that HBV replication precedes the immunologic response. For those who are HBV core antibody positive but SAg negative, these patients are the real challenge. NHANEs data suggest that upwards of 8% of Baby Boomers are HBV core antibody positive. Current case reports of HBV reactivation are certainly cause for concern, and argue for caution until more data is available. In my own practice, we are heading towards monthly HBV DNA levels on all patients who are HBV SAg or isolated core antibody positive, just to simplify the algorithm and reduce error. More data will certainly be welcome to help direct practice.

 XXXXX - Portland - 11/29/2016


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HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

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I agree SF! The research and updates are wayyyyy helpful. I'm glad they are paying better attention to coinfection, whatever the combination. The importance of these studies can't be higher. I believe 2017 is going to be a very good year!

Good luck on those upcoming tests. I remember the pre test mind games. The hardest part is waiting to get it done! You'll be riding the train into SVR station in no time...



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Thank you for the ongoing research and post you make. I am very grateful and I am sure others are also very interested.

Jan 18th, I will find out the status of my HVC and HVB. I am nervously optimistic however. Bottom line, It is what it is.

Happy New Year to you

 

SF



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EOT +12 7/26/16  ALT 25 /AST 22/ ALP 83  platlets 129 C/B VL UND

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Doctor commenting on evolving guidlines for HBV testing for HCV patients, prior to HCV treatment (and how it relates to various practices).

I will still stick by my expensive theory, that it is safer and surer to test all HCV pts by HBV DNA PCR prior to initiating HCV treatment, regardless if they are not showing HBV surface antigen.

How Recent Guideline Updates on HBV Screening in HCV-Infected DAA Recipients Affect Clinical PracticeNorah Terrault, MD, MPH - 11/23/2016 

Updated Guidance on HBV Screening in HCV-Infected Patients 

Coinfection with both HBV and HCV is a relatively rare North American scenario compared with other international populations. In my practice, patients are typically monoinfected with either HCV or HBV, but < 5% of coinfected individuals may require special consideration given recently published data. 

New case reports have described HBV reactivation in HCV-infected patients across various direct-acting antiviral (DAA) regimens, including simeprevir plus sofosbuvir (with or without ribavirin), daclatasvir plus asunaprevir, and ledipasvir/sofosbuvir. These data support the idea that effective elimination of HCV provides a shift in immunological control and a window for HBV resurgence. In part because of this, the latest HCV management guidelines from the AASLD/IDSA now recommend that all patients starting HCV DAA therapy undergo HBsAg, anti-HBs, and anti-HBc testing. Let's examine in what clinical contexts this new guidance may affect patient management. 

The Nonspecialist's Office: Preventing HBV Flares, Augmenting Vaccination Rates

In hepatology offices, routine practice dictates that individuals be evaluated for abnormal liver tests. In that context, patients are often also evaluated for other viral etiologies. Consequently, given elevated ALT levels, or even normal ALT levels with HCV infection, HBV testing has been standard in this setting to inform a recommendation for vaccination.

Where the new AASLD/IDSA guidance might be the most impactful, however, is outside of the specialist's office. More providers are testing for and treating HCV, and not all of them are liver specialists. Thus, this new guidance on testing for HBV is a good addition that reinforces the importance of evaluating for HBV, not only to mitigate the risk of reactivation during HCV DAA therapy but also to increase vaccination rates in individuals without evidence of prior immunity.

In many ways, the treatment algorithms for HBV are a bit more complex than those for HCV. For the HCV-infected patient, detectable HCV RNA means treatment. In contrast, knowing the parameters for when to initiate or to stop HBV treatment requires consideration of ALT levels, HBeAg status, stage of disease, and viral levels. Nonspecialists may not be comfortable managing HBV. Anyone unsure about the best strategy for concomitant management of HBV and HCV can reach out to a specialist for assistance or refer a patient to a specialist.

 The Specialist's Office: Increasing the Frequency of HBV Monitoring 

The published thresholds that currently warrant HBV treatment are an ALT > 2 ULN and HBV DNA > 2000 IU/mL if HBeAg-negative or > 20,000 IU/mL if HBeAg-positive. An additional layer of complexity is added, however, when patients are coinfected with HBV and HCV. Because both of these viruses can contribute to ALT fluctuations, its utility as a marker of HBV disease activity is sometimes unreliable in coinfected patients. Instead, the main parameter used to determine initiation of HBV treatment is the HBV DNA level.

In fact, if a patient slated to begin HCV DAA therapy tests positive for HBsAg, the AASLD/IDSA guidelines now recommend that HBV DNA levels be examined prior to, during, and after HCV treatment. Before this guideline update, my HBV monitoring in coinfected patients was less frequent, occurring at the beginning and end of HCV treatment or at SVR12 - a span of 12-24 weeks. Now, the standardized monitoring interval of 4 weeks is suggested to prevent HBV flares. This codifies and makes clearer how often we should be measuring the HBV DNA level in HCV-infected patients on treatment.

