Factors Predicting Response to Treatment in Chronic HCV Genotype 3 Patients

Abstract

Studies to date have failed to identify the most effective treatment regimes for patients with chronic genotype 3 HCV infection. There is controversy regarding the role of cirrhosis in modifying response and disagreement regarding the impact of ethnicity on treatment outcome. Given the importance of genotype 3 HCV in the global epidemic and the lack of high quality research into this genotype, the purpose of this work has been to address some of the deficiencies in our understanding of the optimal management of this strain of hepatitis C. Specifically we have examined the following hypotheses:- 1) Patients from the Indian sub-continent (South Asians) will respond differently to therapy with pegylated interferon and ribavirin when compared to Caucasians. 2) An analysis of viral and host factors underlying differences between treatment sensitive and treatment refractory cohorts will reveal new insights into the virology of Genotype 3 HCV infection. 3) Increasing the duration of therapy in ‘difficult to manage’ patients with Genotype 3 HCV will improve response rates. 4) Whether non-invasive methods of identifying liver fibrosis are valuable in identifying the stages of fibrosis in Genotype 3 HCV patients. Three different research methodologies were used to address these questions including a metaanalysis of factors associated with treatment failure in patients with genotype 3 HCV, virological and immunological studies on patients with genotype 3 HCV who had failed to respond to therapy and a clinical trial evaluating extended duration therapy in patients with Genotype 3 HCV infection and cirrhosis.