Chronic Hepatitis C Viral Infection: Natural History and Treatment Outcomes in Substance Abusers

Hepatitis C is the most common blood-borne viral illness in the North America. Chronic hepatitis C infection may lead to cirrhosis of the liver, liver failure and liver cancer. In North America, injection drug use is the most important risk factor for infection and substance abusing populations are disproportionately affected by the disease. Antiviral therapy exists and approximately 50% of infected individuals can be cured. The aim of this thesis was to provide information to help clinicians and policy-makers minimize the impact of hepatitis C in substance abusers. The thesis is comprised of three studies. The first assessed the rate of progression to cirrhosis for those acquiring infection through injection drug use, using a meta-analysis of 44 studies from the published literature. We estimated that fibrosis progression occurs at a rate of 8.1 per 1000 person-years (95% Credible Region (CR), 3.9 to 14.7) corresponding to a 20-year cirrhosis prevalence of 14.8% (95% CR, 7.5 to 25.5). The second study measured the association between successful antiviral therapy and quality of life. We demonstrated that sustained responders to therapy had higher scores on the hepatitis-specific Medical Outcomes Survey Short-Form-36 (SF-36), Health Utilities Index Mark 2/3 (HUI2/3), and time-tradeoff (TTO) than treatment failures, an average of 3.7 years following antiviral therapy. The third study assessed rates of adherence to antiviral therapy and rates of sustained response in current or former iii substance abusers on methadone maintenance. We demonstrated that while use of illicit substances prior to therapy negatively affected adherence, rates of sustained response were comparable to non-substance abusing populations. Our work indicates the future burden of disease in current and former substance abusers, demonstrates that antiviral therapy can be successful in this population, and indicates that the benefits of successful therapy may extend beyond decreased disease burden to improved quality of life.Ph