Identification of optimal portal pressure decrease to control ascites while minimizing hepatic encephalopathy after TIPS: A multicenter study

Background & Aims: Clinically-significant portal hypertension (CSPH) in liver cirrhosis patients can lead to refractory ascites. A transjugular-intrahepatic-portosystemic shunt (TIPS) treats CSPH but may cause overt hepatic encephalopathy (oHE). Our aim was to determine the optimal reduction of the portal pressure gradient (PPG) via TIPS to control ascites without raising oHE risk. Approach: This multicenter study screened 1509 patients from three European centers (Hannover, Vienna, Hamburg) undergoing TIPS-implantation between 2000-2023. Patients with TIPS-indications other than refractory ascites/hepatic hydrothorax, vascular-liver-disease, hepatocellular-carcinoma or insufficient PPG data were excluded. PPG was measured before and after TIPS insertion. Outcome data was assessed up to one year after TIPS-insertion. Analyses were conducted utilizing a modern machine leaning model, namely a competing-risk (CR) random survival forest (RSF), partial-dependence-plots (PDP) and CR-analyses with liver transplantation/death as competitors. The cohort was divided into a 60% derivation and 40% validation cohort. Results: Overall, 729 patients (median MELD: 13 (IQR 10-16), 66% male, 23% oHE before TIPS) were analyzed. The derivation cohort comprised 438 and validation cohort 291 patients. The optimal PPG reduction, determined by maximally selected Grays-statistic and PDP of the RSF, was 60-80%. In this range, patients showed significantly fewer hepatic decompensations due to ascites (HDA) (sHR: 0.7 [0.52-0.96]) with similar oHE incidences (sHR: 0.92 [0.67-1.27]). The PPG range was confirmed in the validation cohort (HDA: sHR: 0.66 [0.46-0.96]; oHE: sHR: 0.89 [0.61-1.32]). Conclusions: A targeted PPG reduction of 60-80% showed significantly reduced HDA without increased oHE risk. Therefore, PPG reduction within this range could be a valid reduction target.