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Hep C Discussion Forum -> Knowledge/Info Section -> About "Type" (IL28B) it still does matter
Post Info TOPIC: About "Type" (IL28B) it still does matter
Canuck


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RE: About "Type" (IL28B) it still does matter
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The same line of study ... Dr. Dunn also delves into (perhaps) the importance of determining whether you are a CC, CG or a GG gentoytpe (Rs738409).


HEALTHLINE NEWS - Written by Kristen Fischer on May 5, 2017
 
Genetic Test Could Predict Transplant Success in People with Hep C, Cirrhosis
Lack of viable donors still a problem with fatty liver disease and obesity rising.

A saliva test could identify genetic markers that indicate which people with hepatitis C and cirrhosis will benefit from certain treatments.

Researchers say this test could help doctors predict outcomes after treating hepatitis C, and decrease the need for liver transplants.

"Our findings further the move toward precision medicine, because we can potentially use a person's genetic makeup to identify individuals who can benefit most from hepatitis C treatment, even at a very late stage in the progression of their liver disease," Dr. Winston Dunn, lead author, and an associate professor at the University of Kansas Medical Center, said in a statement.

The study was presented this weekend at Digestive Disease Week 2017.

"This information will help us minimize the need for liver transplantations," Dunn said on a conference call.

"It's very simple to collect the genetic material by doing a cheek swab," Dunn told Healthline.

However, the test is not currently available as a stand-alone evaluation and only available in labs right now, he noted.

Better predicting

Although most people with hepatitis C virus can be cured, about 5 percent have more serious liver damage even after the virus is gone.

Dunn said this test would help determine who would have more success from a liver transplant.

Dunn's team examined part of the PNPLA3 gene, the Rs738409 single nucleotide polymorphism (RSP), a variation in a pair of the gene's DNA.

It can show a significant risk factor for both alcoholic liver disease and nonalcoholic fatty liver disease. There are three genotypes a person can have in the gene: CC, CG, or GG.

The researchers followed 32 people who had decompensated cirrhosis and were in that aforementioned 5 percent. These participants initially achieved a sustained virologic response and were virus-free.

Between 12 and 48 weeks later, researchers tracked their progress according to the Model for End-Stage Liver Disease (MELD) and the Child-Turcotte-Pugh (CTP) rankings.

Those scores are used to determine the severity of chronic liver disease. They found that five out of 16 patients with CG or GG genotypes had worse MELD or CTP scores. One of the people with the CC genotype had worse MELD or CTP scores.

Dunn said that the findings suggest that screening for the Rs738409 CG and GG genotypes in people with hepatitis C with decompensated cirrhosis can pinpoint people who won't recover after they are cured of the virus.

"Until now, we have not had a method to distinguish between the individuals who would recover given equal severity in baseline disease," he said.

He said this will help providers deliver more customized treatment plans based on the individual needs of patients.

In the future, Dunn wants to better understand the mechanisms that explain why having the certain genotypes can lead to poorer outcomes.

Why curing isn't enough

Dr. Richard Gilroy, who heads up the Liver Transplantation Program at Intermountain Medical Center in Utah, said the results of the latest study are promising.

However, people need to keep in mind that people with hepatitis C often have more than one health condition - so curing hepatitis isn't always enough to save their lives.

"There are people we treat for hepatitis C that will not be out of the woods," he explained.

Liver damage can still progress even after hepatitis is removed from one's system.

"Hep C can clear, but you may still develop cirrhosis or liver cancer," he said, adding that the biomarker studied can also show a person's risk for liver cancer.

Dr. Douglas Dieterich, a professor of liver diseases with The Mount Sinai Hospital in New York, said the test is a great way to tell who can recover compared with who is past the point of no return and has to stay on the liver transplant list.

He said he tests for fatty liver disease in people with hep C and finds that those with both conditions are usually the ones who do not get better.

Gilroy added that the United States is experiencing a major health crisis due to obesity and fatty liver disease.

Even if a transplant may save a person's life, it's going to be hard to get enough organs because those diseases are affecting so many potential donors, he noted.

 
 


__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 64 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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This is an interesting take on the il28b alleles. It was very ommon to have these alleles tested for back in the dinosaur days of treatment. That's just a few years ago in Hep C treatment time. I was never tested for them and that concerned me, a lot. They determined so many things when Interferon was the only option, in a combination with one or two other drugs, Ribavirin and Victrelis or Incivek. Knowing your status helped determine your odds of success and how long you were treated.

I haven't heard much about this in pre treatment testing. As the article mentioned, the new DAA's are so effective, this important (to me) bit of information is being left out of current treatment naive testing protocols. I believe the small percentage of DAA relapsers are tested, but with Epclusa + Vox being rolled out, this testing may again be ignored. Hard to say and I'm just opining at this point. I believe I would ask for the determination to be made, were I treating today. Unfortunately, if you aren't familiar with this subject, how will you ever know it's a consideration? Aren't you glad you're a member of this forum? Of course! wink

Good stuff, Chuck!



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Tig

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Canuck


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About "Type" (IL28B) it still does matter

Size (and "type") still does matter (somewhat) at least when we are talking about whether you are a CC, CT, CG, GG or a TT "type". Size? - high viral loads remain worthy of consideration when it comes to simply how potentially infective you might be (one just plain has more virus to offer up, and, they keep decreasing viral load cut-offs as to when they add riba (or soon vox for relapsers) or lengthen courses of DAA's according to a "higher" load (but higher load HAS become less of a consideration than before), but, hi-loads (in us GT3's anyway), does seem to have a co-relation to degrees of steatosis found in us (if and when steatosis is found).  See also - About GT3's and our big ole fatty livers - sometimes size does matter!

