Metabolic liver disease
MASLD = hepatic steatosis + cardiometabolic risk without competing etiology. MASH = inflammation + ballooning ± fibrosis.
New names, same fat, fibrosis decides
MASLD: hepatic steatosis (imaging or biopsy) plus cardiometabolic risk without a competing cause (). MASH: steatosis + inflammation with ballooning ± fibrosis. MetALD: metabolic dysfunction plus 140–350 g/week alcohol in women or 210–420 g/week in men. MASH cirrhosis: cirrhosis with current or prior steatosis/steatohepatitis.
- US prevalence 10–46%; >95% of bariatric-surgery patients; 33–66% of T2DM; ~50% of dyslipidemia. Lean MASLD exists (; ).
- Progression: MASLD → cirrhosis ~3% in 15 . Compensated cirrhosis → first decompensation ~33% in 4 . Obesity, T2DM, HTN, lipids, OSA, PCOS, menopause, alcohol push fibrosis.
- Presentation: mild AST/ALT 2–4× ULN with AST:ALT <1, or steatosis on imaging with normal enzymes in ~70%. Do not population-screen; do have a high index of suspicion with metabolic risk ().
Exclude alcohol (>21 drinks/week men, >14 women), viral hepatitis, Wilson, iron, AIH, A1AT, DILI, celiac, thyroid. Uncommon: hypobetalipoproteinemia, LAL deficiency, carnitine/choline deficiency. Ferritin is often up in MASLD; add HFE testing if transferrin saturation is also high.
Find fibrosis — fat is not the outcome
FIB-4 first, then elastography. Biopsy is rare — competing diagnosis or indeterminate noninvasive tests (Hepatology 2018;67:328).
| Tool | Rule-out | Rule-in | Notes |
|---|---|---|---|
| FIB-4 (first) | <1.3 (Sn 82%, Sp 57%) | >2.67 (Sn 36%, Sp 93%) | Every 1–2 yr if prediabetes/DM or ≥2 metabolic RFs; every 2–3 yr otherwise |
| NAFLD fibrosis score | < −1.455 (Sn 90%) | ≥0.676 (Sp 97%) | Age 35–65; not liver-specific |
| VCTE (FibroScan) | <8.0 kPa (Sn 83%) | ≥11.4 kPa (Sp 71%) | User-dependent; limited by severe obesity and ascites |
| US elastography | <7.1 kPa (Sn 94%) | >9.2 kPa (Sp 81%) | Adds an image; similar caveats |
- Refer hepatology: ALT >30 despite ≥5% weight loss, FIB-4 >2.67, VCTE ≥8 kPa, F≥3, clinical advanced disease, or need for biopsy.
- Look for cirrhosis stigmata and acanthosis. Labs: LFTs, CBC, INR, HCV Ab, lipids, A1c, celiac, TSH; add iron, A1AT, ANA, ASMA, SPEP, HBV if enzymes are up.
Weight first, then the new drugs
Lifestyle is still first-line (). ≥5% weight loss reduces steatosis; 7–10% may improve fibrosis. Mediterranean / lower-carb / higher-protein, less fructose, more exercise. Do not add heavy alcohol.
- Resmetirom (THR-β agonist) for noncirrhotic MASH with F2–F3, or imaging NILDA (VCTE LSM 8–15 kPa and/or MRE 3.1–4.4 kPa).
- Semaglutide 2.4 mg weekly is FDA-approved for moderate-to-advanced (F2–F3) liver fibrosis. GLP-1 / GIP-GLP-1 agonists are safe in compensated cirrhosis for diabetes and obesity. SGLT2i imaging steatosis. Metformin is associated with better transplant-free survival and less primary liver / extrahepatic cancer.
- Not recommended as liver drugs: pioglitazone, vitamin E, omega-3s, UDCA, obeticholic acid, elafibranor — even if some were used historically.
- Bariatric surgery for eligible obesity with MetALD or MASH if compensated.
- Statins are indicated for CV risk and are safe in compensated disease — CV death outruns liver death. Vaccinate HAV/HBV. HCC screening once F≥3 / cirrhosis. Transplant for decompensation or HCC.