 The Sequence of Therapies: Deciding When to Initiate HBV Treatment

Per AASLD/IDSA, HBsAg-positive patients with active HBV infection, as defined by HBV DNA level, can be treated before or simultaneously with HCV DAA therapy. I tend to treat concurrently, especially if the patient demonstrates significant or advanced fibrosis. For example, in the case of a patient with active HBV/HCV coinfection and cirrhosis, both treatments should be initiated as soon as possible. However, if HCV treatment is less urgent, an opportunity does arise to understand the relative contribution of HBV infection to ALT elevation, if desired. If HBV treatment can be initiated prior to HCV DAAs and if ALT levels normalize, you gain more information about how that patient's HBV is factoring in to liver disease activity. Thus, this separation of therapy can yield information that may help in long-term management of HBV, but there is no overall need to delay DAA initiation. If HBV DNA is undetectable or below treatment thresholds in an HBsAg-positive patient, it is appropriate to treat HCV alone, reevaluate every 4 weeks, and initiate HBV treatment if HBV DNA increases. HCV treatment can be continued at the same time.

 The HBsAg-Negative, HBcAb-Positive Patient: A Unique Population

Where the AASLD/IDSA guidelines are less definitive, due to insufficient evidence to date, is for patients who test negative for HBsAg but positive for HBcAb. These individuals have resolved HBV with markers of prior immunity but do not have active infection. No recommendation has been given that HBV DNA should be tracked in these patients, but this is an evolving area of research. Given anecdotal case reports, monitoring may be useful in certain groups (eg, HIV coinfected or immunosuppressed). In addition, if you note during HCV treatment that ALT is increasing (or not decreasing), this would be a case to check for HBV reactivation.

 Final Thoughts

Unlike HCV, HBV is not a curable disease. Long-term follow-up is necessary to reduce overall disease burden, so having additional guidance to monitor and intervene in this population is advantageous. The latest recommendations should help to remind all providers to test, vaccinate, and treat appropriately. How are you evaluating HBV risk in your HCV-infected patients? Will the AASLD/IDSA recommendations change your practice?  



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HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

(SEE UPDATES IN BIO)



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SF,

Ya, I only put it here for it's general interest.

Would be neat, in future, if people could have B immunization done just as effectively but quicker (in 2 months as opposed to 6), as the "time required" has been a bone of contention since they adopted use of the triple dose system as we know it. (Not sure how they would work A into this tho - to keep with the standard "dual" A/B vaccinations we have been "trained"/accustomed to).

They do have that "abbreviated" version of the existing triple A/B, that can be initiated "somewhat more" quickly, say when one is pressed to go on holiday to endemic areas in a hurry, but I am not sure if you end up with your max. protection possible by the time you go on the trip!!

Bigger, better, faster, onward, upward, newer mousetraps and big pharma profits. It's always the next best thing we're lookin for eh! biggrin C.



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

(SEE UPDATES IN BIO)



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It sounds interesting for future. Honestly, I would prefer to not be a pioneer in something like this. I already feel I did my part with the Harvoni and they will learn from the after effects as they kick in and change meds accordingly or at least document them.

A regular booster seems good if and only if the specialist thinks it would be of use.

 

SF



__________________

65 yo, GT1A, , Cirrhosis, F-Scan F4 33.5, TX Naive Harvoni 12 wks

SOT 2/9/16 / ALT 187 AST 114 VL 2.3M.    POSTS

EOT 5/2/16  ALT 35/ AST/25  platlets 126 C/B VL UND

EOT +12 7/26/16  ALT 25 /AST 22/ ALP 83  platlets 129 C/B VL UND

EOT + 24 10/18/16 ALT 27/ AST 20/ ALP 71 platlets 153 C UND

 * SVR *



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A " potentially" shorter B immunization period?

HBV vaccine candidate exhibits tolerability in dose escalation trial  November 25, 2016   

Yisheng Biopharma Co., Ltd. announced its hepatitis B vaccine candidate administered with its PIKA adjunct technology demonstrated tolerability and safety in a phase 1 dose escalation clinical trial.

The proprietary PIKA adjuvant technology uses its own toll-like receptor-3 (TLR-3) agonist molecules to activate the innate immune cells. It is formulated as a component of PIKA-adjuvant based hepatitis vaccine, according to a press release.

In the trial, 32 healthy volunteers received the PIKA hepatitis B vaccine in a three-dose vaccine at Singapore General Hospital and Changi General Hospital, Singapore, as opposed to three-dose vaccination of the standard licensed products. They completed the vaccine dosage within 2 months compared with the standard 6 months. It was both safe and tolerable among the patients, according to the release.

"PIKA's potent anti-viral and robust immune-stimulating capability makes PIKA platform well-suited for the development of both preventive and therapeutic vaccine against hepatitis B virus. Such encouraging data is setting up good foundation to initiate a phase 2 clinical study with expanded study population and to further evaluate the clinical safety, immunogenicity and efficacy of the investigational vaccine," Zhongkai Shi, who is overseeing the clinical program in Singapore, said in the release. "We are pleased with the results of this study in which PIKA hepatitis B vaccine exhibited good safety and tolerability. We are also encouraged by the observation of the robust immunogenicity among the human subjects immunized with the PIKA hepatitis B vaccine."

 

Disclosure: Healio/Hepatology was unable to confirm Shi's relevant financial disclosures at the time of publication.



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HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

(SEE UPDATES IN BIO)



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Hi Canuck,

I do not disagree and it's why I will have that conversation again regarding another B immunization.

I of course have the antibodies (positive)  but Hepatitis B Surface Ag [HBsAg] NEGATIVE .. and that has been from before the start of treatment.

One has to wonder why Three Twinrex did not do the job. A booster would be no problem once they agree it should be done and I will ask about the level of immunity or not as well as I have no clue about the titres as mentioned. Once again, it was my GP, not specialist who gave the Twinrex to me years before I started or knew I would start C TX.

