Lean Non-alcoholic Fatty Liver Disease Research Articles

Metabolic health phenotype better predicts subclinical atherosclerosis than body mass index-based obesity phenotype in the non-alcoholic fatty liver disease population.

Non-alcoholic fatty liver disease (NAFLD), especially lean NAFLD is associated with an increased risk of atherosclerotic cardiovascular disease (CVD). It is not currently known which clinical phenotypes of NAFLD contribute most to individual subclinical atherosclerosis risk. We examined the relationship between body mass index (BMI), the metabolically healthy status, and subclinical atherosclerosis in the NAFLD population. Data from asymptomatic NAFLD subjects who participated in a routine health check-up examination were collected. Participants were stratified by BMI (cutoff values: 24.0-27.9 kg/m2 for overweight and ≥28.0 kg/m2 for obesity) and metabolic status, which was defined by Adult Treatment Panel III criteria. Subclinical atherosclerosis was evaluated by brachial-ankle pulse wave velocity (baPWV) in 27,738 participants and by carotid plaque in 14,323 participants. Within each BMI strata, metabolically unhealthy subjects had a significantly higher prevalence of subclinical atherosclerosis than metabolically healthy subjects, whereas fewer differences were observed across subjects within the same metabolic category. When BMI and metabolic status were assessed together, a metabolically unhealthy status was the main contributor to the association of clinical phenotypes with the subclinical atherosclerosis burden (all p < 0.001). When BMI and metabolic abnormalities were assessed separately, the incidence of subclinical disease did not increase across BMI categories; however, it increased with an increase in the number of metabolic abnormalities (0, 1, 2 and ≥3). A metabolically healthy status in NAFLD patients was closely correlated with subclinical atherosclerosis, beyond that of the BMI-based obesity phenotype. The application of metabolic phenotyping strategies could enable more precise classification in evaluating cardiovascular risk in NAFLD.

Relationship between Non-Alcoholic Fatty Liver Disease and Visceral Fat Measured by Imaging-Based Body Composition Analysis: A Systematic Review

Imaging-based body composition analysis can quantify visceral fat, which is an important feature of lean non-alcoholic fatty liver disease (NAFLD) patients. This review assesses current evidence of the relationship between NAFLD, particularly hepatic steatosis, and visceral fat that is measured using imaging-based body composition analysis. PubMed Central and ScienceDirect were searched for studies that provided quantification of the relationship between NAFLD, hepatic steatosis and visceral fat. Twenty studies comprising 15,763 subjects were included, consisting of the relationship with NAFLD (n = 15) and the relationship with hepatic steatosis (n = 7). All studies reported a positive relationship between NAFLD and visceral fat. For hepatic steatosis regardless of severity, only one study reported no correlation with visceral fat. Further results showed that visceral fat is more related to NAFLD and hepatic steatosis in females than males. More studies including NAFLD of different stages must be performed in the future to validate the degree of association between visceral fat and NAFLD at all stages as well as this relationship difference between genders.

Frequency of Non-Alcoholic Fatty Liver Disease in Adults with Diabetes Mellitus

Objective: To compare the frequency of non-alcoholic fatty liver disease in patients with diabetes of different age groups, body mass indexes and duration of diabetes.&#x0D; Study Design: Comparative cross-sectional study.&#x0D; Place and Duration of Study: Department of General Medicine, Combined Military Hospital, Quetta Pakistan, from Jun to Nov 2019.&#x0D; Methodology: One hundred thirty-two patients of either gender with diabetes for more than one year were included. All patients underwent ultrasound to scan for fatty liver, and a consultant radiologist confirmed the findings. Non-alcoholic fatty liver disease was diagnosed as per operational definition.&#x0D; Results: Of the total 132, 89(67.5%) were males, and 43(32.5%) were females. The mean age of the patients was 49.34±5.76 years. The mean weight of the patients was 72.91±13.40 Kg, the mean height was 1.56±0.09 meters, and 6.35±2.99 years was the mean duration of diabetes. Most patients were 46-60 years (78.8%). NAFLD was seen in 58.5% of patients with diabetes with female preponderance.&#x0D; Conclusion: Non-alcoholic fatty liver disease was found to be more frequent in patients of the age group 46-60 years, and also it has a strong correlation with body mass index of &gt;25 kg/m2 and longer duration of diabetes. A significant proportion of patients with diabetes were also found to have ‘lean non-alcoholic fatty liver disease.

