Treating chronic HCV without interferon and/or ribavirin

Abstract

An estimated 200 million people are currently infected with the hepatitis C virus. The incidence of HCV infection has decreased by more than 50% over the last decade, refl ecting reduced exposure risk [1, 2]. Although the size of the population with chronic HCV infection has been stable since 2000 [3], this is an aging cohort and the proportion of this cohort with cirrhosis will almost treble over the next three decades from 16% to over 45% [4, 5]. As a result, the incidence of both HCV-related hepatocellular carcinoma and HCV-related-mortality will also treble [6– 8]. The only means to avert this projected health burden from the current HCV epidemic is to reduce the total pool of patients with chronic HCV infection by widespread eradication of chronic infection by successful antiviral therapy. However, currently less than 10% of patients have been treated with less than 5% cured. The current treatment numbers would need to increase more than tenfold in order to prevent this projected health burden [1, 8]. This would necessitate not only an improved rate of cure from current treatment regimens but also widespread community uptake of HCV screening, diagnosis, and access to treatment. The latter is signifi cantly hindered by the poor effi cacy and tolerability of the current standard-of-care (SOC) for chronic HCV infection, which is the combination of pegylated-interferon plus ribavirin for between 24 and 48 weeks duration. In global registration studies, the overall reported sustained virological response (SVR) rate in patients infected with HCV genotype (GT) 1 is 45% and in those infected with GT2 or 3 is 79%, respectively [9]. Unfortunately, in the real world where clinic follow- up and support are less intensive, SVR rates are signifi cantly lower. In the largest cohort todate of almost 17,000 patients treated and followed up by the US Department of Veterans’ Affairs, the reported SVR rates were 35% in patients infected with GT1, 72% in those with GT2, and 62% in those with GT3 [10]. HCV GT1 is the predominant genotype globally, accounting for between 55% (Australasia) and 90% (Europe and Asia) of all infections.