Thank you once again for all the very factual and great information.

 

SF

 



-- Edited by Shadowfax on Sunday 27th of November 2016 06:22:05 PM

__________________

65 yo, GT1A, , Cirrhosis, F-Scan F4 33.5, TX Naive Harvoni 12 wks

SOT 2/9/16 / ALT 187 AST 114 VL 2.3M.    POSTS

EOT 5/2/16  ALT 35/ AST/25  platlets 126 C/B VL UND

EOT +12 7/26/16  ALT 25 /AST 22/ ALP 83  platlets 129 C/B VL UND

EOT + 24 10/18/16 ALT 27/ AST 20/ ALP 71 platlets 153 C UND

 * SVR *



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You are right, in that you are at low risk as far as the "method" by which you might ever be exposed to, or catch B again (blood to blood, etc) being that you don't do the high risk behaviours that might get a person there!

You are right, the risk of exposure to A is broader/easier, for anyone.

But the whole idea of immunization is just to best protect, especially "us", the ones who's livers have been beat up, and who never wish to have ANY kind of risk of liver infection/hepatitis/injury ever again!

I have no idea what your B titres ever showed, before your B immunization, or after your B immunization of 3-4 years ago. I am just surprised that your doc's did not follow through, especially after it was mentioned by them that perhaps your B immunity titre should be brought up to snuff by way of B re-immunization. It's pretty routine nowadays, that's all.

Nor do I have a clear picture of what your B surface or core antigen/antibodies show. But it seems they decided to go ahead and "treat you" (just like they would have any "spontaneously resolved person"), i.e. start the C treatment anyway, without needing to treat any "active/or chronic B", but with caution, by (very nicely, generously, pro-actively, and wisely IMO) keeping an eye on your B DNA PCR's for a rise in B level.

Perhaps the problem is that you presented with a "dif" B antigen/antibody profile (just like I did), one that is "open to interpretation". But, if the docs decided to pursue the C treatment, by handling you like an "assumed" spontaneously resolved person, then it is just a curiosity that they did NOT follow thru and dot all the i's and cross all the standard t's and bring your B titre up by re-reimmunizing you for B. 

My B antigen/antibody profile was "dif", in the "open to interpretation" category, but their "best guess" was that I was a spontaneously resolved person and carried on with the C treatment -  but, took extra care to make sure they brought my B titre up first by way of trying to double the strength of my 3 B vaccination inoculations.

Possessing a B core antibody only, leaves one in that odd (somewhat inconclusive) "open to 4 possible interpretations" category. (As I have posted before, and as mentioned many times in the long list of articles in this thread, and, as brought up again in the last good article Tig posted). From re-activation, to "occult" B, this inconclusive status can be of some concern.

HBsAg

Negative

Interpretation unclear 4 possibilities:

Anti-HBc

Positive

1. Resolved infection (most common)

Anti-HBs

Negative

2. False positive

 

 

3. "Low level" chronic infection

 

 

4. Resolving acute infection

 

I am very glad you did get B PCRs all along, I would have preferred to have them done too!

In a perfect world, when C people are about to embark on HCV therapy, (1) their A and B immunity titres should be done prior to any immunization, the A/B titres then guiding what A/B immunization is required, with A/B titres also being drawn post-immunization (to ascertain the required response is met). (2) In the initial assessment of a C person, prior to C treatment, their B surface/core antigen/antibody needs to be determined.  (3) In addition, I think it should be "a standard" that an initial B DNA PCR should be done (for ALL C people being screened for B) prior to entering into C treatment. I also think ALL the standard immunizations that "may" be required (influenza/pneumo/etc) should be done for C people prior to treatment. smile  C.



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

(SEE UPDATES IN BIO)



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Good article Tig. I have read it before. Thank you

Canuck, No clue to your question. It was my GP who gave me those shots 3 or 4 years ago. To be honest, I never heard the word titre until you first said it on this forum. I am not aware he did that. I only know as mentioned that all through my treatment, they monitored my B VL to ensure it did not resurface. It is still resting in peace.

Nobody told me I spontaneously resolved B either, only I know I was extremely sick, then felt better. C was diagnosed in 2002. It is assumed that I fought it off myself but as we know it could have started again but did not. Just as in that article, unless I am subjected to suppressant drugs to fight off something I don't have right now, the likely hood  of it coming back after reaching 24 svr is unlikely. ** We hope.

I do understand I could catch B again as well as C but I know how I got C/B and that just will not knowingly happen again. A on the other hand is always out there and a risk for everyone. I am not saying B is not important and will have that discussion again but A is a huge danger to anybody with a compromised liver and just too easy to get.

I hope everyone has a great weekend.

 

SF



__________________

65 yo, GT1A, , Cirrhosis, F-Scan F4 33.5, TX Naive Harvoni 12 wks

SOT 2/9/16 / ALT 187 AST 114 VL 2.3M.    POSTS

EOT 5/2/16  ALT 35/ AST/25  platlets 126 C/B VL UND

EOT +12 7/26/16  ALT 25 /AST 22/ ALP 83  platlets 129 C/B VL UND

EOT + 24 10/18/16 ALT 27/ AST 20/ ALP 71 platlets 153 C UND

 * SVR *

Tig


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I found a bit more information on the HBV/HCV reactivation discussion. Just wanted to throw it out for review.

