MASLD — Diagnosis & Long-Term Management

Decision support only — not a substitute for hepatology, current Australian product information or local pathways. Fibrosis, rather than steatosis or ALT alone, drives liver prognosis. Treat cardiometabolic risk in every stage; confirm treatment eligibility, contraindications, doses and PBS status locally.

1 Fibrosis-first pathway

The ultrasound report saying “fatty liver” is the start of the assessment, not the endpoint. Most people will never develop liver failure; the useful job is to find the minority with advanced fibrosis while the cardiometabolic disease is still treatable.

Case-find or assess incidental steatosisT2DM · obesity · ≥2 metabolic risk factors · persistently abnormal liver enzymes · steatosis on imaging

Calculate FIB-4: age × AST ÷ [platelets × √ALT]

USE STABLE OUTPATIENT RESULTS

WHEN FIB-4 MISLEADSDo not use during acute illness or acute hepatitis. Accuracy is poor below 35 years; go to elastography/ELF when clinical risk is real. Non-hepatic thrombocytopenia inflates the score. Above 65 years, use 2.0 rather than 1.3 as the low-risk threshold. GESA 2024

LOW RISK

FIB-4 <1.3
Age >65: <2.0. Advanced fibrosis unlikely; Australian primary-care NPV >95%.

Manage metabolic risk. Repeat FIB-4 at least every 3 years; consider 1–2 years with T2DM, several risk factors or rising AST/HbA1c.

INDETERMINATE

FIB-4 1.3–2.7
Age >65: 2.0–2.7. Do VCTE/FibroScan, SWE, ELF or Hepascore; refer if unavailable.

Low second line: VCTE <8 kPa, ELF <9.8 or Hepascore <0.6 → community follow-up; repeat FIB-4 in 2–3 years.

ELEVATED / HIGH RISK

FIB-4 >2.7, VCTE ≥8 kPa, ELF ≥9.8, Hepascore ≥0.6, failed/discordant NIT, or clinical/imaging cirrhosis → hepatology.

VCTE ≥15 kPa is highly specific for advanced fibrosis, but congestion, cholestasis, inflammation and obesity can distort stiffness. Read the whole patient.

2 Name the phenotype properly

Label	Working definition	Why it changes management
SLD	Steatotic liver disease: hepatic steatosis by imaging or histology. An umbrella, not an aetiology.	Assess metabolic risk, alcohol, medicines and alternative/coexisting liver disease.
MASLD	SLD + ≥1 cardiometabolic risk factor: excess adiposity/waist, dysglycaemia or T2DM, hypertension, hypertriglyceridaemia or low HDL. Excludes alcohol in the MetALD range or another dominant explanation. Replaces NAFLD.	A positive diagnosis. Other causes can still coexist; do not stop at “metabolic”.
MetALD	SLD + metabolic risk + alcohol 20–50 g/day in women or 30–60 g/day in men (140–350 or 210–420 g/week).	Alcohol and metabolic injury are synergistic. These cut-offs classify disease; they are not safe-drinking targets.
MASH	Metabolic dysfunction-associated steatohepatitis: steatosis with ballooning and lobular inflammation. Replaces NASH.	Definite MASH is histological. NITs estimate fibrosis risk but do not see ballooning or inflammation.
F2 / F3 / F4	Significant fibrosis / advanced fibrosis / cirrhosis.	F2–F3 defines the current disease-modifying treatment population; F4 triggers cirrhosis care and is excluded from the Australian MASH indication for semaglutide.