"Type" too still does matter - it used to be, knowing your IL28B status (whether you were a CC, CT or TT) or (CG or GG ) had a bearing on predicting how well one might respond to the old treatments, and/or maybe you were going to be "harder to cure" (CC being easier, CT harder,  and TT harder still). With the advent of the new DAA's, it was hinted at that your IL28B status was less important, passé so to speak, not so much of an "issue" for consideration anymore, as we were seeing cures near-approaching 100% with the new DAA's . It made me question then, (1) what were all the reasons my trial folk tested me for my IL28B status prior to giving me the best/ "newest" DAA sof/vel/vox, and, (2) why my doc seemed pleased to find out I was a CC (if IL28B was so much less an issue nowadays).

This below (from a larger article) helps me understand a bit further the nuances of being a CC, and perhaps WHY I am doing SO WELL both in terms of how well my treatment went and maybe how quickly things have turned around for me post-treatment. I am amazed at the speed of resolution of my many hep c related issues, including steatosis, as well as being classed as a technical cirrhotic with a pre-treatment fibroscan  Fscore of F4 (12.6 kPa), to being only one year SVR with a fibroscan Fscore down to F0-1 (4.7 kPa) already.

This excerpt (Digestive Disease Week 2017, William F. Balistreri, MD, July 03, 2017) has to do with a study where they were looking for genetic predictors of how well people cured with DAA's would do with their decompensated cirrhosis after SVR, namely looking at people for their genetic risk factors for steatosis, seeking to possibly use their genetic predispositions and predilections for steatosis, as a "predictor" to more reliably anticipate the very variable rates of decompensation recovery after SVR ... by virtue of this study "looking" at folks with steatosis genetics, this is "additionally" what they found about CC's, CG's and GG's.

 

... They analyzed the rs738409 single-nucleotide polymorphism of the patatin-like phospholipase domain-containing 3 (PNPLA3) gene - an important genetic risk factor for both alcoholic liver disease and nonalcoholic fatty liver disease - in a prospective cohort study of 30 patients with Child-Pugh class B or C cirrhosis due to HCV infection who underwent interferon-free DAA therapy. The demographic and baseline clinical characteristics of the patients were similar, except that patients with the rs738409 CC genotype had a significantly higher mean body mass index.

 

Child-Pugh scores improved by at least 1 point in 81% of the patients with CC genotype, compared with only 56% of patients with the CG or GG genotype.

 

None of the patients with CC genotype had worsening of their Child-Pugh scores.

 

In contrast, Child-Pugh scores worsened by at least 1 point in 13% of those with the CG or GG genotype.

 

Model for End-Stage Liver Disease (MELD) scores improved by at least 1 point in 50% of patients with CC genotype and in 38% of patients with CG or GG genotypes.

 

Conversely, MELD scores worsened by at least 1 point in 6% of patients with CC genotype and in 19% of patients with the CG or GG genotype.

 

The CG/GG genotype was associated with a higher delta Child-Pugh score and a higher delta MELD score in multivariable linear regression adjusting for confounders.

 

In terms of Child-Pugh components, patients with CG/GG genotype had a slower recovery ...



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 64 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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Canuck


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IL28B - Testing for CC, CT, TT
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This IL28B topic keeps coming up, from the old interferon non-responder days, to Mallani making good posts about it, and many others here have entered into this topic in various threads, I also commented on it when I myself was tested for my IL28B (CC) status as pre-requisite baseline data for entering my recent 8 weeek sof/vel/vox. (It was just a stnadard part of Gilead's pre-trial data gathering protocol). I again was reminded of this IL28 subject with mcmaklin's recent postings re: being a TT, prior relapse and querying an Abby trial.

The CC, CT, TT status maintains to have a bearing today, even though the new more potent/pan DAA's (such as my trial drugs) sof/vel/vox (and many of the other new potent DAA's) are proving to work so well, so pan, so effective, across so many GT's and indiscriminate of IL28B status and many RAV's.

Just thought I should post this tidbit about IL28B.

Role of IL28B Genotype in Hepatitis C

Current guidelines do not routinely recommend interleukin 28B (IL28B) genotype testing.8 Nevertheless, it is commonly ordered to obtain information about the probability of treatment response and the duration of treatment. We recommend one-time testing of IL28B in every patient who is infected with genotype-1 hepatitis C who is also a candidate for treatment.

IL28 is a cytokine that plays an important role in the defense against viral infection. It belongs to the IL10 interferon family and, in response to a virus, helps to upregulate the inflammatory potential and the innate immunity. IL28 has two isoforms, namely IL28A and IL28B. The gene for IL28B resides on chromosome 19. Recent studies have identified a single nucleotide pleomorphism near the IL28B gene that can predict the response to treatment in hepatitis C. Three genotypes exist as a result of the nucleotide pleomorphism. They are the CC, CT, and TT genotypes. Among patients who spontaneously clear HCV virus, the CC genotype has been shown to be present more than twice as frequently than the other genotypes. In addition, patients with the CC genotype also show a much better response to treatment with anti-viral therapy as compared with the CT or TT genotype. Those with TT have the least response to treatment. This pattern has been observed among all ethnic groups.

 



__________________

HCV/HBV 1973. HBV resolved. HCV undiagnosed to 2015. 64 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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