Metabolic dysfunction-associated liver disease in Australia: epidemiology and therapeutic applications of medical weight management
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2026
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Melbourne Authors
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Medicine (St Vincent's)
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PhD thesis
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Open Access
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© 2026 Ann Farrell
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of liver disease worldwide, with its rise mirroring the obesity epidemic. It represents a growing cause of morbidity and mortality, yet estimates of disease prevalence within Australia, and identification of those at risk of developing complications, remain lacking. Furthermore, therapeutic options are limited, with weight loss fundamental to management but difficult to achieve and maintain. This thesis explores the epidemiology of MASLD in Australia and investigates whether medical weight management approaches developed for obesity are effective, and whether they can be safely and effectively adapted for the treatment of MASLD.
To provide estimates of MASLD in Australia, a cross-sectional analysis of a large nationwide cohort (n=4,747) study was performed, and found elevated ALT in 13%, and MASLD in 37%. 61% of those with MASLD also had an elevated BARD score, suggesting that a large proportion of Australian adults with MASLD may warrant further investigation for risk of advanced fibrosis.
Real-world weight loss outcomes were examined in a retrospective cohort study (n=411) from a publicly-funded specialist weight management service. Using a very low energy diet (VLED) based approach, 50% achieved clinically significant weight loss (>= 10% total body weight loss (TBWL)) at 12 months, with a mean 10.5% TBWL. However, clinic retention was challenging, with 29% patient retention at 12 months. Metabolic phenotype (specifically presence of MASLD and insulin resistance) and early treatment response were found to be predictors of weight loss outcomes at 12 months.
The DARWIN randomised pilot study compared a 12-week ketogenic VLED to a Mediterranean diet (MD). The VLED achieved significantly greater hepatic steatosis reduction than a Mediterranean diet (77% vs 14% relative reduction), and resulted in greater weight loss (13% TBWL vs 4%). Low-dose semaglutide (0.5mg weekly) maintained these benefits to week 24 at which point superior histological improvement was also demonstrated in the VLED group. Extension follow-up to week 48 (24 weeks after cessation of all active intervention) found that the VLED group maintained clinically significant improvements in weight (10% TBWL) and hepatic steatosis (55% relative reduction), despite some weight regain and modest liver fat increase.
Collectively, these findings establish the substantial burden of MASLD in Australia, and demonstrated that the VLED-based medical weight management approach achieves clinically meaningful hepatic and metabolic benefits in MASLD. These results support the broader use of VLED-based programs as effective, accessible and a pragmatic first-line treatment for MASLD, but also highlight the need for improved engagement strategies in publicly-funded weight management services.
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Keywords
Metabolic dysfunction-associated steatotic liver disease, Nonalcoholic fatty liver disease, Obesity, Mediterranean diet, Very low energy diet, Weight loss, Randomised control trial, Dietary intervention, Epidemiology