Liver cirrhosis leads to clinically significant portal hypertension (CSPH) in 40–70% of patients, increasing the risk of decompensation and death ^[1][2][1,2]. TIPS (transjugular intrahepatic portosystemic shunt) has been shown to effectively reduce the degree of portal hypertension and treat complications such as recurrent/refractory ascites and bleeding from gastroesophageal varices [2]. Cirrhosis and portal hypertension often result in malnutrition and sarcopenia, due to factors such as reduced caloric intake and increased catabolism ^[3][4][3,4]. Eighty percent of decompensated cirrhosis patients experience sarcopenia that further worsens with liver decompensation [5]. These conditions raise the risk of increased mortality and decompensation ^[6][7][6,7]. Interestingly, even without impaired liver function, portal hypertension alone may increase the risk of sarcopenia [8]. Given this relationship, TIPS placement often occurs in the context of malnutrition. Sarcopenia has been shown to be associated with hepatic encephalopathy (HE), acute-on-chronic liver failure (ACLF), and mortality following TIPS placement ^{[9][10][11][12][13]}[9,10,11,12,13]. As a result, sarcopenia is now considered a relative contraindication to TIPS placement in current guidelines [2]. On the other hand, evidence suggests that TIPS placement may improve the nutritional status of cirrhotic patients by increasing the fat-free muscle mass and reducing visceral fat ^[10][14][15][10,14,15]. However, the optimal timing for TIPS placement in sarcopenic cirrhotic patients remains unknown.

2. The Impact of Transjugular Intrahepatic Portosystemic Shunt on Nutrition in Liver Cirrhosis Patients

TIPS placement is a commonly utilized therapeutic intervention for individuals with liver cirrhosis and associated complications of portal hypertension, including refractory ascites and variceal bleeding. This intervention has been demonstrated to significantly improve overall survival in these patients, as evidenced by several clinical studies ^[16][17][31,32]. Despite these benefits, malnutrition, which is prevalent among cirrhotic individuals, has been linked to adverse outcomes after TIPS placement, such as hepatic encephalopathy, acute-on-chronic liver failure (ACLF), and mortality ^[10][11][12][10,11,12]. On the other hand, some studies have suggested an improvement in the nutritional status following TIPS placement in cirrhotic patients. Therefore, the aim of this wsystematic review was to evaluate changes in nutritional status that occur after TIPS placement in patients with liver cirrhosis. ReThisearchers review analyzed data from 15 studies (comprising a total of 850 patients) that were published between 1998 and 2022. The number of participants per study ranged from 11 to 224, with the majority being men. Most of the participants in these studies had alcohol-related liver disease. Alcohol consumption has a multifactorial and complex impact on nutritional status. Firstly, heavy alcohol consumption can significantly reduce dietary intake. Secondly, the metabolism of ethanol involves energy-wasting pathways. Thirdly, chronic alcohol consumption can result in the wastage of fat and muscle. Fourth, many alcohol-related diseases can interfere with dietary intake and contribute to malnutrition, such as chronic alcoholic gastritis, chronic pancreatitis, and chronic liver disease ^[18][33]. Finally, alcohol decreases muscle protein synthesis via inhibition of mTOR-dependent translation initiation ^[19][34]. The indications for TIPS insertion were refractory ascites and variceal bleeding, the most commonly used stent material in the studies was polytetrafluoroethylene, and the post-TIPS portal pressure gradients ranged from 6.0 to 15.5 mmHg. Although the patient populations might have overlapped in some studies ^{[20][21][22][23]}[26,28,29,30], researchers decided to include these studies because they provided unique information, such as a specific measure of nutritional status or a different time point since TIPS insertion. The results of the qualitative analysis showed marked improvements in muscle mass and a shift in fat tissue distribution after TIPS placement. There are several potential explanations for the observed changes in body composition after TIPS placement. These changes may be related to the reduction in portal hypertension [8] and its associated effects on gut permeability, bacterial translocation, proinflammatory cytokines, and chronic inflammation ^{[24][25][26][27]}[35,36,37,38]. Additionally, the TIPS procedure may improve protein-losing enteropathy and reduce frequent hospitalizations due to gastrointestinal bleeding and paracentesis, leading to improved mobility and oral intake. Unfortunately, only limited information was available regarding dietary changes after TIPS. In a study by Tsien et al., only 25% of patients reported an increase in their total dietary intake [15]. It is worth noting the relationship between the nutritional status before TIPS and the reported nutritional improvement after the procedure. Two studies found that the improvement in nutritional status was more pronounced in patients with sarcopenia or who were underweight or of normal weight, rather than in overweight or non-sarcopenic individuals ^[20][28][20,26]. Liu et al. found an increase in SMA, SMI, SFA, and SFT in sarcopenic patients, while they did not observe any significant change in non-sarcopenic patients. Montomoli et al. found an increase in dry lean mass in the group of normal or underweight patients but not in the group of overweight patients. Tsien et al. also reported that younger age, male sex, and lower pre-TIPS muscle area were independent predictors of increased muscle mass after TIPS [15]. These findings create a sort of paradox, as malnutrition and sarcopenia have been associated with increased risk of adverse outcomes after TIPS placement, namely, hepatic encephalopathy, acute on chronic liver failure, or mortality ^{[9][10][11][12][13]}[9,10,11,12,13]. This was the reason why the latest Baveno VII consensus discouraged sarcopenia itself as an indication for TIPS insertion [2], though these patients are likely to benefit the most from TIPS in terms of nutritional improvement. When considering an elective TIPS procedure for a malnourished sarcopenic patient, clinical judgment must account for two factors: the short-term risks of the procedure and the potential long-term benefits—correcting portal hypertension and improving the patient’s nutritional status. Several studies have also observed alterations in adipose tissue composition following TIPS placement. Significant expansion of subcutaneous fat tissue was observed in all studies ^[14][28][29][14,19,20], with the exception of one study [15]. Additionally, a notable reduction in visceral fat tissue was reported in two studies ^[14][29][14,19], while remaining unchanged in one study [15]. There is evidence to suggest that the procedure leads to a decrease in VAT and an increase in SAT. The venous drainage of VAT occurs directly via the portal circulation to the liver. Therefore, changes in portal circulation subsequent to TIPS placement may enhance the availability of these fat deposits to be metabolized as energy sources by the liver ^[30][31][39,40]. Additionally, increased circulating levels of adipokines have been observed post-TIPS placement, potentially reflecting anabolic changes that contribute to the alterations in adipose tissue observed in patients undergoing TIPS ^[23][30]. The considerable clinical and methodological heterogeneity between studies precluded the conduct of a quantitative analysis (meta-analysis). The variability in nutritional status evaluation across studies was identified as a major contributing factor to this limitation. Indeed, the methods used to evaluate nutritional status varied widely across studies, including the use of Body Mass Index (BMI), weight, body cell mass, skeletal muscle volume and function, and measures of adipose tissue. Furthermore, the time interval between TIPS placement and nutritional reassessment ranged from 1–3 to 19 months. Shorter follow-up times might have limited the observation of significant changes, while longer follow-up times may have resulted in significant selection bias, as patients who had died or undergone transplantation were more likely to be excluded from the analysis. Finally, it is crucial to conduct well-designed prospective studies using gold-standard methods for evaluating malnutrition, in order to identify patients who would most benefit from TIPS placement, including from a nutritional perspective. These efforts could provide not only new pathophysiological insights into the relationship between portal hypertension and malnutrition, but could also answer the question of the optimal timing for TIPS insertion in sarcopenic cirrhotic patients.