Alcohol-associated Fatty Liver Disease
Conditions
Keywords
alcohol-associated fatty liver disease（AFLD）, high-animal-protein-diet, high-plant-protein-diet, Intrahepatic lipid (IHL), liver iron concentration (LIC)
Brief summary
Alcohol-associated liver disease (ALD) is a major cause of mortality from advanced liver disease, accounting for 47.9% of cirrhosis-related deaths and 30% of hepatocellular carcinoma-related deaths annually. In China, both per capita alcohol consumption and the prevalence of ALD (approximately 5.15%) are on the rise, making ALD an increasingly significant public health burden. Alcohol-associated fatty liver disease (AFLD), the initial and most reversible stage of ALD, is pathologically characterized by excessive hepatic lipid accumulation, mild hepatocellular injury, and low-grade inflammation. It can progress to alcoholic hepatitis, and in some patients, advance to hepatic fibrosis, cirrhosis, or even hepatocellular carcinoma. Currently, there is no established effective pharmacotherapy for AFLD; although alcohol abstinence remains the optimal strategy for disease reversal, sustained abstinence is often difficult to achieve among individuals with alcohol dependence. Dietary protein source may independently influence metabolic health beyond total protein intake. Plant proteins (primarily derived from legumes and cereals) are rich in arginine, glutamine, and fiber-associated bioactive compounds, whereas animal proteins (mainly from dairy and poultry) are abundant in branched-chain amino acids (BCAAs) and sulfur-containing amino acids. Preclinical studies have demonstrated that, compared with animal proteins such as casein, plant proteins more effectively attenuate high-fat- or alcohol-induced hepatic steatosis by upregulating hepatic PPAR-α expression and suppressing SREBP-1c activity. Human intervention studies further suggest that long-term higher intake of plant protein is associated with lower hepatic fat content and reduced risk of insulin resistance. However, no randomized controlled trial has yet directly compared the effects of high-purity plant protein versus animal protein supplementation on clinical outcomes in patients with AFLD under isocaloric and isonitrogenous conditions. Therefore, this study aims to conduct a randomized controlled trial to evaluate the effects of plant protein versus animal protein supplementation within an isocaloric dietary framework on liver function, hepatic fat content, and glucose-lipid metabolism in individuals with AFLD. The findings will elucidate the efficacy and underlying mechanisms of protein-source modulation in ameliorating AFLD, thereby providing population-based evidence and strategic guidance for health promotion in this patient population.
Interventions
DIETARY_SUPPLEMENTwhey protein powder
In addition to following the baseline diet, participants received daily supplementation with animal-based protein isolate powder.
DIETARY_SUPPLEMENTsoy protein powder
In addition to following the baseline diet, participants received daily supplementation with plant-based protein isolate powder.
Sponsors
Li Lab,MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Group 1: high animal protein diet group Group 2: high plant protein diet group
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
1. Aged between 18 and 74 years old. 2. Able to understand the study and voluntarily sign the informed consent form. 3. Meet the clinical diagnostic criteria for alcohol-associated fatty liver disease (AFLD): a history of alcohol consumption for ≥5 years, with an average daily ethanol intake of ≥20 g/d; clinically diagnosed with fatty liver (indicated by abdominal ultrasound or a liver MRI proton density fat fraction \[MRI-PDFF\] ≥5.2%).
