Body-weight Reduction Effect on Portal Hypertension in Compensated Cirrhosis

Who can take part

Inclusion Criteria: * Aged 18 to 75 years (inclusive), male or female. * Documented etiology of chronic liver disease, limited to chronic hepatitis B, chronic hepatitis C, metabolic dysfunction-associated steatotic liver disease (MASLD), or alcohol-related liver disease. * Cirrhosis confirmed by imaging (ultrasound, CT, or MRI), or pathology showing F3/F4 fibrosis, or liver stiffness measurement (LSM) ≥15 kPa by vibration-controlled transient elastography (VCTE). * Hepatic venous pressure gradient (HVPG) ≥10 mmHg. * Body mass index (BMI) ≥28 kg/m², or BMI ≥26 kg/m² with at least one weight-related comorbidity (e.g., hyperglycemia, hypertension, dyslipidemia, fatty liver, obstructive sleep apnea syndrome). * Stable body weight over the past 6 months, defined as weight fluctuation \<3 kg. * For patients with gastroesophageal varices requiring carvedilol or propranolol, the dose must have been stable for at least 3 months with no planned dose adjustments during the trial. * Voluntarily signed informed consent form. Exclusion Criteria: * Concurrent hepatocellular carcinoma or other malignancies (excluding cured basal cell carcinoma of the skin). * Prior history of clinically significant decompensation events (grade 2/3 ascites, overt hepatic encephalopathy, or gastroesophageal variceal bleeding). * Progressive jaundice during the screening period. * Hepatic impairment defined as Child-Turcotte-Pugh (CTP) score ≥B8 at screening. * Moderate to severe renal impairment (eGFR \<60 mL/min) or current renal replacement therapy. * Contraindications to mazdutide: known allergy, personal or family history of medullary thyroid carcinoma, or multiple endocrine neoplasia syndrome type 2. * Previous or current use of other weight-loss interventions (e.g., bariatric surgery, endoscopic bariatric procedures, other weight-loss drugs). * Participation in another interventional clinical trial within 3 months prior to screening, or previous treatment with mazdutide. * Active infection at screening. * For alcohol-related cirrhosis: alcohol abstinence \<6 months or ongoing alcohol consumption. For viral cirrhosis (hepatitis B/C): failure to achieve virologic suppression (HBV-DNA \<100 IU/mL for hepatitis B; for hepatitis C, HCV-RNA below the lower limit of detection after \>12 weeks of antiviral therapy). * Prior portal-systemic shunt surgery (e.g., splenectomy). * Previous orthotopic liver transplantation. * Known portal vein thrombosis. * Contraindications to trial assessments, e.g., inability to undergo HVPG measurement. * Pregnancy or breastfeeding, or unwillingness to use investigator-approved contraception during the study and for 6 months after the study end. * Psychiatric or cognitive disorders that interfere with study compliance. * Any other condition judged by the investigator to make the participant unsuitable for participation.

Registry changes

No changes recorded since the trial was added.