Comparison between obese and non-obese nonalcoholic fatty liver disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver conditions that are characterized by excess accumulation of fat in the liver, and is diagnosed after exclusion of significant alcohol intake and other causes of chronic liver disease. In the majority of cases, NAFLD is associated with overnutrition and obesity, although it may be also found in lean or non-obese individuals. It has been estimated that 19.2% of NAFLD patients are lean and 40.8% are non-obese. The proportion of patients with more severe liver disease and the incidence of all-cause mortality, liver-related mortality, and cardiovascular mortality among non-obese and obese NAFLD patients varies across studies and may be confounded by selection bias, underestimation of alcohol intake, and unaccounted weight changes over time. Genetic factors may have a greater effect towards the development of NAFLD in lean or non-obese individuals, but the effect may be less pronounced in the presence of strong environmental factors, such as poor dietary choices and a sedentary lifestyle, as body mass index increases in the obese state. Overall, non-invasive tests, such as the Fibrosis-4 index, NAFLD fibrosis score, and liver stiffness measurement, perform better in lean or non-obese patients compared to obese patients. Lifestyle intervention works in non-obese patients, and less amount of weight loss may be required to achieve similar results compared to obese patients. Pharmacological therapy in non-obese NAFLD patients may require special consideration and a different approach compared to obese patients.

Keywords: Lean; Non-obese; Nonalcoholic fatty liver disease.

Figure 1.

The effect of genetic, environmental, and confounding factors in the severity of liver disease and outcomes of lean or non-obese patients compared with obese NAFLD patients. Genetic factors may have a more pronounced effect towards the development of NAFLD in lean or non-obese individuals, but the effect may appear less pronounced in the presence of strong environmental factors, such as poor dietary choices and a sedentary lifestyle, in the obese state. Selection bias, underestimation of alcohol intake, and unaccounted weight loss over time from poorly controlled diabetes mellitus and/or loss of muscle mass from advanced liver disease are important confounding factors for varying severity of liver disease and outcomes in lean or non-obese NAFLD patients compared to obese NAFLD patients, although genetic factors may play a role. NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; PNPLA3, patatin-like phospholipase domaincontaining- 3; TM6SF2, transmembrane 6 superfamily member 2. +: Relative frequency of the corresponding variable when comparing between lean or non-obese NAFLD and obese NAFLD.