Chronic Hepatitis B and C--current treatment and future therapeutic prospects.
In chronic hepatitis B treatment with pegylated interferon can now be considered as therapy of choice in both HBeAg positive and HBeAg negative patients and seems to be more effective than lamivudine monotherapy. Alternatively, treatment with lamivudine is able to suppress HBV DNA and to induce HBeAg conversation in up to 30 % of the patients. In HBeAg negative chronic hepatitis B lamivudine has a similar efficiency in suppressing HBV DNA as in HBeAg positive patients. The frequently developing lamivudine resistant HBV variants can now be successfully be treated with adevofir dipivoxil in both forms of chronic hepatitis B. These nucleosides analogues are generally better tolerated than interferon and can also be given in patients with HBV related liver cirrhosis. Our therapeutic armamentarium will be expanded in the near future by other nucleoside analogues such as entecavir, emtricitapine, telbivudine or clevudine. The treatment of choice in chronic hepatitis C currently is pegylated interferon plus ribavirin. This regimen is able to induce a sustained virologic response in 50 % of treatment naïve cases. The limited effectiveness of this therapeutic approach makes additional drugs highly warranted and inhibitors of the NS3-4a protease region or the NS5B polymerase region of the viral genome are under development. In addition, HCV replication inhibitors based on RNA interference (siRNA) or agonists of toll like receptors (TLR), which are part of the inborn immune system recognizing the presence of invading microorganisms, are currently explored as agents active in inhibiting HCV replication. Although none of these drugs are currently licensed for HCV treatment they are promising antiviral candidates for the future.
Müller
Christian
C
Division of Gastroenterology and Hepatology, Department of Internal Medicine IV, Medical University of Vienna, Vienna, Austria. christian.j.mueller@meduniwien.ac.at
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D006513:Hepatitis B e Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use; D063065:Organophosphonates / Q000009:adverse effects / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use
D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D063065:Organophosphonates; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D019259:Lamivudine; D011092:Polyethylene Glycols; D012254:Ribavirin; D012321:DNA-Directed RNA Polymerases; C417083:peginterferon alfa-2b; D000225:Adenine; C100416:peginterferon alfa-2a; C106812:adefovir dipivoxil