Among environmental factors, alcohol consumption and metabolic syndrome should play a major role on the response to treatment in chronic hepatitis C. In a prospective study, regular alcohol consumption (1 drink/d) within 6 months prior to bi-therapy in patients with chronic hepatitis C was significantly associated with treatment stop, underlining the need for specific and multidisciplinary management of those patients. Metabolic steatosis and overall the degree of insulin resistance assessed by HOMA index, also seem to have negative impact on sustained virological response to treatment. The high prevalence of insulin resistance in chronic hepatitis C warrant performing metabolic investigations before to start antiviral treatment. Efficacy of insulin sensitizing agents on virological response in patients treated with bi-therapy is under investigation in randomized controlled trials.