Unique Genetic Features of Lean NAFLD: A Review of Mechanisms and Clinical Implications.

Non-alcoholic fatty liver disease (NAFLD) affects 25% of the global population. About 20% have a normal body mass index (BMI) and a variant known as lean NAFLD. Unlike typical NAFLD cases associated with obesity and diabetes, lean NAFLD causes liver disease by mechanisms not related to excess weight or insulin resistance. Genetic disorders are among the major factors in developing lean NAFLD, and genome-wide association studies have identified several genes associated with the condition. This review aims to increase awareness by describing the genetic markers linked to NAFLD and the defects involved in developing lean NAFLD.

Diagnostic Performance of the Fibrosis-4 Index and Nonalcoholic Fatty Liver Disease Fibrosis Score in Lean Adults With Nonalcoholic Fatty Liver Disease

The diagnostic performance of the fibrosis-4 index (FIB-4) and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) for advanced fibrosis in lean patients with NAFLD is limited. To evaluate the diagnostic performance of the FIB-4 and NFS in lean individuals with NAFLD. This diagnostic study included adults with biopsy-proven NAFLD from 6 referral centers in Asia from 1995 to 2019. Cohorts were matched by age and sex between the lean and nonlean groups. All statistical analyses were executed from October 2022 to March 2023. The diagnostic performance of the FIB-4 and NFS at the current cutoff for advanced hepatic fibrosis in lean (body mass index [BMI] below 23 [calculated as weight in kilograms divided by height in meters squared]) and nonlean (BMI above 23) patients were evaluated. A total of 1501 patients were included in analysis (mean [SD] age, 46.1 [16.4] years); 788 male (52.5%), 115 lean (7.7%), 472 (30.2%) Korean, 821 (48.7%) Japanese, and 341 (21.3%) Taiwanese. Among the age- and sex-matched cohort, the mean (SD) age was 52.3 (15.1) years and 41.2% (47 of 114) were male. The diagnostic performance and areas under the operating characteristic curve of the FIB-4 (lean, 0.807 vs nonlean, 0.743; P = .28) and NFS (lean, 0.790 vs nonlean, 0.755; P = .54) between the 2 groups were comparable in the age- and sex-matched cohort. The sensitivity and specificity of the NFS showed increasing and decreasing tendency according to the BMI quartiles (P for trend < .001), while those of the FIB-4 did not (P for trend = .05 and P = .20, respectively). Additionally, although the areas under the operating characteristic curve of the FIB-4 and NFS were not significantly different in the lean group (0.807 vs 0.790; P = .09), the sensitivity of the current NFS cutoff values was lower in the lean group than in that of FIB-4 (54.4% vs 81.8%; P = .03). In this cohort study, the performance of the FIB-4 and NFS in diagnosing advanced fibrosis did not differ significantly between the 2 groups overall. However, in lean NAFLD, while the sensitivity for diagnosing advanced hepatic fibrosis remained reasonable at the current cutoff level, the sensitivity of NFS at the current cutoff was too low to be an adequate screening tool.

