Dear Colleagues,

 

The approach to treatment of chronic hepatitis B has dramatically evolved during the past decade. Several new antiviral agents are available today, in addition to interferon alpha, which is currently marketed in its pegylated form. Lamivudine first, followed by adefovir dipivoxil, telbivudine, entecavir, tenofovir, and emtricitabine, have all enriched our panoply to fight this treacherous pathogen.
The aim of chronic hepatitis B therapy is the prolonged suppression of the hepatitis B virus (HBV) replication. This is followed by a reduction of the liver disease activity and of its progression toward cirrhosis. The first-choice drug is pegylated interferon alpha, which, if given as monotherapy, suppresses HBV replication in approximately 40% of cases, albeit burdened with several contraindications and important side effects. Lamivudine, a nucleoside analogue inhibiting HBV reverse transcriptase, is indicated in case of failure or contraindication to interferon. Very well tolerated, its prolonged use may however lead to the selection of resistant HBV variants (about 20% yearly). In these cases, adefovir dipivoxil is indicated. This drug is characterized by a significantly lower risk of selection of resistant strains (about 5% yearly). Telbivudine and entecavir, two drugs with an even lower rate of selection of resistant viral variants, have been licensed recently. In addition, two powerful inhibitors of the human immunodeficiency virus (tenofovir and emtricitabine), also highly active against HBV, may too be used to treat hepatitis B.
Despite this major progress, long-term off-treatment control has not been achieved in a large proportion of patients and several questions remain open. For example, hepatitis B surface antigen (HBsAg) loss is a rare event and observed only in a minority of patients treated with pegylated interferon alpha. Optimal duration of therapy has not been established for any drug, and further studies are clearly warranted to analyze this issue. Despite their proven efficacy against other viruses, so far combination regimens have been disappointing when used to treat HBV infection. As an example, although the combination of pegylated interferon alpha and lamivudine induces greater viral suppression at the end of treatment compared to monotherapy with either drug, it does not improve sustained response at the end of follow-up, suggesting that either the length of combined therapy should be adjusted or new schedules investigated. Finally, robust assays are now available to quantify and monitor HBV deoxyribonucleic acid (DNA) and antigens before and during therapy. These assays are providing us with molecular markers of diagnostic and prognostic interest, but their impact on the routine management of hepatitis B patients remains to be proven.
This current issue of Hot Topics in Viral Hepatitis is completely devoted to the hepatitis B virus and the management of its infection. The four chapters analyze several aspects from the new diagnostic markers and their application to the most recent results of clinical trials. I trust it will help you in the decision-making process while attending your patients who have hepatitis B.