A combination of increased treatment efficacy and greater uptake is required to achieve major reductions in advanced liver disease and related costs. Hepatitis C virus (HCV) infection is a major public health burden in Australia. Acute HCV infection progresses to chronic infection in approximately 75% of cases,[1] and these people are at risk of progressive liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Around 20–30% of people with chronic HCV will develop cirrhosis, generally following at least 20–30 years infection.[2] The previously estimated large pool of chronic HCV in Australia (230 000 cases)[3] and the “aging cohort” effect in this population related

to the high incidence of injecting drug BGJ398 clinical trial use-acquired infection in the 1980s and 1990s means that the already escalating rates of HCV-related cirrhosis, liver failure, and HCC are projected to increase further over the next two decades.[4] While modeling suggests that the incidence of HCV infection is in decline from a peak of 14 000 new infections in 1999 to 9700 new infections in 2005,[4] the number of people in Australia living with

hepatitis C is expected to continue to increase for the foreseeable future. During the PI3K Inhibitor Library 2000s, combined pegylated interferon (PEG-IFN) and ribavirin (RBV) treatment was the standard of care for chronic HCV, and in Australia, this has led to a sustained virological response (SVR) in around 50% for people with HCV genotype 1 and 70% for HCV genotype 2/3.[5] However, treatment uptake remained low (2000–4000 people/year; 1–2% of the infected population), even following the removal of mandatory pretreatment liver biopsy in 2006 and broadening of inclusion criteria to include all fibrosis stages and normal alanine aminotransferase levels.[6] Several factors many contribute to low HCV treatment

rates, including toxicity of interferon-based therapy, prolonged treatment course (24–48 weeks), social marginalization of people with chronic HCV, lack of treatment infrastructure (particularly opiate pharmacotherapy, prison, community health, and primary care settings), and lack of awareness of the curative potential of treatment. Lower HCV treatment responses in those with advanced liver disease also limited the impact of antiviral therapy on disease burden. The initial phase of direct-acting antiviral (DAA) therapy, involving PEG-IFN/RBV and either telaprevir or boceprevir for chronic HCV genotype 1[7-11] commenced in Australia with government subsidization through the Pharmaceutical Benefits Scheme from April 2013 (patients provide a small monthly copayment of $AUS 7–25). However, early indications are that treatment numbers are unchanged, presumably based on the continued barriers to interferon-containing therapy and increased complexity and safety concerns with the addition of first generation protease inhibitors.