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Background To increase cure rates for Hepatitis C, barriers to treatment adherence and completion must be identified and overcome. Aims This study systematically reviewed evidence on the psychological, lifestyle and social determinants of achieving viral eradication with antiviral therapy. Methods An electronic search strategy was used to identify relevant studies that examined psychological, lifestyle and social factors related to achieving a sustained virological response ( SVR). Results Thirty-four studies that matched our criteria were identified. Of the factors that predict response to treatment, Asian ethnicity was an independent predictor of SVR. We found an indirect relationship between diet and SVR, with non-responders to treatment consuming more polyunsaturated fatty acids, fats and carbohydrates than those who attained SVR. The effect of alcohol consumption relied on the amount consumed; fewer than 30 grams daily had no effect on SVR, whereas >70 grams daily had an adverse impact on a patient's ability to achieve SVR, with termination rates up to 44% in those who drank >2 drinks a day. Patients with psychiatric illnesses had comparable SVR rates to controls if they continued psychological therapy (average 42%), although discontinuation rates were high with 11 studies reporting rates from 14 to 48%. Conclusions There are major gaps in current knowledge of the impact of variables such as diet, exercise, attitudes and coping skills on cure rates in chronic Hepatitis C. Those who drink limited amounts of alcohol or have psychiatric disorders should be offered treatment for their disease, with adjunctive education and support to improve treatment completion. [ABSTRACT FROM AUTHOR]