Determinants of severe liver disease in obese subjects: the leading role of central obesity

Background and aims: The obesity epidemic is closely associated with the rising prevalence and severity of nonalcoholic fatty liver disease (NAFLD): obesity has been linked not only with simple steatosis, but also with advanced liver disease, i.e. nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis and hepatocellular carcinoma (HCC). A great amount of evidence on the role of genetics in NAFLD/NASH has been produced during the last 10-15 years by candidate gene and, mainly, genome-wide association studies (GWAS). Many polymorphisms have been proposed, a few of which have already acquired a recognized role in the physiopathology of NAFLD. The reliance on measurements of body mass index (BMI) alone has proven inadequate to help clinicians assess and manage severe liver disease in their obese patients. The waist circumference (WC) revealed to be a simple method to assess abdominal adiposity, easy to standardize and to be clinically applied, and is strongly associated with severe liver disease (SLD) with or without adjustment for BMI. Methods: The UK biobank contains data on 502.536 persons. After adoption of exclusion criteria we selected a population of 330.046 persons, from these we identified the obese population (80.224). Cox regression was performed to estimate the risk of severe liver disease and to examine risk factors in patients with obesity. Results: Risk for severe liver disease was increased in patients with obesity compared to general population. BMI alone is not sufficient, waist circumference is a simple measure of abdominal adiposity, easy to standardize and to be clinically applied. For any given BMI the variation in waist circumference is considerable and in any given BMI category, adults with higher waist circumference values are at increased risk of severe liver disease compared with those with a lower waist circumference. Conclusions: Combination of BMI and WC can identify the phenotype of obesity at highest risk to develop SLD, far better than either measure alone. WC should be routinely measured in clinical practice, as it can provide additional information to guide patient management.