Lean NAFLD Research Articles

Central Obesity is an Independent Determinant of Advanced Fibrosis in Lean Patients With Nonalcoholic Fatty Liver Disease

BackgroundThe current definition of lean is based on BMI. However, BMI is an imperfect surrogate for adiposity and provides no information on central obesity (CO). Hence, we explored the differences in clinical profile and liver disease severity in lean patients with NAFLD with and without CO. Methods170 lean patients with NAFLD (BMI <23 kg/m2) were divided into two groups depending upon the presence or absence of CO (waist circumference ≥80 cm in females and ≥90 cm in males). Non-invasive assessment of steatosis was done by ultrasound and controlled attenuation parameter (CAP) while fibrosis was assessed with FIB-4 and liver stiffness measurement (LSM). FibroScan-AST (FAST) score was used for non-invasive prediction of NASH with significant fibrosis. ResultsOf 170 patients with lean NAFLD, 96 (56.5%) had CO. Female gender (40.6% vs 17.6%, p=0.001), hypertriglyceridemia (58.3% vs 39.2%, p=0.01) and metabolic syndrome (23.9% vs 4.1%, p<0.001) were more common in CO group. There was a poor correlation between BMI and waist circumference (r=0.24, 95% CI: 0.09-0.38). Grade 2-3 steatosis on ultrasound was significantly more common in CO patients (30% vs 12.3%, p=0.007). CAP [312.5 (289.8-341) dB/m vs 275 (248-305.1) dB/m, p=0.002], FAST score [0.42 (0.15-0.66) vs 0.26 (0.11-0.39), p=0.04], FIB-4 and LSM were higher in those with CO. Advanced fibrosis was more prevalent among CO patients using FIB-4 (19.8% vs 8.1%, p=0.03) and LSM (9.5% vs 0, p=0.04). CO was independently associated with advanced fibrosis after adjusting for BMI and metabolic risk factors (aOR: 3.11 (1.10-8.96), p=0.03). Among these 170 patients, 142 fulfilled MASLD criteria. CO was also an independent risk factor for advanced fibrosis in MASLD (3.32 (1.23-8.5), p=0.02). ConclusionLean patients with NAFLD or MASLD and CO have more severe liver disease compared to those without CO.

Dietary inflammatory impact on NAFLD development in obese vs. lean individuals: an analysis based on NHANES 2003–2018

BackgroundNon-alcoholic fatty liver disease (NAFLD), often linked with obesity, can also affect individuals with normal weight, a condition known as “lean NAFLD”, imposing comparable burdens and adverse effects. However, the impact of diet on lean NAFLD remains underexplored. The objective of this study is to investigate the correlation between the Dietary Inflammatory Index (DII) and NAFLD among Americans, stratified by waist-to-height ratio (WHtR) and body mass index (BMI).MethodsFive thousand one hundred fifty-two participants from the National Health and Nutrition Examination Survey (NHANES) 2003–2018 were comprised in the final analysis. NAFLD and advanced liver fibrosis were diagnosed by serological markers. Lean and abdominal lean individuals were identified using BMI and WHtR, separately. DII was determined by assigning scores to 28 distinct food parameters based on their inflammatory potential, obtained from the NAHNES website. Differences across DII quartiles were evaluated using the Kruskal-Wallis H Test, Chi-Square Test along with One-Way ANOVA. The correlation between DII and NAFLD was determined by multiple regression models and subgroup analyses.ResultsAmong the 5152 subjects, 2503 were diagnosed with NAFLD, including 86 cases of lean NAFLD and 8 cases of abdominal lean NAFLD. DII was positively linked with NAFLD (Odds Ratio (OR) = 1.81 [1.48–2.21], P < 0.001) and advanced liver fibrosis (OR = 1.46 [1.02–2.07], P = 0.037). Further analysis revealed that this association was primarily observed in obese or abdominal obese participants (In BMI ≥ 25.00 kg/m^2, OR = 1.56 [1.23–1.98], P < 0.001. In WHtR> 0.50, OR = 1.48 [1.23–1.79], P < 0.001.), rather than their lean counterparts. Subgroup analyses indicated that female individuals, without a diagnosis of hypertension or diabetes appeared to be more sensitive to the rise in DII.ConclusionsOur data demonstrated a significant positive correlation between DII and NAFLD in the general population. However, the impact of a pro-inflammatory diet was less prominent in lean individuals compared to obese ones.

