Red Flags
- MASLD with FIB-4 ≥2.67 or transient elastography ≥12 kPa — advanced fibrosis (F3/F4); hepatology referral and HCC surveillance[1]
- Lean MASLD (BMI <25) with metabolic risk factors — does not exclude advanced disease; investigate fully and screen for genetic predisposition (PNPLA3)[1]
- Decompensated cirrhosis — admit; hepatology and transplant evaluation[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-style diet adapted to local food culture, physical activity ≥150 min/week
- Address metabolic syndrome[1]Treat T2DM with kidney/cardio-protective agents (SGLT2 inhibitor, GLP-1 RA), hypertension, dyslipidaemia (statin); smoking cessation; alcohol abstinence; address sleep apnoea
- Lean MASLD pathway[1]Indian populations and South Asians have higher MASLD risk at lower BMI; lean MASLD (BMI <25) requires same metabolic and fibrosis assessment; not less serious
- Bariatric surgery[1]Selected obese patients with MASH; sustained weight loss reverses steatohepatitis and fibrosis; 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 |
|---|---|---|---|---|
| Semaglutide or tirzepatide (DM or obesity)[1] | GLP-1 / GIP-GLP-1 receptor agonist | Semaglutide 2.4 mg SC weekly (Wegovy); tirzepatide 5–15 mg SC weekly | — | MASLD with concurrent T2DM or obesity; weight-loss-mediated steatohepatitis improvement; ESSENCE trial confirmed histologic benefit with semaglutide |
| Pioglitazone[1] | Thiazolidinedione | 30 mg PO once daily | — | Selected biopsy-confirmed MASH; weight gain and fluid retention concerns; avoid in heart failure; lower cost option |
| 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[1] | HMG-CoA reductase inhibitor | Per cardiovascular risk | — | Statins safe in MASLD including compensated cirrhosis; reduce CV mortality (leading cause of death in MASLD) |
Semaglutide or tirzepatide (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
- Paediatric
- —
MASLD with concurrent T2DM or obesity; weight-loss-mediated steatohepatitis improvement; ESSENCE trial confirmed histologic benefit with semaglutide
Pioglitazone[1]
Thiazolidinedione
- Adult
- 30 mg PO once daily
- Paediatric
- —
Selected biopsy-confirmed MASH; weight gain and fluid retention concerns; avoid in heart failure; lower cost option
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[1]
HMG-CoA reductase inhibitor
- Adult
- Per cardiovascular risk
- Paediatric
- —
Statins safe in MASLD including compensated cirrhosis; reduce CV mortality (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 progression in MASLD[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]
- Lean MASLD with metabolic risk factorsHepatology and endocrinology for joint workup[1]
- BMI ≥35 with MASH considering bariatric surgeryMultidisciplinary obesity / bariatric service[1]
Clinical summary
Diagnosis and stratified management of MASLD/NAFLD with emphasis on lean phenotype and metabolic risk in adults.