Boxed Warning, HCV Guidelines Give Impetus for HBV Testing, Monitoring



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61 yo GT1A - 5 Mil - A2/F3 - (1996) Intron A - Non Responder, (2013) Peg/Riba/Vic SOT:05/23/13 EOT:12/04/13 SVR 1-4 years!

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Shadowfax wrote:

About three years ago, I had the Twinrex shots for A and B. I am still immune to A and never achieved B immunity. A booster for B was recommended but I am unsure about all of this considering I resolved it as well. To know (post-immunization) that you were "immune to A", but "not immune to B", you MUST have had your A and B titres drawn, in order for your doc(s) to tell you that status ... so, why did you and your docs just not go ahead and ensure you WERE re-immunized for B until you were showing "immunity to B", ideally a titre value of >10 mIU/ML? (just like I described below). 

Wise or not, I am more concerned with A, being so easily contracted than B that is sitting there hiding still and hope it always will. (If you have been deemed a "spontaneously resolved B" then "occult B" is extremely remote and a whole dif. kettle of fish). Seriously, I do not know if I can be made immune to B having had it and still not being immune. If you are a "spontaneously resolved B", but with a "too low" B titre, then your titre can and should be increased by re-immunization (as I outlined below).

If you have been "deemed" a "spontaneously resolved B", (humour me and just say you are indeed a spontaneously resolved B, for explanation purposes here) ... you had B and fought it off, you converted your surface antigens to antibodies. When you have your B titre done now, it detects the current amount of surface antibody seen, thus serves as a rough guide of your level of immunity. If you are spontaneously resolved (like me) and have too low an antibody titre (like I was), then you would do well to be "making your body" shown more (increase) B surface antibodies, (your B titre) by way of re-immunization.

An antibody titre of >10 affords you "more ability/memory" of how to fight off a "new" exposure to B.  Owning a B antibody titre of >10 (whether you got there by actually having a case of B once, or by being immunized) DOES not guarantee you will NOT ever catch B (or in our case, to catch B again!), but it certainly helps!, and the higher the titre (over 10) the better. 

I could be wrong, but this is the best I can think this through.

SF


 



-- Edited by Canuck on Friday 25th of November 2016 12:15:25 AM

__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

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About three years ago, I had the Twinrex shots for A and B. I am still immune to A and never achieved B immunity. A booster for B was recommended but I am unsure about all of this considering I resolved it as well.

Wise or not, I am more concerned with A, being so easily contracted than B that is sitting there hiding still and hope it always will. Seriously, I do not know if I can be made immune to B having had it and still not being immune.

SF



__________________

65 yo, GT1A, , Cirrhosis, F-Scan F4 33.5, TX Naive Harvoni 12 wks

SOT 2/9/16 / ALT 187 AST 114 VL 2.3M.    POSTS

EOT 5/2/16  ALT 35/ AST/25  platlets 126 C/B VL UND

EOT +12 7/26/16  ALT 25 /AST 22/ ALP 83  platlets 129 C/B VL UND

EOT + 24 10/18/16 ALT 27/ AST 20/ ALP 71 platlets 153 C UND

 * SVR *



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uh oh, here she goes again, no "off" button!

I gained some immunity to B, the hard way, severely ill with B back in the 70's. I required no treatment, as it was deemed I had managed to spontaneously "resolve" my B all by myself. (Only wish I had known I had also picked up C then as well!, but, at least I eventually found out about the C last year!)

In preparation for getting into my C trial, my A and B titres were drawn. Results said that I had no immunity to A, and for my B titre I was at about 6ish mIU/ml (too low) - therefore I was "technically not immune" to B either. Too low (below 10) is deemed not immune "or not immune enough" to be well protected. I believe >10 mIU/ml is the min. required for both A and B titres, if you are 10 or less then immunization (or re-immunization) is in order. It is thought though, that any prior immunity level can retain "some" helpful immunity "memory".

I had never been immunized for A, or B, until just before my trial. It mattered not to them that I had been deemed as having a spontaneously resolved case of B 40 some years ago. Based on titre levels alone, the start of the immunization series was justified (3 shots for A/B over 6 months). We commenced before trial and were still finishing immunization during trial. Another A/B titres was drawn part way through immunization, and then again a month after the last of the 3 shots were completed, to check for response.

One of my initial docs, a very experienced general practitioner, well versed in handling hepc pts., made the suggestion, that my "series of 3" A/B immunization shots (over 6 months), should have the strength "doubled" (for the B portions only). The immunization had already started, so her advice to "double" B was not instituted in time for the first shot. But, both subsequent  2nd and 3rd shots of B were double-dosed, and later condoned by my later hep doc.

So, pre-immunization - my titres  for A=0, and for B=6ish.

Shot #1 - Single dose A, Single dose B.

One month later - Shot #2 - Double dose B.

6 months later - Shot #3 - Single dose A, Double dose B.

3 months after my first and 2nd shots were completed (with the 2nd shot of B being doubled) - my B titre had increased from 6ish to about 15.6mIU/ml, and I still had no immunity to A.

It was not until a month after all of the shots (in the series of 3) were completed (in month 7) that I finally showed "reactive/discordant/ immunity" to A, and my titre to B had not really increased much more, 15.7.

My hepdoc recommended in a year to re-check the A and B titre levels. (I now appreciate him recommending that).

