Lucan · Conditions

Metabolic-associated fatty liver disease

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Australian guidance: RACGP MAFLD Assessment Recommendations + ADS for diabetes overlap

1. Definition and epidemiology

Metabolic-associated fatty liver disease (MAFLD) is hepatic steatosis occurring in the context of metabolic dysfunction, including overweight or obesity, type 2 diabetes mellitus (T2DM), or two or more features of metabolic syndrome, even if alcohol intake is present. It supersedes the older term non-alcoholic fatty liver disease (NAFLD) because it identifies the condition by what it is rather than by what it excludes. In Australian diabetes centre studies, approximately 15 to 20% of people with T2DM have severe liver fibrosis on transient elastography, and T2DM is recognised as a major independent risk factor for hepatocellular carcinoma (HCC) and liver failure. The related term metabolic dysfunction associated steatohepatitis (MASH) refers to MAFLD with hepatic inflammation and hepatocyte injury, with or without fibrosis.

2. Pathophysiology

The central driver is hepatic lipid accumulation resulting from insulin resistance, which promotes increased delivery of free fatty acids to the liver via lipolysis of visceral adipose tissue. Simultaneously, de novo lipogenesis is upregulated by hyperinsulinaemia. Per Robbins Ch 18, the resulting steatosis (lipid droplets within hepatocytes) creates vulnerability to a second hit: oxidative stress, mitochondrial dysfunction, gut-derived endotoxin signalling via Toll-like receptors, and adipokine dysregulation. These second hits drive hepatocyte ballooning, lobular inflammation, and stellate cell activation, producing collagen deposition and progressive fibrosis. In people with T2DM, glucolipotoxicity, advanced glycation end products, and systemic inflammation accelerate fibrogenesis beyond that seen with obesity alone. Advanced fibrosis progresses to cirrhosis and substantially raises HCC risk, with T2DM worsening liver-related mortality at each stage.

3. Clinical presentation and diagnostic criteria

MAFLD is predominantly silent in its early stages. Most patients are identified incidentally through deranged liver function tests or hepatomegaly on imaging performed for another reason. Symptoms, when present, include fatigue and right upper quadrant discomfort. Risk factors prompting active case finding include obesity, T2DM, prediabetes, and features of metabolic syndrome such as hypertension, hypertriglyceridaemia, and low high-density lipoprotein (HDL) cholesterol. Signs of advanced disease include hepatomegaly, splenomegaly, ascites, peripheral oedema, and stigmata of chronic liver disease such as palmar erythema and spider naevi. The Australian Diabetes Society (ADS) and Gastroenterology Society of Australia (GESA) recommend that clinicians regard any person with obesity, prediabetes, or T2DM as being at increased risk and screen proactively for advanced liver fibrosis.

4. Investigations and AU-specific cutoffs

The preferred first-line non-invasive risk stratification tool is the Fibrosis-4 (FIB-4) index, calculated from age, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and platelet count. The ADS living guideline defines risk categories as follows:

Second-line tests, for those with indeterminate or high FIB-4, include liver stiffness measurement (LSM) by transient elastography (Fibroscan) or the Enhanced Liver Fibrosis (ELF) blood panel. AU-specific cutoffs from the ADS guideline are:

Note that Fibroscan and ELF testing currently lack a Medicare Benefits Schedule (MBS) item number in Australia, which limits access in some settings. The RACGP T2DM Handbook lists MAFLD as a multimorbidity and complication requiring monitoring in the diabetes cycle of care. Additional investigations include fasting glucose, HbA1c, fasting lipid panel, and liver function tests including gamma-glutamyl transferase (GGT). Liver biopsy remains the gold standard for histological staging but is reserved for cases where non-invasive tests give discordant results or when hepatologist assessment prompts further workup.

5. Management

The cornerstone of management is lifestyle modification targeting sustained weight reduction. The ADS recommends a goal of at least 5% body weight loss, with 10% or greater producing greater liver histology improvement and cardiometabolic benefit, and advocates structured exercise programs tailored to individual preference. Dietary approaches include caloric restriction, a Mediterranean dietary pattern, and very low energy diets (VLEDs) where available through specialist obesity services. Alcohol intake should be minimised even though its presence does not exclude the diagnosis. Where lifestyle measures alone fail to achieve targets in those with body mass index (BMI) 27 kg/m2 or above, obesity pharmacotherapy is recommended as an adjunct, aligned with the Australian Obesity Management Algorithm. The ADS strongly recommends preference for incretin-based agents, specifically semaglutide 2.4 mg/week subcutaneously or tirzepatide, over other weight-loss agents in those with MAFLD or MASH. Bariatric surgery is an option for those with BMI 35 kg/m2 or above (32.5 kg/m2 in Asian populations), particularly when T2DM coexists. Statins are not contraindicated and should be continued for dyslipidaemia management in people with MAFLD.

6. Pharmacology and AU PBS notes

Semaglutide 2.4 mg/week (Ozempic 1 mg/Wegovy 2.4 mg): The ADS gives this agent top preference for chronic weight management in MAFLD or MASH with BMI 27 kg/m2 or above. The Australian Therapeutic Goods Administration (TGA) provisionally approved semaglutide 2.4 mg for non-cirrhotic MASH with moderate to advanced liver fibrosis in 2026. PBS access for weight management in T2DM is via streamlined authority for obesity with comorbidity; the specific MASH indication is currently under separate TGA provisional approval pathway and PBS listing is pending as of June 2026.

Tirzepatide (Mounjaro): A dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist; listed by ADS as an alternative twincretin option with comparable evidence. PBS listed for T2DM glycaemic management; obesity indication PBS listing is separate.

Agents with no hepatic benefit in MASH: Metformin, sulphonylureas, acarbose, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose co-transporter 2 inhibitors (SGLT2i), and insulin have no demonstrated efficacy on hepatocyte necrosis, inflammation, or fibrosis, and are not recommended for steatohepatitis treatment, though they may be continued for glycaemic management in T2DM.

Statins: HMG-CoA reductase inhibitors are not contraindicated in MAFLD; the ADS explicitly endorses their continuation for dyslipidaemia. Although they can rarely elevate liver enzymes as an adverse effect, this does not reflect clinically significant hepatotoxicity in the context of pre-existing MAFLD.

7. Complications and monitoring

Progressive fibrosis across approximately 8 years leads to cirrhosis in a significant minority, estimated at 30 to 40% of those with any fibrosis stage at baseline, with T2DM accelerating this trajectory. Key complications are:

Monitoring schedule per ADS guidance:

Any patient presenting with overt signs of advanced liver disease, including ascites, hepatic encephalopathy, oesophageal varices, or evidence of hepatic synthetic dysfunction, warrants immediate referral to a hepatologist.

Practise this in Lucan

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.