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DDW 2013: Does HBV Suppression Prevent Liver Disease Progression?

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Chronic hepatitis B patients with cirrhosis may still experience liver disease progression even if they undergo antiviral treatment and achieve good virological response, according to a poster presented at the Digestive Disease Week meeting (DDW 2013) last month in Orlando.

Over years or decades, chronic hepatitis B virus (HBV) infection can lead to advanced liver damage including severe fibrosis, cirrhosis (scarring), and hepatocellular carcinoma (HCC, a form of primary liver cancer). This is largely related to immune activation and the liver's attempt to repair itself.

Treatment that suppresses HBV replication can slow liver disease progression and may even reverse some of the damage. A study presented at the recent EASL International Liver Congress in Amsterdam, for example, showed that long-term treatment with tenofovir (Viread) significantly lowered the risk of developing liver cancer after 5 or more years.

But lowering the risk of disease progression does not mean that it falls to zero.

Poh Seng Tan and colleagues from the National University of Singapore looked at outcomes among more than 260 chronic hepatitis B patients with cirrhosis who were on long-term nucleoside/nucleotide analog therapy using either lamivudine (Epivir-HBV) plus adefovir (Hepsera) combination therapy or entecavir (Baraclude) monotherapy. About 40% were hepatitis B "e" antigen (HBeAg) positive.

Lamivudine/adefovir recipients had been on treatment for a mean duration of about 40 months with a mean follow-up time of about 70 months. In the entecavir group the corresponding durations were about 35 and 45 months, respectively.

Results

  • 60% of participants in the lamivudine/adefovir group achieved undetectable HBV viral load at 1 year, rising to 92% at 3 years and 96% at 5 years.
  • Virological response rates in the entecavir monotherapy group the were 75%, 95%, and 100%, respectively.
  • Nevertheless, rates of liver disease progression in the lamivudine/adefovir group -- defined as liver decompensation, development of HCC, or death -- were 5% at 1 year, 18% at 3 years, and 33% at 5 years.
  • Progression rates in the entecavir group somewhat lower at 8%, 13%, and 18%, respectively.
  • The cumulative probability of liver disease progression was not dependent on achieving undetectable viral load.
  • Among virological responders, there was no significant difference in risk of disease progression between the lamivudine/adefovir and entecavir groups.
  • Decompensation at baseline and serum albumin level -- but not virological response -- were significant predictors of disease progression in a multivariate analysis.

Based on these findings, the researchers concluded, "Among cirrhotics treated with long-term [lamivudine/adefovir] combination therapy or entecavir monotherapy, despite the excellent antiviral efficacy, there was still significant probability of liver disease progression."

6/19/13

Reference

PS Tan, YY Dan, K Lim, and SG Lim. Virological Response Does Not Lower Liver Disease Progression Among Chronic Hepatitis B Cirrhotic Patients Treated With Long-Term Nucleos(t)ide-Analogue. Digestive Disease Week (DDW 2013). Orlando, May 18-21, 2013. Abstract Sa1012.