Cirrhosis is a major global cause of morbidity and mortality in chronic liver disease patients, accounting for 2.4% of global deaths in 2019. A 1990-2017 Global Burden of Disease study showed rising cirrhosis-related deaths, bringing heavy health and economic burdens. It often leads to portal hypertension and subsequent complications like ascites, gastroesophageal variceal bleeding (20% 6-week mortality), and hepatic encephalopathy (HE). Transjugular intrahepatic portosystemic shunt (TIPS) is an important treatment for variceal bleeding and refractory ascites per guidelines from EASL, AASLD, and the Chinese Medical Association.
Malnutrition affects 20% of compensated and over 50% of decompensated cirrhotic patients; sarcopenia (severe malnutrition) is linked to higher cirrhosis-related complications, impaired quality of life, survival, and poor prognosis in TIPS-treated patients. Thus, concurrent sarcopenia intervention during TIPS may improve outcomes.
Baveno VII, EASL, and AASLD guidelines recommend branched-chain amino acid (BCAA) and leucine-rich supplements for decompensated cirrhosis to ensure adequate nitrogen intake. RCT evidence shows BCAAs improve skeletal muscle index (SMI) in cirrhotic patients with sarcopenia and reduce HE risk, but evidence for TIPS-treated patients is lacking. This study aims to compare muscle mass changes and clinical prognosis between TIPS patients with sarcopenia, portal hypertension, and variceal bleeding who receive TIPS with or without BCAA supplements.
Age between 18 and 80 years old;
Diagnosed with cirrhosis complicated by sarcopenia;
Patients admitted due to variceal bleeding or refractory ascites who meet the indications for transjugular intrahepatic portosystemic shunt (TIPS).
Hepatocellular carcinoma and/or other malignant tumors;
Severe cardiopulmonary insufficiency;
Child-Pugh score > 13 points;
Spontaneous recurrent hepatic encephalopathy (HE);
Parallel
The BCAA Group (experimental group) takes oral branched-chain amino acid (BCAA) supplements for 3 months starting after TIPS.
Dietary supplementThis prospective randomized controlled trial (RCT) aims to compare changes in muscle mass and clinical outcomes between sarcopenic cirrhotic patients with portal hypertension and variceal bleeding who undergo transjugular intrahepatic portosystemic shunt (TIPS) plus branched-chain amino acid (BCAA) supplementation versus TIPS plus placebo. Eligible patients are aged 18-75 years, with cirrhosis, sarcopenia (defined by EASL guidelines: L3 skeletal muscle index \[L3-SMI\] \<50 cm²/m² for males, \<39 cm²/m² for females, measured via preoperative abdominal CT), and TIPS eligibility due to variceal bleeding or refractory ascites; exclusions include malignancies, severe cardiopulmonary insufficiency, Child-Pugh score \>13, recurrent hepatic encephalopathy (HE), and prior use of nutrition supplements within 3 months. TIPS is standardized with 8mm covered Viatorr stents, intraoperative variceal embolization if needed, and a postoperative portal pressure gradient (PPG) target of \<12 mmHg or ≥50% base
The Placebo Group (control group) takes oral placebo for 3 months postoperatively-prepared by an independent third party, the placebo is identical to BCAA supplements in appearance, odor, and packagin
Dietary supplementThe Placebo Group (control group) takes oral placebo for 3 months postoperatively-prepared by an independent third party, the placebo is identical to BCAA supplements in appearance, odor, and packaging to maintain blinding.
Differences in the sarcopenia reversal rate between the two groups (BCAA and Non-BCAA)
Sarcopenia is defined per the European Association for the Study of the Liver (EASL) clinical practice guidelines: the skeletal muscle index (SMI) is calculated as the ratio of the total cross-sectional area of all skeletal muscles at the third lumbar (L3) level (measured via abdominal CT, unit: cm²) to the square of height (unit: m²), with males having SMI \< 50 cm²/m² and females \< 39 cm²/m² diagnosed as sarcopenic. SMI is measured preoperatively and at 3 and 6 months post-TIPS to determine the reversal rate (proportion of patients no longer meeting sarcopenia criteria), and the difference in this rate between the two groups is compared to evaluate the effect of BCAA supplementation.
