Outcomes after hepatic encephalopathy in population-based cohorts of patients with cirrhosis

Background Hepatic encephalopathy is a devastating complication of cirrhosis. Aim To describe the outcomes after developing hepatic encephalopathy among contemporary, aging patients. Methods We examined data for a 20% random sample of United States Medicare enrolees with cirrhosis and Part D prescription coverage from 2008 to 2014. Among 49 164 persons with hepatic encephalopathy, we evaluated the associations with transplant-free survival using Cox proportional hazard models with time-varying covariates (hazard ratios, HR) and incidence rate ratios (IRR) for healthcare utilisation measured in hospital-days and 30-day readmissions per person-year. We validated our findings in an external cohort of 2184 privately insured patients with complete laboratory values. Results Hepatic encephalopathy was associated with median survivals of 0.95 and 2.5 years for those >= 65 or <65 years old and 1.1 versus 3.9 years for those with and without ascites. Non-alcoholic fatty-liver disease posed the highest adjusted risk of death among aetiologies, HR 1.07 95% CI (1.02, 1.12). Both gastroenterology consultation and rifaximin utilisation were associated with lower mortality, respective adjusted-HR 0.73 95% CI (0.67, 0.80) and 0.40 95% CI (0.39, 0.42). Thirty-day readmissions were fewer for patients seen by gastroenterologists (0.71 95% CI [0.57-0.88]) and taking rifaximin (0.18 95% CI [0.08-0.40]). Lactulose alone was associated with fewer hospital-days, IRR 0.31 95% CI (0.30-0.32), than rifaximin alone, 0.49 95% CI (0.45-0.53), but the optimal therapy combination was lactulose/rifaximin, IRR 0.28 95% CI (0.27-0.30). These findings were validated in the privately insured cohort adjusting for model for endstage liver disease-sodium score and serum albumin. Conclusions Hepatic encephalopathy remains morbid and associated with poor outcomes among contemporary patients. Gastroenterology consultation and combination lactulose-rifaximin are both associated with improved outcomes. These data inform the development of care coordination efforts for subjects with cirrhosis.