New developments in the therapy of chronic hepatitis B. What are the indications for nucleoside analogues?

Nucleoside analogues are promising agents for the treatment of chronic hepa titis B infection (HBV-DNA-positive by hybridization assay). The drug being studied most intensively is. Lamivudine (Zeffix((R))) which has recently b een approved in Germany. When given orally once daily (100 mg) Lamivudine i s well-tolerated and suppresses HBV-DNA to undetectable levels in the major ity of patients. Since relapse is frequent when medication is stopped long- term treatment (at least until seroconversion of HBeAg) is warranted. Indic ations for lamivudine monotherapy are patients with chronic hepatitis B in which interferon (IFN) is contraindicated or patients who did not respond t o a previous course of interferon, Further indications are the HBV-DNA-posi - tive cirrhosis prior to liver transplantation (OLT) and the HBV-reinfecti on after OLT. The main problem of longterm monotherapy with lamivudine is v iral resistance. The clinical impact of the resistant mutants is often not clear. Withdrawal or even continuation of the medication may he acceptable approaches. Other nucleoside analogues like Entecavir or Adefovir are curre ntly being tested in clinical studies. Famciclovir was investigated prefera bly in patients with decompensated liver disease or HBV-reinfection after O LT. Because of conflicting results the drug should only be used under study conditions, In IFN-naive patients with chronic hepatitis B (and compensate d liver disease) alpha-interferon is still the first-line therapy With a st andard course of interferon 30-40% of the patients become sero-negative for HBeAg as compared with 16-17% when treated with lamivudine: for twelve mon ths. Combination of lamivudine and interferon is not more effective than IF N alone. In the future combined antiviral treatment is likely to replace mo notherapy.