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Lean Fatty Liver Disease, NAFLD & Visceral Adiposity
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"The risk of mortality in NAFLD can be affected by the presence of visceral obesity, especially in the lean BMI group."
AGA Clinical Practice Update: Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Lean Individuals: Expert Review
https://www.natap.org/2022/HIV/081822_06.htm
Description
Nonalcoholic fatty liver disease (NAFLD) is well recognized as a leading etiology for chronic liver disease, affecting >25% of the US and global populations. Up to 1 in 4 individuals with NAFLD have nonalcoholic steatohepatitis, which is associated with significant morbidity and mortality due to complications of liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Although NAFLD is observed predominantly in persons with obesity and/or type 2 diabetes mellitus, an estimated 7%-20% of individuals with NAFLD have lean body habitus. Limited guidance is available to clinicians on appropriate clinical evaluation in lean individuals with NAFLD, such as for inherited/genetic disorders, lipodystrophy, drug-induced NAFLD, and inflammatory disorders. Emerging data now provide more robust evidence to define the epidemiology, natural history, prognosis, and mortality of lean individuals with NAFLD. Multiple studies have found that NAFLD among lean individuals is associated with increased cardiovascular, liver, and all-cause mortality relative to those without NAFLD. This American Gastroenterological Association Clinical Practice Update provides Best Practice Advice to assist clinicians in evidence-based approaches to the diagnosis, staging, and management of NAFLD in lean individuals.
Individuals with NAFLD who were lean by BMI but obese by WC had higher risk of all-cause mortality. Individuals with NAFLD with normal BMI but obese WC had a higher risk of cardiovascular mortality (hazard ratio 2.63 [95% CI: 1.15-6.01]) as compared with overweight (by BMI) NAFLD with normal WC. Conclusion: The risk of mortality in NAFLD can be affected by the presence of visceral obesity, especially in the lean BMI group. These data have important management implications for patients with NAFLD.
As noted, components of metabolic syndrome (visceral obesity, insulin resistance, type 2 diabetes [T2DM], dyslipidemia, and HTN) not only increase the risk of NAFLD but also lead to increased risk for developing nonalcoholic steatohepatitis (NASH), advanced hepatic fibrosis, and experiencing liver-related mortality.(7, 8) Although NAFLD is strongly associated with obesity and metabolic syndrome, a portion of patients with NAFLD are not obese. The prevalence of lean NAFLD can range from 7% to 10% in the United States and up to 19% in some Asian countries.(9-12) The definition of lean NAFLD can vary based on the use of body mass index (BMI) or waist circumference (WC) thresholds.(9, 13) It has also been suggested that BMI reflects the total body fat and may not accurately reflect the presence of visceral obesity, which is more relevant for patients with NAFLD.(14) Despite the importance of visceral obesity according to waist circumference in NAFLD, most long-term studies could not provide consistent WC data. Nevertheless, the importance of visceral obesity as a predictor of long-term outcomes has been established.(15) In this context, it is highly plausible that assessment of visceral adiposity can be an important predictor of long-term outcome among those with NAFLD, even those who are considered lean by BMI classification. Therefore, the aim of the current study was to determine the effect of different combinations of abdominal adiposity (WC) and overall adiposity (BMI) on the prevalence and mortality of NAFLD in the United States.
Of the 9,341 individuals (47.9% male; 76.8% non-Hispanic white; 9.9% non-Hispanic black; 5.4% Hispanic; mean [SEM] age, 43.6 [0.4] years), NAFLD was present in 3,140 (33.6%), of whom 25.4% were lean, 33.2% were overweight, and 41.4% were obese as per their BMI, whereas of the 6,201 (66.4%) individuals without NAFLD, 50.7% were lean, 33.6% were overweight, and 15.7% were obese.
Individuals with lean BMI-obese WC accounted for 2.1% of the study cohort (1.7% of individuals with NAFLD vs. 2.2% of individuals without NAFLD, P = 0.168) and 4.9% of individuals with lean BMI (6.9% of NAFLD individuals with lean BMI vs. 4.4% of individuals without NAFLD with lean BMI, P = 0.028). Across BMI categories, individuals with obese WC were more likely to be older, female, have low income, less education, higher proportion of sedentary physical activity, more components of metabolic syndrome, higher CVD risk, and higher CKD rates (Supporting Table S1). These associations in the full sample were preserved among both individuals with NAFLD and individuals without NAFLD, but the differences by WC in each BMI category were more pronounced among individuals with NAFLD (Supporting Tables S2 and S3).
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