Abstract
Chronic hepatitis B infection (CHB) is common and can lead to serious consequences
including liver cirrhosis, failure, and hepatocellular carcinoma (HCC). The hepatitis
B virus (HBV) has a simple genome, but a complex lifecycle that includes the production
of covalently closed circular DNA (cccDNA). Currently approved antiviral treatments
for CHB include interferon (IFN) and nucleos(t)ide analogues. These drugs work either
by stimulating the immune system to eliminate virus-infected cells or to inhibit viral
replication, respectively. The drugs do not affect the cccDNA pool in the nucleus;
therefore, this molecule represents a persistent source of recurrent infection that
is difficult to eradicate. With longer-term follow-up of patients treated with antiviral
therapy, investigators have looked at whether treatment can prevent the development
of HCC. Unfortunately, the data are fairly heterogeneous in terms of both quality
and conclusions. IFN appears to reduce the risk of HCC, but the benefit seems to be
restricted to cirrhotic patients who have a lasting response to therapy. Oral agents
successfully suppress HBV DNA replication and slow or even reverse hepatic fibrosis.
Studies suggest that long-term therapy reduces the risk of HCC in patients with active
disease and again primarily in those with advanced fibrosis or cirrhosis. The mechanism
by which any of the therapies reduce the risk of HCC is not clear. The authors review
the lifecycle of HBV and mechanisms by which the virus may be carcinogenic followed
by a review of the literature on the efficacy of therapy in reducing the risk of HCC.
Keywords
chronic hepatitis B infection - hepatocellular carcinoma - antivirals - interferon
- nucleos(t)ide analogues
