Fuzheng Huayu Tablets for Metabolic Dysfunction-Associated Fatty Liver Cirrhosis (Compensated): A Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Study

Efficacy and Safety of Fuzheng Huayu Tablets in Patients With Metabolic Dysfunction-Associated Fatty Liver Cirrhosis (Compensated): A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Study

This is a multicenter, randomized, double-blind, placebo-controlled clinical study to evaluate the efficacy and safety of Fuzheng Huayu Tablets in patients with metabolic dysfunction-associated fatty liver cirrhosis (compensated). Eligible patients will be randomly assigned to receive either Fuzheng Huayu Tablets or placebo for 72 weeks. The primary objective is to assess the improvement in liver fibrosis, measured by liver stiffness reduction via FibroScan. Secondary objectives include changes in liver function indicators, liver fibrosis markers, Child-Pugh score, and safety profile.

This study aims to enroll 459 eligible patients aged 18-75 years with compensated metabolic dysfunction-associated fatty liver cirrhosis. Patients will be randomized to the treatment group (Fuzheng Huayu Tablets, 4 tablets three times daily) or the control group (matching placebo, 4 tablets three times daily) for 72 weeks. The primary efficacy endpoint is the proportion of patients with ≥10% reduction in liver stiffness measurement (LSM) at Week 24 compared to baseline. Secondary endpoints include changes in liver function, fibrosis markers, Child-Pugh score, and adverse event incidence. All safety assessments will be performed throughout the study.

Inclusion Criteria:

1. Aged 18 to 75 years (inclusive of both upper and lower limits).
2. Diagnosed with compensated metabolic dysfunction-associated fatty liver cirrhosis, meeting all three of the following conditions:

(1) At screening, FibroScan liver stiffness measurement (LSM) ≥ 20 kPa, OR LSM ≥ 15 kPa AND any one of the following: platelet count < 150×10⁹/L, or FIB-4 ≥ 3.48, or Agile4 ≥ 0.57; (2) Has a history of metabolic dysfunction or metabolic dysfunction-associated fatty liver disease (MAFLD); (3) Child-Turcotte-Pugh score < 7 and MELD score < 12. 3. Voluntarily participates in the clinical study and agrees to sign the informed consent form.

Exclusion Criteria:

1. History or current hepatic decompensation events at screening, including but not limited to the following: a) Esophagogastric variceal bleeding; b) Hepatic ascites requiring diuretic treatment; c) Hepatic encephalopathy (West Haven grade 2 or above); d) Hepatorenal syndrome.
2. Having a history or evidence of other chronic liver diseases, such as alcoholic liver disease, drug-induced liver disease, primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis or overlap syndrome, Wilson's disease, alpha-1 antitrypsin deficiency, hereditary hemochromatosis, history of biliary obstruction or biliary shunt, metastatic liver cancer; Hepatitis B (HBsAg positive); Hepatitis C (HCV antibody positive and HCV-RNA positive). Subjects with previous hepatitis C treatment must maintain negative HCV-RNA results for at least 3 years before screening to be eligible.
3. History of liver transplantation, on the liver transplantation waiting list, or history of TIPS operation.
4. Use of anti-obesity drugs within 3 months prior to screening and during the whole trial is prohibited, including bupropion-naltrexone, orlistat, phentermine, phentermine/topiramate and anti-obesity supplements. Subjects planning to receive metabolic bariatric surgery during the study will be excluded (excluding acupuncture weight loss, liposuction or abdominal lipectomy performed more than 1 year before screening).
5. Type 1 diabetes mellitus; uncontrolled type 2 diabetes mellitus, defined as HbA1c > 9% at screening or within 60 days before randomization. Subjects with HbA1c > 9% may be re-screened once no less than 3 months after the initial screening failure; insulin dosage adjustment more than 20% within 60 days before randomization is also excluded.
6. Unstable use of drugs that may affect efficacy evaluation within 3 months prior to screening, including but not limited to Vitamin E (dose > 400 IU/d), thiazolidinediones (TZDs), SGLT-2 inhibitors, GLP-1 receptor agonists, and chiglitazar. Those who have taken stable dosage continuously until screening visit and will maintain relatively stable dosage throughout the study period are allowed to enroll.
7. Use of drugs that may induce hepatic steatosis or steatohepatitis for at least 4 weeks within 6 months prior to screening (e.g., valproic acid, tamoxifen, methotrexate, amiodarone, long-term oral corticosteroids > 5 mg/d prednisone equivalent, or estrogen at doses higher than contraception or hormone replacement therapy). The above drugs are prohibited throughout the trial until the end of follow-up. Subjects requiring bronchodilators, topical, inhaled, nasal corticosteroids or caudal steroid injections are not excluded.
8. Use of Chinese herbal medicine and proprietary Chinese medicines with anti-fibrotic or MAFLD therapeutic effects within 3 months prior to screening, including but not limited to Compound Biejia Ruangan Capsules, Anluo Huaxian Pills, Qianggan Capsules/Tablets. If the medication course is no more than 3 months, subjects can be enrolled after a 1-month washout period.
9. Uncontrolled hypertension at screening, defined as systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg.
10. Occurrence of myocardial infarction, unstable angina, malignant arrhythmia, percutaneous coronary intervention, coronary artery bypass grafting, ischemic or hemorrhagic stroke, transient ischemic attack, acute peripheral vascular events within 6 months prior to screening.
11. Active severe diseases or malignant tumors with a life expectancy of less than 5 years.
12. Uncontrolled hypothyroidism or hyperthyroidism at screening (assessed by the investigator). Participants with hypothyroidism receiving stable-dose thyroid hormone replacement therapy for at least 2 months before screening can be enrolled.
13. Abnormal laboratory indicators at screening: ALT > 5 × ULN, AST > 5 × ULN, ALP ≥ 2 × ULN (unless ALP elevation is non-hepatic origin), eGFR < 45 mL/min/1.73m², INR > 1.5 × ULN, total bilirubin > 1.5 × ULN (for participants with Gilbert syndrome, TBIL threshold ≥ 3 × ULN), ALB < 28 g/L.
14. Thrombocytopenia caused by hematological diseases such as immune thrombocytopenic purpura, drug influence or active infection.
15. Female subjects who are pregnant, breastfeeding or planning to become pregnant during the trial.
16. Allergy to the investigational drug or its ingredients.
17. Subjects who are expected to be unable to comply with the study protocol or fail to complete the trial as planned.