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

Abstract

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)vs59(50-67) years, p<0.001], had lower albumin [3.1(2.8-3.5)vs3.25(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. Results' robustness was increased following propensity score matching.

Conclusion

Episodic OHE after TIPS is not associated with mortality in patients undergoing TIPS, regardless of the indication.

Impact and implications

Overt hepatic encephalopathy (OHE) is a common complication in patients with advanced liver disease and it is particularly frequent following transjugular intrahepatic portosystemic shunt (TIPS) placement. In cirrhotic patients outside the setting of TIPS, the development of OHE negatively impacts survival, regardless of the severity of cirrhosis or the presence of acute on chronic liver failure. With this multicenter, non-inferiority observational study we demonstrated that post-TIPS OHE does not increase the risk of mortality in patients undergoing TIPS, irrespective of the indication. This finding alleviates concerns regarding the weight of this complication after TIPS. Thus, intensive research of factors improving patient selection, and allowing risk stratification remains crucial to ameliorate the quality of life of patients and caregivers and to avoid undermining the positive effects on survival in patients undergoing TIPS.