New aspects characterizing non-obese NAFLD by the analysis of the intestinal flora and metabolites using a mouse model.

Patients and healthcare professionals have little awareness and understanding of NAFLD in non-obese individuals. In fact, about 40% of people with NAFLD worldwide are non-obese, and nearly one-fifth are lean. Lean NAFLD unfortunately may be unnoticed for years and remains undetected until hepatic damage is advanced and the prognosis is compromised. This study focused on the lean NAFLD, screened therapeutic agents, and biomarkers for the prognosis and diagnosis using MCD-induced male C57BL/6J mice. The metabolites tyramine glucuronide, 9,12,13-TriHOME, and pantetheine 4'-phosphate, together with the predominant flora including g_Tuzzerella, s_Bifidobacterium pseudolongum, and s_Faecalibaculum rodentium, were specific in non-obese NAFLD mice and might be used as targets for non-obese NAFLD drug exploration. This study is particularly significant for non-obese NAFLDs that need to be more actively noticed and vigilant.

Reply: Concerns regarding the use of Fatty Liver Index in studies of lean NAFLD.

Reply: Concerns regarding the use of Fatty Liver Index in studies of lean NAFLD.

Letter to the Editor: Concerns regarding the use of fatty liver index in studies of lean NAFLD.

Letter to the Editor: Concerns regarding the use of fatty liver index in studies of lean NAFLD.

Risk Stratification of Advanced Fibrosis in Patients With Human Immunodeficiency Virus and Hepatic Steatosis Using the Fibrosis-4, Nonalcoholic Fatty Liver Disease Fibrosis, and BARD Scores.

Nonalcoholic fatty liver disease (NAFLD) and subsequent progression to fibrosis is increasingly prevalent in people with HIV (PWH). We used noninvasive methods to stratify risk and identify associated factors of advanced fibrosis in PWH with NAFLD. We conducted a retrospective study of PWH in our clinic from 2005 to 2022. We used liver imaging or biopsy reports to identify cases of hepatic steatosis after excluding specified etiologies. We used the Fibrosis-4 (FIB-4), NAFLD Fibrosis (NFS), and body mass index, aspartate transaminase/alanine transaminase ratio, and diabetes score scores to stratify fibrosis. We used logistic regression to identify factors associated with advanced fibrosis. Among 3959 PWH in care, 1201 had available imaging or liver biopsies. After exclusions, 114 of 783 PWH had evidence of hepatic steatosis (14.6%). Most were male (71.1%), with a median age of 47 years, and median body mass index of 30.1 kg/m2. Approximately 24% had lean NAFLD (ie, body mass index < 25 kg/m2). Based on the FIB-4 and NFS, 34 (29.8%) and 36 (31.6%) had advanced fibrosis, whereas 1 in 4 had low risk of fibrosis based on FIB-4, NFS, and BARD scores. In adjusted analysis using FIB-4, advanced fibrosis was associated with age > 45 years (adjusted odds ratio, 6.29; 95% confidence interval, 1.93-20.50) and hypoalbuminemia (adjusted odds ratio, 9.45; 95% confidence interval, 2.45-32.52) in addition to elevated transaminases and thrombocytopenia, whereas using the NFS did not identify associations with advanced fibrosis. We found 14.6% of PWH had NAFLD, with 1 in 3 having advanced fibrosis. Our study provides practical insights into fibrosis risk stratification in HIV primary care settings.