 Now, all I can glean (from my reading, figuring and surmizing) is that I am "immune enough" for the kinda gals they go with. No real idea as to why I had the "small" responses and "slow" responses, even to double-dosed B.  I had heard they seldom worry much about A "taking" in folk, as generally it "takes" quite well, quick-like (readily) and yes, A "took" in me, but seemed a little slow on the uptake (considering potential exposure and for safety-sake in the interim). I think the "theory" in double-dosing the B (I believe) has to do with (1) perhaps one's lac-lustre general health and liver function disadvantages, so, the "more-is-better/safer double-dose rule" may be employed, and, (2) given the circumstances of them wanting you to be in a state of  "B immune" as soon as possible, and wanting the B to "take" and "take as soon as possible", so that you are at your best prior to C treatment, that may prompt them to double-dose B as an "extra" guarantee?

In general population, if your A/B did not take, they would just make you go through the whole series again (eh hem, lessee, that's 6 months, and then another 6 months! - hope you weren't going 3rd world soon or exposing yerself unduly in the meantime!). But then again, in most people, A/B vaccinations DO take, readily we trust, and it seems even a little dab 'il do ya in a pinch and affords some protection, and besides, not many of the general pop. are even getting their titres done to know how well their immunizations took in the first place!

In the past, there was much more "talk" on how "best" to immunize for A/B, age, timing, products. Current practices seem pretty universal now, and there is less arguing over nuances now, compared to pre-90's. Post-90's, studies can be found, about mathematical predictions/percentages of how much/how soon immunity/titres will be lost/drop each year.

If you are told or have heard you are "good for 10 years", it might be true, and, it might not be true for another person.How long will my "whopping" tiny B titre of 15.6 last me, before it drops to below 10 again? Who knows. I'll get to see how it's doing about next May.

Aside from A and B, I had influenza and pneumococcal immunizations too, all first time for me, and all recommended for C people preparing for treatment.

I wish a "standard" for a C people getting ready for treatment, included these before, during and after immunization A/B titres, not to mention (my bone of contention) that we should all have a standard B DNA PCR screening test prior to C treatment too, so no status is left out. C.



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HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

(SEE UPDATES IN BIO)

Tig


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The things that exist just beyond our thoughts can be powerful in nature. Something simple and innocuous can blow up in a flash. The sharing of information helps keep us better informed and as a result, healthier. Peace of mind is good...

SF, I will address this revaccination subject next time I speak to my doc. In the meantime, I'll give raw oysters a pass and wash my veggies well! 



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I guess it's more common than I thought.  As usual, the forum is on top of things.

 



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Tig56 wrote:

Same thing happened to me. My last showed no antibodies to A or B and have to do it again. I had my vaccinations a long while ago, so something went wrong. Repeat was the same. Easy enough to do it again, but it requires another visit to the doctor. I think most of us here have earned a vacation from the doctors. A mental time-out is necessary sometimes!


 ... but you will visit your doctor for those vaccinations again right?

I usually get my GP to add A antibody to most lab req's he does. Peace of mind to know that I am still protected.

 

SF



-- Edited by Shadowfax on Tuesday 22nd of November 2016 01:05:35 PM

__________________

65 yo, GT1A, , Cirrhosis, F-Scan F4 33.5, TX Naive Harvoni 12 wks

SOT 2/9/16 / ALT 187 AST 114 VL 2.3M.    POSTS

EOT 5/2/16  ALT 35/ AST/25  platlets 126 C/B VL UND

EOT +12 7/26/16  ALT 25 /AST 22/ ALP 83  platlets 129 C/B VL UND

EOT + 24 10/18/16 ALT 27/ AST 20/ ALP 71 platlets 153 C UND

 * SVR *



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As far as I know, an A titre, or a B titre (to be of a protective level) needs to be > 10mIU/ml. Under 0 to 10 calls for immunization, or re-immunization, even though "some" protective antibody "memory" may still persist from past active or passive immunity.

The healthier, low-risk, general population don't even seem to get pre-assessment titres done, even if their immunization status is in doubt or unknown - they err on the side of re-vaccinating. I guess the assumption is, over-vaccinating, no harm done - lack of immunity is the risk. Nor do I think the general population get post-immunization titres done! 

Have read old studies about falling titres. After A immunization for instance, an A titre can get up to be in the thousands, or hundreds, and then falls over time. Interesting to me.smile C.



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HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

(SEE UPDATES IN BIO)

Tig


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Same thing happened to me. My last showed no antibodies to A or B and have to do it again. I had my vaccinations a long while ago, so something went wrong. Repeat was the same. Easy enough to do it again, but it requires another visit to the doctor. I think most of us here have earned a vacation from the doctors. A mental time-out is necessary sometimes!



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Hey SF,

Let me add to that:  I saw my hep specialist last week to follow up on my 6 month SVR.  All is well biggrin but oddly I showed insufficient antibodies to hep A and B (but no infection).  I say "oddly" because I had my Hep B series 2 years ago before traveling to India (2 injections before and 1 after).  Also, I have had antibodies for Hep A since I was a teenager, having picked up a serious case, babysitting in hippy squalor.  None the less, my hep specialist has me doing them again, saying it just happens sometimes.  Go figure.

Anyway, I am still celebrating that I have no hep of any kind.  If things keep going the way they are, nobody will!

Oh boy, let's dance.

 

Cheddy

 



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GT2a, VL 681,500, Less than F1, Treatment Naive

12 wks Sovaldi/Ribavirin, SOT 2/25/16, EOT 5/17/16

UND at 2,4,8 and 12 wks during treatment but ribavirin crazy.