Exclusion criteria
1. Average daily ethanol intake \>80 g/d. 2. Presence of other hepatobiliary diseases, such as autoimmune liver disease, viral hepatitis, liver fibrosis, or cirrhosis. 3. Presence of severe cardiovascular or cerebrovascular diseases, or renal insufficiency. 4. Patients with tumors or other severe systemic diseases. 5. Patients with gastrointestinal disorders, or those with known protein allergy or intolerance. 6. Long-term use of medications known to cause hepatic steatosis or steatohepatitis (e.g., amiodarone or tamoxifen), nutritional supplements, or probiotics. 7. Total daily energy intake (excluding energy from alcohol) \<1900 kcal or ≥2900 kcal. 8. Participation in another interventional study within the past year, or scheduled to receive non-study treatments during the trial period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Intrahepatic lipid (IHL) | Baseline, up to 60 days of the study | IHL content was assessed by MRI using a 3.0-T scanner |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| low-density lipoprotein cholesterol (LDL-C, mmol/L) | Baseline, up to 60 days of the study | Fasting blood samples were collected at baseline and week 12 after an overnight fast. Serum was separated from blood samples after centrifugation with 3,000 rpm at 4°C for 10 min, and immediately stored at -80°C until use. LDL-C was measured using an automated biochemical analyzer (HITACHI LABOSPECT 008, Sysmex, Kobe, Japan) |
| high-density lipoprotein cholesterol (HDL-C, mmol/L) | Baseline, up to 60 days of the study | Fasting blood samples were collected at baseline and week 12 after an overnight fast. Serum was separated from blood samples after centrifugation with 3,000 rpm at 4°C for 10 min, and immediately stored at -80°C until use. HDL-C was measured using an automated biochemical analyzer (HITACHI LABOSPECT 008, Sysmex, Kobe, Japan) |
| alanine aminotransferase (ALT, U/L) | Baseline, up to 60 days of the study | Fasting blood samples were collected at baseline and week 12 after an overnight fast. Serum was separated from blood samples after centrifugation with 3,000 rpm at 4°C for 10 min, and immediately stored at -80°C until use. AST was measured using an automated biochemical analyzer (HITACHI LABOSPECT 008, Sysmex, Kobe, Japan) |
| γ-glutamyltransferase (GGT, U/L) | Baseline, up to 60 days of the study | Fasting blood samples were collected at baseline and week 12 after an overnight fast. Serum was separated from blood samples after centrifugation with 3,000 rpm at 4°C for 10 min, and immediately stored at -80°C until use. GGT was measured using an automated biochemical analyzer (HITACHI LABOSPECT 008, Sysmex, Kobe, Japan) |
| aspartate aminotransferase (AST, U/L) | Baseline, up to 60 days of the study | Fasting blood samples were collected at baseline and week 12 after an overnight fast. Serum was separated from blood samples after centrifugation with 3,000 rpm at 4°C for 10 min, and immediately stored at -80°C until use. AST was measured using an automated biochemical analyzer (HITACHI LABOSPECT 008, Sysmex, Kobe, Japan) |
| Hemoglobin A1c (HbA1c, %) | Baseline, up to 60 days of the study | Fasting blood samples were collected at baseline and week 12 after an overnight fast. Serum was separated from blood samples after centrifugation with 3,000 rpm at 4°C for 10 min, and immediately stored at -80°C until use. HbA1c was measured using an automated biochemical analyzer (HITACHI LABOSPECT 008, Sysmex, Kobe, Japan) |
| Fasting blood glucose (FBG, mmol/L) | Baseline, up to 60 days of the study | Fasting blood samples were collected at baseline and week 12 after an overnight fast. Serum was separated from blood samples after centrifugation with 3,000 rpm at 4°C for 10 min, and immediately stored at -80°C until use. FBG was measured using an automated biochemical analyzer (HITACHI LABOSPECT 008, Sysmex, Kobe, Japan) |
| total cholesterol (TC, mmol/L) | Baseline, up to 60 days of the study | Fasting blood samples were collected at baseline and week 12 after an overnight fast. Serum was separated from blood samples after centrifugation with 3,000 rpm at 4°C for 10 min, and immediately stored at -80°C until use. TC was measured using an automated biochemical analyzer (HITACHI LABOSPECT 008, Sysmex, Kobe, Japan) |
| serum triglycerides (TG, mmol/L) | Baseline, up to 60 days of the study | Fasting blood samples were collected at baseline and week 12 after an overnight fast. Serum was separated from blood samples after centrifugation with 3,000 rpm at 4°C for 10 min, and immediately stored at -80°C until use. TG was measured using an automated biochemical analyzer (HITACHI LABOSPECT 008, Sysmex, Kobe, Japan) |
Countries
China
Contacts
CONTACTQingling Huang
CONTACTXianjun Liu
STUDY_CHAIRSongtao Li
Zhejiang Chinese Medical University
Outcome results
None listed