The purpose of this study is to evaluate the efficacy and safety of a short-term (12-week) prehabilitation strategy combining mazdutide (a novel GLP-1/GCG receptor dual agonist) with lifestyle optimization, compared to lifestyle optimization alone, in potential living liver transplantation donors with metabolic dysfunction-associated steatohepatitis (MASLD).
Overweight or obese individuals who intend to donate a portion of their liver but are temporarily disqualified due to hepatic steatosis will be recruited across multiple clinical centers. Participants will be randomly assigned in a 1:1 ratio to either the experimental group (mazdutide subcutaneous injection once weekly plus standardized lifestyle counseling) or the control group (placebo subcutaneous injection once weekly plus standardized lifestyle counseling).
The primary objective is to determine whether the short-term addition of mazdutide can significantly increase the proportion of donors achieving histological resolution of hepatic steatosis without the worsening of fibrosis within 12 weeks. The study ultimately aims to provide high-quality evidence for a rapid, safe, and effective surgical prehabilitation protocol to expand the living donor pool and optimize perioperative outcomes for both donors and recipients.
Inclusion Criteria:
Exclusion Criteria:
xiekun@scu.edu.cn8618980607259
Subcutaneous injection of mazdutide once weekly following a 12-week dose-escalation regimen: 2 mg q1w for Weeks 1-2, 4 mg q1w for Weeks 3-4 (if gastrointestinal tolerated), and a target dose of 6 mg q1w from Week 5 to Week 12 (if gastrointestinal tolerated). Standardized lifestyle optimization consists of an energy-restricted diet (deficit of 500-750 kcal/day, total daily intake \<=1500 kcal/day) and structured physical exercise (\>=150 minutes/week of moderate-to-high intensity exercise). A mandatory 1-week drug washout period is enforced prior to surgery.
Subcutaneous injection of a matching placebo once weekly with identical appearance, volume, and injection device for 12 weeks. Standardized lifestyle optimization is identical to the experimental group, consisting of an energy-restricted diet (deficit of 500-750 kcal/day, total daily intake \<=1500 kcal/day) and structured physical exercise (\>=150 minutes/week of moderate-to-high intensity exercise). A matching 1-week placebo washout period is enforced prior to surgery to maintain blinding.
Hefei, Anhui 230036, China
zsg0517@ustc.edu.cn8615945965885
weilin@ccmu.edu.cn8618610932626
xiekun@scu.edu.cn8618980607259
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