LAUSR

The recent advent of all-oral direct-acting antivirals (DAAs) has revolutionized the treatment of hepatitis C virus (HCV). Although access to HCV treatment has been improving in the United States (attributed to increased competition, negotiated lower drug prices, and evolving payer policies), considerable barriers to linkage to care remain for many such as those on Medicaid, the uninsured, and incarcerated patients. Though payer policies are highly variable, restrictions based on the prescribing provider, psychosocial comorbidities, and degree of fibrosis persist, and the past authorization process can be burdensome for many practitioners. Traditionally, fibrosis-based HCV coverage restrictions stem from the fact that HCV is characterized as a slowly progressive disease with a low annual fibrosis rate. However, estimates come from retrospective studies with heterogeneous populations and can range widely, whereas the effects of HCV on chronic inflammation and healthrelated quality of life are not considered. Among patients with advanced fibrosis (AF), previous data have consistently shown the long-term benefits of viral eradication in decreasing liver-related mortality, decompensation, and hepatocellular carcinoma (HCC), both for interferon (IFN)-based and all-oral DAA regimens. However, the impact of DAA therapy on clinical outcomes in the absence of advanced liver disease has not yet been well characterized. In the current issue of HEPATOLOGY, Dr. Backus et al. examine an important and understudied issue of the impact of DAA therapy on all-cause mortality in HCV-infected patients receiving care in the U.S. Department of Veterans Affairs (VA). As the largest integrated health care system in the United States and the largest provider of HCV care nationally, the VA has prioritized HCV screening and eradication, treating nearly 100,000 veterans with sustained virological response (SVR) rates above 90%. The researchers report on outcomes among 40,664 of these HCV monoinfected veterans who were engaged in VA care and had no apparent evidence of advanced liver disease (defined either the absence of cirrhosis or liver decompensation diagnosis codes, including HCC and history of liver transplantation, or fibrosis 4 [FIB-4] scores of <3.25). Of this cohort, nearly 97% of the treated patients with available data achieved SVR, and their outcomes were compared to the other 3% of non-SVR patients as well as 62,882 DAA unexposed patients without apparent AF. Impressively, around 90% of eligible patients had end-of-treatment data available, underscoring the success of this single integrated system of care for maintaining patient follow-up. In this cohort without advanced liver disease, SVR was associated with a 59% unadjusted all-cause mortality reduction when compared to no-SVR, and a 69% reduction compared to no treatment when calculated in deaths per 100 person-years. In absolute terms, 1year mortality rates were reduced by 1.3% with SVR Abbreviations: AF, advanced fibrosis; DAAs, direct-acting antivirals; EHD, extrahepatic disease; HCV, hepatitis C virus; HR, hazard ratio; IL, interleukin; SVR, sustained virological response; VA, U.S. Department of Veterans Affairs.