Long-term treatment with entecavir can
reduce the likelihood that people with chronic hepatitis B will develop
hepatocellular carcinoma, according to findings presented this week at The
Liver Meeting 2013, the 64th annual meeting of the American
Association for the Study of Liver Diseases (AASLD) in Washington, DC. Another
study, however, found that while entecavir and tenofovir can reduce the risk, people
with hepatitis B should continue to undergo regular monitoring for liver cancer
and better predictive models may be needed for Caucasian patients.
Over years or decades, chronic hepatitis B
virus (HBV) infection can lead to severe liver disease including cirrhosis and
hepatocellular carcinoma (HCC), a type of primary liver cancer.
Chronic hepatitis B is treated with oral nucleoside/nucleotide
analogues including adefovir (Hepsera),
entecavir (Baraclude), lamivudine (Epivir), telbivudine (Sebivo
or Tyzeka) and tenofovir (Viread). While
these drugs can reduce HBV viral load to an undetectable level, they typically
do not eradicate the virus completely and cure hepatitis B; nevertheless,
suppressing viral replication lessens disease progression.
Tung-Hung Su of
National Taiwan University Hospital presented findings from the Cirrhosis
Taiwanese Entecavir Multicenter Study (C-TEAM), which assessed whether
entecavir reduces liver cancer incidence in people with HBV-related cirrhosis.
also looked at the effect of treatment on cirrhosis complications including
ascites (abdominal fluid accumulation), hepatic encephalopathy, oesophageal or
gastric bleeding and bacterial peritonitis (inflammation of the abdominal
lining), as well as liver-related death.
observational cohort study included 666 chronic hepatitis B patients with liver
stage A, Metavir F4 or Ishak 5) from 17 academic medical centres in Taiwan,
followed from 2006 through to March 2013. Participants were on long-term entecavir
monotherapy, with entecavir being the first hepatitis B drug they had used.
Three quarters were men, the mean age was 55 years and 77% were hepatitis B 'e'
antigen (HBeAg)-negative. People who
developed HCC within the first year of treatment and those who also had hepatitis C were
participants were compared against a historical control group of 621 untreated
chronic hepatitis B patients with compensated cirrhosis followed from 1985
through to 1995. In this group, 75% were men, the mean age was 49 years and 75%
were HBeAg-negative. Compared with the control group, treated patients were significantly
older and had more advanced liver disease.
total of 16 cases of HCC were recorded in the entecavir group over an average
follow-up period of 2.6 years, while in the control group there were 141 cases
over 8.5 years of follow-up.
the first three years of follow-up, 16 people (2.4%) in the entecavir group and
32 people (5.2%) in the untreated group developed HCC, giving incidence rates
of 9.19 and 14.19 per 1000 person-years, respectively, a difference that fell
short of statistical significance (p=0.08). Over a lifetime, liver cancer
incidence was about 60% lower for entecavir-treated patients (adjusted hazard
multivariate analysis entecavir treatment was the only factor that
significantly predicted increased risk of developing HCC (hazard ratio 0.41;
p=0.015). Age, sex, being HBeAg positive or negative and HBV viral load were
not significant after controlling for other factors.
other outcomes over the first three years, entecavir treatment was not
associated with decreased risk of cirrhosis complications including hepatic
encephalopathy (two new cases in both the treated and control groups) and bleeding
(10 vs 8 new cases), nor with reduced liver-related mortality (0.2 vs 0.6%,
noted, follow-up in the entecavir group is still too short for many of these
secondary complications to have occurred and differences may emerge with longer
Based on these findings, the researchers
concluded, "Prolonged entecavir therapy possibly reduces HCC development
in hepatitis B-related compensated cirrhotic patients and a longer-term
follow-up is required to see its impact on cirrhotic complications."