Pre-Transplant Hepatic Encephalopathy (He) Is Associated With He in Patients With Recurrent Cirrhosis After Liver Transplantation

Background. We hypothesized that patients with recurrent cirrhosis are more likely to develop post-transplant HE if they had pre-transplant HE.Methods. We evaluated patients who developed cirrhosis after transplantation (1987 to 2023 at a tertiary transplant center) who also developed West-Haven stage 2 or greater HE. Patients with ALF were excluded. Post-transplant HE patients were matched using a case control design to post-transplant cirrhosis patients without post-transplant HE.Results. 194 patients developed post-transplant cirrhosis; 78/194 (40%) developed post-transplant HE. The most common cause of post-transplant cirrhosis was HCV, and among all patients with cirrhosis post-transplant, HE developed approximately 7 years after liver transplantation (median [IQR]: 6.8 [11] years). In the 78 patients with HE after transplant, pre-transplant HE was identified in 31 (40%) patients. Patients with HE pre-transplant developed post-transplant HE faster than those without HE pre-transplant (4 years vs 9 years; log-rank test: p < 0.05). In patients with post-transplant cirrhosis but without post-transplant HE, pre-transplant HE was identified in 8 (7%) patients (8/116 vs 31/78 who had HE pretransplant, p < 0.001). In multivariable analysis, the strongest predictor of post-transplant HE was HE pre-transplant (OR = 10.8, 95% CI 4.0-33.6, p < 0.001).Conclusions. Patients with post-transplant cirrhosis who develop HE are more likely to have had pre-transplant HE, suggesting intrinsic biological factors in HE pathogenesis – perhaps related to mesenteric shunts or perhaps the microbiome. The data raise the possibility that patients who had HE pre-transplant who develop cirrhosis after liver transplantation may benefit from prophylactic lactulose/rifaximin.