Therapeutic strategies for chronic hepatitis B virus infection in 2008

Reducing progression of disease and preventing development of hepatocellular carcinoma in patients with chronic hepatitis B (CHB) is best achieved through durable suppression of viral replication without the development of resistance. Suitability of a patient for therapy depends on several factors, notably hepatitis B e antigen (HBeAg) status, serum alanine aminotransferase (ALT) level, and serum HBV DNA level. Interferon therapy can produce durable responses (HBeAg clearance) in approximately one third of patients with HBeAg-positive disease, but has limited use in HBeAg-negative patients owing to relapse after discontinuation of therapy. Oral antiviral agents have superior tolerability and ease of administration, but the long-term treatment that may be necessary can be associated with the development of resistance. The high propensity for development of resistance to lamivudine and telbivudine means that adefovir and entecavir, and where available tenofovir, are now considered the preferred oral agents. Monitoring patients during therapy enables assessment of response and adherence, such that treatment can be modified accordingly; genotypic testing in cases of virologic breakthrough is important to identify presence of resistant strains, which may be found months or years before elevation of serum ALT. In cases of confirmed antiviral resistance, treatment should be promptly adjusted either by switching to another agent, or more commonly, adding a second agent, depending on the circumstances. Long-term studies indicate that effective suppression of viral replication improves clinical outcome, with improvement of liver histology and, it is assumed, a decreased risk for development of hepatocellular carcinoma.