“As of 2015, WHO estimated that despite an effective vaccine that provides 98% to 100% protection against the hepatitis B virus (HBV), an estimated 292 million people were still living with chronic hepatitis B infection (CHB) worldwide. Left untreated, CHB can progress to cirrhosis and hepatocellular carcinoma,” EiichiOgawa, MD, PhD, of the division of gastroenterology and hepatology at Stanford University Medical Center, and colleagues wrote. “However, the number of people aware of having CHB is strikingly low. In 2016, the WHO suggested that only 10.5% (27 million) of those with CHB were aware of their illness; and of those, only 16.5% (4.5 million) were receiving treatment.” 

To provide an accurate accounting of the number of patients with CHB aged 6 years or older in the U.S. who have not yet been diagnosed, Ogawa and colleagues performed a cross-sectional study using the commercial U.S. Truven Health Market Scan Database to identify patients with CHB diagnosis and the National Health and Nutrition Examination Survey to estimate the actual number of privately insured persons with CHB.

According to the study, the researchers calculated the total population with CHB and the proportion of those who remained undiagnosed among 198,073,302 privately insured individuals and identified diagnosed CHB patients who received one or more prescription for CHB medications to calculate the treatment rate for those with severe disease.

Results showed that only 18.6% (95% CI, 13.5%-29.92%) of the 511,029 (95% CI, 317,733-704,325) individuals with CHB had been diagnosed, meaning that 81.4% (95% CI, 70.08%-86.5%) were undiagnosed. Additionally, treatment rates were 34.79% (95% CI, 33.31%-36.27%) for those with cirrhosis and 48.64% (95% CI, 45.59%-51.69%) for those with hepatocellular carcinoma.

“This study found low rates of hepatitis B diagnosis among privately insured individuals, suggesting that barriers to diagnosis may be both financial and nonfinancial,” the authors concluded. “Additional research is needed to characterize these barriers and to develop interventions to improve diagnosis rates.” – by Caitlyn Stulpin

Disclosures: Ogawa reports no relevant financial disclosures. Please see the study for all other author’s relevant financial disclosures.

Previously approved to treat HCV in adults, Epclusa (sofosbuvir/velpatasvir, Gilead Sciences) is indicated in pediatric patients aged 6 years and older or weighing at least 37 pounds.

“This approval will provide additional treatment options for children and adolescents with HCV,” Debra Birnkrant, MD, director of the division of antivirals in the FDA’s Center for Drug Evaluation and Research, said in the release. “This approval will also be important in settings where there is limited ability for health care professionals to conduct HCV genotype testing.”

Epclusa was evaluated in an open-label study of 173 pediatric patients with and without mild cirrhosis. Investigators found no difference between the pharmacokinetics seen in children and those found in adults. Additionally, among 102 patients between ages 12 and 17 years, 93% of patients with genotype 1 and 100% of patients with genotypes 2, 3, 4 and 6 had no detectable virus in the blood 12 weeks after finishing treatment.

For 71 patients between ages 6 and 11 years with HCV genotypes 1, 2, 3 and 4, 93% with genotype 1, 91% with genotype 3 and 100% with genotypes 2 and genotype 4 had no virus detected in the blood 12 weeks after finishing treatment.

“Gilead’s continued commitment to HCV elimination includes bringing our medicines to the most difficult-to-cure populations and today’s decision by the FDA represents an important step toward that goal,” Merdad Parsey, MD, PhD, chief medical officer at Gilead Sciences, said in a company press release. “With consistently high cure rates in clinical trials and in the real world, Epclusa has the potential to help many of the children living with HCV in the United States.”

Reference:

FDA.gov

Gilead.com

“The introduction of direct-acting antiviral agents (DAAs) has led to a paradigm shift in the way HCV is approached. Several studies have now demonstrated their efficacy and safety in the posttransplant population,” Nikhil Kapila, MD, from the Cleveland Clinic in Florida and colleagues wrote. “More recently, HCV viremic allografts have been utilized successfully in viremic recipients, however their use in aviremic recipients is an area of intense interest.”

