Chronic Liver Disease and Metabolic Comorbidities in Healthy Young Males Followed for 65 Years: The Manitoba Follow-up Study

Abstract

The prevalence of chronic liver disease (CLD) is largely derived from cross-sectional epidemiologic surveys. The goal of this long-term, prospective study was to document the lifetime risk of developing chronic liver disease and determine the impact of common metabolic conditions associated with metabolic syndrome (MetS) on the development and outcomes of CLD. 3,983 air force men were enrolled in the Manitoba Follow-up Study in 1948. The comprehensive database on results of routine physicals and health encounters was examined for evidence of CLD and MetS. The joint relationship between CLD and components of MetS on mortality was examined using Cox proportional hazard model. In 65 follow-up years, 5.2% of men developed CLD and 6.4% MetS. Hypertension was the strongest predictor of CLD (HR 2.958, 95% CI - 2.065 to 4.236, p < .0001), followed by insulin resistance /diabetes mellitus (IR/DM) (2.008, 95% CI - 1.332 to 3.027, p = .0009) and obesity (1.958, 95% CI - 1.419 to 2.703, p < .0001). Relative to men without MetS comorbidities, an increasing gradient of risk for CLD was apparent with increasing numbers of MetS components; the HR of 3.67, 5.97 and 14.3 for IR/DM, IR/DM+ one component, and IR/DM+ two or more components respectively. The relative risk of mortality in men with vs. without CLD was 3.33 (95% CI - 2.83 to 3.91, p < .0001) and 1.505 (95% CI - 1.31 to 1.73, p < .0001) in men with vs. without MetS. CLD and MetS independently increase the relative risk of mortality; the magnitude of the effect is greater in CLD.