MASLD and Steatohepatitis
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Direct answer
Losing 7–10 per cent of body weight is the treatment that matters in metabolic dysfunction-associated steatotic liver disease: it resolves steatohepatitis, and around 10 per cent regression is the goal when fibrosis is present. The 2023 nomenclature replaced NAFLD with MASLD, defined by hepatic steatosis plus at least two cardiometabolic criteria with alcohol below 20 g daily in women and 30 g in men; the overlapping category MetALD covers moderate alcohol intake on top of metabolic steatosis. Fibrosis, not steatosis, drives mortality, so every newly diagnosed patient is risk-stratified with FIB-4 — below 1.3 reassures, above 2.67 sends the patient for elastography. Pharmacotherapy is adjunctive: pioglitazone, GLP-1 receptor agonists, vitamin E in selected patients and, per current guidance, resmetirom for biopsy-proven F2–F3 steatohepatitis.
What you must remember
- New names: steatotic liver disease is the umbrella; MASLD requires steatosis plus two of enlarged waist or BMI, diabetes or prediabetes, hypertension, hypertriglyceridaemia or low HDL; MASH is the inflammatory subtype (formerly NASH).
- FIB-4 thresholds: below 1.3 low risk (above 2.0 if over 65), above 2.67 high risk — the first-line triage that spares most patients elastography.
- Weight-loss gradients: 5 per cent reduces steatosis, 7–10 per cent resolves steatohepatitis, 10 per cent or more can regress fibrosis — the numbers exams quote.
- Indian phenotype: a substantial minority of Indian MASLD patients are lean, with normal BMI but central adiposity and insulin resistance — screening by waist circumference matters more than BMI alone.
- Drugs with evidence: pioglitazone 30–45 mg (best in diabetes; weight gain, fluid retention, fracture risk), GLP-1 agonists such as semaglutide for weight and liver enzymes, vitamin E 800 IU daily in non-diabetic biopsy-proven MASH.
- Resmetirom, a thyroid-hormone-receptor-beta agonist, is the first approved MASH-specific drug for F2–F3 fibrosis per current guidance — monitor for diarrhoea and nausea.
- Cardiovascular disease is the leading cause of death — statins are not contraindicated by the fatty liver and are usually indicated.
- Caveats: no alcohol during active treatment, coffee is protective, and cirrhotic MASLD enters six-monthly hepatocellular carcinoma surveillance.
How to work through a fatty-liver clinic letter
A 46-year-old man with type 2 diabetes and BMI 31 has ultrasound-reported bright liver and ALT 68 IU/L; hepatitis B and C serology, ANA and ferritin are normal. Step one, confirm metabolic framing: he has diabetes plus a large waist plus triglycerides of 190 mg/dL — three criteria, so MASLD. Step two, stage fibrosis non-invasively: FIB-4 is 1.9 — indeterminate, so elastography; a liver stiffness of 8 kPa suggests F2. Step three, set the target: he weighs 88 kg, so 7–10 per cent means 6–9 kg over six to twelve months through diet, exercise and, if appropriate, semaglutide for his diabetes. Step four, consider drugs: with diabetes and F2, pioglitazone is the evidence-backed add-on. Step five, protect the future — statin for his cardiovascular risk, vaccination, and repeat elastography in two to three years. If his stiffness had exceeded 12 kPa, the letter would instead read: cirrhosis pathway, endoscopy and surveillance ultrasound.
Where students slip
The first slip is treating the ultrasound, not the patient — steatosis on scan predicts nothing without a fibrosis stage, and the exam tests the FIB-4 cut-offs precisely. The second is old vocabulary: writing NAFLD when the question stem uses MASLD, or missing that MetALD now covers the drinker with metabolic disease who fell between the old categories. The third is overprescribing vitamin E — it is for non-diabetic, biopsy-proven MASH, not for every fatty liver, and it carries a discussable haemorrhagic-stroke signal. The final slip is forgetting that this patient is more likely to die of myocardial infarction than of liver failure.
Frequently asked questions
What criteria define MASLD?
Hepatic steatosis plus at least two cardiometabolic features — waist or BMI, glycaemia, blood pressure, triglycerides or HDL — with alcohol intake below 20 g daily in women and 30 g in men.
Which score triages fibrosis risk at diagnosis?
FIB-4: below 1.3 is low risk (2.0 if aged over 65), above 2.67 is high risk and merits elastography or specialist referral.
How much weight loss improves liver histology?
Around 5 per cent reduces steatosis, 7–10 per cent resolves steatohepatitis, and 10 per cent or more is the target for fibrosis regression.
When is pioglitazone preferred in MASH?
In patients with type 2 diabetes or proven steatohepatitis, at 30–45 mg daily, accepting weight gain and the small fracture risk.
What is resmetirom used for?
Biopsy-confirmed MASH with F2–F3 fibrosis per current guidance — the first approved liver-directed drug for this indication.