Hepatitis C genotype 4: What we know and what we don't yet know

Hepatitis C virus genotype 4 (HCV-4) is the most common variant of the hepatitis C virus (HCV) in the Middle East and Africa, particularly Egypt. This region has the highest prevelance of HCV worldwide, with more than 90% of infections due to genotype 4. HCV-4 has recently spread in several Western countries, particularly in Europe, due to variations in population structure, immigration, and routes of transmission. The features of HCV-4 infection and the appropriate therapeutic regimen have not been well characterized. This review discusses the virology, epidemiology, natural history, histology, clinical data, and treatment options for patients with HCV-4 infections. Early reports on the treatment of patients with chronic HCV-4 with conventional interferon (IFN)-alpha monotherapy indicated poor rates of sustained viral response (SVR), which improved slightly when combined with ribavirin. Pegylated IFN and ribavirin combination therapy has dramatically improved the response rates, with recent clinical trials showing rates that exceed 60%. These data can now be used as a platform for further research to define optimal treatment duration and predictors of SVR in patients with HCV-4 infection. Conclusion: HCV-4 infection is spreading beyond its strongholds in Africa and the Middle East. Recent clinical trials show that HCV-4 is not difficult to treat, as the response to treatment may be at an intermediate level compared with genotype 1 and genotypes 2 or 3. Tailored treatment options that are comparable to the treatment approaches for genotype 1, 2, and 3 patients to optimize treatment for each patient are now being developed.