Eight Week Pangenomic HCV Treatment Approved

FDA Announcement Aug 3, 2017: FDA approves Mavyret for Hepatitis C

An excerpt:

The U.S. Food and Drug Administration today approved Mavyret (glecaprevir and pibrentasvir) to treat adults with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis (liver disease) or with mild cirrhosis, including patients with moderate to severe kidney disease and those who are on dialysis. Mavyret is also approved for adult patients with HCV genotype 1 infection who have been previously treated with a regimen either containing an NS5A inhibitor or an NS3/4A protease inhibitor but not both. 

Mavyret is the first treatment of eight weeks duration approved for all HCV genotypes 1-6 in adult patients without cirrhosis who have not been previously treated. Standard treatment length was previously 12 weeks or more.

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Gravelly Point, Arlington, VA

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Hepatitis B Reactivation with Direct-Acting Antiviral Hepatitis C Therapy

“I refuse to accept the view that mankind is so tragically bound to the starless midnight of racism and war that the bright daybreak of peace and brotherhood can never become a reality.” Martin Luther King, Jr

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More information on hepatitis B virus (HBV) reactivation with direct-acting antiviral (DAA) hepatitis C virus (HCV) therapy has been published:

  • PS Belperio et al. Hepatology 2017; 66: 27-36
  • G Chen et al Hepatology 2017; 66: 13-26
  • Editorial: RP Perrillo. G Chen et al Hepatology 2017; 66: 4-6.

In a previous post on this topic (:), it was noted that physicians need to be aware of HBV reactivation with DAAs. It appears that HCV can suppress HBV replication and that successful HCV therapy allows for HBV reactivation.

Belperio et al reviewed data from an observational study on more than 62,000 HCV-infected veterans, including 377 who had HBsAg-positivity and 7295 who had anti-HBc-positivity.

Key findings:

  • 8 of 377 HBsAg-positive had reactivation (defined as HBV DNA increase of >1000 IU/mL) of HBV during DAA treatment of HCV. Only one of these eight had a severe hepatitis (ALT 154o IU)
  • 1 of 7295 HBc-positive had HBV reactivation. This rate of reactivation is actually lower than HBV reactivation reported with ‘inactive’ disease (1-2% per year).
  • For HBV screening, the authors recommend HBsAg and anti-HBc testing

Chen et al performed a systematic review (of 28 studies included) and meta-analysis had identified overt  HBV reactivation in 12.2% of those receiving DAAs.  This was a lower rate of HBV reactivation than with interferon (14.5%); however, reactivation during DAA therapy occurred earlier (typically 4-12 weeks into treatment) and was more clinically significant. There was significant variation in the virologic and ALT criteria used to define HBV reactivation.  The authors conclude that it is “important to have HBV serology (HBsAg, anti-HBc) in all HCV patients prior to therapy.

Perillo recommends that in addition to screening, “it is my belief that anti-HBV prophylaxis be given to all HBsAg-positive patients, ” regardless of HBV DNA level.

My take: These articles help quantitate the risk of HBV reactivation during HCV therapy.

Ben Sawyer Bridge, Sullivans Island

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What Can Be Done for Patients with Hepatitis C Who Do Not Respond to the Newest Medications

While the emergence of multiple highly-active agents for Hepatitis C has been a terrific advance, there are a small subset of patients who have not responded to them in almost all clinical trials.  A recent study (M Bourliere et al. NEJM 2017; 376: 2134-46) has identified a highly-effective combination regimen for this population: sofosbuvir/velpatasvir/voxilaprevir x 12 weeks

The authors conducted two phase 3 trials in patients who had not responded to a direct-acting antiviral (DAA) regimen previously.  POLARIS-1 and POLARIS-4. 46% of patients had compensated cirrhosis Key findings:

  • POLARIS-1: 96% of combination group had a sustained virologic response (SVR) compared with 0% of patients receiving placebo
  • POLARIS-4: the triple combination had a SVR of 98%, whereas 90% had SVR with dual therapy (sofosbuvir-velpatasvir)
  • Among patients receiving active treatment, less than 1% discontinue treatment due to advers events.

My take: This triple therapy is highly effective in patients who were  previously-treated with DAA for HCV.

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Will Emerging Therapies for Fatty Liver Disease Be Affordable?

With non-alcoholic steatohepatitis (NASH), there are currently no established medical therapies.  However, several candidate medications look promising. However in recent years, many new medications have come with an impressive price tag and this has led to questions about whether emerging therapies for NASH will be affordable.

A recent article looked at the medication Obeticholic Acid, which was approved for treating primary biliary cholangitis.  It is possible that it will be helpful for NASH.  Yet, its cost , currently, is about $70,000 per year

GIHepNews: Despite clinical promise, obeticholic acid may be too expensive for treating NASH

Here’s an excerpt:

In the 72-week Phase II trial, called FLINT, 273 men and women with NASH were randomly assigned to receive OCA or placebo (Lancet 2015;385:956-965). Liver histology improved in 45% of those receiving OCA versus 21% in those receiving sham therapy (P=0.002). An increased risk for pruritus was the most notable adverse event among patients taking OCA (23% vs. 6% for placebo), according to the researchers. Based on the favorable benefit–risk results of the Phase II study, a Phase III trial is ongoing…

The expected benefit of OCA over lifestyle modifications for all the major long-term outcomes, such as decompensated cirrhosis (10% vs. 9.4%), liver-related mortality (9% vs. 8.1%) and transplant-free survival (72.2% vs. 71.5%), were relatively modest, the researchers reported. Those differences resulted in a cost per quality-adjusted life-year saved of $5.2 million with the assumption that 16% of patients would relapse…

 “If the efficacy compared to placebo is of the same order found in the FLINT trial, the current cost of the drug would be prohibitive in a population-based context,” said Dr. Lavine, who was a co-investigator on the trial.

My take: Given the growing burden of NASH, new effective treatments are needed.  In my view, though, cost-effectiveness has to be a consideration.

Prague Castle

NASH: What Helps Beyond Weight Loss?

Full text from ACG article: NASH: What Helps Beyond Weight Loss?

The article reinforces the value of weight loss and exercise for nonalcoholic steatohepatitis (NASH).  It suggests that Vitamin E and/or pioglitazone may be helpful. Many more medications are being evaluated.

My take: As of now, losing weight and exercise remain the cornerstone for NASH treatment.