Red Flags
- MASLD with FIB-4 ≥2.67 or transient elastography ≥12 kPa — advanced fibrosis (F3/F4); hepatology referral and HCC surveillance[1]
- Decompensated cirrhosis (ascites, variceal bleed, encephalopathy) — admit; hepatology and consider transplant evaluation[1]
- Alcohol use disorder concurrent with MASLD — manage as MetALD or alcohol-associated liver disease per CAGE/AUDIT screen; alcohol cessation transformative[1]
- Suspected HCC on surveillance — multiphasic CT or MRI; hepatobiliary multidisciplinary meeting[1]
First-line treatment
Interventions
- Weight reduction 7–10% via lifestyle modification[1]Cornerstone treatment; ≥7% weight loss reverses steatohepatitis, ≥10% reduces fibrosis. Mediterranean diet, physical activity ≥150 min/week
- Bariatric surgery[1]Selected obese patients with MASH; sustained weight loss reverses steatohepatitis and fibrosis in many; multidisciplinary team
- HCC surveillance for cirrhotics[1]Ultrasound + AFP every 6 months for compensated cirrhosis; non-cirrhotic high-risk MASH (PNPLA3 risk variant, family history) per local protocol
First-line drug therapy
| Drug | Class | Adult | Paediatric | Notes |
|---|---|---|---|---|
| Resmetirom[1] | Selective thyroid hormone receptor-β agonist | 80–100 mg PO once daily (weight-based) | — | First FDA-approved MASLD therapy (2024); for biopsy-confirmed MASH with significant or advanced fibrosis (F2-F3); MAESTRO-NASH trial |
| Semaglutide or tirzepatide (in DM or obesity)[1] | GLP-1 / GIP-GLP-1 receptor agonist | Semaglutide 2.4 mg SC weekly (Wegovy); tirzepatide 5–15 mg SC weekly (Mounjaro) | — | MASLD with concurrent T2DM or obesity; weight loss-mediated steatohepatitis improvement; ESSENCE trial demonstrated histologic benefit with semaglutide |
| Pioglitazone[1] | Thiazolidinedione | 30 mg PO once daily | — | Selected biopsy-confirmed MASH (with or without DM); weight gain and fluid retention concerns; avoid in HF |
| Vitamin E[1] | Antioxidant | 800 IU PO daily | — | Selected non-diabetic biopsy-confirmed MASH; small risk of haemorrhagic stroke and prostate cancer (long-term) |
| Statin therapy (cardiovascular indication)[1] | HMG-CoA reductase inhibitor | Per cardiovascular risk | — | Statins safe in MASLD including compensated cirrhosis; reduce CV mortality which is the leading cause of death in MASLD |
Resmetirom[1]
Selective thyroid hormone receptor-β agonist
- Adult
- 80–100 mg PO once daily (weight-based)
- Paediatric
- —
First FDA-approved MASLD therapy (2024); for biopsy-confirmed MASH with significant or advanced fibrosis (F2-F3); MAESTRO-NASH trial
Semaglutide or tirzepatide (in DM or obesity)[1]
GLP-1 / GIP-GLP-1 receptor agonist
- Adult
- Semaglutide 2.4 mg SC weekly (Wegovy); tirzepatide 5–15 mg SC weekly (Mounjaro)
- Paediatric
- —
MASLD with concurrent T2DM or obesity; weight loss-mediated steatohepatitis improvement; ESSENCE trial demonstrated histologic benefit with semaglutide
Pioglitazone[1]
Thiazolidinedione
- Adult
- 30 mg PO once daily
- Paediatric
- —
Selected biopsy-confirmed MASH (with or without DM); weight gain and fluid retention concerns; avoid in HF
Vitamin E[1]
Antioxidant
- Adult
- 800 IU PO daily
- Paediatric
- —
Selected non-diabetic biopsy-confirmed MASH; small risk of haemorrhagic stroke and prostate cancer (long-term)
Statin therapy (cardiovascular indication)[1]
HMG-CoA reductase inhibitor
- Adult
- Per cardiovascular risk
- Paediatric
- —
Statins safe in MASLD including compensated cirrhosis; reduce CV mortality which is the leading cause of death in MASLD
Safety-net
- Weight loss is the most powerful treatment — even 5% reverses some damage; sustained 10% reverses fibrosis in many[1]
- Avoid alcohol — even moderate amounts accelerate MASLD progression[1]
- Watch for fatigue worsening, swelling, easy bruising, vomiting blood, or yellow eyes — call clinician same day (cirrhosis decompensation)[1]
Referral criteria
- FIB-4 ≥2.67 or transient elastography ≥12 kPa (advanced fibrosis)Hepatology[1]
- Decompensated cirrhosisHepatology and transplant centre[1]
- Biopsy-confirmed MASH with F2–F3 fibrosis considering resmetiromHepatology specialist[1]
- BMI ≥35 with MASH considering bariatric surgeryMultidisciplinary obesity / bariatric service[1]
Clinical summary
Diagnosis and stratified management of MASLD (formerly NAFLD/NASH) with FIB-4 risk-stratification and resmetirom for advanced fibrosis.