Epigenetic Regulation in Lean Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD), the most prominent cause of chronic liver disease worldwide, is a rapidly growing epidemic. It consists of a wide range of liver diseases, from steatosis to nonalcoholic steatohepatitis, and predisposes patients to liver fibrosis, cirrhosis, and even hepatocellular carcinoma. NAFLD is strongly correlated with obesity; however, it has been extensively reported among lean/nonobese individuals in recent years. Although lean patients demonstrate a lower prevalence of diabetes mellitus, central obesity, dyslipidemia, hypertension, and metabolic syndrome, a percentage of these patients may develop steatohepatitis, advanced liver fibrosis, and cardiovascular disease, and have increased all-cause mortality. The pathophysiological mechanisms of lean NAFLD remain vague. Studies have reported that lean NAFLD demonstrates a close association with environmental factors, genetic predisposition, and epigenetic modifications. In this review, we aim to discuss and summarize the epigenetic mechanisms involved in lean NAFLD and to introduce the interaction between epigenetic patterns and genetic or non genetic factors. Several epigenetic mechanisms have been implicated in the regulation of lean NAFLD. These include DNA methylation, histone modifications, and noncoding-RNA-mediated gene regulation. Epigenetics is an area of special interest in the setting of lean NAFLD as it could provide new insights into the therapeutic options and noninvasive biomarkers that target this under-recognized and challenging disorder.

The relative contributions of soft tissue mass components as risk or protective factors of non-alcoholic fatty liver disease in children.

Several body components are known to be associated with non-alcoholic fatty liver disease (NAFLD) in children. However, the relative contributions of soft tissue mass components as risk or protective factors of NAFLD are largely unknown because measurements of these components are often highly correlated. Therefore, we aimed to estimate levels of association between soft tissue mass components and NAFLD. We collected the medical records of 555 Chinese children (aged 3-18 years). Five mutually exclusive and exhaustive components of soft tissue mass were measured using dual energy X-ray absorptiometry. NAFLD was diagnosed with abdominal B-ultrasound scan. We fit Dirichlet regression and multivariate linear regression models wherein age and NAFLD were used as predictors of the proportional measurements of soft tissue mass components. The proportion of android fat was significantly higher in children with NAFLD than in those without NAFLD (ratio of proportions ranged from 1.18 to 1.30), whereas proportions of trunk lean and limb lean were significantly lower (ratio of proportions ranged from 0.87 to 0.92 for trunk lean and from 0.82 to 0.91 for limb lean). The proportion of gynoid fat was slightly higher in boys with NAFLD than in those without NAFLD (ratio = 1.05), but this proportion was not significantly higher in girls. The association between the proportion of android fat and NAFLD appeared to be somewhat greater than the associations between proportions of trunk lean or limb lean components and NAFLD. Our findings suggest that lowering fat mass and increasing lean mass can both be used to combat NAFLD in children and that more studies are needed to determine the association between gynoid fat and NAFLD.

Genetic and Metabolic Characteristics of Lean Nonalcoholic Fatty Liver Disease in a Korean Health Examinee Cohort.

The pathophysiology of lean nonalcoholic fatty liver disease (NAFLD) is unclear but has been shown to be associated with more diverse pathogenic mechanisms than that of obese NAFLD. We investigated the characteristics of genetic or metabolic lean NAFLD in a health checkup cohort. This retrospective cross-sectional study analyzed single nucleotide polymorphism data for 6,939 health examinees. Lean individuals were categorized according to a body mass index cutoff of 23 kg/m2. Single nucleotide polymorphisms were analyzed using genotyping arrays. The prevalence of lean NAFLD was 21.6% among all participants with NAFLD, and the proportion of lean NAFLD was 18.5% among lean participants. The prevalence of metabolic syndrome and diabetes among lean patients with NAFLD was 12.4% and 10.4%, respectively. Lean NAFLD appeared to be metabolic-associated in approximately 20.1% of patients. The homozygous minor allele (GG) of PNPLA3 (rs738409) and heterozygous minor alleles (CT, TT) of TM6SF2 (rs58542926) were associated with lean NAFLD. However, the prevalence of fatty liver was not associated with the genetic variants MBOAT7 (rs641738), HSD17B13 (rs72613567), MARC1 (rs2642438), or AGXT2 (rs2291702) in lean individuals. Lean NAFLD appeared to be associated with PNPLA3 or TM6SF2 genetic variation in approximately 32.1% of cases. Multivariate risk factor analysis showed that metabolic risk factors, genetic risk variants, and waist circumference were independent risk factors for lean NAFLD. In a considerable number of patients, lean NAFLD did not appear to be associated with known genetic or metabolic risk factors. Further studies are required to investigate additional risk factors and gain a more comprehensive understanding of lean NAFLD.