ALT/AST normal EOT

SVR12 8/13/2016!!!!!!!!!  I WON!!

EOT 6 Months 11/12/2016  CURED

 



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A vaccination against A is so very important. B as we know must also be blood to blood/ body fluids  but A, you can pick up from your grocery store on a lettuce. It happens way too often. If you have Hep, you must get an A vaccination and should get a B as well for peace of mind.

 

SF



__________________

65 yo, GT1A, , Cirrhosis, F-Scan F4 33.5, TX Naive Harvoni 12 wks

SOT 2/9/16 / ALT 187 AST 114 VL 2.3M.    POSTS

EOT 5/2/16  ALT 35/ AST/25  platlets 126 C/B VL UND

EOT +12 7/26/16  ALT 25 /AST 22/ ALP 83  platlets 129 C/B VL UND

EOT + 24 10/18/16 ALT 27/ AST 20/ ALP 71 platlets 153 C UND

 * SVR *

Tig


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Thanks for that information, Chuck! I speak for everyone, we appreciate all of the help you provide here. We're fortunate to have a research geek among our ranks! Very cool, thanks!

Great idea to our readers, confirm you have been tested for A, B and C. Easy to do and if you need vaccinations, it's your chance to get it done. Best to determine everything now and limit surprises for something fun!



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Tig

61 yo GT1A - 5 Mil - A2/F3 - (1996) Intron A - Non Responder, (2013) Peg/Riba/Vic SOT:05/23/13 EOT:12/04/13 SVR 1-4 years!

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Canuck wrote:

Shadow,

Yes, we have to be reasonable about the "likelihood" of things! We don't want people going all paranoid on top of every other scary thing we go through with just dealing with having HCV and getting rid of it.



 

Exactly but this sums it up for us quite well. We need to be reasonable or we will never have peace of mind. Once again, thank you for your continued contributions. I hope you are doing great.

 

SF



__________________

65 yo, GT1A, , Cirrhosis, F-Scan F4 33.5, TX Naive Harvoni 12 wks

SOT 2/9/16 / ALT 187 AST 114 VL 2.3M.    POSTS

EOT 5/2/16  ALT 35/ AST/25  platlets 126 C/B VL UND

EOT +12 7/26/16  ALT 25 /AST 22/ ALP 83  platlets 129 C/B VL UND

EOT + 24 10/18/16 ALT 27/ AST 20/ ALP 71 platlets 153 C UND

 * SVR *



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Shadow,

Yes, we have to be reasonable about the "likelihood" of things! We don't want people going all paranoid on top of every other scary thing we go through with just dealing with having HCV and getting rid of it.

 (1) There are not many of us HCV people, who also have (or had) B, period (we guess! - if you have trust in the current limited screening identifying a B status!). 

 (2) There are not very many C's who do NOT receive "some form" of B screening before treatment (as limited as that screening may be).

 (3) There are not many of us, who get their B status inaccurately deemed immune or non-active (and then are later found to actually be occult B's or active).

 (4) There are very few C's who have had B re-activation, period.

 (5) There is not enough proof to demonstrate that "thought" naturally-resolved B people are, or are not, at risk of reactivation.

 (6) There is a much higher incidence of B reactivation more with other drugs (oncology/rheumatology), B reactivation is thought much less so with HCV drugs.

Justifiable costs in health care can be based on good reason and likelihood. But my bone of contention is that for the "few" who will be "missed" in weighing how much they "might" be at risk, by their B status NOT being screened more completely by means of B DNA PCR - for these few, they are test-cost orphans without the benefit of a better guess at their status (with no B PCR being done).

I think it costly, and NOT unreasonable, to screen ALL HCV pts. for B prior to C treatment, which mostly is happening to various degrees, but most importantly, that the B DNA PCR SHOULD BE included in this screening FOR ALL (similar to the protocols used for oncology and rheumatology pts.). We cannot rely on the current surface/core antigen nor surface/core antibody testing to make the fullest determinations.

I note in guidelines for higher risk oncology pts. who are about to embark on therapy, where potential B reactivation is unwanted to say the least, they are automatically having B PCR DNA testing done, included, in part, as a fuller standard assessment protocol. Oncology pts. are subjected to higher risk drugs long demonstrated to be associated with B reactivation.

Reactivation of B (or even herpes zoster) is certainly not new to immunological treatment of afflictions (other than HCV), just newly discussed in relation to advent of the newer DAA treatments for HCV, and of late, the focus has fallen to the seemingly rare select cases of B reactivation they have found in the HCV population on newer DAA's. I have found articles referring to B reactivation with HCV treatment from 2010.

In this link - (geared to higher risk populations) the model shows B DNA testing for pts. showing surface antigen pos OR surface antigen neg, and, as well, for those showing for core antibody pos ONLY (the exact same testing results that might be found in any HCV pt. being assessed for B), even for those with core antibody pos ONLY, the DNA is tested, and if the DNA is negative, then they are still, further very closely surveilled, with ALTs and DNAs every 1 - 3 months after. (Quite thorough and cautious I'd say!).

 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4548361/figure/f01/



-- Edited by Canuck on Saturday 19th of November 2016 06:58:09 AM

__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

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*********************************************

So far, we don't have strong evidence to believe this is an issue pertaining to patients who have completed therapy or who have achieved sustained virologic response at the 12 week timepoint after the end of treatment. If cases of reactivation were to appear at that late date, it would add to the concern.

