High BMI in late adolescence linked to severe liver disease, HCC risks
Adolescent males with a high body mass index (BMI) appear to be at a greater risk of severe liver disease including hepatocellular carcinoma (HCC), and this risk is more pronounced in men who develop type 2 diabetes mellitus (T2DM), according to a population-based cohort study.
“It is likely that the increased prevalence of overweight and obesity will lead to an increase in the total number of cases with severe liver disease in the future, including an increasing incidence of HCC,” researchers said. The present data may thus have important implications for public health decision-making.
In a cohort of more than 1.2 million Swedish men (n=1,256,461) aged 17 to 19 years who underwent conscription into military service between 1969 and 1996, 5,281 cases of severe liver disease including 251 cases of HCC occurred during a follow-up of more than 34 million person-years. [Gut 2017 doi: 10.1136/gutjnl-2016-313622]
Cox regression analysis found young adult males with a higher BMI to have an elevated risk of severe liver disease compared with those who had normal weight (overweight: hazard ratio [HR], 1.49; 95 percent CI, 1.35 to 1.64; obesity: HR, 2.17; 1.82 to 2.59). Development of T2DM further increased the said risk in men across all BMI categories. For example, men with obesity and T2DM were more likely to develop severe liver disease (HR, 3.28; 2.27 to 4.74) compared with those who were obese but free of T2DM (HR, 1.72; 1.72 to 2.54).
The mean BMI at conscription was 21.6 kg/m2, with 104,137 men being overweight (BMI 25 to 25 kg/m2; 8.5 percent) and 19,671 being obese (BMI ≥30 kg/m2; 1.6 percent). Data on new events of severe liver disease and T2DM during follow-up were collected by using record linkage to population-based registers.
Researchers noted that the risk of future severe liver disease remained elevated in a sensitivity analysis excluding men with diagnoses of any other liver disease or alcohol use disorders (HR, 2.26; 1.78 to 2.76) during follow-up. “[This indicates] that the excess risk is not attributed to reversed causality or development of concurrent liver diseases.”
A common cause of morbidity and mortality globally, liver diseases including chronic viral hepatitis B and C, alcoholic liver disease and nonalcoholic liver disease (NAFLD) can all lead to end-stage liver disease. NAFLD particularly shows a strong association with overweight and obesity via impaired insulin signalling and proinflammatory properties, among other mechanisms. [Lancet 2015;386:2145–91; J Hepatol 2006;44:217–31; JAMA 2015;313:2263–73; Mol Nutr Food Res 2014;58:147–171]
Given that the risk of severe liver disease associated with a high BMI seems to be present in young adult males and is highly accentuated by development of T2DM, a targeted intervention against overweight and obesity at an early age is warranted, researchers pointed out.
Young adult males as well as men with T2DM, regardless of their BMI in young adulthood or midlife, should be informed about an increased risk of severe liver disease and screened for the possible presence of manifest liver disease to reduce the future burden of severe liver disease on individuals and society, they added.
Noting the limitations of the study, researchers acknowledged that they were unable to ascertain the changes in BMI during the follow-up period, as well as to study the association between BMI and subsequent liver disease in women. In addition, there was a lack of data on baseline alcohol consumption or smoking, and the limited HCC cases in the cohort prevented stratification on T2DM status.