Differences in Short Physical Performance Battery (SPPB) scores between the two groups (BCAA and Non-BCAA)
The SPPB consists of three subtests: balance test, gait speed test, and Chair Stand Test. Each subtest is scored from 0 to 4 points, with a total score ranging from 0 to 12 points-higher scores indicate better physical fitness. The SPPB is assessed preoperatively and at 3 and 6 months post-TIPS to compare changes in physical performance between the BCAA and Non-BCAA groups, reflecting the effect of BCAA supplementation on functional capacity in cirrhotic patients with sarcopenia.
The cumulative incidence of hepatic encephalopathy (HE) in the two groups (BCAA and Non-BCAA)
Hepatic encephalopathy (HE) is diagnosed and graded in accordance with the West-Haven criteria, with overt HE (OHE) defined as Grades II-IV. Data are collected during follow-up at 3 and 6 months after TIPS to compare whether branched-chain amino acid (BCAA) supplementation reduces the risk of HE compared with placebo. The Kaplan-Meier method is used to plot the cumulative incidence curves of HE in the two groups, and the Log-rank test is applied to compare the differences in the risk of HE occurrence between the two groups.
The cumulative incidence of death in the two groups (BCAA and Non-BCAA)
Death is defined as all-cause mortality occurring during the follow-up period after TIPS. Data on mortality events (including the time and cause of death) are collected through regular follow-up assessments at 3 and 6 months post-TIPS, as well as active follow-up via medical records and telephone inquiries for any unplanned hospitalizations or death reports. The aim is to compare whether branched-chain amino acid (BCAA) supplementation reduces the risk of death compared with placebo. The Kaplan-Meier method is used to plot the cumulative survival curves (and corresponding cumulative mortality curves) of the two groups, and the Log-rank test is applied to compare the differences in mortality risk between the two groups.
The cumulative incidence of Variceal Rebleeding in the two groups (BCAA and Non-BCAA)
Variceal rebleeding is diagnosed in accordance with the Baveno VII consensus criteria, defined as recurrent melena or hematemesis leading to any of the following: hospitalization, blood transfusion requirement, a decrease in hemoglobin of ≥3 g within 24 hours, or death within 6 weeks of the index bleeding event. Relevant data (including the time of rebleeding, clinical manifestations, and diagnostic evidence) are collected during scheduled follow-up at 3 and 6 months post-TIPS, as well as through emergency department and hospitalization records for acute bleeding episodes. The goal is to evaluate whether BCAA supplementation lowers the risk of variceal rebleeding compared with placebo. The Kaplan-Meier method is used to plot the cumulative incidence curves of variceal rebleeding in the two groups, and the Log-rank test is applied to compare the differences in rebleeding risk between the two groups.
The cumulative incidence of Shunt Dysfunction in the two groups (BCAA and Non-BCAA)
Shunt dysfunction is diagnosed based on the following criteria: color Doppler ultrasound detects a maximum shunt tract blood flow velocity ≤50 cm/s, ≥200 cm/s, or no blood flow signal; or recurrence of clinical symptoms (such as variceal rebleeding or refractory ascites) suggestive of shunt malfunction, which is further confirmed by transjugular portography showing \>50% stenosis of the shunt tract. Data on shunt function are collected through color Doppler ultrasound examinations during follow-up at 3 and 6 months post-TIPS, as well as through portography for suspected cases. The purpose is to compare whether BCAA supplementation affects the risk of shunt dysfunction compared with placebo. The Kaplan-Meier method is used to plot the cumulative incidence curves of shunt dysfunction in the two groups, and the Log-rank test is applied to compare the differences in the risk of shunt dysfunction between the two groups.
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Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Lead sponsor
The First Affiliated Hospital of Zhengzhou University
Collaborator
The First Affiliated Hospital of Henan University of Science and Technology
Collaborator
