AASLD · 2025

Fatty Liver Disease (MASLD/NAFLD) — Management Guideline

Source: AASLD Practice Guidance on the Clinical Assessment and Management of NAFLD (2023), with AASLD updates on resmetirom (October 2024) and semaglutide (November 2025)

✓ Edition checked 3 Oct 2026 — AASLD 2025 is the current edition as of this date.

View the official source ↗

Guideline: Strong Guideline: Conditional Guideline: Not recommended ClinicoQ pathway suggestion (not from the cited guideline)

Diagnosis

Diagnostic criteria Suspected in patients with hepatic steatosis on imaging plus at least one cardiometabolic risk factor, in the absence of significant alcohol use or other causes of liver disease.

⚠ Alarm features (investigate before diagnosing)

Signs of decompensated cirrhosis (ascites, jaundice, encephalopathy, variceal bleeding)
Significant unexplained weight loss
Markedly abnormal liver enzymes suggesting an alternative diagnosis

Initial workup

Test	When to order
Liver ultrasound	Initial imaging to confirm hepatic steatosis.
FIB-4 score	Primary fibrosis risk assessment in all patients with suspected MASLD. FIB-4 below 1.3 (below 2.0 above age 65) indicates low risk.
VCTE (FibroScan), MRE, or ELF test	If FIB-4 is 1.3 or higher (2.0 or higher above age 65), to exclude or confirm advanced fibrosis.
Noninvasive selection for drug therapy (VCTE, MRE, or ELF)	Likely F2-F3: VCTE 8-15 kPa, MRE 3.1-4.4 kPa, ELF 9.2-10.5. Cirrhosis must be excluded when VCTE is 15-20 kPa, MRE 4.4-5.0 kPa, or ELF 10.5-11.3. Cirrhosis: VCTE above 20 kPa, MRE above 5.0 kPa, ELF above 11.3, or portal hypertension.
Referral to hepatology	FIB-4 above 2.67, aminotransferases persistently above normal for more than 6 months (to exclude other causes), or liver stiffness suggesting advanced fibrosis.

✕ Tests the guideline advises against

FIB-4 in acutely ill patients: AASLD advises that FIB-4 should not be used in acutely ill patients.

Decision Points

❓ What do the noninvasive fibrosis tests (FIB-4, VCTE, MRE, ELF) suggest?

Low fibrosis risk (e.g., FIB-4 below 1.3) → All patients (lifestyle and cardiovascular risk)

Consistent with F2-F3 (VCTE 8-15 kPa, MRE 3.1-4.4 kPa, or ELF 9.2-10.5) → MASH with moderate-to-advanced fibrosis (F2-F3 by noninvasive tests)

Suggests cirrhosis or advanced fibrosis (VCTE above 20 kPa, MRE above 5.0 kPa, ELF above 11.3, or portal hypertension) → Cirrhosis or suspected advanced fibrosis

❓ For biopsy-proven MASH without F2-F3 therapy options: does the patient have type 2 diabetes?

Yes, type 2 diabetes → MASH with type 2 diabetes

No diabetes (and no cirrhosis) → MASH without diabetes or cirrhosis

Treatment

All patients (lifestyle and cardiovascular risk)

1 Lifestyle modification (weight loss, dietary change, individualized exercise) Guideline recommendation — cornerstone of management, alongside any drug therapy

Dose: Weight loss of 3-5% improves steatosis; more than 10% is generally required to improve NASH and fibrosis
Duration: Ongoing
Evidence level: High
Avoid if: Lean patients: weight-loss advice may not be appropriate, although dietary changes and exercise remain beneficial
If no response ClinicoQ pathway: If MASH with F2-F3 fibrosis is identified by noninvasive tests, consider resmetirom or semaglutide

2 Statin therapy for cardiovascular risk reduction Guideline recommendation — statins are safe and recommended for CVD risk reduction across the NAFLD spectrum, including compensated cirrhosis

Dose: Per lipid levels and ASCVD risk
Duration: Ongoing
Evidence level: High
Avoid if: Decompensated cirrhosis: data are limited, use only with careful monitoring

MASH with moderate-to-advanced fibrosis (F2-F3 by noninvasive tests)

1 Resmetirom AASLD practice guidance (October 2024) — can be considered for adults with MASH and moderate-to-advanced fibrosis (F2-F3), selected by noninvasive tests

Dose: 80 mg once daily if weight is below 100 kg; 100 mg once daily if 100 kg or above
Duration: Ongoing; repeat liver stiffness (VCTE or MRE) at 12 months to assess response; hepatic function panel every 6 months is suggested after 12 months
Evidence level: Phase 3 trial evidence
Avoid if: Cirrhosis or decompensation; strong CYP2C8 inhibitors such as gemfibrozil (per FDA label); moderate CYP2C8 inhibitors such as clopidogrel need a dose reduction (per FDA label); statin dose limits apply (e.g., atorvastatin and pravastatin 40 mg, rosuvastatin and simvastatin 20 mg, per label). Stop if hepatotoxicity develops
If no response ClinicoQ pathway: Consider semaglutide instead (AASLD makes no recommendation on combining the two) or refer to hepatology