Normal enzymes do not clear the liver

ALT/ASTMay be normal in MASH and advanced fibrosis. Persistently abnormal results increase concern, but enzyme height does not stage fibrosis.
UltrasoundAustralian first-line test for steatosis; limited sensitivity for mild fat and poor at fibrosis staging. CT attenuation is not a fibrosis test either.
Burnt-outAdvanced MASH or cirrhosis may lose visible steatosis. Absence of fat on later imaging does not negate prior disease or established fibrosis risk.
ScreeningNo general-population screening. Use active case-finding in T2DM, obesity plus metabolic risk, abnormal enzymes or incidental steatosis. EASL 2024

3 Baseline work-up — liver and whole-patient risk

Define liver severity

HistoryWeight trajectory, T2DM duration/control, alcohol quantity/pattern, family liver disease, prescribed/OTC/herbal agents.
ExamineBMI + waist, BP, sarcopenia; hepatosplenomegaly, ascites, oedema, encephalopathy or chronic liver stigmata.
BloodsFBC/platelets, ALT/AST, ALP/GGT, bilirubin, albumin, INR; calculate FIB-4 from a stable sample.
ImageUltrasound for steatosis, morphology, spleen, portal vein and focal lesions; add elastography when indicated.

Exclude or identify co-drivers

CoreHBsAg, anti-HCV; ferritin + transferrin saturation when enzymes are elevated or iron overload is plausible.
AlcoholAUDIT-C/full AUDIT; convert drinks to grams. Consider PEth when the history and phenotype disagree.
DirectedANA/ASMA/IgG, AMA, coeliac serology, A1AT phenotype/genotype or ceruloplasmin according to age and pattern.
DrugsAmiodarone, methotrexate, tamoxifen, corticosteroids, valproate and selected antiretrovirals; attribution needs timing and context.

Find the outcomes that usually matter first

GlycaemiaHbA1c/fasting glucose; optimise diabetes therapy and screen complications.
CVCVD is the commonest cause of death in MASLD. Assess lipids, BP, smoking and absolute cardiovascular risk; treat these as primary outcomes, not background comorbidity.
KidneyeGFR + urine ACR; treat CKD and choose cardiorenal-protective diabetes therapy when indicated.
OtherOSA, PCOS, hypothyroidism and obesity complications; involve dietetics, diabetes/obesity care and exercise physiology.

Ferritin is often noisy

Metabolic inflammation commonly raises ferritin. Check transferrin saturation and the phenotype before diagnosing iron overload. Venesection is not treatment for dysmetabolic hyperferritinaemia without haemochromatosis or demonstrable iron overload. GESA 2024

4 Treatment foundation — make the metabolic plan specific

Weight targets predict liver response

≥5%Reduces liver fat.
7–10%Improves steatohepatitis/inflammation.
≥10%Best chance of fibrosis improvement. Aim for sustained loss, not a short-lived nadir. EASL 2024
Lean MASLDStill use diet quality + exercise; investigate genetic/secondary drivers when disease is severe or unusually early.

Food and movement

PatternMediterranean-style, minimally processed food; cut sugar-sweetened drinks, excess fructose, saturated fat and ultra-processed food.
Exercise>150 min/week moderate or 75 min vigorous aerobic activity, plus resistance training; benefit occurs even before major weight loss.
PrescribeAgree on one measurable diet change and one activity target; review barriers, sleep and medications that promote weight gain.
DietitianUse an APD for calorie deficit, protein adequacy, cultural fit and sarcopenia prevention.

Alcohol and supplements

AlcoholDiscourage use in SLD; complete abstinence with advanced fibrosis or cirrhosis. Binge pattern matters even below weekly thresholds.
CoffeeObservational benefit is plausible; do not turn it into a prescription for someone who cannot tolerate it.
SupplementsNo nutraceutical, “liver detox”, silymarin or probiotic has evidence sufficient for routine disease-modifying use.
SurgeryConsider metabolic/bariatric surgery for standard obesity indications in non-cirrhotic MASLD; specialist MDT if compensated cirrhosis, and avoid in decompensated disease.