S1539 Central Obesity Is Independently Associated With Advanced Fibrosis in Lean NAFLD

S1539 Central Obesity Is Independently Associated With Advanced Fibrosis in Lean NAFLD

S1432 Assessing Liver Transplant Outcomes in Lean vs Non-Lean NAFLD Patients

S1432 Assessing Liver Transplant Outcomes in Lean vs Non-Lean NAFLD Patients

Correlation between FIB- 4 Score and Liver Biopsy in Lean Egyptian Patients with Non-Alcoholic Fatty Liver Disease

Background Nonalcoholic fatty liver disease (NAFLD) is a worldwide epidemic with global prevalence estimated at 25%. Although NAFLD is usually associated with obesity, patients who are not obese can also present with NAFLD; this is known as “lean NAFLD.” Lean NAFLD is defined as NAFLD that develops in patients with a body mass index (BMI) &amp;lt;25 kg/m2. The prevalence of lean NAFLD varies from 7% in the United States to as high as 19% in Asia. Unfortunately, being lean (not overweight) does not necessarily lead to better health. A recent large meta analysis by Sookoian and Pirola of almost 2,000 patients with NAFLD who were lean demonstrated that patients with NAFLD who are lean or obese share a common altered metabolic and cardiovascular profile, which in turn may lead to collective risk for adverse cardiometabolic outcomes, including diabetes and ischemic heart disease. Indeed, atherosclerotic cardiovascular disease remains the most common cause of death in all weight categories. NAFLD comprises a wide pathological spectrum ranging from simple steatosis to steatohepatitis (NASH) with variable degrees of fibrosis and cirrhosis. The strongest predictor of fibrosis progression in NAFLD is the presence of steatohepatitis (Trenell et al., 2017). The diagnosis of NASH mandates a liver biopsy, yet the risks and costs associated with a liver biopsy preclude its widespread use. Pain is almost universal, and there is bleeding in approximately 1 in 500 liver biopsies and death in 1 in 10,000, dissuading patients from undergoing the procedure. Moreover, the disproportionately increasing incidence of NAFLD calls for practical and costeffective care and monitoring (Estes et al.,2018). Methods for non-invasive assessment of fatty liver disease and studies in the field have exponentially appeared over the last three decades, offering a safe and more non-invasive practical approach to hepatic fibrosis and steatosis quantification (Castera et al.,2019). Aim of the study Determining the correlation of Fib-4 score and NAFL diagnosed by liver biopsy in lean Egyptian patients Patients and Methods This study had been carried out on 30 subjects, age range above 18 years old, with BMI (18.5-24.9) selected from transplantation donor outpatient clinic at Ain shams university specialized hospital in Cairo after informed consent were taken from the patients Subjects were divided as follow: •Group I: 15 adult patients with NAFLD. •Group II: 15 adult patient with normal liver biopsy who will be educated about lean NAFLD and how to prevent it. Results In the current study we concluded that FIB-4 score is not significant with degree of fibrosis while it has a negative correlation with steatosis assessed by biopsy. FIB-4 failed to discriminate advanced fibrosis. Conversely, it showed acceptable diagnostic performances in exclusion of advanced fibrosis in overweight, obese, and severely obese patients in other studies. (FATIH et al., 2020) Conclusion FIB-4 failed to discriminate advanced fibrosis. Conversely, it showed acceptable diagnostic performances in exclusion of advanced fibrosis in overweight, obese, and severely obese patients. FIB-4 was able to exclude advanced fibrosis with the highest diagnostic accuracy in the subgroup of overweight patients. so fib 4 score can’t be used as a marker of fibrosis nor steatosis in lean NAFLD patients but more like a prognostic value.

OR13-03-23 The Effect of Genetic Polymorphisms in PIK3CG Gene on the Risk of Lean NAFLD in the Elderly: Mediation by Total Cholesterol

OR13-03-23 The Effect of Genetic Polymorphisms in PIK3CG Gene on the Risk of Lean NAFLD in the Elderly: Mediation by Total Cholesterol

Association between the lean nonalcoholic fatty liver disease and risk of incident type 2 diabetes in a healthy population of Northwest China: a retrospective cohort study with a 2-year follow-up period.

