A Tansel et al. Clin Gastroenterol Hepatol 2017; 15: 1207-17. This systematic review and meta-analysis identified 25 studies and 6528 patients examining the relationship between autoimmune hepatitis (AIH) and hepatocellular carcinoma (HCC) . In these studies the median followup was 8.0 years. Key findings:
- The pooled incidence of HCC was 3.06 per 1000 patient-years
- 92 of 93 patients who had HCC had evidence of cirrhosis before or at the time of their diagnosis
My take: This study demonstrates that AIH patients with cirrhosis are at increased risk for HCC. In patients with AIH who do not have cirrhosis, there does not appear to be a significant risk of HCC.
Also: Link for Online Resource for Hepatopulmonary Syndrome (Canadian Sponsored site). This site has content for patients and for practitioners, including a useful video.
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There have been a number of studies suggesting a beneficial effect of statins for individuals chronic liver disease due to HBV infection, HCV infection, and nonalcoholic steatohepatitis. The potential reasons include lower portal hypertension due to increased nitric oxide availability, anti-inflammatory effects through reduction in some cytokines, and antifibrotic effects. In addition, statins may inhibit tumor initiation/hepatocellular carcinoma (HCC).
The background on these prior studies is detailed in a new population-based study (F-M Chang et al Hepatology 2017; 66: 896-907, editorial 697-9) of statins in patients with cirrhosis. In this nested case-control study from Taiwan, the authors examined patients (n=1350) with cirrhosis from 2000 to 2013. The index cases of cirrhosis were identified among a representative, well-validated general population database of 1,000,000 people.
- “Statin use decreased the risk of decompensation, mortality, and HCC in a dose-dependent manner.”
- Risk of decompensation among chronic HBV statin users, HR 0.39
- Risk of decompensation among chronic HCV statin users, HR 0.51
- Risk of decompensation among alcohol-related cirrhosis patients taking statins, HR 0.69
My take: In adults with cirrhosis, particularly HBV-related and HCV-related, taking a statin was associated with a 50-60% lower likelihood of decompensation. A prospective study could confirm these findings.
Prague -Charles Bridge
FDA Announcement Aug 3, 2017: FDA approves Mavyret for Hepatitis C
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
“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
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 (Word of Caution with New Hepatitis C Medications:), 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.
- 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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Swing bridge, Ben Sawyer Bridge, Sullivans Island
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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Arthur Ravenel Jr Bridge, Charleston
In case you missed this yesterday –World Hepatitis Day July 28, 2017