By Liz Highleyman

The development of new drugs and accumulation of long-term data has led to the evolution of therapy for chronic hepatitis B. Hepatology experts Fabien Zoulim and Robert Perrillo presented an overview of the current state of hepatitis B treatment in the February 2004 advance online edition of the Journal of Hepatology.

The authors noted that "strict adherence to liver association practice guidelines may result in missed opportunities to treat patients with significant underlying liver disease." In particular, they wrote, recommended alanine aminotransferase (ALT) thresholds "may not appropriately reflect disease activity or degree of fibrosis." ALT is a marker of liver inflammation, but does not always correlate with fibrosis; some patients have persistently normal liver enzymes despite advanced fibrosis or cirrhosis.

Drs. Zoulim and Perillo added that there is "growing evidence that an alternative treatment paradigm for preventing late-stage disease complications may be indicated in highly viremic patients with early life exposure to hepatitis B." Numerous studies have shown that the natural history and outcomes of hepatitis B vary based on whether an individual was infected at or soon after birth (as is common in much of Asia) or later in life.

Pegasys (peginterferon alfa-2a)

Epivir-HBV (Lamivudine)

The authors wrote that pegylated interferon therapy is often a better choice for young to middle-aged patients with HBV genotypes A and B; only pegylated interferon alfa-2a (Pegasys) is currently FDA approved for hepatitis B treatment. Compared with nucleoside analog drugs such as lamivudine (Epivir-HBV), pegylated interferon produces a higher rate of hepatitis B "e" antigen (HBeAg) seroconversion and a greater likelihood of hepatitis B surface antigen (HBsAg) seroconversion in both HBeAg positive and negative patients.

Nucleoside/nucleotide analog monotherapy is the current standard of care for many patients, Drs. Zoulim and Perillo noted. However, they wrote, "long-term monotherapy results in resistance to a variable degree and sequential monotherapy may result in multi-drug resistant virus." Further, which patients would benefit most from early combination therapy remains "poorly defined." They recommended that the "rapidity and robustness" of HBV suppression with nucleoside analogs should be monitored during early therapy, since this affects ultimate treatment outcomes and the rate of resistance.

In summary, the authors concluded, "While great progress has been made in treating hepatitis B, many important issues require further study."

3/07/08

Reference
F Zoulim and R Perrillo. Hepatitis B: Reflections on the current approach to antiviral therapy. Journal of Hepatology. February 4, 2008 [Epub ahead of print].