We aimed to explore the metabolic features of lean nonalcoholic fatty liver disease (Lean-NAFLD) and its association with the risk of incident type 2 diabetes in young and middle-aged people. We conducted a retrospective cohort study of 3001 participants who were enrolled in a health check-up program from January 2018 to December 2020 in the Health Management Center of Karamay People's Hospital. The age, sex, height, weight, body mass index (BMI), blood pressure, waist circumference (WC), fasting plasma glucose (FPG), lipid profiles, serum uric acid and alanine aminotransferase (ALT) of the subjects were collected. The cutoff point of BMI for lean nonalcoholic fatty liver disease is <25 kg/m2. A COX proportional hazard regression model was used to analyze the risk ratio of lean nonalcoholic fatty liver disease to type 2 diabetes mellitus. Lean NAFLD participants had many metabolic abnormalities, such as overweight and obesity with nonalcoholic fatty liver disease. Compared with lean participants without nonalcoholic fatty liver disease, the fully adjusted hazard ratio (HR) for lean participants with nonalcoholic fatty liver disease was 3.83 (95% CI 2.02-7.24, p<0.01). In the normal waist circumference group (man<90cm, woman<80 cm), compared with lean participants without NAFLD, the adjusted hazard ratios (HRs) of incident type 2 diabetes for lean participants with NAFLD and overweight or obese participants with NAFLD were 1.93 (95% CI 0.70-5.35, p>0.05) and 4.20 (95% CI 1.44-12.22, p<0.05), respectively. For excess waist circumference (man≥90 cm, woman ≥80 cm) compared with lean participants without NAFLD, the adjusted hazard ratios (HRs) of incident type 2 diabetes for lean participants with NAFLD and overweight or obese participants with NAFLD were 3.88 (95% CI 1.56-9.66, p<0.05) and 3.30 (95% CI 1.52-7.14, p<0.05), respectively. Abdominal obesity is the strongest risk factor for type 2 diabetes in lean nonalcoholic fatty liver disease.

SAT-475 - Diagnostic performance of NAFLD fibrosis score in lean NAFLD

SAT-475 - Diagnostic performance of NAFLD fibrosis score in lean NAFLD

Lean individuals with NAFLD have more severe liver disease and poorer clinical outcomes (NASH-CO Study).

The severity of liver injury and clinical outcomes in lean individuals with NAFLD is a subject of debate and very few studies have been performed in the general population. The aim of this study was to compare subject characteristics and mortality between lean and nonlean NAFLD in a community setting. The study population included 169,303 participants from the nationwide Constances cohort. Subjects with excessive alcohol consumption, viral hepatitis, or other liver diseases were excluded and 137,206 subjects were analyzed. The diagnosis of NAFLD and fibrosis was performed using the Fatty Liver Index and the Forns Index. The median follow-up was 3.58 years. The prevalence of NAFLD was 5.3% (95% CI: 5.2-5.4) in lean subjects, while 16.3% (95% CI: 15.7-16.8) of NAFLD subjects were lean. Despite their better metabolic profile, the prevalence of advanced fibrosis was significantly higher in lean than in nonlean NAFLD (3.7% vs. 1.7%, respectively, p < 0.01). Among NAFLD subjects and after adjustment for demographics, metabolic risk factors and lifestyle, lean status was associated with advanced fibrosis (OR=1.26, 95% CI: 1.20-1.65, p = 0.005), an increased risk of liver-related events (adjusted HR=5.84, 95% CI: 4.03-8.46), chronic kidney disease (adjusted HR=2.49, 95% CI: 1.49-4.16), and overall mortality (adjusted HR=3.01, 95% CI: 2.21-4.11). Liver-related events and overall mortality were related to the severity of fibrosis, both in lean and nonlean NAFLD subjects, whatever the usual risk factors. This study in a large community-based cohort confirms that NAFLD in lean subjects is more severe for fibrosis, the progression of liver disease, chronic kidney disease, and overall mortality.