 

*********************

 

Lets hope that is remains the case. Thank you for your ongoing research Canuck.

 

SF



__________________

65 yo, GT1A, , Cirrhosis, F-Scan F4 33.5, TX Naive Harvoni 12 wks

SOT 2/9/16 / ALT 187 AST 114 VL 2.3M.    POSTS

EOT 5/2/16  ALT 35/ AST/25  platlets 126 C/B VL UND

EOT +12 7/26/16  ALT 25 /AST 22/ ALP 83  platlets 129 C/B VL UND

EOT + 24 10/18/16 ALT 27/ AST 20/ ALP 71 platlets 153 C UND

 * SVR *



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My bone of contention again ... this article (showing the current guidelines) points out that the few who may be "occult" HBV or those thought to be B "resolved", still remain at more risk because they are not being offered screening using HBV DNA PCR's. The problem, of possibly keeping "some" people at more risk (no matter how few) by not doing B PCR DNA's, is still not fully addressed by current protocol. I think standard HBV DNA PCR testing should be done for everyone who is about to be treated for HCV - a surer way to know if one IS "likely" resolved or an occult B. In HBV, indications of "resolved", does not necessarily make it so!!  It seems, being that there are so few B people at risk, and because the risk is deemed so low, the cost of standard B PCR DNA testing (to best fully screen) is still not being "justified". They truly gamble on these "few" who may or may or may not be candidates for "re-activation", who (currently) only receive the limited screening protocols.

Boxed Warning, HCV Guidelines Give Impetus for HBV Testing, Monitoring

HCV Next, November 2016

Just when HCV therapy seemed as if it has never been more straightforward, we have witnessed the emergence of an unexpected caveat regarding HCV-infected patients with concomitant hepatitis B virus infection or, seemingly, even markers of what most people would have regarded as prior infection that has resolved.

A recent update to the AASLD/IDSA HCV Guidelines on September 16, 2016, (found at HCVGuidelines.com) recommended assessment for hepatitis B infection in all patients with hepatitis C infection, followed by a highly publicized Safety Communication from the FDA on October 4, 2016, with a concomitant black box warning about direct-acting antiviral HCV therapy implicated in HBV reactivation.

Many of us did not know what to make of the warning. I, for example, have never seen a reactivation of HBV during DAA therapy and neither have the majority of my colleagues with whom I've discussed the issue. But, while the concern may seem exaggerated to those of us who've treated hundreds or even thousands of patients without experiencing problems, it's not negligible. The dilemma for us as clinicians is what to do with this information.

To be sure, HBV testing prior to HCV therapy has been a standard measure to eliminate other causes of liver disease and to ensure immunization of patients with HCV against HBV and, for that matter, hepatitis A. There's nothing new about the recommendation to test HCV-infected patients for HBV. What's new is the added rationale put forth by the boxed warning in approved HCV regimens. If reactivations are at risk of occurring, we need to know about it so we can either offer preventive therapy or monitor appropriately for early detection. If for any reason a clinician has not implemented this testing, the warning is a wake-up call.

The boxed warning is based on 24 cases of HBV reactivation reported to FDA and from the published literature in HCV/HBV co-infected patients treated with HCV DAAs during the 31 months from November 2013 to July 2016, including two deaths and a third patient who required a liver transplantation. Most of the cases occurred within 4 to 8 weeks of initiating therapy.

So far, we don't have strong evidence to believe this is an issue pertaining to patients who have completed therapy or who have achieved sustained virologic response at the 12 week timepoint after the end of treatment. If cases of reactivation were to appear at that late date, it would add to the concern.

Although a reading of the FDA Safety Communication leaves one wanting more details about these cases, it does provide us with enough information to underscore considerable heterogeneity in the patients with hepatitis B reactivation. Of the 24 patients, seven had detectable HBV DNA and were presumably HBsAg-positive; four had positive hepatitis B surface antigen (HBsAg) and undetectable HBV DNA; and three had both undetectable HBsAg and undetectable HBV DNA. The status of the remaining 10 was unknown.

The patients with undetectable HBsAg and undetectable viral load - even though there were "only" three - is perhaps of greatest concern because such patients are by far more common than those who are HBsAg-positive. Our experience with reactivation in patients with hepatitis B core antibody without HBsAg has thus far mostly been limited to patients who take certain types of immunosuppressive drugs like rituximab or those who are profoundly immune suppressed in settings such as bone marrow transplantation.

If hepatitis B can reactivate with similarly serious consequences with HCV DAA therapy even in patients with anti-HBc alone, whether with or without anti-HBs, we're going to have to be cautious with a large number of patients. So the question is: Right now, how should one interpret these revised guidelines and new warning?

The revised AASLD/IDSA Guidelines offer what seems a very reasonable group of recommendations. The Guidelines reiterate the need to test all patients initiating HCV DAA therapy for HBsAg, anti-HBs, and anti-HBc, with HBV vaccination of all susceptible individuals. Patients who are HBsAg positive should have a quantitative test for HBV DNA and receive HBV antiviral therapy before or simultaneous with initiation of HCV DAAs if they meet the criteria for treatment of active HBV infection set forth in the AASLD Guidelines for Treatment of Chronic Hepatitis B.

The HCV Guidelines state that patients with low or undetectable HBV DNA levels should be monitored for HBV reactivation and treated if the aforementioned criteria are then met. In my practice, I might consider giving a top-line HBV antiviral regardless of viral level if HBV DNA is detectable, especially in patients with advanced fibrosis.

