www.hivandhepatitis.com

Antiviral Therapy Safe and Effective for Hep B Patients with Advanced Cirrhosis

Antiviral drugs including entecavir (Baraclude), lamivudine (Epivir-HBV), telbivudine (Tyzeka), and tenofovir (Viread) are generally well-tolerated and effective against hepatitis B virus (HBV) in people with liver cirrhosis, and may lower mortality even among patients with severe decompensated cirrhosis, according to 2 recently published studies.

Over years or decades, chronic HBV infection can lead to serious liver disease including fibrosis, cirrhosis (scarring), and hepatocellular carcinoma (liver cancer). Antiviral therapy with nucleoside/nucleotide analogs can lower HBV viral load and reduce the risk of these outcomes, but treatment is potentially risky for people with advanced cirrhosis -- especially those with decompensated cirrhosis, or liver failure.

In the first study, reported in the October 9, 2012, issue of Clinical Gastroenterology and Hepatology, Seyfettin Köklü from Hacettepe University School of Medicine in Ankara, Turkey, and colleagues assessed the long-term safety and efficacy of entecavir and tenofovir in hepatitis B patients with compensated or decompensated cirrhosis, comparing results to those of lamivudine, an older drug with more clinical experience.

This retrospective analysis included 227 adult chronic hepatitis B patientswho were diagnosed with cirrhosis at 18 centers throughout Turkey starting in 2005; of these, 104 had decompensated cirrhosis. Most (about 87%) were treatment-naive. Approximately one-third of the participants were treated with entecavir (mean follow-up 24 months), one-third received tenofovir (21 months), and one-third received lamivudine (37 months).

Results

• Virological response rates were high overall, with 93% of entecavir recipients, 92% of tenofovir recipients, and 77% of lamivudine recipients achieving HBV DNA levels < 400 copies/mL.
• Alanine aminotransferase (ALT) normalization occurred in 92%, 87%, and 72%, respectively.
• Child-Turcotte-Pugh scores -- a measure of liver function impairment -- increased overall, but more so in the lamivudine arm (16%, 9%, and 27%, respectively).
• Frequency of cirrhosis complications -- including hepatic encephalopathy, bleeding varices, and hepatocellular carcinoma -- was similar across arms.
• Mortality rates were also similar regardless of which treatment was used.
• 32% of patients receiving lamivudine had to switch to another drug, mostly due to resistance.

Based on these findings, the study authors concluded, "Tenofovir and entecavir are effective and safe for long-term use in patients with compensated or decompensated cirrhosis from HBV infection."

However, while antiviral treatment did reduce HBV viral load and liver inflammation as indicated by ALT levels, it did not appear to improve liver function or reduce the likelihood of adverse clinical outcomes.

Decompensated Cirrhosis

In the second study, published in the September 30, 2012, advance online edition of Digestive Diseases and Sciences, Yingnan Huang from Zhongshan Hospital of Fudan University in Shanghai and colleaguesperformed a meta-analysis to evaluate outcomes of nucleoside/nucleotide analog treatment of patients with decompensated cirrhosis.

The researchers searched online medical databases including PubMed, Web of Science, Embase, Cochrane Central of Register of Controlled Trials, and China Biology Medicine, looking for relevant studies published between January 1998 and September 2011.

Results

• The researchers identified 8 relevant studies, with a total of 511 participants, for inclusion in the analysis.
• Lamivudine and telbivudine significantly improved outcomes among patients with decompensated cirrhosis:

o   Improved Child-Turcotte-Pugh scores: mean decrease of 3.23 points;

o   Promoted hepatitis B "e" antigen (HBeAg) seroconversion: relative risk 7.48, or 7-fold greater likelihood.

Decreased mortality rate: relative risk 0.36, or about a one-third reduction.

"For patients with decompensated cirrhosis, lamivudine and telbivudine significantly decrease the mortality rate and disease severity," the researchers wrote. "Also, they promote their HBeAg seroconversion."

A limitation of this study is that due to its long time-frame, less data were available for newer drugs such as tenofovir.

11/6/12

References

Y Huang, H Wu, S Wu, et al. A Meta-Analysis of Nucleos(t)ide Analogues in Patients with Decompensated Cirrhosis Due to Hepatitis B. Digestive Diseases and Sciences. September 30, 2012 (Epub ahead of print).

S Köklü, Y Tuna, MT Gülşen, et al. Long-Term Efficacy and Safety of Lamivudine, Entecavir, and Tenofovir for Treatment of Hepatitis B Virus-Related Cirrhosis. Clinical Gastroenterology and Hepatology S1542-3565(12)01157-1153. October 9, 2012.