Episodic overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt does not increase mortality in patients with cirrhosis

Background and Aims In patients with cirrhosis, transjugular intrahepatic portosystemic shunt (TIPS) is indicated for the prophylaxis of variceal re-bleeding and treatment of refractory ascites. Overt hepatic encephalopathy (OHE) is a major complication after TIPS, given its high incidence and possibility of refractoriness to medical treatment. Nevertheless, the impact of post-TIPS OHE on mortality has not been investigated in a large population. Methods We designed a multicenter non-inferiority observational study to evaluate the mortality rate at 30 months in patients with and without OHE after TIPS. We analyzed a database of 614 patients submitted to TIPS in three Italian centers and estimated the cumulative incidence of OHE and mortality with competitive risk analyses, setting the non-inferiority limit at 0.12. Results During a median follow-up of 30 months (IQR 12-30), 293 patients developed at least one episode of OHE. Twenty-seven (9.2%) of them experienced recurrent/persistent OHE. Patients with OHE, compared to those without, were older [64(57-71) vs 59(50-67) years, p<0.001], had lower albumin [3.1(2.8-3.5) vs 3.25(2.9-3.6) g/dl, p=0.023], and had a higher prevalence of pre-TIPS OHE (15.4% vs. 9.0%, p=0.023). Child-Pugh and MELD scores were similar between the two groups. The 30-month difference in mortality between patients with and without post-TIPS OHE was 0.03(95% CI: -0.042 - 0.102). Multivariable analysis showed that age [sHR 1.04 (1.02 -1.05), p<0.001] and MELD [sHR 1.09 (1.05;1.13), p<0.001], but not post-TIPS OHE, were associated with a higher mortality rate. Similar results were obtained when patients undergoing TIPS for variceal re-bleeding prophylaxis (n=356) or refractory ascites (n=258) were analyzed separately. The proportion of patients with persistent OHE after TIPS was significantly higher in the group of patients who died. Conclusion Episodic OHE after TIPS does not increase mortality in patients undergoing TIPS, regardless of the indication.