Editor's Note: Recently, a study by Italian scholar Dr. Silvia Nardelli, published in the Journal of Hepatology, found that even if cirrhotic patients develop overt hepatic encephalopathy (OHE) after undergoing transjugular intrahepatic portosystemic shunt (TIPS) surgery, their mortality rate does not significantly increase. This conclusion challenges previous perceptions of the negative impact of OHE in non-TIPS contexts, offering new hope and management strategies for cirrhotic patients.

TIPS is an increasingly used non-surgical radiological intervention to treat complications of portal hypertension. It establishes a connection between the portal and hepatic veins, diverting blood flow from the portal circulation directly to the systemic vasculature, effectively reducing portal venous pressure. Since its introduction in the late 1980s, TIPS has become an established treatment method for patients with complications of portal hypertension, primarily used to treat variceal rebleeding and recurrent or refractory ascites. In these cases, TIPS has been shown to improve survival rates, although studies indicate some variability in outcomes.

OHE is the main shunt-related complication following TIPS insertion. Reports indicate that the incidence of OHE in cirrhotic patients post-TIPS can be as high as 35%-50% within the first year after surgery, with up to 8% of patients potentially experiencing persistent OHE. In selected cases, reducing the diameter of the stent can control persistent OHE. These findings have spurred numerous studies aiming to identify risk factors for developing OHE after TIPS, to improve patient selection, and to explore pharmacological strategies for preventing OHE before TIPS surgery. Factors such as older age, higher Model for End-Stage Liver Disease (MELD) or Child-Pugh scores, a history of overt or covert hepatic encephalopathy, sarcopenia, impaired renal function, large shunt diameter, and lower post-TIPS portosystemic pressure gradient have been shown to increase the likelihood of OHE after TIPS. Therefore, current guidelines encourage selecting TIPS patients based on these reported factors. The pharmacological management of preventing post-TIPS OHE remains controversial.

In cirrhotic patients outside of the TIPS context, the development of OHE adversely affects survival regardless of the severity of cirrhosis or the presence of acute or chronic liver failure. For patients awaiting liver transplantation (LT), experiencing at least one episode of OHE increases the 6-month mortality rate and significantly enhances the predictive value of the MELD score. However, whether patients who develop OHE after TIPS also experience increased mortality has not been specifically addressed. Several existing scores, such as the Child-Pugh score, MELD score, Freiburg index of post-TIPS survival (FIPS) score, and the recently published ExPeCT score, help identify high-risk patients for poor prognosis after TIPS. However, these scores do not consider post-TIPS OHE as a potential factor affecting survival, and the impact of post-TIPS OHE on mortality has not been studied in large populations. It remains uncertain whether the occurrence of OHE after TIPS increases mortality in TIPS patients.

Given this context, Dr. Silvia Nardelli and her team designed a multicenter, non-inferiority observational study to compare the mortality rates of TIPS patients based on the incidence of OHE after TIPS. The study, conducted by multiple Italian medical centers, followed 614 cirrhotic patients who underwent TIPS for up to 30 months. The results showed that although 47% of patients experienced at least one episode of OHE after surgery, multivariate analysis indicated that age and MELD score were independent factors affecting mortality, while OHE did not increase the risk of death. This finding overturns the traditional view that OHE is often seen as a strong indicator of poor prognosis in cirrhotic patients not undergoing TIPS.

However, the research team also noted that TIPS patients might undergo more rigorous screening and closer monitoring, which could be a reason why OHE does not increase mortality. While episodic OHE does not increase mortality, its impact on patients’ quality of life and morbidity should not be overlooked, especially in patients with persistent OHE, who have significantly higher mortality rates than those without OHE.

This study provides important evidence for the management of cirrhotic patients and emphasizes the importance of personalized treatment and patient selection. The researchers suggest that stricter preoperative assessment, intraoperative management, and postoperative strategies should be implemented for potential high-risk patients to reduce the incidence of OHE and focus on the prevention and treatment of persistent OHE.

Subsequently, based on the findings of this article, Dr. Lukas Hartl from the University of Vienna further analyzed and discussed whether early encephalopathy after TIPS affects patient mortality. Through a retrospective study, they analyzed 237 patients who underwent TIPS treatment in Vienna between September 2000 and November 2022, excluding those with vascular liver disease, hepatocellular carcinoma, prior liver transplantation, or prophylactic TIPS placement. The primary endpoint was 30-month mortality, with milestones set at 1, 3, and 6 months to analyze the impact of OHE on mortality.

The results showed that patients who developed OHE at 3 and 6 months post-TIPS did not show significant differences in mortality rates, supporting Dr. Silvia Nardelli’s findings. However, the study found that patients who developed OHE within 1 month post-TIPS showed significantly higher mortality rates. Cumulative incidence analysis showed that these patients had 1-year and 2-year mortality rates of 43.6% and 48.1%, respectively, compared to 13.9% and 20.2% in patients without OHE (P=0.004, Figure 2).

Although OHE occurring at 3 and 6 months post-TIPS does not significantly impact mortality, early OHE (within 1 month) is associated with significantly increased mortality. This suggests that patients with early OHE may face higher mortality risks, warranting further research and attention.

Dr. Lukas Hartl’s study provides new insights into the impact of post-TIPS OHE on mortality, highlighting the importance of early identification and intervention for OHE. The study also reminds physicians to closely monitor patients after TIPS to detect and manage OHE promptly.

In summary, current research on the impact of post-TIPS OHE on mortality has significant implications for improving the prognosis and quality of life of cirrhotic patients and provides new directions for future clinical research and treatment. With further research, we have reason to believe that more effective management and treatment strategies will be discovered, offering better health prospects for cirrhotic patients.