ORF15-06 - The Triglyceride-Glucose Index in Non-Diabetic Adults and Its Association with End Stage Liver Disease: A Nationwide Cohort Study

Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent and underdiagnosed and may lead to liver-related morbidity and mortality. Identifying individuals at risk for progressing to end-stage liver disease (LD) remains challenging. The triglyceride-glucose (TYG) index, a marker of insulin resistance, is a strong predictor of MASLD. We assessed whether elevated TYG index predicts incident end-stage LD in a general population of non-diabetic adults.

Methods: This nationwide retrospective cohort study was based on the electronic medical records data of Clalit health services, Israel. It included adults aged ≥40 years with TYG index measurements during 2005–2020, excluding those with diabetes, glucose/lipid-lowering medications, or chronic liver disease (MASLD not excluded). The primary outcome was incident end-stage LD, including cirrhosis, cirrhosis-related complications, or hepatocellular carcinoma. Associations between sex-stratified TYG quartiles and incident end-stage LD were examined by cox model, adjusting for age, sex, ethnicity, and BMI.

Results: Among 948,317 participants followed for a median of 13.1 years (10,736,020 person-years), 2,165 developed end-stage LD (incidence rate: 20.2 per 100,000 person-years; mean age at diagnosis 56.2±12.6 years). Compared with the lowest quartile, the highest TYG quartile was associated with a 22% increased risk of end-stage LD (adjusted HR 1.22, 95% CI 1.08–1.38), with results consistent across sensitivity analyses. A significant interaction with sex was observed (p for interaction = 0.03), with stronger associations in women (HR 1.37, 95% CI 1.13–1.65) than in men (HR 1.16, 95% CI 0.98–1.37).

Conclusions: Elevated TYG index was associated with end-stage LD risk, with a stronger association observed in women, suggesting possible sex-related differences in fibrosis progression. Further studies are required to assess whether TYG index could contribute to risk stratification among individuals who are not currently being offered screening for liver steatosis.