5 Medicines — separate MASH therapy from comorbidity therapy

Intervention	Best fit	Evidence signal	Australian position / cautions
Semaglutide (Wegovy) 0.25 mg weekly ×4 wk → 0.5 → 1.0 → 1.7 → 2.4 mg	Adults with confirmed non-cirrhotic MASH and F2–F3 fibrosis; diet + activity continue. Specialist assessment is sensible where staging or diagnosis is uncertain.	ESSENCE at 72 weeks: MASH resolution without fibrosis worsening 62.9% vs 34.3%; ≥1-stage fibrosis improvement without MASH worsening 36.8% vs 22.4%. Clinical-outcome phase continues.	Provisional TGA approval Mar 2026; maximum MASH maintenance dose 2.4 mg weekly. GI effects, gallbladder disease, dehydration/AKI and pancreatitis warning; monitor retinopathy risk with rapid glycaemic improvement. No MASH-specific PBS item was identified at compilation; recheck the live Schedule.
GLP-1/GIP therapy for obesity or T2DM	Use semaglutide, tirzepatide or another agent according to its Australian indication and the patient’s obesity, glycaemic, CV and renal profile.	SYNERGY-NASH phase II: tirzepatide achieved MASH resolution in 44–62% vs 10% placebo at 52 weeks; long-term liver outcomes and phase III confirmation remain pending.	Do not infer a MASH indication or PBS subsidy from class membership. Ozempic PBS authority is for defined T2DM use, not treatment of MASH.
Pioglitazone	Selected patients with T2DM and biopsy-confirmed MASH when metabolic benefit outweighs harm.	Improves steatohepatitis; convincing antifibrotic or liver-outcome benefit has not been shown.	Weight gain, oedema/HF, fracture risk. Treat as a diabetes drug with possible liver benefit, not a universal MASLD prescription.
SGLT2 inhibitor / metformin	T2DM, CKD or HF according to standard indications.	SGLT2 inhibitors reduce liver fat in small studies; neither class has adequate histological evidence as MASH-targeted therapy.	Use for proven glycaemic/cardiorenal outcomes and follow current PBS restrictions.
Statin	Dyslipidaemia or elevated CV risk, including compensated chronic liver disease.	Reduces cardiovascular events; not a MASH treatment.	MASLD or mild stable transaminase elevation is not a reason to withhold a statin. Use more caution in decompensated cirrhosis.
Vitamin E	Occasionally considered by hepatology in non-diabetic, non-cirrhotic, biopsy-proven MASH.	Can improve steatohepatitis; no proven fibrosis or clinical-outcome benefit. Long-term bleeding/prostate-cancer signals complicate use.	AASLD allows selective use; EASL 2024 does not recommend it as MASH-targeted therapy. Shared decision, not routine supplementation.
Resmetirom	Overseas: non-cirrhotic MASH with F2–F3 fibrosis.	MAESTRO-NASH met both 52-week histology endpoints: MASH resolution 25.9–29.9% vs 9.7%; fibrosis improvement 24.2–25.9% vs 14.2%. Outcome benefit is unproven.	EASL/AASLD discuss it, but no Australian TGA or PBS listing was identified at compilation. Do not import US prescribing into local practice.

Surrogate endpoints are doing a lot of work

Semaglutide and resmetirom approvals/recommendations rest on histological improvement. That is meaningful, but neither trial has yet shown fewer episodes of decompensation, HCC, transplant or death. The placebo arms also improved, which is a useful reminder that sustained weight and metabolic treatment remain active therapy.

6 Refer, biopsy or enter the cirrhosis pathway

Refer to hepatology

NITFIB-4 >2.7; VCTE ≥8 kPa; ELF ≥9.8; Hepascore ≥0.6; failed, unreliable or discordant testing.
BloodsAminotransferases persistently elevated >6 months, synthetic dysfunction or falling platelets.
ClinicalSplenomegaly, nodular liver, collaterals, ascites, jaundice, encephalopathy, variceal bleed or focal lesion.
TherapySuspected F2–F3 MASH where semaglutide treatment, a trial or bariatric intervention is being considered.

Biopsy is selective

Use whenNITs disagree with clinical risk; alternative/overlap disease remains plausible; definite MASH or fibrosis stage will change therapy.
Avoid whenLow-risk sequential NITs answer the management question, or cirrhosis is already clear clinically and on imaging.
RememberSampling and reader variability exist. A biopsy is a small piece of liver, not an oracle.

