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

BACKGROUND & AIMS: Overt hepatic encephalopathy (OHE) is a major complication of transjugular intrahepatic portosystemic shunt (TIPS) placement, 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 who underwent 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 were older (64 [57-71] vs. 59 [50-67] years, p <0.001), had lower albumin (3.1 [2.8-3.5] vs. 3.25 [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. The 30-month difference in mortality between patients with and without post-TIPS OHE was 0.03 (95% CI -0.042 to 0.102). Multivariable analysis showed that age (subdistribution hazard ratio 1.04, 95% CI 1.02-1.05, p <0.001) and MELD score (subdistribution hazard ratio 1.09, 95% CI 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. The robustness of these results 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 patients with cirrhosis 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. In 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. Intensive research to improve patient selection and risk stratification remains crucial to enhance the quality of life of patients and caregivers and to avoid undermining the positive effects of TIPS on survival.

Dynamics of Liver Stiffness Measurement and Clinical Course of Primary Biliary Cholangitis.

BACKGROUND & AIMS: In primary biliary cholangitis (PBC), static liver stiffness measurement (LSM) has proven prognostic value. However, the added prognostic value of LSM time course in this disease remains uncertain. METHODS: We conducted an international retrospective cohort study among patients with PBC treated with ursodeoxycholic acid and followed by vibration-controlled transient elastography between 2003 and 2022. Using joint modeling, the association of LSM trajectory and the incidence of serious clinical events (SCE), defined as cirrhosis complications, liver transplantation, or death, was quantified using the hazard ratio and its confidence interval. RESULTS: A total of 6362 LSMs were performed in 3078 patients (2007 on ursodeoxycholic acid alone; 13% with cirrhosis), in whom 316 SCE occurred over 14,445 person-years (median follow-up, 4.2 years; incidence rate, 21.9 per 1000 person-years). LSM progressed in 59% of patients (mean, 0.39 kPa/year). After adjusting for prognostic factors at baseline, including LSM, any relative change in LSM was associated with a significant variation in SCE risk (P < .001). For example, the adjusted hazard ratios (95% confidence interval) associated with a 20% annual variation in LSM were 2.13 (1.89-2.45) for the increase and 0.40 (0.33-0.46) for the decrease. The association between LSM trajectory and SCE risk persisted regardless of treatment response or duration, when patients with cirrhosis were excluded, and when only death or liver transplantation was considered. CONCLUSIONS: Tracking longitudinal changes in LSM using vibration-controlled transient elastography provides valuable insights into PBC prognosis, offering a robust predictive measure for the risk of SCE. LSM could be used as a clinically relevant surrogate end point in PBC clinical trials.