2 Semaglutide 2.4 mg once weekly (Wegovy formulation) AASLD practice guidance (November 2025) — recommended for adults with MASH and F2-F3 fibrosis identified by noninvasive tests; lifestyle modification remains foundational

Dose: 2.4 mg subcutaneously once weekly (the trial started at 0.25 mg weekly and escalated over 16 weeks)
Duration: Ongoing; response is judged at 72 weeks with the same noninvasive tests used for selection (VCTE down 30% or more, MRE down 20% or more, ALT down 17 U/L or 20%, or ELF down 0.5 or more suggest response)
Evidence level: Phase 3 trial evidence (ESSENCE): MASH resolution without worsening of fibrosis in 62.9% vs 34.3% with placebo
Avoid if: MASH cirrhosis (not approved); personal/family history of medullary thyroid carcinoma or MEN2; history of pancreatitis. Monitor for GI intolerance, volume-related kidney injury, symptomatic gallbladder disease, pancreatitis, retinopathy progression, and lean-mass loss; hepatic panels when clinically indicated
If no response: Non-response may be suspected if ALT or noninvasive tests worsen; refer to hepatology

MASH with type 2 diabetes

1 Pioglitazone Conditional (AASLD 2023: improves NASH and can be considered); ADA 2026 also lists it as an option for glycemic management in type 2 diabetes with MASH (level B)

Dose: 30-45 mg once daily
Duration: Ongoing, reassess with follow-up liver enzymes and noninvasive tests
Evidence level: Moderate
Avoid if: Heart failure; active bladder cancer; significant fluid retention. No antifibrotic benefit has been shown and it has not been carefully studied in cirrhosis
If no response ClinicoQ pathway: Consider a GLP-1 receptor agonist instead of or in combination

2 GLP-1 receptor agonist (e.g., semaglutide) AASLD 2023: semaglutide can be considered for NASH with type 2 diabetes or obesity. ADA 2026 (separate source): a GLP-1 RA is preferred for glycemic management with biopsy-proven MASH or high fibrosis risk (level A)

Dose: Per product labeling, with dose titration (for F2-F3 fibrosis use semaglutide 2.4 mg weekly, see the F2-F3 pathway)
Duration: Ongoing
Evidence level: Moderate-High
Avoid if: Personal/family history of medullary thyroid carcinoma or MEN2; history of pancreatitis
If no response ClinicoQ pathway: Refer to hepatology for advanced therapy options

MASH without diabetes or cirrhosis

1 Vitamin E Conditional (AASLD 2023: can be considered in select individuals) — non-diabetic adults with NASH, without cirrhosis

Dose: 800 IU (rrr-alpha-tocopherol) daily
Duration: Ongoing, reassess with follow-up biopsy or noninvasive markers
Evidence level: Moderate
Avoid if: Type 2 diabetes or cirrhosis; history of hemorrhagic stroke; caution with long-term high-dose use and prostate cancer risk. No antifibrotic benefit has been shown
If no response ClinicoQ pathway: Refer to hepatology for further evaluation

Cirrhosis or suspected advanced fibrosis

1 Referral to hepatology Guideline recommendation — direct referral is advised for FIB-4 above 2.67, persistently abnormal aminotransferases for more than 6 months, or liver stiffness suggesting advanced fibrosis

Dose: —
Duration: At identification
Evidence level: Moderate
Avoid if: —
If no response: Statins remain safe in compensated cirrhosis. Semaglutide and resmetirom are not approved for MASH cirrhosis; patients with compensated cirrhosis who take semaglutide for another approved indication should be monitored carefully

✕ Treatments the guideline advises against

Expecting an antifibrotic effect from pioglitazone or vitamin E: AASLD notes that available data on semaglutide, pioglitazone, and vitamin E do not demonstrate an antifibrotic benefit, and none has been carefully studied in patients with cirrhosis.

Vitamin E for NASH in patients with type 2 diabetes or cirrhosis: AASLD limits vitamin E to select non-diabetic adults with NASH without cirrhosis.

Semaglutide (Wegovy) for MASH cirrhosis: Not approved for MASH cirrhosis; AASLD advises careful monitoring only for patients with compensated cirrhosis who receive semaglutide for another approved indication.

Combining semaglutide with resmetirom: AASLD makes no recommendation on combined use because there are no clinical trial data.

⚠️ This is an educational summary of current international clinical practice guidelines and does not replace individualized clinical judgment. Final treatment decisions remain the responsibility of the treating physician.