Current pharmacotherapy for the treatment of chronic hepatitis B.
The virological profile of infection with the hepatitis B virus (HBV) is changing in many parts of the world from the classical hepatitis B e antigen (HBeAg)-positive serological pattern to a HBeAg-negative pattern, linked to the replacement of wild-type HBV by HBV variants with mutations in the core-promoter and in the precore region that prevent the secretion of HBeAg. The wild-type HBV disease is characterised by steady levels of alanine aminotransferase (ALT) and high HBV-DNA levels, responding relatively well to IFN treatment (3 - 5 MU/day or 10 MU every other day for 16 weeks), which induces anti-HBe seroconversion and normalises ALT levels in approximately 30% of the adults, with a minimal risk of relapse. Pegylated-IFN appears to have superior efficacy over conventional IFN-alpha. Mutant-type disease (anti-HBe-positive/HBeAg-negative) is less responsive to IFN given for 6 - 12 months. This has led to the use of novel nucleoside analogues, of which the prototype is lamivudine. The response to lamivudine therapy shares with IFN a rapid decline in ALT accompanied by an improvement in histology; at variance with IFN, in HBeAg-positive chronic hepatitis B (CHB) there is delayed seroconversion to anti-HBe which accumulates over time, the switch to anti-HBs is more rare and in the long-term, the activity of the drug is abolished by the emergence of viral mutations (YMDD-motif mutants) that may rekindle the disease. The combination of IFN plus lamivudine may be more efficacious than IFN or lamivudine monotherapy. Lamivudine therapy needs to be prolonged in HBeAg-negative CHB. Short-term lamivudine-therapy is highly efficacious in preventing HBV reinfection in liver transplants. Recent data suggest that long-term IFN therapy (24 months) may achieve a response in 30% of HBeAg-negative patients. The advent of adefovir, an analogue of adenosine monophosphate, may provide a safer alternative to lamivudine in the control of HBV disease; the drug is well-tolerated and treatment raises drug-resistant mutants in < 2% of the patients over 2 years of therapy. Adefovir provides rescue therapy against YMDD mutants raised by lamivudine therapy.
Lagget
M
M
Division of Gastroenterology, Ospedale Molinatte, Torino, Italy.
Rizzetto
M
M
D015075:2-Aminopurine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D000077595:Famciclovir; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D019259:Lamivudine / Q000627:therapeutic use; D016031:Liver Transplantation; D009154:Mutation; D009705:Nucleosides / Q000627:therapeutic use; D063065:Organophosphonates
D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D009705:Nucleosides; D063065:Organophosphonates; D019259:Lamivudine; D015075:2-Aminopurine; C053001:adefovir; D007372:Interferons; D000225:Adenine; D000077595:Famciclovir