Long working hours and increased risks of lean non-alcoholic fatty liver disease among Korean men and women

Despite the increasing prevalence of lean nonalcoholic fatty liver disease (NAFLD), its risk factors are not well established. We examined the association between long working hours and incident NAFLD in lean Korean workers with emphasis on sex-based effect modification. This cohort study involved 46,113 non-overweight (BMI < 23 kg/m2) and NAFLD-free Korean workers (mean age, 35.5 years). Working hours were categorized into 35–40 (reference), 41–52, and ≥ 53 h. The presence of fatty liver and its severity were determined using ultrasonography and NAFLD fibrosis score (NFS), respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using parametric proportional hazards models. Incident cases of 5901 lean NAFLD developed over a median follow-up of 3.8 years. The incidence of lean NAFLD increased with increasing working hours with a stronger association in men than in women (P for interaction < 0.001). For men, multivariable-adjusted HRs (95% CIs) for lean NAFLD in time-dependent models comparing working hours of 41–52 and ≥ 53 h compared to the reference category were 1.17 (1.07–1.28) and 1.25 (1.12–1.39), respectively. The excess relative risk of developing lean NAFLD with intermediate/high NFS was observed in working hours of 41–52 and ≥ 53 h with a corresponding HR of 1.66 (1.13–2.43) and 1.54 (0.94–2.51), respectively. Conversely, no significant associations were found between working hours and incidence of lean NAFLD in women. In conclusion, long working hours were significantly associated with an increased incidence of lean NAFLD and its severe form in men but not in women.

Lean Indian patients with non-alcoholic fatty liver disease (NAFLD) have less metabolic risk factors but similar liver disease severity as non-lean patients with NAFLD.

Although most patients with NAFLD are obese or overweight, some are lean with normal BMI. Our aim was to assess differences in clinicopathological profile and liver disease severity among lean and non-lean NAFLD. Data of 1040 NAFLD patients over last 10 years was analysed. BMI < 23 kg/m2 categorised lean patients. 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. Histology was reported using NASH-CRN system. 149 (14.3%) patients were lean while 891 (85.7%) patients were non-lean. Diabetes mellitus [25 (16.7%) vs 152 (17.05%), p > 0.99], elevated triglycerides [81 (54.3%) vs 525 (58.9%), p = 0.33] and low HDL [71(47.6%) vs 479(53.7%), p = 0.18] were observed in a similar proportion. Lean patients were less likely to have central obesity [72 (48.3%) vs 788 (88.4%), p < 0.001], hypertension [16 (10.7%) vs 239(26.8%), p < 0.001] and metabolic syndrome [21 (14.09%) vs 290 (32.5%), p < 0.001]. No difference in steatosis assessment was noted using ultrasound (p = 0.55) or CAP (0.11). FAST [0.38 (0.18-0.66) vs 0.39 (0.27-0.73), p = 0.53], FIB-4 [1.08 (0.65-1.91) vs 1.09 (0.66-1.94), p = 0.94] and LSM [6.1 (4.8-7.9) vs 6.2 (4.7-8.6), p = 0.19) were similar. Liver biopsy was available in 149 patients [lean: 19 (12.7%), non-lean: 130 (87.3%)]. There was no difference in the number of patients with NASH [4 (21.05%) vs 20 (15.3%), p = 0.51], significant fibrosis [2 (10.5%) vs 32 (24.6%), p = 0.25] or advanced fibrosis [1 (5.26%) vs 18 (13.84%), p = 0.47]. Although metabolic co-morbidities are less common, there is no difference in liver disease severity among both groups.

