What is known about HCV comorbidities and viral clearance?

HCV infection has an estimated global prevalence of 1.0%, corresponding to roughly 71.1 million of infected individuals in 2015, with major geographical heterogeneity.1 Due to the large burden of infected individuals in the general population, the likelihood of co-occurrence of chronic HCV infection and common comorbidities is substantial regardless of causal linkages. Population-based studies show a higher overall mortality, both for liver-related and unrelated causes in HCV infected subjects compared with those uninfected, and cross-sectional and cohort studies identify HCV as an independent risk factor for extrahepatic manifestations.2 These issues are summarised in two meta-analyses reporting that HCV-infected patients are at higher risk of mixed cryoglobulinaemia, lymphoma, lichen planus, Sjögren’s syndrome, porphyria cutanea tarda, rheumatoid-like arthritis, depression, chronic kidney or end-stage renal disease, type 2 diabetes and cardiovascular disorders/mortality.3 4 While the link between HCV and some of these comorbidities—mixed cryoglobulinaemia, lymphoma and glomerulonephritis—is well established and driven by recognised pathophysiological mechanisms, the nature of the association between the infection and other common extrahepatic comorbidities is less clear. Clinical and experimental evidences suggest an intrinsic link between HCV infection and insulin-resistance/diabetes driven by the ability of the virus to interfere with insulin signalling, even if the strength of this association is not always confirmed. Emerging data also support a link between HCV infection and cardiovascular alterations. However, relative to this topic, contrasting data exist and the basis of this association stems on associative data, theoretical speculations and inconclusive experimental evidence.5

This mass of data and the recent availability of highly effective antiviral regimens, able …