JHEP Rep. 2026 Feb 19:101787. doi: 10.1016/j.jhepr.2026.101787. Online ahead of print.
ABSTRACT
BACKGROUND & AIMS: Weight loss is the cornerstone of treatment for metabolic dysfunction associated steatotic liver disease (MASLD). This pilot study compared the efficacy and safety of a very low energy ketogenic diet (VLED) versus a Mediterranean diet (MD) in improving hepatic steatosis and liver histology in individuals with overweight or obesity and MASLD.
METHODS: We conducted a pilot randomised controlled trial in adults with histologically confirmed MASLD and BMI 27-35 kg/m2. Participants were assigned to either a 12-week VLED (3151 kJ/day) or MD program (8950 kJ/day) and monitored for 24 weeks. The VLED group received low-dose semaglutide (0.5 mg/weekly) from week 13 for weight maintenance. Primary outcome was change in hepatic steatosis by MRI liver-fat-fraction (MRI-LFF) at 12 weeks. Secondary outcomes included total body weight loss (TBWL) and change in liver histology over 24 weeks.
RESULTS: The VLED group (n=14) achieved significantly greater reduction in MRI-LFF (-77% relative reduction (IQR 51, 88)) compared to the MD group (n=11, -14% (IQR 0, 30), p<0.01). The VLED also produced TBWL at week 12 (-13% (IQR -17, -9) vs -4% (-4.4, -0.2), p<0.01). At 24 weeks, the VLED/semaglutide group maintained a -14% TBWL (IQR -17,-10) from baseline vs -3% TBWL (IQR -4, 0) in the MD. Liver histology improved in both groups, with greater improvements in the VLED group (NAFLD activity score reduction VLED: -2 (IQR -3.5, -2) vs MD: -1 (IQR -1, -1), p<0.01).
CONCLUSIONS: The very low energy diet resulted in significantly greater reduction in hepatic steatosis and weight loss compared to Mediterranean diet. The very low energy diet is widely available, easily accessible and should be more commonly considered for MASLD patients with overweight/obesity. Clinical trial registration www.anzctr.org.au trial ID: ACTRN12623000756628 IMPACT AND IMPLICATIONS: This pilot randomised control trial provides the first direct comparison between a ketogenic Very Low Energy Diet (VLED) and a Mediterranean diet (MD) for MASLD treatment, demonstrating superior outcomes with the VLED including 77% vs 14% hepatic steatosis reduction and 13% vs 4% weight loss. The growing burden of people who are overweight and obese with early-stage MASLD means that effective dietary weight loss interventions with proven hepatic and metabolic benefits are urgently required. The VLED’s accessibility, effectiveness and ease of implementation in clinical practice suggest it should be a more widely considered first-line therapy for MASLD patients with overweight or obesity.
PMID:41831607 | DOI:10.1016/j.jhepr.2026.101787
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