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Lean NAFLD can range from 7% to 10% in the United States
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In this study, using a representative sample of the U.S. adult population, we have demonstrated the importance of anthropometric assessment on the long-term outcomes of patients with NAFLD. In this context, our results show associations of different combinations of BMI and WC to all-cause, CVD-related, and cancer-related mortality. Our analyses show that individuals with NAFLD with lean BMI and obese WC had an elevated risk of all-cause mortality, which is higher than individuals with NAFLD with other combinations of BMI and WC. Furthermore, the risk of CVD mortality among individuals with NAFLD with lean BMI with obese WC was almost 3 times higher than among individuals with NAFLD with overweight BMI and normal WC. However, the associations of obesity patterns with cancer-related mortality among patients with NAFLD could not be clearly discerned.
Across BMI categories, individuals with obese WC were more likely to have NAFLD than individuals with normal WC (Supporting Table S1).
During an average follow-up of 22.4 years (interquartile range: 18.7-22.4 years), 2,253 (24.1%) individuals died. Among deceased individuals, 41.7% had NAFLD at baseline.
Among individuals with NAFLD with lean BMI, previous CVD (HR 3.02, 95% CI: 1.93-4.72) was the strongest predictor of all-cause mortality, followed by presence of CKD and T2DM. Among individuals with NAFLD with normal WC, previous CVD (HR 2.79, 95% CI: 1.63-4.78), was the strongest independent predictor of all-cause mortality, followed by male gender and low income (Table 4). Among individuals with NAFLD with non-lean BMI, active smoking (HR 1.68, 95% CI: 1.43-1.99) and previous CVD (HR 1.66, 95% CI: 1.38-1.99) were the strongest predictors of all-cause mortality, followed by the presence of CKD and T2DM. For individuals with NAFLD with obese WC, the predictors of all-cause mortality were the same as those among individuals with NAFLD with non-lean BMI (Table 4).
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.
Although NAFLD is observed predominantly in persons with obesity and/or type 2 diabetes mellitus (T2DM), an estimated 7%-20% of individuals with NAFLD have lean body habitus.
Although similar NASH pathogenesis may be observed in lean patients with NAFLD, rates of disease progression, associated conditions, and diagnostic and management approaches differ for lean vs nonlean patients with NAFLD. There is a major unmet need to provide clear guidance to clinicians regarding the evaluation and management of NAFLD among lean patients.
there is a lack of awareness that NAFLD occurs in lean individuals, especially in those who have diabetes.
The authors suggest that lean patients with NAFLD follow lifestyle interventions, such as exercise, diet modification, and avoidance of fructose- and sugar-sweetened drinks, to achieve weight loss of 3%-5%.
screening should be considered for individuals older than 40 years with type 2 diabetes.
they write that the condition should be considered in lean individuals with metabolic diseases, such as type 2 diabetes, dyslipidemia, and hypertension, as well as elevated values on liver biochemical tests or incidentally noted hepatic steatosis.
After other causes of liver diseases are ruled out, the authors note that clinicians should consider liver biopsy as the reference test if uncertainties remain about liver injury causes and/or liver fibrosis staging.
Lean NAFLD is generally defined by the presence of NAFLD in an individual who does not have an overweight or obese BMI. For adults, the Centers for Disease Control and Prevention and the World Health Organization define a normal range BMI to be between 18.5 and 24.9 kg/m2; BMI of 25-29.9 kg/m2 is considered overweight and BMI of 30-34.9 kg/m2 is grade 1 obesity.
The World Health Organization recommends a lower BMI cutoff for overweight and obesity (BMI 23-27.5 kg/m2 for overweight and BMI >27.5 kg/m2 for obesity) for those of Asian ancestry, recognizing that different populations may experience metabolic risk at a lower BMI.
We suggest using the term lean NAFLD when discussing NAFLD in the setting of a normal range BMI, while considering race-based cutoffs. Although the terms nonobese NAFLD and lean NAFLD are sometimes used interchangeably, this review will focus on lean patients, as defined by normal BMI. Recent findings from the Global NAFLD/NASH Registry revealed that approximately 6.8% of patients with confirmed NASH have lean body habitus and, relative to overweight/obese patients, this cohort appeared to be older, more often Asian, and had fewer components of the metabolic syndrome, while retaining a similar risk for advanced liver fibrosis.
Data from the National Health and Nutrition Epidemiology Survey III epidemiology survey revealed that 10.8% of lean individuals had evidence of NAFLD and were characterized as more likely to be older and were more frequently men.
AGA Clinical Practice Update: Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Lean Individuals: Expert Review
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.
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Mortality of NAFLD According to the Body Composition and Presence of Metabolic Abnormalities
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).
Across BMI categories, individuals with obese WC were more likely to have NAFLD than individuals with normal WC (Supporting Table S1). Logistic regression analyses were performed to assess the association between NAFLD and BMI/WC combinations (Supporting Table S4). Even after multivariable adjustments, compared to patients with lean BMI and normal WC, individuals with obese WC in each BMI category were at increased risk of NAFLD. The higher risk of NAFLD was significant only among individuals with obese BMI-obese WC (odds ratio 4.08, 95% CI: 2.17-7.67). In the whole study cohort, the prevalence of NAFLD with no metabolic syndrome component was 3.26% (95% CI: 2.62 to 3.90%), with most of these subjects having lean BMI (79.2%) (Fig. 1).
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.
https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep4.1534
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