Letter to the editor: Association between birth weight, preterm birth, and nonalcoholic fatty liver disease in a community-based cohort.

To the editor, While we commend Amadou et al.1 for their fine study reporting a U-shaped association between birth weight and risk of NAFLD, we have some concerns. NAFLD was defined using the fatty liver index. This index was, however, developed as a risk stratification tool (not as a diagnostic instrument) and has a rather low positive predictive value for the diagnosis of NAFLD (67%).2 Furthermore, the fatty liver index may perform poorly in young individuals with normal body mass index,3 as in the current French study population (mean age 38 y, normal body mass index).1 Given that the fatty liver index formula is largely driven by body mass index and waist circumference, the question arises whether the found associations rather explain a higher risk of obesity and would especially miss individuals with lean NAFLD. While in women, there was a positive association between high birth weight and risk of NAFLD, the mediation analysis revealed that in men high birth weight did neither have a direct nor a total effect on the later risk of NAFLD—in contrast the indirect effect seemed even protective. Against this background, how do the authors explain the contradictive results on high birth weight and NAFLD risk in men andwomen? The authors found a slight negative association between birth weight and the Forns index, which was used as proxy for liver fibrosis. Here, we see two limitations that make the interpretation of these results challenging: first, the Forns index was originally developed to noninvasively rule-out significant fibrosis and has not been validated to be used as a continuous variable. Second, it was derived in high-risk cohorts of patients with chronic hepatitis C infection,4 while the current study applied it in a general population setting. Hence, we are eager to know if the authors could confirm these results using FIB-4 instead, which is recommended by international guidelines.5

Obesity and Non Alcoholic Fatty Liver Disease in Females in tertiary care Hospital

Background: Obesity is now recognized as a disease in its own right due to increase in morbidity and mortality. Obesity is strongly associated with metabolic disorders like diabetes hypertension cardiovascular disease and NAFLD. NAFLD is the most common liver disorder affecting the world and it is now considered as the most common cause of abnormal liver function tests. Aim: To study biochemical profile NAFLD in females and to study its association with obesity. Methodology: This is a descriptive study done in female patients who were diagnosed with fatty liver were enrolled in the study after detailed clinical, anthropometric study and lab work up. Focus was on biochemical and components of metabolic syndrome. Subjects were divided into two groups according to BMI as lean and obese NAFLD and various biochemical and metabolic parameters were compared. Results: This study concluded NAFLD is common in obese middle aged females.90% patients had truncal obesity. Two third of patients had metabolic syndrome with 90% having one component of metabolic syndrome. Biochemical and metabolic dysfunction were more significant in the obese NAFLD group showing that obesity plays a key role in the pathogenesis of NAFLD. Conclusion: Obesity is prevailing in rural Indian population. Lack of awareness and health care programmes directed toward identifying obesity as a disease on its own needs to be strengthened. Lifestyle modification and weight is the only effective treatment modality in liver diseases due to obesity.

The Association of Sarcopenia and Visceral Obesity with Lean Nonalcoholic Fatty Liver Disease in Chinese Patients with Type 2 Diabetes Mellitus.

