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Unravelling the enigma: Metabolic associated fatty liver disease (MAFLD) and liver cancer

Keeping up-to-date with the latest terms and acronyms linked with liver cancer can be overwhelming. Here we talk about recognising and treating metabolic associated fatty liver disease (MAFLD) – the updated term for non-alcoholic fatty liver disease.

What is MAFLD?

‘Metabolic associated fatty liver disease (MAFLD)’ is the name given to fatty liver disease that is caused by metabolic dysfunction.1

The term was suggested in 2020 to replace the name ‘non-alcoholic fatty liver disease (NAFLD)’.1 It’s generally felt that MAFLD better reflects the disease process.1

Unlike NAFLD, MAFLD has specific diagnostic criteria.2 MAFLD can also coexist with other liver diseases, including alcoholic liver disease and viral hepatitis.2

Who is at risk of MAFLD?

MALFD affects 25% of Australian adults and many children.2 Anyone with metabolic abnormalities is at risk of developing MAFLD.

With the increasing rates of obesity seen in Australia, it’s unsurprising to discover that the results of a recent modelling study show that rates of MAFLD will increase substantially in the next 10 years.3

How is MAFLD diagnosed?

The change in name to MAFLD was also accompanied by a change in the diagnostic criteria.1

The diagnosis of MAFLD is based on the presence of hepatic steatosis AND:

  • type 2 diabetes mellitus; OR
  • obesity; OR
  • metabolic dysregulation.4

Metabolic dysregulation is defined as the presence of at least two of the following metabolic risk factors.

  • Waist circumference ≥ 102/88 cm in Caucasian men/women or ≥ 90/80 cm in Asian men/women.
  • Blood pressure ≥ 130/85 mmHg (or antihypertensive medication).
  • Plasma triglycerides ≥ 150 mg/dl (or triglyceride-lowering medication).
  • Plasma high-density lipoprotein (HDL) cholesterol < 40 mg/dl for men and < 50 mg/dl for women (or lipid-lowering medication).
  • Pre-diabetes.
  • Homeostasis model assessment of insulin resistance score >2.5.  Plasma high-sensitivity C-reactive protein (CRP) level > 2 mg/L.4

How is MAFLD managed?

The cornerstone of MAFLD management is lifestyle modification. This includes:

  • dietary change;
  • weight loss;
  • structured exercise intervention;
  • diabetes control;
  • quitting smoking; and
  • limiting or stopping alcohol intake.

Treatments to target risk factors such as hypertension and dyslipidaemia are also essential.2

Most patients with MAFLD are able to be successfully managed in primary care.2 However, patients with stage 2–4 fibrosis should be referred to a specialist.2

At least one in 10 people with MAFLD will develop liver fibrosis over time if it’s not adequately treated.2 This in turn can progress to cirrhosis and liver failure or liver cancer.2

How does MAFLD progress to liver cancer?

Once a diagnosis of MAFLD is made, the next step is to assess the stage of fibrosis. Fibrosis is the most important predictor of liver-related morbidity and mortality in patients. Those with cirrhosis have the highest risk.2

The good news is that fibrosis progression in MAFLD is slow. Most patients with MAFLD will die from cardiovascular disease or extrahepatic cancer. However, liver cancer can develop in patients with more advanced fibrosis.2

It’s predicted that in the next 10 years, MAFLD will become the leading cause of liver transplantation in Australia.3 This will occur even if rates of obesity in Australia stabilise.

Note: In this article, the term MAFLD is used even when the terms NASH or NAFLD have been used in the original publication.


1. Gofton C, Upendran Y, Zheng MH, George J. MAFLD: How is it different from NAFLD? Clin Mol Hepatol. Feb 2023;29(Suppl):S17-S31. doi:10.3350/cmh.2022.0367
2. Gofton C, George J. Updates in fatty liver disease: Pathophysiology, diagnosis and management. Aust J Gen Pract. Oct 2021;50(10):702-707. doi:10.31128/AJGP-05-21-5974
3. Adams LA, Roberts SK, Strasser SI, et al. Nonalcoholic fatty liver disease burden:
Australia, 2019-2030. J Gastroenterol Hepatol. Sep 2020;35(9):1628-1635. doi:10.1111/jgh.15009
4. Boccatonda A, Andreetto L, D’Ardes D, et al. From NAFLD to MAFLD: Definition, Pathophysiological Basis and Cardiovascular Implications. Biomedicines. Mar 13

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