Finally, the AASLD Guidelines state "there are insufficient data to provide clear recommendations for the monitoring of patients testing positive either for anti-HBc alone (isolated anti-HBc) or for anti-HBs and anti-HBc (immune recovery)." At present, my perspective is that while we must acknowledge the apparent reality of the potential for HBV reactivation in such patients, the incidence must be so low that assays for viral levels could be limited to patients whose ALT levels fail to normalize or rise as HCV replication is suppressed.

This FDA boxed warning underscores the importance of doing something that we're supposed to be doing already, but with newly understood ramifications.

- Ira M. Jacobson, HCV Next, Co-Chief Medical Editor

ASSLD Guidelines (basically) lay out - B DNA PCR only if you are B surface antigen pos.! Not far enough, IMHO.

 

 



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HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

(SEE UPDATES IN BIO)



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Pablo,

Hee hee . Brief, concise, succinct .... I am not! 

But to glean what I am trying to "get" across as important ... (without one having to read all the article and studies posted here), just review my pre-ambles or end-thoughts included on most of these posts ... about how B PCR's should be donesmile C.



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

(SEE UPDATES IN BIO)



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Hi Canuck

I can see you've gone deep on this topic.  Any chance you could summarise the situation, as I'm losing the plot when I read the thread?

I know being brief is not your strong suit...so set yourself a challenge...one para, maybe two ;)

Pablo



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44 y.o. male, HCV G4 since 1996, F-scan score 9, F2, Failed prior I/R, finished sof/vel/vox 8 weeks 5/16, pre-treatment VL 2 million, EOT UND, EOT+4 UND, EOT+12 UND.



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More about testing to detect HBV - especially those with B who do not show (or show with inconclusive antibody/antigen results) via "standard" testing.

Although this study was in relation to B only, some of the info can be applied to B/C co-infected, as it highlights the same problem (in prior post) - about inconclusive B testing, and how using core antigen is not an optimal method.  

In Dr. Seto's study, he "partially" addresses the problem, and demonstrates how limited using core antigen is, as a rough indication guide.

B DNA PCR is the only reliable method to rule out a B load when B is occult, thus, enables knowing the existence of occult B, before that patients C is treated. 

Serum HBcrAg status indicates HBV prophylactic therapy candidates

Seto WK, et al. Am J Gastroenterol. 2016:doi:10.1038/ajg.2016.436.

October 6, 2016

 ... "Patients with a positive HBcrAg (a positive core antigen) were noted to be at a significantly higher risk of HBV reactivation when compared to HBcrAg-negative (negative core antigen) patients," Seto told Healio.com/Hepatology.

Seto noted that 13% to 68% of the East Asian population has been exposed to HBV, putting them at risk for HBV recurrence during immunosuppressive therapy. While past exposure to HBV could explain the positive serum anti-HBc readings, it cannot be used to distinguish patients with previous self-limiting HBV exposure, according to the research.

Differentiating between positive and negative patients may be difficult since a majority of HBsAg-negative, anti-HBc-positive patients have undetectable serum HBV DNA. However, Seto said HBcrAg measurements would help clinicians separate their patients into either a positive or negative group and better manage their treatment. He also said HBcrAg-positive patients may be more suitable for antiviral therapy compared with HBcrAg-negative patients.

"HBcrAg-positive (core antigen positive) patients, given their higher risk of HBV reactivation, might be suitable candidates for prophylactic antiviral therapy, while HBcrAg-negative (core antigen negative) patients, given their relatively lower risk, might be more suitable for routine monitoring," Seto told Healio.com/Hepatology. "This risk stratification would optimize the management and monitoring of patients undergoing high-risk immunosuppressive therapy in HBV-endemic regions." - by Janel Miller

Further: from current American guidelines

---  all patients initiating HCV DAA therapy should be assessed for HBV coinfection with testing for HBsAg, anti-HBs, and anti-HBc. HBV vaccination is recommended for all susceptible individuals. A test for HBV DNA should be obtained prior to DAA therapy in patients who are HBsAg positive. Patients meeting criteria for treatment of active HBV infection should be started on therapy at the same time (or before) HCV DAA therapy is initiated (AASLD Guidelines for Treatment of Chronic Hepatitis B). Patients with low or undetectable HBV DNA levels should be monitored at regular intervals (usually not more frequently than every 4 weeks) for HBV reactivation with HBV DNA, and those patients with HBV DNA levels meeting treatment criteria should initiate HBV therapy (AASLD Guidelines for Treatment of Chronic Hepatitis B). There are insufficient data to provide clear recommendations for the monitoring of patients testing positive either for anti-HBc alone (isolated anti-HBc) or for anti-HBs and anti-HBc (immune recovery). However, the possibility of HBV reactivation should be considered in these groups in the event of unexplained increases in liver enzymes during and/or after completion of DAA therapy.

 

My "easy" solution for those with questionable B status, and to not miss an occult B person ... just routinely include, in screening, a HBV PCR test, for  ALL patients being assessed for HCV therapy!



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 63 y.o. F. Canada.

GT3a, Fibroscan F3/12 kPa - F4/12.6 kPa, VL log 7.01 (10,182,417), steatosis, high iron load.

SOF/VEL with/without GS-9857 trial - NCT02639338.

SOT March 10 - EOT May 5, 2016 - SOF/VEL/VOX 8 week trial.

 

(SEE UPDATES IN BIO)

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