NON-ALCOHOLIC fatty liver disease (NAFLD) is a leading chronic liver condition globally, primarily characterised by hepatic steatosis, excluding significant alcohol consumption or secondary liver damage. Recently, the definition of NAFLD has evolved to include metabolic dysfunction-associated steatotic liver disease (MASLD), reflecting its link to systemic metabolic disorders. MASLD affects over 25% of adults, with a higher prevalence in individuals with diabetes, and is closely associated with cardiometabolic risks, particularly in low-income nations. Enhanced surveillance and cost-effective prognostic measures are critical to addressing its rising burden.
The Haemoglobin Glycation Index (HGI), introduced in 2002, measures an individual’s glycation capacity by quantifying the difference between observed HbA1c and predicted values based on fasting plasma glucose. HGI has been linked to macrovascular complications and mortality in conditions like diabetes and hypertension, yet its role in MASLD remains underexplored. A recent study of 8,257 MASLD patients revealed a U-shaped relationship between HGI and both all-cause and cardiovascular mortality. Lower HGI levels correlated with decreased mortality, while higher levels were associated with increased risks, suggesting its potential as an independent prognostic marker.
Inflammatory and oxidative processes underpin the connection between high HGI and disease progression. Elevated HGI is associated with increased advanced glycation end-products (AGEs), which trigger inflammation, oxidative stress, and endothelial damage, exacerbating MASLD and cardiovascular risks. Subgroup analysis confirmed consistent U-shaped mortality correlations across diverse populations, though thresholds varied, underscoring the need for personalised management strategies.
The study’s strengths include its large, representative sample and pioneering focus on HGI’s prognostic value in MASLD. However, limitations such as reliance on the NHANES database, lacking advanced imaging data, and its focus on US patients warrant further investigation in global contexts. Future research should compare HGI to traditional non-invasive tests, evaluating its role in diagnosing and managing MASLD across different clinical settings. Despite these constraints, the findings highlight HGI’s potential to inform tailored treatments and improve outcomes for MASLD patients.
Katie Wright, EMJ
Reference
Zhao M et al. Hemoglobin glycation index and mortality risk in metabolic dysfunction-associated steatotic liver disease patients: a novel U-shaped association. Sci Rep. 2025;15(1):1465.