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.

Lean nonalcoholic fatty liver disease and sarcopenia.

Nonalcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in the world. The risk factor for NAFLD is often considered to be obesity, but it can also occur in people with lean type, which is defined as lean NAFLD. Lean NAFLD is commonly associated with sarcopenia, a progressive loss of muscle quantity and quality. The pathological features of lean NAFLD such as visceral obesity, insulin resistance, and metabolic inflammation are inducers of sarcopenia, whereas loss of muscle mass and function further exacerbates ectopic fat accumulation and lean NAFLD. Therefore, we discussed the association of sarcopenia and lean NAFLD, summarized the underlying pathological mechanisms, and proposed potential strategies to reduce the risks of lean NAFLD and sarcopenia in this review.

Risk of cardiovascular disease in lean patients with nonalcoholic fatty liver disease

BackgroundPatients with nonalcoholic fatty liver disease (NAFLD) are highly at risk for cardiovascular disease (CVD). However, the risk of developing CVD in patients with lean NAFLD is not yet fully understood. Therefore, this study aimed to compare the CVD incidence in Japanese patients with lean NAFLD and those with non-lean NAFLD.MethodsA total of 581 patients with NAFLD (219 with lean and 362 with non-lean NAFLD) were recruited. All patients underwent annual health checkups for at least 3 years, and CVD incidence was investigated during follow-up. The primary end-point was CVD incidence at 3 years.ResultsThe 3-year new CVD incidence rates in patients with lean and non-lean NAFLD were 2.3% and 3.9%, respectively, and there was no significant difference between two groups (p = 0.3). Multivariable analysis adjusted for age, sex, hypertension, diabetes, and lean NAFLD/non-lean NAFLD revealed that age (every 10 years) as an independent factor associated with CVD incidence with an odds ratio (OR) of 2.0 (95% confidence interval [CI]: 1.3–3.4), whereas lean NAFLD was not associated with CVD incidence (OR: 0.6; 95% CI: 0.2–1.9).ConclusionsCVD incidence was comparable between patients with lean NAFLD and those with non-lean NAFLD. Therefore, CVD prevention is needed even in patients with lean NAFLD.

Impact of body mass index on disease progression and outcomes in patients with nonalcoholic fatty liver disease.

The relationship between body mass index (BMI) and outcomes in patients with nonalcoholic fatty liver disease (NAFLD) is not well defined. This study aimed to assess the presentations, outcomes, and development of liver-related events (LREs) and non-LREs in patients with NAFLD stratified by BMI. Records of NAFLD patients from 2000-2022 were reviewed. Patients were categorized as lean (18.5-22.9kg/m2), overweight (23-24.9kg/m2), and obese (>25kg/m2) based on BMI. Stage of steatosis, fibrosis, and NAFLD activity score were noted in the patients undergoing liver biopsy in each group. Out of 1051 NAFLD patients, 127 (12.1%) had normal BMI, 177 (16.8%) and 747 (71.1%) were overweight and obese, respectively. Median [interquartile range] BMI was 21.9 [20.6-22.5], 24.2 [23.7-24.6], and 28.3 [26.6-30.6] kg/m2 in each group, respectively. Prevalence of metabolic syndrome and dyslipidemia were significantly higher in the obese. Obese patients had significantly higher median [interquartile range] liver stiffness (6.4 [4.9-9.4] kPa) than overweight and lean subjects. A higher proportion of obese patients had significant and advanced liver fibrosis. At follow-up, there were no significant differences in the progression of liver disease, new LREs, coronary artery disease, or hypertension across the BMI groups. Overweight and obese patients were more likely to develop new-onset diabetes by follow-up. The mortality rates in the three groups were comparable (0.47, 0.68, and 0.49 per 100 person-years, respectively), with similar causes of death (liver-related vs non-liver-related). Patients with lean NAFLD have similar disease severity and rates of progression as the obese. BMI is not a reliable determinant of outcomes in NAFLD patients.

