Hepatitis C virus infection in patients receiving opiate substitution therapy in Sweden.

The hepatitis C virus (HCV) is a blood borne virus effectively spread through injection practices. Consequently, people who inject drugs (PWID) are at the center of the current HCV epidemic in industrialized countries, with regards both to prevalence and incidence. Through progressive liver fibrosis, chronic HCV infection conveys a substantial risk of liver cirrhosis and end-stage liver disease. These complications can be prevented by successful HCV treatment resulting in HCV clearance. HCV treatment uptake has hitherto been low among PWID, due to barriers on patient- as well as health care provider levels. PWID also have a multitude of other risk factors affecting morbidity and mortality. The major causes of death are directly drug related. Opiate substitution therapy (OST) reduces drug related mortality in heroin using PWID, which might allow for chronic conditions, such as HCV infection, to impact morbidity and mortality. OST also improves social functioning and has been shown to improve HCV treatment outcomes for heroin users, hence OST clinics could serve as important points of contact for HCV management. The aim of this thesis was to investigate different aspects of HCV infection in Swedish OST recipients. In a cross-sectional multi center study of OST receiving patients in Stockholm, Gothenburg and Malmo we assessed the prevalence of HCV infection and the burden and severity of liver fibrosis in relation to potential risk factors. We evaluated feasibility of peginterferon/ribavirin based HCV treatment, in the same cohort, with special attention to psychiatric status and health related quality of life (HRQoL). In a register based study we evaluated liver related mortality in relation to OST exposure in heroin users recruited from a needle exchange program. In the OST cohort we found high rates of HCV exposure (88% anti-HCV positive) and 67% of viremic patients showed significant fibrosis with association to alcohol intake, elevated BMI and exposure to hepatitis B virus. In HCV treated subjects we observed rates of completion (83%) and SVR rates (46%) in line with previous reports on peginterferon/ribavirin based HCV treatment in PWID, in spite of low scores on HRQoL and high occurrence of depression already at baseline. In the heroin using population recruited from a needle exchange program we found a significantly elevated (HR 3.08, 95%CI (1.09, 8.68), p=0.03) risk of liver related death related to OST exposure. In conclusion, HCV related liver disease is a significant problem in Swedish OST patients and may be an increasingly common cause of death. Thus, targeted management of HCV and risk factors for liver fibrosis progression should be an integral part of comprehensive care provided in OST clinics. Our findings of satisfactory completion rates with treatment based on peginterferon/ribavirin holds promise of even higher rates of both completion and SVR once new interferon free treatment regimens with higher efficacy, less toxicity and shorter duration, are implemented. However, for more efficient therapies to be able to impact morbidity and mortality, increasing uptake of HCV assessment and treatment for OST recipients is essential