Hepatitis C: therapeutic perspectives.
Continuous efforts are vital to develop new treatment strategies to improve sustained response rates, especially for difficult to treat patients infected with the hepatitis C virus. Despite the introduction of ribavirin, more than 50% of the patients do not eliminate the virus with the current standard therapy of interferon-a (IFN) and ribavirin. Options to further enhance response rates include modification of the IFN-dosing schedule with daily dosing of IFN, new IFN such as consensus interferon or modified IFN with longer half-life and more favourable pharmacokinetics such as pegylated IFN (PEG-IFN). Clinical trials with new IFN showed that consensus IFN may improve response rates in unsuccessfully pre-treated patients and patients with HCV-genotype-1. Treatments with PEG-IFN will double response rates achieved with standard IFN monotherapy. The combination of PEG-IFN and ribavirin improves the virological response to more than 50% and even to more than 80% in patients with genotype 2 or 3. By now, standard therapy of chronic hepatitis C has been changed to the combination of PEG-IFN plus ribavirin. Future anti-viral drugs may comprise molecules that directly inhibit HCV proteins and interfere with viral replication. NS3/4A serine protease, ribonucleic acid (RNA) helicase, RNA-dependent RNA polymerase may be potential targets for new drugs. Furthermore antisense oligonucleotides or ribozymes may become new treatment options to inhibit HCV replication. Finally, immunotherapies to enhance HCV-specific immune responses are also attractive strategies to control HCV infection and to prevent chronic liver disease.
Cornberg
M
M
Department of Gastroenterology and Hepatology, Medical School Hannover, Germany.
Wedemeyer
H
H
Manns
M P
MP
D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D016174:Hepacivirus; D006526:Hepatitis C / Q000188:drug therapy*; D019698:Hepatitis C, Chronic / Q000188:drug therapy; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D016337:RNA, Catalytic; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D014764:Viral Proteins; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D016337:RNA, Catalytic; D011994:Recombinant Proteins; D014764:Viral Proteins; D012254:Ribavirin