Treatment of naive patients with chronic hepatitis C

Treatment of chronic hepatitis C virus (HCV) infection in naive patients with interferon alpha alone or in combination with ribavirin is reviewed. Two placebo-controlled randomised studies including 150 patients have shown that ribavirin as single therapy at standard dosage (15 mg/kg bodyweight in two divided doses daily) only reduces ALT levels transiently during therapy, whereas HCV RNA levels are not substantially reduced. Interferon alpha (IFN) alone at standard dosage (3 MU t.i.w.) given for 12 months results in sustained virological response (SR) rates of some 15-25% depending on the genotype and baseline HCV RNA levels. Ribavirin in combination with alpha interferon, in standard doses for 6-12 months significantly improves the sustained biochemical and virological response rates 2-3 times compared with IFN alone for 12 months. In the future, combination therapy will become standard therapy for most naive patients, at least those with unfavourable viral parameters such as a high baseline viral load (>2-3 million gE/ml serum) and genotype 1a+1b. In patients with favourable baseline viral characteristics (genotypes 2 and 3, irrespective of viral load) 6 months of combination therapy is likely to be sufficient, whereas those with unfavourable viral baseline characteristics will need longer combination treatment. Both genotype and baseline viral load need to be assessed to optimise the choice of therapy. Many questions must still be answered, such as the optimal dose of ribavirin and IFN in combination regimens, and the optimal treatment length. Furthermore, should induction treatment be used in combination regimens? What regimen should be used for patients with more advanced disease such as those with cirrhosis and decompensation?