Once cirrhosis is suspected

HCCA minority of MASLD-related HCC occurs without cirrhosis, but absolute incidence is too low for routine non-cirrhotic surveillance; individualise advanced F3 with hepatology. In cirrhosis, use ultrasound ± AFP every 6 months; obesity may impair visualisation, prompting specialist-selected CT/MRI. GESA 2024
Portal HTNApply Baveno/cirrhosis pathway for CSPH, varices and carvedilol; manage nutrition, bone and vaccines.
DecompAscites, bleeding, jaundice or encephalopathy → urgent decompensated-cirrhosis pathway and transplant consideration.
DrugsNo MASH-targeted pharmacotherapy is recommended for F4. The Australian Wegovy MASH label excludes cirrhosis.

7 Follow-up by fibrosis and metabolic risk

Group	Review	Repeat testing	Escalation trigger
Low FIB-4	Weight/waist at least annually; BP, HbA1c/glucose, lipids, renal risk, alcohol, OSA and lifestyle plan.	FIB-4 at least every 3 years. Use 1–2 years with T2DM, multiple metabolic risks, rising AST or deteriorating glycaemia.	Crosses age-adjusted threshold, persistent enzyme rise, platelet fall or new clinical/imaging concern.
Indeterminate + low second line	Same metabolic work, with explicit weight and activity targets.	FIB-4 in 2–3 years; earlier if trajectory changes. Repeat elastography according to local pathway.	VCTE/ELF/Hepascore rises, discordance develops or treatment eligibility is being considered.
F2–F3 / high-risk NIT	Hepatology + metabolic MDT; confirm stage, alcohol, competing disease and treatment access.	Specialist-selected NITs and labs. Do not use ALT normalisation alone as proof of fibrosis regression.	Synthetic dysfunction, portal-hypertension signal, rising stiffness or new focal lesion.
Cirrhosis	Cirrhosis bundle: decompensation, nutrition/sarcopenia, CSPH, medicines, transplant suitability.	HCC surveillance q6 months; portal-hypertension/endoscopy strategy and MELD/Child-Pugh as indicated.	Any first decompensation, suspicious lesion, frailty/sarcopenia or worsening synthetic function.

Primary sources. Gastroenterological Society of Australia. Recommendations for assessment of MAFLD in primary care: Australian consensus statement. 2024. EASL–EASD–EASO. Clinical Practice Guidelines on MASLD. Diabetologia 2024;67:2375–2392. Rinella ME et al. Multisociety Delphi consensus on SLD nomenclature. Hepatology 2023;78:1966–1986. Rinella ME et al. AASLD practice guidance on clinical assessment and management of NAFLD/MASLD. Hepatology 2023;77:1797–1835; see AASLD 2024 resmetirom and 2025 semaglutide updates. TGA. Wegovy MASH registration, 30 Mar 2026; current ARTG entry and Product Information. PBS. Semaglutide/Ozempic item and restriction; verify current Schedule.
Key trials. Sanyal AJ et al. ESSENCE: semaglutide in MASH. N Engl J Med 2025;392:2089–2099. Harrison SA et al. MAESTRO-NASH: resmetirom in NASH/MASH with fibrosis. N Engl J Med 2024;390:497–509. Loomba R et al. SYNERGY-NASH: tirzepatide in MASH with fibrosis. N Engl J Med 2024;391:299–310.
Caveats. GESA 2024 uses the MAFLD definition; the current international MASLD/MetALD labels differ, but the Australian fibrosis pathway and thresholds remain clinically transferable. NIT thresholds are approximations and depend on platform, fasting state, technical quality and pre-test probability. VCTE and direct serum tests may lack MBS funding or local access. Semaglutide’s Australian MASH approval is provisional and excludes cirrhosis; longer-term clinical outcomes remain under study. No MASH-specific PBS listing or Australian resmetirom registration was identified at compilation; access changes, so check live sources. Recommendations and trial results are paraphrased.