Metabolic and Anthropometric Determinants of Liver Disease – A Study in Population-based Cohorts

Abstract

Background: The incidence and prevalence of chronic liver disease are increasing, primarily due to harmful alcohol consumption and the growing prevalence of metabolic risk factors such as obesity and diabetes. To reduce morbidity and mortality from liver disease, it is important to identify individuals at risk of developing complications. This thesis aimed to evaluate the association between cardiometabolic risk factors and the development of elevated liver function tests and manifest liver disease. Methods: For that purpose, data were obtained from prospective, population-based cohort studies conducted in Gothenburg. These studies were initiated in the 1960s and aimed to examine the risk of cardiovascular disease in middle-aged men and women. Various cardiometabolic risk factors were evaluated, and participants underwent periodic follow-up examinations. Clinical diagnoses were obtained from patient and cause-of-death registries. Results: In men, a high body mass index (BMI) and high triglyceride levels were associated with the development of liver cirrhosis. In women, however, a higher waist-to-hip ratio was associated with incident cirrhosis. Higher insulin levels were associated with elevated liver function tests in both cross-sectional and longitudinal analyses. Higher coffee intake and greater physical activity were associated with a lower risk of abnormal liver function test results. Insulin levels were also associated with an increased risk of developing liver disease and cirrhosis. The combination of elevated insulin levels and harmful alcohol consumption was associated with a further increase in risk. Conclusion: The association of insulin levels and anthropometric measures of adiposity with the development of liver disease and cirrhosis over a follow-up period of more than 20 years may suggest a causal relationship. The inclusion of insulin levels in predictive models to identify individuals at risk of liver disease in the general population should be considered. Overweight, physical inactivity, and other lifestyle factors can be modified and could potentially mitigate the risk of morbidity and mortality from liver disease.