The Abdominal Ultrasonography Results of Cappadocia Cohort Study of Turkey Reveals High Prevalence of Fatty Liver.

There is limited data about the prevalence of frequent gastrointestinal diseases in developing parts of the world based on community-based screening studies. Therefore, we aimed to present the detailed transabdominal ultrasonography results of the previously completed Turkey Cappadocia cohort study, which included a population-based evaluation of gastrointestinal symptoms and diseases in adults. This cross-sectional study was conducted in Cappadocia cohort. The transabdominal ultrasonography, anthropometric measurements, and disease questionnaires were applied to cohort persons. Transabdominal ultrasonography was performed in 2797 subjects (62.3% were female and the mean age was 51 ± 15 years). Among them, 36% were overweight, 42% were obese, and 14% had diabetes mellitus. The most common pathological finding in transabdominal ultrasonography was hepatic steatosis (60.1%). The severity of hepatic steatosis was mild in 53.3%, moderate in 38.8%, and severe in 7.9%. Age, body mass index, liver size, portal vein, splenic vein diameter, hypertension, diabetes mellitus, and hyperlipidemia were significantly higher while physical activities were significantly lower in hepatic steatosis group. Ultrasonographic grade of hepatic steatosis was positively correlated with liver size, portal vein and splenic vein diameter, frequency of diabetes mellitus, hypertension, and coronary artery disease. Hepatic steatosis was observed in none of the underweight, 11.4% of the normal weights, 53.3% of the overweight, and 86.7% of the obese subjects. The percentage of hepatic steatosis cases with normal weight (lean nonalcoholic fatty liver disease) was 3.5%. The rate of lean nonalcoholic fatty liver disease in the entire cohort was 2.1%. Regression analysis revealed male gender (hazard ratio [HR]: 3.2), hypertension (HR: 1.5), and body mass index (body mass index: 25-30 HR: 9.3, body mass index >30 HR: 75.2) as independent risk factors for hepatic steatosis. The second most common ultrasonographic finding was gallbladder stone (7.6%). In the regression analysis, female gender (HR: 1.4), body mass index (body mass index: 25-30 HR: 2.1, body mass index >30 HR: 2.9), aging (30-39 age range HR: 1.5, >70 years HR: 5.8), and hypertension (HR: 1.4) were the most important risk factors for gallbladder stone. Cappadocia cohort study in Turkey revealed a high prevalence of hepatic steatosis (60.1%) while the prevalence of gallbladder stones was 7.6% among the participants. The results of the Cappadocia cohort located in central Anatolia, where overweight and lack of physical activity are characteristic, showed that Turkey is one of the leading countries in the world for nonalcoholic fatty liver disease.

THU-431 - Genetic and metabolic characteristics of lean non-alcoholic fatty liver disease in Asian

THU-431 - Genetic and metabolic characteristics of lean non-alcoholic fatty liver disease in Asian

Lean nonalcoholic fatty liver disease: Age-dependent differences in pathology, prognosis, and liver-related events.

