metabolic associated fatty liver disease
Conditions
Interventions
Hua-Zhi Rou-Gan Granule Treatment Group:Hua-Zhi Rou-Gan Granule, one packet each time, three times daily. Take the medication for six consecutive days, followed by a one-day break, for a total treatme
Placebo Granule Control Group:Placebo Granule, one packet each time, three times daily. Take the medication for six consecutive days, followed by a one-day break, for a total treatment course of 52 we
Sponsors
Shuguang Hospital affiliated to Shanghai Universtiy of Traditonal Chinese Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1) Age 18-65 years, gender. 2) Meet the diagnostic criteria for MAFLD in the "Chinese Guidelines for the Prevention and Treatment of Metabolism-Related Fatty Liver Disease (2024 Edition)". (1) Imaging diagnosis of fatty liver disease, and/or histopathological evidence of =5% hepatocyte macrovesicular steatosis (2) Exclude excessive alcohol consumption (weekly ethanol intake =210 g for males, =140 g for females) (3) Exclude other causes of fatty liver disease, including HCV infection, drug-induced fatty liver, Wilson's disease, autoimmune liver diseases (PBC, PSC, AIH), malnutrition, hypobetalipoproteinemia, and congenital lipodystrophy; (4) Have at least one component of metabolic syndrome: a. Overweight/obesity: BMI =24.0 kg/m², or waist circumference =90 cm (males) and =85 cm (females) b. Elevated arterial blood pressure/hypertension: arterial blood pressure =130/85 mmHg, or on antihypertensive therapy c. Prediabetes or type 2 diabetes: fasting blood glucose =6.1 mmol/L, or 2-hour post-load blood glucose =7.8 mmol/L or HbA1c =5.7%, or history of type 2 diabetes, or HOMA-IR =2.5 d. Elevated serum TG: fasting serum TG =1.70 mmol/L, or on lipid-lowering therapy e. Reduced serum HDL-C: serum HDL-C =1.0 mmol/L (males) and =1.3 mmol/L (females), or on lipid-lowering therapy. 3) Meet the diagnostic criteria for phlegm-stasis intermingling syndrome in the "Expert Consensus on the Diagnosis and Treatment of Non-Alcoholic Fatty Liver Disease in Traditional Chinese Medicine (2023)" (1) Principal symptoms: or stabbing pain in the right hypochondrium (2) Secondary symptoms: a. Poor appetite and aversion to greasy food b. Chest and epigastric c. Dull complexion (3) Tongue and pulse: pale dark tongue with ecchymoses at the edges, greasy coating, stringy slippery or pulse. (4) Combined diagnosis: principal symptoms + 2 secondary symptoms, with reference to tongue and pulse. 4) Liver biopsy within the past 6 months showing MASH with liver fibrosis, NAS score =4, and each of steatosis, lobular inflammation, and ballooning scored =1. (1) Histological scoring uses the NASH CRN system, requiring a NAS score =4, with steatosis, lobular inflammation, and ballooning each scoring =1. (2) Patients with fibrosis stage F1 are eligible, but their proportion among all subjects must not exceed 10% (3) Subjects with F4 fibrosis identified during the screening period via liver biopsy for this study may be enrolled if the investigator determines that the subject's safety and ability to complete the intervention are ensured, but their total number must be combined with F1 subjects, with the proportion not exceeding 10%. (4) Patients with prior biopsy showing F4 fibrosis are excluded. 5) Informed consent.
