MASLD and Alcohol-Associated Liver Disease

GI NOTES

MASLD and Alcohol-Associated Liver Disease

Key points

MASLD is hepatic steatosis plus at least one cardiometabolic risk factor, without another cause. MetALD is MASLD with moderate alcohol intake.
Fibrosis drives outcomes. Use FIB-4 first, then elastography (VCTE) or ELF for anyone not clearly low risk.
Weight loss is the core treatment: 7 to 10% improves inflammation and 10% or more can regress fibrosis.
For MASH with F2 or F3 fibrosis, resmetirom and semaglutide are FDA approved.
Severe alcohol-associated hepatitis (MELD above 20): consider prednisolone 40 mg for 28 days and stop if the Lille score at day 7 is 0.45 or higher.

1. Steatotic liver disease terminology

Term	Definition
MASLD	Steatosis plus at least 1 cardiometabolic risk factor (raised BMI or waist, prediabetes or diabetes, high blood pressure, high triglycerides, low HDL), with little or no alcohol
MASH	MASLD with steatohepatitis (inflammation and ballooning)
MetALD	MASLD plus alcohol about 140 to 350 g/week (women) or 210 to 420 g/week (men)
ALD	Alcohol above those ranges is the main driver

2. Who has advanced fibrosis?

FIGURE: FIBROSIS RISK STRATIFICATION

Steatosis or cardiometabolic risk

FIB-4 (age, AST, ALT, platelets)

Below 1.3: low risk; repeat in 1 to 3 years

1.3 or higher: elastography (VCTE) or ELF

VCTE below 8 kPa: low risk, primary care

8 kPa or higher: hepatology referral; 12 kPa or higher suggests advanced fibrosis

Original diagram based on the AASLD 2023 practice guidance.

FIB-4 is less accurate under age 35 and over 65 (use a cut-off of 2.0 instead of 1.3 above age 65).

3. Treating MASLD

Intervention	Key points
Weight loss	5% reduces fat, 7 to 10% improves inflammation, 10% or more can improve fibrosis. Mediterranean-style diet plus at least 150 minutes per week of exercise.
Alcohol	Advise abstinence in advanced fibrosis or cirrhosis; even modest intake raises risk.
Semaglutide (GLP-1 receptor agonist)	FDA approved in 2025 for MASH with F2 or F3 fibrosis; also treats obesity and diabetes.
Resmetirom (thyroid hormone receptor beta agonist)	FDA approved in 2024 for MASH with F2 or F3 fibrosis, alongside diet and exercise.
Pioglitazone	Improves MASH, especially in type 2 diabetes; weight gain and edema are side effects.
Vitamin E 800 IU/day	Option for biopsy-proven MASH without diabetes.
Bariatric surgery	Effective for MASH and fibrosis in eligible patients with obesity.
Statins	Safe in MASLD and compensated cirrhosis; use for cardiovascular risk, which is the leading cause of death.

Cirrhosis due to MASH needs HCC surveillance (ultrasound every 6 months) and portal hypertension assessment.

4. Alcohol-associated hepatitis

Clinical definition (NIAAA): jaundice starting within 8 weeks, heavy drinking for over 6 months with less than 60 days of abstinence, bilirubin above 3 mg/dL, AST above 50 U/L, AST:ALT above 1.5, and both AST and ALT below 400 U/L.
Severity: MELD above 20 (or Maddrey discriminant function of 32 or more) means severe disease with high 90-day mortality.
Exclude and treat infection before steroids: blood and urine cultures, chest X-ray, paracentesis.
Prednisolone 40 mg daily for 28 days in severe disease without contraindications (uncontrolled infection, active GI bleeding, AKI). Pentoxifylline is not recommended.
Lille score at day 7: 0.45 or higher means non-response; stop steroids.
Nutrition: 35 to 40 kcal/kg/day and 1.2 to 1.5 g/kg/day protein; enteral feeding if intake is poor. Give thiamine.
Early liver transplant can be considered in carefully selected patients at experienced centers.

Treating alcohol use disorder

Combine counseling with medication: acamprosate, baclofen, gabapentin, or topiramate are options in liver disease. Naltrexone is generally avoided in decompensated cirrhosis. Avoid disulfiram.
Abstinence is the single most important factor for survival in all alcohol-associated liver disease.

5. High-yield pearls

AST:ALT above 2 suggests alcohol; ALT-predominant pattern fits MASLD.
Normal ALT does not exclude MASH or advanced fibrosis.
Cardiovascular disease, not liver disease, is the commonest cause of death in MASLD.
In alcohol-associated hepatitis, AST and ALT rarely exceed 400 U/L; much higher levels suggest another cause (ischemia, drugs, viral).

Self-check questions

FIB-4 is 1.8. Next step?
Which two drugs are FDA approved for MASH with F2 to F3 fibrosis?
Bilirubin 12, MELD 26, no infection. Treatment?
Lille score 0.6 at day 7. What now?

Answers: (1) Elastography (VCTE) or ELF test. (2) Resmetirom and semaglutide. (3) Prednisolone 40 mg daily, with Lille score at day 7. (4) Stop steroids; supportive care and consider transplant evaluation.

References

Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797-1835.
Rinella ME, Lazarus JV, Ratziu V, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023;78(6):1966-1986.
Harrison SA, Bedossa P, Guy CD, et al. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis. N Engl J Med. 2024;390(6):497-509.
Sanyal AJ, Newsome PN, Kliers I, et al. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis. N Engl J Med. 2025;392(21):2089-2099.
Jophlin LL, Singal AK, Bataller R, et al. ACG Clinical Guideline: Alcohol-Associated Liver Disease. Am J Gastroenterol. 2024;119(1):30-54.

For educational purposes only. This note does not replace clinical judgment or local protocols. Check doses against current labeling and institutional guidance.