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. 2025 Sep;13(7):1171-1183.
doi: 10.1002/ueg2.70095. Epub 2025 Aug 9.

Plasma Ammonia Levels Predict Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt Placement

Lisa Sandmann  1   2 , Julius F M Egge  1   3 , Anja Tiede  1 , Alena F Ehrenbauer  1   3 , Martin A Kabelitz  1 , Hannah Rieland  1 , Jim B Mauz  1 , Bernhard C Meyer  4 , Heiner Wedemeyer  1   2 , Karin Weissenborn  3 , Benjamin Maasoumy  1   2
Affiliations

Plasma Ammonia Levels Predict Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt Placement

Lisa Sandmann et al. United European Gastroenterol J. 2025 Sep.

Abstract

Background: Placement of a transjugular intrahepatic portosystemic shunt (TIPS) is an effective treatment for portal hypertension. Overt hepatic encephalopathy (oHE) is a complication after TIPS associated with increased morbidity. Elevated ratio of plasma ammonia (AMM) levels compared to the local upper limit of normal (ULN) has been associated with oHE, hepatic complications and increased mortality in patients with cirrhosis without TIPS. The role of AMM in risk stratification of post-TIPS oHE is unclear.

Objective: To investigate the role of AMM in the prediction of oHE in patients receiving TIPS placement.

Methods: Patients with TIPS placement were recruited within a prospective observational study protocol with follow-up (FU) visits at 1, 3, 6, and 12 months after TIPS. Post hoc analyses of AMM levels for the association with the primary (oHE) and secondary endpoints (hepatic decompensation, infections, death/liver transplantation) during the first year after TIPS placement were performed.

Results: Of 188 patients with TIPS placement, 148 patients with available baseline AMM levels were included. During follow-up, 37% (55/148) of patients developed oHE. In multivariable competing risk analysis, baseline AMM/ULN (HR 2.03 [CI 1.42-2.89], p = 0.001) and Freiburg index of post-TIPS survival (FIPS) score (HR 1.52 [CI 1.03-2.24], p = 0.037) were independently associated with oHE. The published cut-off AMM/ULN > 1.4 showed comparable results (HR 2.40 [CI 1.24-4.65], p = 0.01). AMM at FU1 was available in 100 patients, of whom 28% (28/100) developed oHE after FU1. In multivariable competing risk analysis, AMM/ULN (HR 5.48 [CI 2.37-12.67], p < 0.001), psychometric hepatic encephalopathy score (HR 0.86 [0.78-0.96], p = 0.005) and FIPS (HR 3.57 [CI 1.79-7.14], p < 0.001) at FU1 were independently associated with oHE after FU1. No significant association between AMM/ULN and the secondary endpoints was detected.

Conclusion: AMM levels before TIPS are independently associated with oHE after TIPS placement. AMM levels may serve as an additional marker for risk stratification of patients.

Trial registration: Clinical trial number NCT04801290.

Keywords: Freiburg index of post‐TIPS survival (FIPS); liver cirrhosis; overt hepatic encephalopathy; plasma ammonia levels; portal hypertension; post‐TIPS outcomes; transjugular intrahepatic portosystemic shunt (TIPS).

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Conflict of interest statement

L.S. reports lecture honoraria and personal fees from Falk Pharma e.V., Gilead and Roche, and travel support from AbbVie. Heiner Wedemeyer has received fees for lectures and/or consultations from Abbvie, Aligos, Altimmune, Biotest, BMS, BTG, Dicerna, Enanta, Gilead, Janssen, Merck/MSD, MYR GmbH, Roche, and Vir Biotechnology. B.M. served as a speaker and/or advisory board member for AbbVIe, Fujirebio, Gilead, Luvos, MSD, Norgine, Roche, W. L. Gore & Associates and received research support from Altona, EWIMED, Fujirebio and Roche. K.W. has taken part in the development of the Psychometric Hepatic Encephalopathy Score (PHES) and the copyright of this test is held by Hannover Medical School. The remaining authors disclose no conflicts.

Figures

FIGURE 1
FIGURE 1
Outline of the study cohort. FU1: follow‐up 1; LT: liver transplantation; oHE: overt hepatic encephalopathy; TIPS: transjugular intrahepatic portosystemic shunt.
FIGURE 2
FIGURE 2
Cumulative incidence of overt hepatic encephalopathy during follow‐up. Cumulative incidence of overt hepatic encephalopathy during follow‐up of patients stratified by plasma ammonia levels at baseline (a) and after 1 month after TIPS insertion (b). Time‐dependent Fine‐Gray model for competing risk analysis treating death or liver transplantation as competitor. HE: hepatic encephalopathy; HR: hazard ratio; TIPS: transjugular intrahepatic portosystemic shunt; ULN: upper limit of normal.
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References

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