Between January 2018 and December 2018, 297 patients without HCV underwent solid organ transplants with viremic organs at the Cleveland Clinic. These included 64 cases of kidney transplantation, seven cases of heart transplantation, four cases of liver transplantation, two patients who underwent combined liver-kidney transplant, and one who underwent combined heart-kidney transplant.

“The optimal timing for initiation of DAA therapypost-transplant remains controversial,” the researchers wrote. “Initially, our center’s approach was to initiate DAA therapy within one month of transplant, however 10 patients were observed to have detectable HCV after 4 weeks of treatment. The persistence of HCV, despite DAA treatment, led to a modification in our protocol whereby we aimed to begin DAA therapy 12 weeks after transplant.”

As of April 20, 2019, 58 patients who received HCV-infected kidneys have either started or completed DAA treatment. Forty-one patients achieved SVR, 10 patients achieved undetectable viral loads posttreatment without clinical SVR, and seven patients remain on treatment. One patient did not respond to DAA therapy due to NS5A resistance and remains on treatment.

All patients who received liver transplants started treatment with Mavyret (glecaprevir/pibrentasvir, AbbVie) without ribavirin posttransplant. Three achieved SVR, one completed therapy and is awaiting SVR readout, and two remain on treatment.

Patients who received heart transplants also started DAA therapy posttransplant, of whom four received glecaprevir/pibrentasvir and the other half received Harvoni (ledipasvir/sofosbuvir, Gilead Sciences). Six achieved SVR and the others remain on treatment.

“Based on our center’s real-world experience, we believe that DAA therapy should be ordered and initiated once a patient is confirmed to be viremic, clinical parameters have stabilized, and insurance approval is obtained,” Kapila and colleagues wrote. “As transplant centers expand their donor pool and increase utilization of HCV viremic organs, the early initiation of anti-viral therapy should become the standard of care.” – by Talitha Bennett

Disclosures:  The authors report no relevant financial disclosures.

The FDA approved changes to the product labels for direct-acting antivirals Harvoni, Epclusa, and Vosevi to include new efficacy and safety data for adults with hepatitis C and severe renal impairment, including those who require dialysis.

“The product labeling updates for Epclusa, Harvoni and Vosevi recognize the high unmet need for effective HCV treatments for patients with severe renal impairment, including those with end stage renal disease (ESRD) who are on dialysis,” Gilead said in a statement sent to Healio Gastroenterology and Liver Disease. “People with chronic HCV who are on dialysis as a result of ESRD have an increased risk of morbidity and mortality. Prior HCV treatment options for this population have been associated with clinical barriers resulting in continued unmet medical need, and these approvals provide important new options for these patients.”

Harvoni (sofosbuvir/ledipasvir, Gilead Sciences) required no dosage adjustment for patients with mild, moderate or severe renal impairment including end-stage renal disease. The most common adverse events among patients with ESRD were insomnia and headache.

In a trial of adults with chronic HCV and ESRD requiring dialysis, the sustained virologic response was 93% in 45 treatment-naive patients who received 8 weeks of sofosbuvir/ledipasvir, 100% in 12 patients who received 12 weeks of treatment, and 83% in six treatment-experienced patients with cirrhosis who received 24 weeks of treatment.

Similarly, Epclusa (sofosbuvir/velpatasvir, Gilead Sciences) required no dosage adjustment for any degree of renal impairment and the most common adverse event among patients with ESRD was nausea.

Results from a trial of 59 patients with HCV and ESRD requiring dialysis showed an overall SVR rate of 95% after 12 weeks of treatment with sofosbuvir/velpatasvir, including patients with cirrhosis (29%) and those who were treatment-experienced (22%).

Vosevi (sofosbuvir/velpatasvir/voxilaprevir or SOF/VEL/VOX, Gilead Sciences) also required no dosage adjustment for any degree of renal impairment.

Pharmacokinetics of sofosbuvir and velpatasvir among patients with HCV and ESRD requiring dialysis for 12 weeks were consistent with patients with ESRD without HCV. The pharmacokinetics of voxilaprevir have not been studied in patients with ESRD; however, the FDA noted that voxilaprevir exposure following treatment with SOF/VEL/VOX combination is not expected to be meaningfully altered in patients with HCV and ESRD requiring dialysis compared with patients with normal renal function.

