Reduced Incidence of Hepatic Encephalopathy and Higher Odds of Resolution Associated With Eradication of HCV Infection

Background & Aims: It is unclear whether a sustained virologic response (SVR) to direct-acting antiviral (DAA) therapy reduces the risk of incident hepatic encephalopathy (HE) in patients with hepatitis C virus (HCV) infection or whether it leads to resolution of pre-existent HE. Methods: We identified 71,457 patients who initiated antiviral treatments in the Veterans Affairs Healthcare System from January 1, 1999 through December 31, 2015; 35,871 patients (58%) received only interferon, 4535 patients (7.2%) received DAAs plus interferon, and 21,948 patients (35%) received DAA-only regimens. We collected data from patients through October 31, 2018, for an average of 6.6 years. We evaluated the association between SVR and the development of incident HE or the resolution of pre-existent HE (defined by cessation of pharmacotherapy) as well as the risk of hospitalization with HE after adjusting for potential confounders. Results: Compared to no SVR, SVR after DAA therapy was associated with a significantly lower risk of developing HE (0.28 vs 1.39 per 100 person-years; adjusted hazard ratio [AHR] 0.41; 95% CI, 0.32–0.51). This association persisted among patients with co-morbid alcohol use disorder and diabetes as well as patients with cirrhosis (AHR, 0.36; 95% CI, 0.31–0.43) and model for end-stage liver disease (MELD) scores of 9 or more (AHR, 0.36; 95% CI, 0.30–0.44). SVR was also associated with reduced risk of hospitalization with HE (AHR, 0.59; 95% CI, 0.43–0.81). Among 2396 patients who were receiving pharmacotherapy for HE at the time of antiviral treatment, SVR was associated with a significantly increased likelihood of HE resolution for those with MELD scores below 9 (AHR, 2.26; 95% CI, 1.74–2.93) but not those with MELD scores of 9 or more. Conclusions: In a retrospective study of veterans, we found DAA eradication of HCV infection to be associated with a 59% reduction in risk of development of HE and a > 2-fold increased likelihood of resolution of pre-existing HE in all subgroups except patients with MELD scores of 9 or more