Few studies have specifically observed the relationship of sarcopenia, visceral obesity, or their joint effects with lean NAFLD in patients with diabetes. We aimed to investigate the associations of lean NAFLD with sarcopenia, visceral obesity, and sarcopenic visceral obesity (SV) in Chinese patients with type 2 diabetes mellitus (T2DM). Altogether, 1,112 T2DM patients with BMI <25 kg/m2 were enrolled, and 33.18% of them were diagnosed with lean NAFLD by abdominal ultrasonography. Body composition markers were measured by bioelectrical impedance (BIA). Skeletal muscle mass index (SMI) was calculated as appendicular skeletal muscle mass (ASM) divided by weight, and sarcopenia was defined as SMI < 1 standard deviation (SD) below the sex-specific average for a young reference population. Visceral obesity was defined as visceral fat area (VFA) ≥ 100 cm2. Participants were categorized into one of the four body composition groups: nonsarcopenia/nonvisceral obesity (NN), nonsarcopenia/visceral obesity (NV), sarcopenia/nonvisceral obesity (SN), and SV. Compared to those in the NN group, patients in the NV and SN groups had a higher risk of lean NAFLD after full adjustments (NV: OR = 1.74; 95% CI: 1.09, 2.78; SN: OR =2.07; 95% CI: 1.23, 3.46). Of note, patients in the SV group had the highest odds of lean NAFLD (OR = 3.29; 95% CI: 2.10, 5.17). There were no significant interaction effects between sarcopenia and metabolic risk factors on prevalent lean NAFLD. The current study demonstrated that SV was more closely associated with higher prevalent lean NAFLD than sarcopenia or visceral obesity alone in Chinese patients with T2DM. Besides, the harmful effect of sarcopenia on lean NAFLD was not influenced by visceral obesity or other metabolic risk factors. We hypothesize that increasing skeletal muscle mass more than just reducing visceral fat might be more optimal for the prevention and management of lean NAFLD, which needs further investigation in future studies.

S1188 NAFLD Prevalence in BMI Subclass and Outcomes in 2019

Introduction: NAFLD has been historically associated with obesity but was recently found to have an association with lean individuals as well. We thereby conducted a nationwide study to identify the prevalence of NAFLD in different BMI categories and their association with mortality. Methods: We queried the 2019 NIS database to identify all adult ( >18 years) patients with NAFLD using appropriate ICD-10-CM codes. We categorized BMI into category I (19.9 or less), category II (20-24.9), category III (25-29.9), category IV (30-34.9), category V (35-39.9), and category VI (> 40) using appropriate ICD-10-CM codes. An univariate screen followed by multivariate logistic regression was performed to adjust for potential hospital and patient level confounders. Stata 17.0 software was used to perform all statistical analyses. Results: A total of 532,485 NAFLD patients were identified which corresponds to 1.5% of the total US hospitalizations in the year 2019. Of which, 7,964 (1.5%) were category I, 7,530 (1.4%) were category II, 13,450 (2.5%) were category III, 36,650 (6.8%) were category IV, 42,715 (8%) were category V, and 94,425 (17.7%) were category VI. On multivariate analysis, we found that category I NAFLD patients had increased odds of mortality compared to other BMI subgroups [OR 1.71 (1.3-2.2); p< 0.001]. Conclusion: Obesity has been linked with the development of NAFLD. As expected, our study demonstrated an increasing prevalence of NAFLD with higher BMI. However, we found that 2.9% of NAFLD patients were not obese. This group of patients had been termed “lean NAFLD”. The hypothesis for lean NAFLD is poorly understood with theories including higher bile production and genetic variations. Interestingly, we found that category I NAFLD patients had higher odds of mortality compared to other BMI groups. These findings could be a result of lean individuals suffering chronic medical conditions or certain malignancies and is beyond the scope of our study. Further studies regarding etiologies for lean NAFLD might bring clarity to this subject.

Differential progression of unhealthy diet-induced hepatocellular carcinoma in obese and non-obese mice.