Reference: www.fda.gov

The label expansion of Mavyret (glecaprevir/pibrentasvir, AbbVie) was based on data from the phase 3b EXPEDITION-8 study that included patients with any of the six HCV genotypes. Twelve weeks after treatment, 98% of the 343 enrolled patients achieved sustained virologic response.

“This approval provides a treatment duration of 8 weeks for both pediatric and adult patients with compensated cirrhosis regardless of HCV genotype,” Jeffrey Murray, MD, deputy director of the division of antiviral products in the FDA’s Center for Drug Evaluation and Research, said in the FDA brief. “[Glecaprevir/pibrentasvir] is a combination of direct-acting antiviral drugs that reduce the amount of HCV in the body to undetectable levels by preventing the virus from multiplying, and in most cases, curing HCV infection.”

Additional data from the EXPEDITION-8 study showed that the most common adverse events were fatigue (8%), pruritus (7%) and headache (6%).

“While over 100,000 patients have been prescribed [glecaprevir/pibrentasvir] for chronic HCV in the U.S., there are still a significant number of patients that need options,” Janet Hammond, MD, PhD, vice president of the general medicine and virology therapeutic area at AbbVie, said in a press release. “This approval provides more HCV patients an option to treat their disease in as little as 8 weeks.”

Reference: www.fda.gov; www.abbvie.com

In a follow-up analysis of participants in clinical trials, researchers found that patient-reported outcome scores increased in patients who achieved sustained virologic response after treatment for hepatitis C, whereas scores decreased in those who did not.

“Although historical treatment regimens with interferon were plagued by low efficacy and significant side effects impairing patients’ well-being and, thus, PROs, the trajectory of HCV treatment changed about 5 years ago with the development of direct-acting antiviral (DAA) agents,” Zobair M. Younossi, MD, chairman of the department of medicine at Inova Fairfax Hospital in Virginia, and colleagues wrote. “The PRO evidence generated by these two prospective registry studies support the unquestionable benefit of SVR for patients’ experience as opposed to the clear deleterious impact of HCV viremia.”

Younossi and colleagues assessed the health-related quality of life of 4,234 patients who achieved SVR and 242 patients who did not using the SF-36 instrument. Before treatment, PRO scores of both groups were similar to or higher than the general U.S. population and similar to each other.

At baseline for this study, patients who achieved SVR experienced improvements in all eight domains of the SF-36 (range increase, 3.6-8.1; P < .0001), while the scores of those without SVR remained the same with the exception of the General Health domain, which decreased by 2.8 points (P = .008).

Patients without SVR experienced further PRO decrements at 12-week follow-up: up to –7 points from before treatment in the Role Physical, General Health, Social Functioning and Role Emotional domains and both summary scores; up to –9.2 points in all PRO domains at week 24; up to –8.3 points in five domains at week 48; and up to –9 points in four domains at week 96 (P < .05).

In contrast, patients with SVR experienced sustained improvement of PRO scores with up to 7 points at week 24, up to 6.9 points at week 48, and up to 6.1 points at week 96 (P < .001). Multivariate analysis confirmed that SVR correlated independently with superior scores in all PRO domains with an increased range of 4.8 points to 15.9 points (P < .01).

“In order to fully understand the comprehensive benefit of HCV cure, these PRO gains should always accompany the clinical consequences of SVR, such as lower rates of cirrhosis and hepatocellular carcinoma,” Younossi and colleagues concluded. “These data must be considered by providers, payers, and policy makers to fully appreciate the comprehensive benefit of HCV cure and to assure that all HCV patients are identified and treated with the most effective antiviral regimens.” – by Talitha Bennett

Disclosures: Younossi reports that the study was partially supported by Gilead Sciences and that he has received research funds or served as consultant to AbbVie, Bristol-Myers Squibb, Gilead Sciences, Intercept, Novo Nordisk, Terns and Viking. Please see the full study for all other authors’ relevant financial disclosures.