Hepatitis B patients on long-term entecavir or tenofovir have low mortality, but liver cancer remains a risk

More than 95% of people with chronic hepatitis B were still alive after five years on antiviral therapy with entecavir (Baraclude) or tenofovir (Viread) and most deaths were due to non-liver-related causes, according to research presented at the European Association for the Study of the Liver (EASL) 50th International Liver Congress recently held in Vienna, Austria. Liver cancer was still a major factor affecting mortality, however.

Antiviral therapy using nucleoside/nucleotide analogues such as lamivudine, entecavir or tenofovir is the mainstay of chronic hepatitis B treatment. While these drugs can effectively suppress hepatitis B virus (HBV) replication during therapy, they usually do not lead to a cure and long-term treatment may be needed.

Over years or decades, chronic HBV infection can lead to advanced liver disease including cirrhosis and hepatocellular carcinoma, a type of liver cancer. Prior research indicates that maintaining viral suppression on treatment can help prevent disease progression. But as entecavir and tenofovir were approved for hepatitis B treatment in 2005 and 2008, respectively, long-term data are still needed.

George Papatheodoridis from Athens University Medical School in Greece and colleagues evaluated outcomes and survival among Caucasian people with chronic hepatitis B treated with entecavir or tenofovir. Hepatitis B is endemic in Asia and much of the research to date has involved people of Asian origin, so less is known about Caucasians with HBV.

This ongoing cohort study included 1815 people with chronic hepatitis B, with or without liver cirrhosis, all Caucasian, at nine centres in Europe, Turkey and Canada. About 70% of participants were men and the mean age was 53. Over a quarter had compensated cirrhosis at baseline, but none had hepatocellular carcinoma. All participants received either entecavir or tenofovir for at least 12 months. A majority (60%) had not previously used antiviral therapy before this study.

Among the total patient population, survival rates without liver transplantation were high overall: 99.5% at one year, 98.5% at two years, 97.5% at three years and 95.0% at five years. Survival rates were significantly higher for people without cirrhosis (100%, 99.0%, 98.5% and 97.0%, respectively) compared to those with cirrhosis (98%, 96.5%, 95.0% and 92.0%).

When only liver-related deaths or liver transplantation were taken into account, survival rates were even higher: 99.7%, 99.4%, 99.0% and 97.5%, respectively. Again, survival was significantly higher among people without cirrhosis (100%, 100%, 100% and 99.0%) compared to people with cirrhosis (99.0%, 98.0%, 97.0% and 95.0%).

When people who developed hepatocellular carcinoma were excluded, survival rates were 99.5%, 99.0%, 98.0% and 96.5%, respectively. Here again, survival was higher for people without cirrhosis compared to those with cirrhosis.

However, among the 85 people who developed hepatocellular carcinoma, survival rates after liver cancer diagnosis were much lower: 76.0% at one year and 56.0% at three years. Within this group there was no longer a survival difference between people with or without cirrhosis.

In a multivariate analysis, higher overall survival was independently associated with absence of hepatocellular carcinoma (hazard ratio [HR] 6.45) and younger age (HR 1.04 per year), but not with sex or cirrhosis. Considering only liver-related deaths, higher survival was independently associated only with absence of hepatocellular carcinoma (HR 22.45).

"The survival of Caucasian chronic hepatitis B patients treated with [entecavir or tenofovir] is excellent with >95% of cases surviving at five years and a significant proportion of deaths coming from liver unrelated causes," the researchers concluded.

However, they continued, "Hepatocellular carcinoma development is a major factor affecting the overall mortality and the only factor affecting liver-related mortality in such patients."