Editor's note: Recently, a study published in the Journal of Hepatology by Italian scholar Professor Silvia Nardelli et al. found that the mortality rate of patients with liver cirrhosis did not increase significantly after receiving transjugular intrahepatic portosystemic shunt (TIPS), even if overt hepatic encephalopathy (OHE) occurred. This conclusion overturns the previous understanding of the negative impact of OHE in the context of non-TIPS, and provides new treatment hope and management strategies for patients with liver cirrhosis.
Figure 1. Summary of Important Charts and Figures of the Article (https://doi.org/10.1016/j.jhep.2023.11.033)
Transjugular intrahepatic portosystemic shunt (TIPS) is an increasingly widely used non-surgical radiological intervention for the treatment of complications of portal hypertension. TIPS establishes a communication between the portal vein and the hepatic vein, transferring blood flow directly from the portal vein circulation to the systemic vascular bed, effectively decompressing the portal venous system by reducing the portosystemic pressure gradient. Since its introduction in the late 80s, TIPS has become an established treatment for patients with complications of portal hypertension, primarily for the treatment of variceal rebleeding and recurrent or refractory ascites [1-3]. In these settings, TIPS has been shown to improve patient survival, but studies have shown some discrepancies [4-9].
Overt hepatic encephalopathy (OHE) is a major shunt-related complication after TIPS placement. The incidence of postoperative OHE after TIPS in patients with cirrhosis has been reported to be as high as 35 to 50 percent within the first postoperative year, and persistent OHE may occur in up to 8 percent of patients treated with TIPS [10-14], which in selected cases requires reduction in stent diameter [14,15]. These findings have led to a number of studies aimed at identifying risk factors for the development of OHE after TIPS to improve patient selection, as well as studies exploring pharmacological strategies to prevent preoperative OHE with TIPS. Older age, higher end-stage liver disease (MELD) or Child-Pugh scores, a prior history of significant or mild HE, sarcopenia, impaired renal function, large shunt diameters, and a lower derived portosystemic pressure gradient have been shown to increase the likelihood of OHE following TIPS [14,16-22]. Therefore, existing guidelines encourage the selection of patients with TIPS based on the factors reported above, whenever possible [1-3]. The pharmacological management of OHE after TIPS prophylaxis remains controversial [23,24].
In patients with cirrhosis outside of TIPS, the development of OHE can adversely affect survival regardless of the severity of cirrhosis or the presence or absence of acute or chronic liver failure [25]. In patients awaiting liver transplantation (LT), at least one episode of OHE increases mortality at six months and significantly improves the predictive value of the MELD score [26]. However, whether an increase in mortality is also observed in patients who develop OHE after TIPS has not been specifically addressed. Several existing scores, such as the Child-Pugh score, the MELD score, the FIPS (Freiburg Index of Survival After TIPS) score, and the recently published ExPeCT score, are helpful in identifying patients at high risk for poor prognosis after TIPS [27-30]. However, these scores do not consider OHE after TIPS to be a potential factor affecting survival, and the effect of OHE after TIPS on mortality has not been studied in large populations [31]. Whether the occurrence of OHE after TIPS increases mortality in patients with TIPS remains uncertain.
In view of this, Italian scholar Professor Silvia Nardelli et al. designed a multicenter, non-inferiority observational study [32] to compare the mortality rate of patients with TIPS according to the incidence of OHE after TIPS. The study, conducted jointly by several medical centers in Italy, followed 614 patients with cirrhosis treated with TIPS for up to 30 months. The results showed that although 47% of patients had at least one postoperative OHE, multivariate analysis showed that age and MELD score were independent factors for mortality, and OHE did not increase the risk of death. This finding breaks with the conventional wisdom that OHE is often seen as a strong indicator of poor prognosis in patients with cirrhosis who are not treated with TIPS.
However, the research team also noted that patients after TIPS may have undergone more rigorous screening and closer monitoring, which may be one of the reasons why OHE does not increase mortality. In addition, although paroxysmal OHE does not increase mortality, its impact on the quality of life and morbidity of patients cannot be ignored, especially in patients with persistent OHE, whose mortality rate is significantly higher than that of patients without OHE.
This study not only provides an important basis for the management of patients with cirrhosis, but also highlights the importance of personalized treatment and patient selection. The investigators suggest that for potentially high-risk patients, more rigorous preoperative evaluation, intraoperative procedures, and postoperative management strategies should be adopted to reduce the occurrence of OHE, with a special focus on the prevention and treatment of persistent OHE.
Based on the results of this paper, Professor Lukas Hartl of the University of Vienna in Austria further analyzed and explored whether the early onset of encephalopathy after TIPS affects the mortality rate of patients [33]. Through a retrospective study, they analyzed 237 patients treated with TIPS in Vienna between September 2000 and November 2022, excluding patients with vascular liver disease, hepatocellular carcinoma, prior liver transplantation, or prophylactic TIPS engraftment. The primary endpoint was 30-month mortality, and milestones were set after 1, 3 and 6 months to analyse the effect of OHE on mortality.
The findings showed no significant difference in mortality between patients who developed OHE at 3 and 6 months after TIPS, supporting the findings of Professor Silvia Nardelli. However, the study found that patients who developed OHE at 1 month after TIPS showed significantly higher mortality. The cumulative incidence analysis showed that the mortality rate at 1 and 2 years was 43.6% and 48.1%, respectively, while the patients without OHE were 13.9% and 20.2%, respectively (P=0.004, Figure 2).
Figure 2. Cumulative incidence in patients with OHE at 1 month after TIPS (https://doi.org/10.1016/j.jhep.2024.05.035)
Although OHE at 3 and 6 months after TIPS had no significant effect on mortality, early (within 1 month) OHE was associated with significantly increased mortality. This suggests that patients with early onset of OHE may be at higher risk of death and warrants further research and attention.
This study by Professor Lukas Hartl provides new insights into understanding the impact of OHE on mortality after TIPS and highlights the importance of early identification and intervention of OHE. At the same time, the results of this study also remind doctors to closely monitor patients after TIPS so that OHE can be detected and treated in a timely manner.
In conclusion, the current research results based on the effect of OHE on mortality after TIPS are of great significance for improving the prognosis and quality of life of patients with liver cirrhosis, and also provide a new direction for future clinical research and treatment. With the deepening of research, we have reason to believe that more effective management and treatment strategies will be discovered, bringing better health prospects to patients with cirrhosis.
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