Current therapy and new molecular approaches to antiviral treatment and prevention of hepatitis C.
Current therapeutic options for hepatitis C are limited, especially for genotype 1. For genotypes 2 and 3, pegylated interferon in combination with ribavirin, can lead to a sustained virological response in up to 80% of patients. Unfortunately, adverse effects of IFN and ribavirin are a major problem and the list of contraindications for HCV therapy is long, including decompensated cirrhosis of the liver and psychiatric disorders. Therefore, alternative therapeutic approaches are needed. New delivery options for IFN and ribavirin are aimed at optimising efficiency and reducing adverse effects. Recent progress in the molecular virology of HCV has identified new targets for antiviral intervention. Inhibition of HCV gene expression and replication as well as immunotherapeutic concepts aimed at enhancing the cellular immune response against HCV are being explored. Solution of the crystal structures of HCV key enzymes led to the design of specific inhibitors including compounds active against the well characterised NS3 serine protease and RNA-dependent RNA polymerase which are currently in the early phase clinical investigation. New strategies for inhibiting HCV gene expression include the use of antisense oligodeoxynucleotides and ribozymes. Immunomodulation by agents such as inosine monophosphate dehydrogenase inhibitors, thymosin-alpha 1, histamine or amantadine are being studied in combination with IFN and/or ribavirin. Immunotherapeutic vaccination with recombinant HCV E1 protein improved host immunity against HCV and thus seems to be a promising new option.
Hügle
Thomas
T
Clinica Medica, Ospedale Civico, CH-6903 Lugano, Switzerland.
Cerny
Andreas
A
D000547:Amantadine / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000517:prevention & control* / Q000821:virology; D006632:Histamine / Q000627:therapeutic use; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D020319:Oligodeoxyribonucleotides, Antisense / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use; D016337:RNA, Catalytic / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000627:therapeutic use; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D014765:Viral Vaccines / Q000627:therapeutic use; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; D012324:RNA-Dependent RNA Polymerase
D000547:Amantadine; D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D006632:Histamine; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D020319:Oligodeoxyribonucleotides, Antisense; D011092:Polyethylene Glycols; D011480:Protease Inhibitors; D016337:RNA, Catalytic; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D012254:Ribavirin; D000077596:Thymalfasin; D013947:Thymosin; D014409:Tumor Necrosis Factor-alpha; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C100416:peginterferon alfa-2a