Exclusion criteria
Exclusion criteria: 1) Other causes of fatty liver or long-term use of drugs causing fatty liver (refer to inclusion criteria item 2); 2) Severe underlying diseases, malignant tumors, or mental disorders (1) Severe underlying diseases include: uncontrolled hypertension (systolic blood pressure >160 mmHg, or diastolic blood pressure >100 mmHg), history of Decompensated liver disease (including ascites, hepatic encephalopathy, variceal bleeding), organ transplant history, uncontrolled arrhythmia (Fridericia-corrected QT interval (QTcF = QT/RR^0.33), males >450 ms, females >470 ms), myocardial infarction, unstable angina, stroke (excluding TIA), history of percutaneous coronary intervention, history of coronary artery bypass grafting, and other diseases judged by the investigator to affect the safety of the subject, including but not limited to active HBV infection, COPD, heart failure, renal failure, etc. (2) Mental disorders include: history of drug abuse, and mental disorders requiring hospitalization or emergency treatment before enrollment. 3) Active hyperthyroidism, untreated hypothyroidism (TSH >7 mIU/L with clinical symptoms, or TSH >10 mIU/L without clinical symptoms), or post-thyroidectomy 4) Uncontrolled type 2 diabetes, defined as HbA1c =9%, or insulin dose adjustment exceeding 35%, or history of hypoglycemia-related unconsciousness, hospitalization due to hypoglycemia, or severe hypoglycemia 5) Weight loss or gastric bypass surgery within the past 5 years 6) Weight fluctuation =5% within 12 weeks (3 months) prior to enrollment 7) Body mass index =35 kg/m² 8) Currently using drugs that may treat MAFLD, and recent changes in the medication regimen (1) Potential MAFLD treatment drugs include: vitamin E =268 mg/d (400 IU), thiazolidinediones, GLP-1RA, SGLT2i, other types of antidiabetic drugs, weight-loss drugs. If the above drugs were initiated or had their dosage changed within 12 weeks (3 months) before screening or liver histology biopsy, it is considered a change in the medication regimen (2) Subjects taking hepatoprotective and enzyme-lowering drugs must have a washout period of more than 5 half-lives of the drug before screening or liver histology biopsy. If the half-life is unclear, a 1-month washout period must be set (3) Subjects taking traditional Chinese medicine or Chinese patent medicine must have a 1-month washout period before screening or liver histology biopsy. 9) Adjustment of lipid-lowering treatment regimen within 12 weeks (3 months) prior to enrollment 10) Severe hepatic or renal insufficiency, defined as ALT or AST >2.5 times the upper limit of normal, or TBil >1.5 times the upper limit of normal, or eGFR <45 mL/min/1.73 m² 11) Confirmed cirrhosis before screening (via liver histology biopsy F4, or non-invasive examination highly suggesting the possibility of cirrhosis (VCTE assessment LSM =20.4 kPa or MRE =4.2 kPa)), hepatocellular carcinoma, or highly suspected liver malignancy (AFP =400 ng/mL) 12) Allergy to components of the study drug or placebo, or subjects with a history of allergies 13) Pregnant or breastfeeding women, and females who refuse to use contraception approved by the investigator throughout the study period 14) Presence of contraindications for liver biopsy. Subjects meeting any of the above criteria will be excluded.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of subjects achieving an improvement in fibrosis by at least one stage with no worsening of MASH based on histological assessment of liver tissue; | — |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of subjects achieving MASH resolution without worsening of fibrosis based on histological assessment of liver tissue;Proportion of patients achieving improvement in liver histology assessed by imaging;Changes before and after treatment in serological glycemic and lipid metabolic profiles;Changes before and after treatment in serological markers of liver injury;Changes before and after treatment in anthropometric measurements;Changes before and after treatment in Controlled Attenuation Parameter and Liver Stiffness Measurement levels measured by Vibration-Controlled Transient Elastography;Changes before and after treatment in scores on the Metabolic Associated Fatty Liver Disease Quality of Life scale;Exploratory evaluation of metabolic biomarkers for the Phlegm-Stasis Coupling Syndrome (Tan Yu Hu Jie Zheng) provided by Project 2; | — |
Countries
China
Contacts
Public ContactSun Xuehua
Shuguang Hospital affiliated to Shanghai Universtiy of Traditonal Chinese Medicine
Outcome results
None listed