Introduction: Metabolic-dysfunction Associated Steatotic Liver Disease (MASLD) is a common cause of chronic liver disease. This review assessed the efficacy of a Low-Calorie Diet (LCD) on liver health and body weight in people living with MASLD and obesity. Methods: The study was registered with PROSPERO (CRD42021296501), and a literature search was conducted using multiple databases. The key inclusion criteria were randomised controlled trials or cohort studies, obesity/overweight and MASLD. Two authors screened abstracts, reviewed full texts and performed data extraction and quality assessment. The primary outcome was the change in the serum ALT, and secondary outcomes included the changes in the serum AST, intrahepatic lipid content (IHL), quantified non-invasively via MRI/MRS, and body weight. Results: Fifteen studies were included. The LCD reduced body weight by 9.1 kg versus the control (95%CI: −12.4, −5.8) but not serum ALT (−5.9 IU/L, −13.9, 2.0). Total Dietary Replacement (TDR) reduced IHL by −9.1% vs. the control (−15.6%, −2.6%). The Mediterranean-LCD for ≥12 months reduced ALT (−4.1 IU/L, −7.6, −0.5) and for 24 months reduced liver stiffness versus other LCDs. The Green-Mediterranean-LCD reduced IHL, independent of body weight. Limited studies assessed those of Black or Asian ethnicity, and there was heterogeneity in the methods assessing the liver fat content and fibrosis. Conclusions: In people with MASLD and obesity, an LCD intervention reduces IHL and body weight. Trials should focus on the recruitment of Black and Asian ethnicity participants.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with multiple extrahepatic complications, but its relationship with peripheral neuropathy, even without co-existing type 2 diabetes (T2D), remains poorly understood. Furthermore, to what extent addressing liver and metabolic health would be associated with improvements in small nerve fibre morphology (that mediate neuropathy) is unknown. We investigated the relationship between liver health and small nerve fibre morphology in adults with MASLD before and after diet-induced weight loss and improvements in liver health. Methods: Adults with MASLD (n = 12) and controls without MASLD or T2D (n = 16) underwent anthropometry, biochemistry, transient elastography (TE) and corneal confocal microscopy (CCM). Participants with MASLD then completed a 12-week low-calorie diet (LCD; Counterweight-Plus, ~850 kcal/day) with repeat assessments including multi-organ magnetic resonance imaging (MRI). TE quantified hepatic steatosis (controlled attenuation parameter, CAP), while MRI measured hepatic and pancreatic fat (proton density fat fraction, PDFF) and fibroinflammation (iron-corrected T1, cT1). Neuropathy was assessed using validated questionnaires and CCM-derived corneal nerve fibre density (CNFD), branch density (CNBD) and fibre length (CNFL). The primary outcome measure was change in liver PDFF. Associations between hepatic and neuropathy measures were assessed using correlation and multivariable linear regression. Results: Compared with controls, MASLD participants had higher liver fat and metabolic dysfunction, with reduced CNFD (25.7 vs. 28.4 fibres/mm², p = 0.03) and CNFL (14.1 vs. 17.1 mm/mm², p = 0.02). In multivariable regression, TE-derived CAP was independently associated with CNFD (β −0.03 (95% CI −0.06, −0.01), p < 0.05), while total cholesterol was associated with CNFL (β −1.54 (95% CI −2.81, −0.27), p < 0.02). After LCD, participants lost 12.5 kg with reductions in metabolic syndrome components (p = 0.04) and liver fat (ΔPDFF −5.0%, p = 0.03). Neuropathic symptoms improved and CNFD increased (+1.87 fibres/mm², p = 0.05). Reduction in liver fat correlated with increased CNFL (r = −0.63, p = 0.03), while change in hepatic fibroinflammation (ΔcT1) correlated with neuropathy disability (r = 0.62, p = 0.04) and small-fibre symptom scores (r = 0.47, p = 0.05). Conclusions: These exploratory findings suggest that MASLD, even without T2D, may be associated with small nerve fibre abnormalities and neuropathic symptoms. Diet-induced weight loss improved liver, metabolic and neural health in parallel. Larger prospective confirmatory studies are required to more precisely establish this relationship both at baseline and with interventions.