MASLD

Most common chronic liver disease worldwide — present in ~30% of adults. The 2023 nomenclature reclassifies NAFLD → MASLD (requires ≥1 cardiometabolic risk factor) and NASH → MASH. Fibrosis stage, not steatohepatitis grade, drives liver-related outcomes. Screen with FIB-4 → if indeterminate/high, proceed to LSM (see cirrhosis). Weight loss ≥10% can reverse fibrosis. Resmetirom is the first approved pharmacotherapy for MASH with fibrosis. GLP-1 RAs (semaglutide) resolve steatohepatitis but fibrosis benefit is emerging. Cardiovascular disease, not liver disease, is the leading cause of death.

nomenclature (2023 Delphi consensus)

old term	new term	definition
NAFLD	MASLD	hepatic steatosis + ≥1 cardiometabolic criterion (BMI ≥25, T2DM, elevated BP, dyslipidaemia, elevated waist circumference)
ASH + NAFLD overlap	MetALD	MASLD + alcohol 140–350 g/week (women) or 210–420 g/week (men)
NASH	MASH	MASLD with steatohepatitis (ballooning + inflammation ± fibrosis)
cryptogenic	cryptogenic SLD	steatosis without cardiometabolic criteria or other known cause

The cardiometabolic criteria are intentionally broad — most patients with hepatic steatosis qualify for MASLD.

fibrosis staging and risk stratification

Fibrosis stage is the strongest predictor of liver-related mortality and all-cause mortality. Steatohepatitis grade (NAS score) matters less for prognosis.

screening pathway

Screen patients with metabolic risk factors, persistently elevated ALT, or incidental steatosis on imaging.

flowchart TD
    A["metabolic risk factors or<br>incidental steatosis"] --> B["FIB-4"]
    B -->|"< 1.3"| C["low risk — reassess<br>in 2–3 years"]
    B -->|"1.3–2.67"| D["LSM (FibroScan)"]
    B -->|"> 2.67"| D
    D -->|"< 8 kPa"| E["advanced fibrosis<br>unlikely"]
    D -->|"8–12 kPa"| F["indeterminate —<br>repeat or specialist"]
    D -->|"> 12 kPa"| G["advanced fibrosis<br>likely → hepatology"]

FIB-4 pitfalls

FIB-4 is unreliable at age <35 (underestimates) and >65 (overestimates). In these age groups, proceed directly to LSM if clinical suspicion is present. Full FIB-4 and LSM interpretation in cirrhosis.

management

weight loss — the most effective intervention

weight loss	expected benefit
≥5%	reduces hepatic steatosis
≥7%	resolves steatohepatitis in ~50%
≥10%	reverses fibrosis by ≥1 stage in ~45%

Bariatric surgery achieves these targets more durably than lifestyle alone — consider in BMI ≥35 (or ≥30 with comorbidities). No specific diet is superior; Mediterranean diet has the most supportive data.

pharmacotherapy

No drug is approved specifically for MASLD in Canada as of mid-2026 — resmetirom (US-approved March 2024) is anticipated.

agent	evidence	role
resmetirom (Rezdiffra)	MAESTRO-NASH (2024) — MASH resolution in 26–30% vs 10% placebo; fibrosis improvement in 24–26% vs 14% at 52 weeks. F2–F3 fibrosis.	first-in-class thyroid hormone receptor beta agonist; FDA-approved for MASH with F2–F3 fibrosis
semaglutide	Newsome, NEJM 2021 — phase 2: MASH resolution 59% vs 17%; fibrosis improvement NS. ESSENCE (2024) — phase 3 in F2–F3: MASH resolution + fibrosis improvement achieved.	GLP-1 RA; best evidence for steatohepatitis resolution; concurrent weight loss + CV benefit
pioglitazone	Cusi, Ann Intern Med. 2016 — improves histology in T2DM/prediabetes with MASH	thiazolidinedione; limited by weight gain, fluid retention, fracture risk; reasonable if T2DM + MASH
vitamin E (800 IU/day)	PIVENS trial — improves histology in non-diabetic MASH	avoid in T2DM (no benefit in PIVENS diabetic arm); safety concerns with long-term high-dose use

choosing pharmacotherapy

Semaglutide is the pragmatic first choice in most patients — addresses MASH, weight, T2DM, and CV risk simultaneously. Resmetirom for patients with biopsy-confirmed MASH and significant fibrosis (F2–F3) where available. Pioglitazone is an option when GLP-1 RAs are contraindicated or unavailable, particularly in T2DM.

manage cardiovascular risk

CV disease is the #1 killer in MASLD — more so than liver disease at every fibrosis stage below cirrhosis.

statin therapy is safe in MASLD/MASH and should not be withheld (see approach to elevated liver enzymes — statin hepatotoxicity is over-diagnosed)
treat hypertension, diabetes, dyslipidaemia per standard guidelines
SGLT2 inhibitors may offer hepatic benefit in addition to cardiorenal protection — data emerging

when to refer to hepatology

LSM ≥8 kPa or FIB-4 persistently >2.67
suspected cirrhosis (thrombocytopaenia, splenomegaly, clinical stigmata)
diagnostic uncertainty (overlap with AIH, alcohol)
candidate for MASH-specific pharmacotherapy (biopsy confirmation often needed before resmetirom)

common traps

Treating the steatosis, not the fibrosis — an US showing “fatty liver” without fibrosis assessment (FIB-4 → LSM) is incomplete. Steatosis alone rarely progresses; fibrosis determines outcomes.
Stopping statins for mild ALT elevation — MASLD itself causes the ALT rise. Statins reduce CV events, the actual leading cause of death.
Ignoring alcohol in MASLD — MetALD (MASLD + moderate alcohol) accelerates fibrosis. Quantify intake; advise reduction or abstinence if >moderate.
Biopsy as first-line — reserve for diagnostic uncertainty, clinical trial eligibility, or when histology will change management (e.g. confirming MASH before resmetirom).
Assuming lean patients don’t get MASLD — ~20% of MASLD patients have BMI <25. Visceral adiposity and metabolic dysfunction drive disease, not BMI alone.