We read with interest the recent article by Spaan et al. 1. Hepatic encephalopathy (HE) remains a frequent and clinically relevant complication following transjugular intrahepatic portosystemic shunt (TIPS), substantially affecting quality of life and post-procedural outcomes. Spaan reported an association between diabetes mellitus (DM) and post-TIPS HE, primarily based on cohorts dominated by patients with metabolic-associated steatotic liver disease (MASLD). In such populations, DM is highly prevalent and may reflect more advanced metabolic liver disease, raising uncertainty as to whether DM confers additional HE risk independent of cirrhosis aetiology. We therefore evaluated the association between DM and HE after TIPS in a large real-world cohort predominantly composed of patients with viral hepatitis–related cirrhosis. A total of 1142 patients undergoing TIPS with 8-mm covered stent were included, of whom 186 (16.3%) had DM. Viral hepatitis was the most common cause of cirrhosis in both groups (51.0% vs. 69.8%). Patients with DM more frequently had MASLD as the underlying aetiology (18.8% vs. 0.2%), whereas sex distribution, liver function indexes and TIPS indications were broadly comparable between groups. HE events were prospectively recorded during follow-up. Time-to-event analyses were performed using Kaplan–Meier methods, with group differences assessed by the log-rank test, and Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). During a follow-up period of up to 9 years, patients with DM exhibited a higher cumulative incidence of HE after TIPS compared with those without DM (41.4% vs. 32.2%). At 1 year, the cumulative incidence of HE was 33.3% in patients with DM versus 24.0% in those without DM (Figure 1A). DM was associated with an increased risk of HE (HR 1.47, 95% CI 1.10–1.96, p = 0.008). We further examined overt HE as a clinically meaningful endpoint, given that prior studies primarily reported ‘severe HE’, which does not fully correspond to overt HE as currently defined 2. Patients with DM demonstrated a higher 1-year cumulative incidence of overt HE compared with those without DM (26.6% vs. 20.2%), with a consistent direction of effect that did not reach statistical significance (HR 1.36, 95% CI 0.98–1.89; p = 0.06; Figure 1B). Subgroup analyses showed a consistent association between DM and HE across clinically relevant strata, including age, MELD-Na score and presence of portal vein thrombosis (Figure 1C), supporting that the observed risk was not solely driven by liver disease severity or haemodynamic factors. Notably, routine lactulose prophylaxis was commonly implemented after TIPS in our cohort, which may partly explain the overall lower incidence of HE compared with previously reported cohorts 1, 3. Collectively, these findings extend existing evidence by demonstrating that DM is associated with an increased risk of post-TIPS HE across different cirrhosis aetiologies and under contemporary preventive management. DM is a readily identifiable clinical feature that may help identify patients at higher risk of HE after TIPS. Whether improved glycaemic control can reduce the risk of hepatic encephalopathy after TIPS warrants further investigation. Miao Yi: validation, investigation, data curation, writing – original draft. Yuanyuan Li: data curation, investigation, writing – review and editing. Xiaoze Wang: conceptualization, formal analysis, methodology, supervision, writing – review and editing, writing – original draft, funding acquisition, project administration. This study was funded in part by the National Natural Science Foundation of China (grant number 82570727) and in part by the 1·3·5 Project for Disciplines of Excellence of West China Hospital, Sichuan University (grant number ZYGD23031). Ethical approval for the retrospective data analysis was obtained from the Ethics Committees of our institution in compliance with the Declaration of Helsinki. Informed consent was waived due to the nature of the study. The waiver of informed consent was approved by the Institutional Review Board to ensure that the research could be conducted ethically and scientifically while protecting the rights and welfare of the subjects. The authors declare no conflicts of interest. This article is linked to Spaan et al. papers. To view these articles, visit https://doi.org/10.1111/apt.70453 and https://doi.org/10.1111/apt.70584. The data and materials used in this study are not publicly available due to ethical restriction. Requests should be directed to the corresponding author.
Yi et al. (Sun,) studied this question.