title: Treatment of hepatitis C: critical appraisal of the evidence.
abstract: Chronic hepatitis C virus infection is currently the most common cause of end stage liver disease worldwide. Although the conclusions of the last National Institutes of Health Consensus Development Conferences on Hepatitis C have recently been published, several important issues remain unanswered. This paper reviews the available data using an evidence-based approach. Current evidence is sufficient to recommend IFN treatment for all patients with acute hepatitis. A later initiation of therapy yields the same likelihood of response as early treatment. A daily induction dose during month 1 is the best treatment option. The current gold standard of efficacy for treatment-naive patients with chronic hepatitis C is the combination of pegylated IFN and ribavirin. The overall sustained viral response rate to these regimens is 54 - 56% following a 48-week course of therapy. Patients with genotype 1 infection will have a 42 - 51% likelihood of response to 48weeks of therapy. Those with genotypes 2 or 3 infection will respond to 24weeks in 78 - 82% of cases. Debate continues regarding the optimal dose and duration of peginterferon (PEG-IFN), not only in patients infected with genotype 2 or 3 but also in those infected with genotype 1. The optimal dose of ribavirin has yet to be determined. Available data show the need to give the highest tolerable doses (1000-1200mg/day) to the difficult-to-treat patients (genotype 1, cirrhotics, obese), although there is a greater likelihood of intolerance. Genotypes 2 and 3 may receive 800mg/day, which is also the most appropriate lower dose for those patients who require dosage modification for anaemia or other side effects. Tolerability and compliance to therapy are still a problem, as approximately 15- 20% of patients within trials and > 25% in clinical practice withdraw from therapy. New PEG-IFNs are more effective than conventional IFN in improving liver histology. Monotherapy with PEG-IFN induces a marked reduction in staging in virological sustained responders, and to a lesser degree in relapsers, but provides no benefit to nonresponders after 24-48weeks of treatment. The use of maintenance therapy in virological nonresponders aiming to improve histology should be considered experimental and of unproven benefit. Pooling data from the literature suggests a slight preventive effect of IFN on hepatocellular carcinoma development in patients with HCV-related cirrhosis. The magnitude of this effect is low and the observed benefit may be due to spurious associations. The preventive effect is more evident among sustained responders to IFN.
authors.affiliation: University of Palermo, Cattedra di Gastroenterologia, Istituto di Clinica Medica, Italy. camma@ibim.cnr.it
authors.forename: Calogero
authors.initials: C
authors.lastname: Cammà
authors.forename: Anna
authors.initials: A
authors.lastname: Licata
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cabibbo
authors.forename: Federica
authors.initials: F
authors.lastname: Latteri
authors.forename: Antonio
authors.initials: A
authors.lastname: Craxì
mesh_terms: D000208:Acute Disease; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000517:prevention & control; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy*; D019698:Hepatitis C, Chronic / Q000188:drug therapy; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000150:complications; D008113:Liver Neoplasms / Q000517:prevention & control; D011092:Polyethylene Glycols / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a