The annual rate of progression to
cirrhosis in patients with chronic HBV is 0.4 to 14.2% and that of death 4 to 10%. HCC risk increases in parallel with the severity and duration of
infection, with an annual incidence less than 0.5% in carriers and 6% in patients with
cirrhosis. The main aim of
antiviral therapy for chronic "wild-type" HBV
infection is to suppress viral replication before
cirrhosis and HCC develop. Two drugs are approved: IFN alpha and
lamivudine. IFN alpha is costly, has a narrow range of efficacy, safety, and tolerability.
Lamivudine is active, cheaper, and better tolerated but has limited efficacy, being associated with increasing resistance and loss of clinical response in the long term. IFN may be the first choice treatment in
HBeAg-positive patients with a favourable profile and compensated
liver disease. Patients with
HBeAg-negative active disease can benefit from 12-24 months IFN treatment if early response is observed.
Lamivudine should be started only after considering the uncertainties about
duration of therapy and risks of stopping it. In patients with slowly progressive
liver disease, treatment is better postponed until effective combination regimens are available.
Lamivudine is of paramount importance in end-stage chronic
liver disease to suppress HBV replication and allow successful
transplantation. The role of
interferon in preventing HCC is controversial. In two studies comparing the incidence of HCC in patients with
HBeAg-negative
chronic hepatitis treated with IFN, HCC developed less frequently in sustained responders than in non-responders in Greece (2 vs. 10%, P = 0.045), but not in Milan (7 vs. 10%, P = ns).