Overview.
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD, formerly NAFLD) affects 25-30% of the global population, making it the most common chronic liver disease worldwide. It is strongly associated with obesity, insulin resistance, and metabolic syndrome. Most cases are asymptomatic and detected incidentally through elevated liver enzymes. The key clinical question is not whether fat is present, but whether fibrosis has developed — and the FIB-4 score answers this non-invasively.
MASLD is defined as hepatic steatosis (fat accumulation in >5% of hepatocytes) in the presence of at least one cardiometabolic risk factor, without significant alcohol consumption or other secondary causes. The 2023 multi-society Delphi consensus renamed NAFLD to MASLD and NASH to MASH (metabolic dysfunction-associated steatohepatitis), shifting to a positive diagnostic criteria based on metabolic risk rather than excluding alcohol. The spectrum ranges from simple steatosis (low risk) through steatohepatitis (MASH) to fibrosis and cirrhosis.
Prevalence: 25-30% of the global adult population. Prevalence rises to 50-70% in patients with type 2 diabetes and 80-90% in those with severe obesity. It is the leading cause of chronic liver disease and the fastest-growing indication for liver transplantation in Western countries.
Medical name: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
Symptoms.
Early warnings
- Incidentally elevated ALT on routine blood work
- Elevated GGT without significant alcohol intake
- Fatty liver found on ultrasound or CT scan
- AST:ALT ratio >1 (may suggest advancing fibrosis)
- Elevated fasting insulin or HOMA-IR with normal liver enzymes
Classic symptoms
- Most patients are completely asymptomatic
- Fatigue (most commonly reported symptom when present)
- Right upper quadrant discomfort or dull ache
- Hepatomegaly (enlarged liver on examination)
- In advanced fibrosis/cirrhosis: spider angiomata, palmar erythema, ascites, jaundice
Progression
Simple steatosis (MASLD) carries a benign liver prognosis — the primary risk is cardiovascular disease, not liver failure. MASH (steatohepatitis with inflammation) progresses to significant fibrosis in 20-40% over 10-20 years. Once cirrhosis develops, hepatocellular carcinoma risk is ~1-2% per year. The fibrosis stage — not the degree of steatosis — is the strongest predictor of liver-related outcomes and mortality.
Risk factors.
- Obesity (BMI >30), particularly central/visceral adiposity
- Type 2 diabetes mellitus
- Insulin resistance / metabolic syndrome
- Dyslipidaemia (elevated triglycerides, low HDL)
- Hypertension
- Obstructive sleep apnoea
- Polycystic ovary syndrome (PCOS)
- Hypothyroidism
- Hispanic ethnicity (PNPLA3 gene variant)
- Family history of liver disease or cirrhosis
Lab interpretation.
Key biomarkers
- ALT — Often mildly elevated (30-100 U/L); can be normal in up to 30% of MASLD patients. Optimal cutoff: <30 U/L for men, <19 U/L for women (primary)
- GGT — Elevated in MASLD and biliary injury; sensitive to alcohol use; correlates with metabolic syndrome severity (primary)
- Fasting Insulin / HOMA-IR — Elevated; insulin resistance is present in the vast majority of MASLD cases (secondary)
- HbA1c — Often elevated or high-normal; screen for diabetes in all MASLD patients (secondary)
- Triglycerides — Frequently elevated; part of the metabolic syndrome cluster (supportive)
Diagnostic criteria
- Hepatic steatosis on imaging (ultrasound, CT, MRI) or histology (>5% hepatocytes with fat)
- Plus at least one cardiometabolic risk factor: BMI ≥25, waist circumference elevated, prediabetes/T2DM, hypertension, dyslipidaemia
- Exclusion of significant alcohol use (>20g/day women, >30g/day men) and other liver diseases
- FIB-4 score for non-invasive fibrosis staging: <1.3 = low risk; 1.3-2.67 = indeterminate (refer for FibroScan); >2.67 = high risk (hepatology referral)
- FIB-4 = (Age x AST) / (Platelets x √ALT) — calculated from standard blood work
Recommended panels
When & next steps.
When to test
- Incidentally elevated ALT or GGT on routine blood work
- Fatty liver on imaging (ultrasound, CT)
- Type 2 diabetes mellitus (screen all patients)
- Obesity with metabolic syndrome features
- PCOS (elevated MASLD prevalence)
- Family history of cirrhosis or liver disease
- Before and during hepatotoxic medication use
If suspected
- Confirm with full liver panel: ALT, AST, GGT, ALP, bilirubin, albumin
- Calculate FIB-4 score from existing blood work (age, AST, ALT, platelets)
- Check fasting glucose, HbA1c, fasting insulin, lipid panel (metabolic risk assessment)
- Rule out other causes: hepatitis B/C serology, autoimmune hepatitis (ANA, anti-smooth muscle), iron studies (haemochromatosis)
If confirmed
- FIB-4 <1.3: low fibrosis risk — lifestyle modification, reassess in 2-3 years
- FIB-4 1.3-2.67: indeterminate — refer for transient elastography (FibroScan) or ELF test
- FIB-4 >2.67: high fibrosis risk — hepatology referral
- Lifestyle intervention: 7-10% weight loss significantly improves steatosis and fibrosis
- Mediterranean diet reduces liver fat independent of weight loss
- No approved pharmacotherapy for MASLD (as of 2026); resmetirom (thyroid hormone receptor agonist) FDA-approved for MASH with fibrosis (2024)
- Cardiovascular risk management is paramount — CVD is the leading cause of death in MASLD
FAQs.
What's the difference between NAFLD and MASLD?
MASLD is the new name for NAFLD, adopted in 2023 by a multi-society Delphi consensus. The key change: MASLD uses positive diagnostic criteria (requiring at least one cardiometabolic risk factor) rather than the old exclusion-based definition. NASH is now MASH. The clinical management is identical.
My ALT is normal — can I still have fatty liver?
Yes. Up to 30% of patients with MASLD have normal ALT. Traditional lab reference ranges (up to 40-55 U/L) are too high — optimal ALT is <30 U/L for men and <19 U/L for women. An ultrasound can detect steatosis even when ALT is normal.
What is FIB-4 and should I calculate it?
FIB-4 is a simple fibrosis index calculated from age, AST, ALT, and platelet count — all from routine blood work. It identifies patients at low risk (score <1.3) who can be reassured, and high risk (>2.67) who need hepatology referral. It avoids unnecessary imaging or biopsy in the majority of patients.
Can fatty liver be reversed?
Yes. Weight loss of 7-10% significantly improves both steatosis and inflammation. Even 3-5% weight loss reduces liver fat. Mediterranean diet, regular exercise, and addressing insulin resistance are the cornerstone of treatment. Fibrosis can also improve with sustained lifestyle change.