Letter: Association of Diabetes Mellitus With Post‐ <scp>TIPS</scp> Hepatic Encephalopathy in a Predominantly Viral Cirrhosis Cohort—Authors' Reply

We read with great interest the letter by Yi et al. published in Alimentary Pharmacology & Therapeutics. Importantly, their study, based on a large Chinese cohort of 1142 patients with cirrhosis undergoing transjugular intrahepatic portosystemic shunt (TIPS) placement, confirms diabetes mellitus as a risk factor for the development of hepatic encephalopathy (HE) following TIPS [1]. Their cohort primarily consisted of patients with viral hepatitis (54.1%). This contrasts with our study, in which only 11.8% of patients had viral hepatitis-related liver disease as the predominant aetiology was alcohol-related liver disease (53.6%) [2]. The consistency of findings across both cohorts despite the markedly different etiological compositions strengthens the robustness and generalizability of the association between diabetes mellitus and post-TIPS HE. In our study, the cumulative 6-month incidence of HE after TIPS was 59.6% (95% CI 43.7–81.4) in patients with MASH, 67.5% (95% CI 53.6–85.1) in patients with viral hepatitis, and 35.4% (95% CI 27.9–44.8) in those with alcohol-related cirrhosis. Despite the relatively high incidence of HE observed in the MASH group, MASH was not independently associated with an increased risk of post-TIPS HE after adjustment for relevant confounders, suggesting that metabolic comorbidity rather than aetiology per se may be the key driver of risk [2]. In our study, severe HE was defined as HE which required hospitalisation. Severe HE thereby represents a clinically meaningful endpoint, also in the context of retrospective data collection. The diagnosis of overt HE, although commonly used in the literature, is inherently subjective and dependent on clinician judgement, interobserver variability, local practice and the quality of clinical documentation. While overt HE is a valuable endpoint in prospective studies with standardised and repeated assessments, its reliability may thus be limited in retrospective analyses. In contrast, hospitalisation for HE reflects clear escalation of care and is less susceptible to misclassification, thereby reducing potential bias and strengthening the validity of the findings. Taken together, these data underscore the importance of metabolic comorbidities—particularly diabetes mellitus—when assessing the risk of HE after TIPS and highlight the complementary nature of results derived from cohorts with differing etiological distributions. Michelle Spaan: conceptualization, writing – original draft, investigation. Raoel Maan: conceptualization, writing – review and editing, supervision. Adriaan J. van der Meer: conceptualization, writing – review and editing, supervision. The authors have nothing to report. 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.70520. The data that support the findings of this study are available from the corresponding author upon reasonable request.