Hepatitis C advances in antiviral therapy: what is accepted treatment now?

The vast number of patients with hepatitis C represent a huge medical and economic burden. While 20-30% of these patients progress and develop advanced liver disease, the majority do not. Thus, it is crucial to identify patients suitable for treatment and those who may benefit most from therapy. Anti-viral therapy is recommended for those patients with chronic hepatitis C who also have elevated liver tests, detectable hepatitis C virus ribonucleic acid and significant inflammation and/or fibrosis on liver biopsy. Currently, the most effective initial therapy is the combination of interferon plus ribavirin. The sustained viral response rate (SVR) is 36-41% following a 24- or 48-week course of therapy. In general, patients with the genotype 1 infection should receive 48 weeks of therapy, and those with genotypes 2 or 3 infection only 24 weeks. Viral load estimations are problematic because of normal fluctuations (up to 0.5-10 log), assay variability and lack of a universally accepted standard; thus, viral load testing is not recommended routinely at present. The sustained viral response rate produces improvements in quality of life and liver histology (including reversal of bridging fibrosis and cirrhosis is some), and durable responses lasting 5-11 years in 95-97% of cases. While the optimal dose of ribavirin is currently unknown, available data suggest that higher doses increase efficacy (albeit with a greater degree of anemia). The dose of 800 mg/day may be the most appropriate lower dose for those patients who require dosage modification for anemia or other side-effects. Patients who have relapsed after interferon monotherapy can be successfully retreated with higher doses of interferon for 1 year or the combination of interferon and ribavarin for 24-48 weeks. Preliminary data suggest that patients with an unfavorable profile, including those with genotype 1 infection, should probably be retreated with interferon and ribavirin for 48 rather than 24 weeks. With our current best therapies, the majority of patients still do not achieve the benefits of a sustained response. Re-treatment with interferon and ribavirin may achieve a sustained response in approximately 10-25% of these patients. In the immediate future, once-weekly pegylated interferons will replace standard interferons. Initial data suggest that SVR achieved with these drugs in combination with ribavirin is increased to 54-61%, but dose modifications and side-effects are more frequent. They will thus provide an incremental benefit in terms of efficacy, particularly for genotype 1-infected patients.