BackgroundNon-alcoholic fatty liver disease (NAFLD) ranks first among liver diseases in Western countries. NAFLD is typically associated with obesity and diabetes, however it also develops in lean individuals without metabolic syndrome. The prevalence of lean NAFLD is 7 percent in the U.S. and 25–30 percent in some Asian countries. NAFLD starts with excess liver fat accumulation (NAFL), progresses to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis of lean NASH-HCC and how it differs from obese NASH-HCC is not well understood.MethodsIn this work, we generated a mouse model of lean and obese NASH-HCC using a choline deficient/high trans-fat/fructose/cholesterol diet and a choline supplemented/high trans-fat/fructose/cholesterol diet, respectively, to compare progression to NASH-HCC in lean versus obese mice. Comparisons were made at the organismal, histological, and molecular level by investigating fatty acid metabolism in the plasma of these mice.ResultsObese mice showed more pronounced glucose intolerance and insulin resistance, higher levels of plasma cholesterol and triglycerides, and higher penetrance of NASH compared to lean mice. Despite the abnormal metabolic profile of obese mice, male obese and lean mice developed HCC with similar penetrance (53.3% and 53.8%, respectively), albeit lean mice showed faster tumor progression as evidenced by the larger tumor size and lower HCC-free survival. None of the female lean mice developed HCC, while 50% of female obese mice developed HCC. Both groups of mice showed a reduction in plasma polyunsaturated fatty acids (PUFAs), however, the levels were higher towards the endpoint in obese mice compared to lean mice.ConclusionsUnhealthy diet composition appears to drive progression to NASH-HCC rather than the organismal effects of obesity. PUFA levels may increase due to systemic inflammation in obese mice and act as suppressors of tumor progression, thus delaying HCC progression in obese mice compared to lean mice. These models could be used to further dissect the molecular pathogenesis of lean and obese NASH-HCC and address the mechanisms whereby PUFAs may be implicated in hepatocarcinogenesis.

Lean non-alcoholic fatty liver disease (Lean-NAFLD) and the development of metabolic syndrome: a retrospective study

Lean NAFLD is a special phenotypic closely correlated with metabolic syndrome (MS). The aim of this study is to investigate the MS development and the gender differences in lean NAFLD population. Participants were divided into 4 groups by BMI and NAFLD status. Descriptive analysis was performed to characterize baseline information. A total of 18,395 subjects were participated, and 1524 incident cases of MS were documented. Then, Kaplan–Meier curves were used to present the MS outcomes in different groups, and the NAFLD was found to be a riskier factor than obesity for MS. Subgroup analysis showed significantly higher MS incidence in female than male among lean NAFLD group, which is different from other groups. Although with higher prevalence in male, lean NAFLD seems to be a more harmful phenotype for females according to the TG, ALT and GGT levels. The logistic regressive analysis was performed to show the impact of NAFLD status and BMI changes on MS risk. Lean non-NAFLD subjects merely developed to NAFLD with no BMI status changes exhibited highest MS risk (ORs = 1.879, 95% CI 1.610–2.292) than that with both BMI increase and NAFLD development (ORs = 1.669, 95% CI 1.325–2.104). It also suggests the metabolic specificity of this population.

Distinctive clinical and genetic features of lean vs overweight fatty liver disease using the UK Biobank.

Lean NAFLD may differ from NAFLD found in overweight or obese patients. We used the UK biobank to conduct a cross-sectional study that examined features that distinguish lean NAFLD from overweight or obese NAFLD. MRI-PDFF data were used to identify patients with NAFLD, with NAFLD defined as PDFF ≥ 5%. BMI patient cohorts were identified, with lean defined as a BMI < 25, and overweight or obese defined as a BMI ≥ 25. Variables of interest to fatty liver disease, including single nucleotide polymorphisms, were chosen from the UK biobank data portal. Logistic regression was used to generate models predictive of NAFLD in each cohort. 1007 patients had NAFLD, and of these, 871 had BMI ≥ 25, and 136 BMI < 25. Factors associated with NAFLD in patients with BMI < 25 included male sex, white blood cell count, red blood cell count, triglycerides, ALT, creatinine, visceral adipose tissue, rs58542926 T, and rs738409 G. In contrast, factors associated with NAFLD in patients with BMI ≥ 25 included male sex, waist circumference, HDL cholesterol, triglycerides, serum glucose, ALT, creatinine, urate, visceral adipose tissue, rs1260326 T, rs1044498 C, rs58542926 T, and rs738409 G. For lean patients, our generated prediction score had an AUC of 0.92, sensitivity of 0.90 and specificity of 0.81. For overweight or obese patients, the prediction score had an AUC of 0.86, sensitivity of 0.87 and specificity of 0.70. Our analysis suggests that lean and overweight or obese NAFLD are distinct entities. We have developed a risk score incorporating both clinical and genetic factors that accurately classify lean patients with NAFLD, with the potential to serve as a tool for screening purposes.