This study aimed to evaluate the age-specific characteristics, prognosis, and complications of patients with lean nonalcoholic fatty liver disease (NAFLD). Background factors (age, sex, diabetes, dyslipidemia, hypertension, and PNPLA3 gene polymorphism), blood test results, liver histology findings, muscle mass, and grip strength were investigated in 782 patients with NAFLD who underwent liver biopsy. Prognosis and complications were compared among 549 patients with nonlean or lean NAFLD who were followed up for 6.5years. Additionally, background factors, blood test results, liver histology findings, prognosis, and complications were compared according to age (≥60years vs. <60years) in patients with lean NAFLD. Lean NAFLD patients showed lower aspartate aminotransferase, alanine aminotransferase, homeostasis model assessment-insulin resistance, high-sensitivity C-reactive protein, ferritin, and leptin but higher adiponectin and hemoglobin A1c (HbA1c) levels than patients with nonlean NAFLD. Furthermore, lean NAFLD patients showed less liver fibrosis, inflammation, steatosis, and ballooning. Among lean NAFLD patients, those aged 60years and older were more frequently female, showed higher rates of hypertension, diabetes, and dyslipidemia, had higher HbA1c and type IV collagen 7S levels, lower platelet count, higher liver fibrosis and inflammation grades, and lower muscle mass and grip strength. Lean NAFLD was associated with a worse prognosis in patients aged 60years and over than in those younger than 60years of age and with a higher incidence of liver-related disease, cerebrocardiovascular events, and nonliver cancer. Age is an important consideration in patients with lean NAFLD. Compared with nonlean NAFLD, lean NAFLD was associated with a worse prognosis and higher risk of complications in patients aged 60years and older.

Lean nonalcoholic fatty liver disease and risk of incident type 2 diabetes mellitus: A literature review and meta-analysis

ObjectiveThere is limited data regarding the risk of incident type 2 diabetes mellitus (T2DM) among lean nonalcoholic fatty liver disease (NAFLD) individuals. We performed a meta-analysis of relevant studies. Research design and methodsWe collected data using PubMed, Scopus, Cochrane and Web of Science from the databases' inception until December 2022. We included cohort studies in which lean NAFLD was diagnosed through imaging methods or biopsy. Eligible studies were selected according to predefined keywords and clinical outcomes. ResultsA total of 16 observational studies with 304,975 adult individuals (7.7% with lean NAFLD) and nearly 1300 cases of incident diabetes followed up over a median period of 5.05 years were included in the final analysis. Patients with lean NAFLD had a greater risk of incident diabetes than those without NAFLD (random-effects hazard ratio [HR] 2.72, 95% CI 1.56–4.74; I2 = 93.8%). Compared with the lean without NAFLD group, the adjusted HRs (95% CIs) of incident diabetes for participants in the overweight/obese without NAFLD and overweight/obese with NAFLD groups were 1.32 (0.99– 1.77) and 2.98(1.66–5.32). It appeared to be even greater among NAFLD patients with advanced high NAFLD fibrosis score (random-effects HR 3.48, 95% CI 1.92–6.31). Sensitivity analyses and publication bias did not alter these findings. ConclusionsLean NAFLD is significantly associated with at least twofold increased risk of incident diabetes in non-overweight subjects. This risk parallels the underlying severity of NAFLD. The presence of NAFLD in non-overweight individuals had a more significant impact on the development of diabetes than being overweight itself.

Metabolic disorders across the body mass index spectrum in a Colombian population with nonalcoholic fatty liver disease

Background and aimsThe relationship between obesity and nonalcoholic fatty liver disease (NAFLD) has long been established, and the prevalence of both conditions has grown together. Recent interest in NAFLD in nonobese individuals has led to an increasing number of studies, especially in Asia. Despite the fact that the prevalence of NAFLD in Latin America is one of the highest in the world, there is a lack of information on lean NAFLD populations from the region. The aim of the present study was to assess the risk of metabolic comorbidities across the whole body mass index spectrum when nonalcoholic steatohepatitis (NASH) was first diagnosed in a Latin American population. MethodsA single-center, cross-sectional study on Colombian patients newly diagnosed with NAFLD, within the time frame of 2010–2020, compared their metabolic biochemical profile, liver enzymes, risk of prevalent metabolic abnormalities, and liver disease. ResultsData from 300 patients were collected. Ninety-two percent of the patients were men and the median patient age was 47 (IQR 20) years. We found no significant differences in the biochemical, metabolic profile, or liver enzyme plasma concentration between lean, overweight, and obese individuals. Obese patients had significantly higher LDL cholesterol, and a higher risk of dyslipidemia (OR 1.86, 95% CI 1.14–3.05). Every 1kg increase in body weight increased the risk of having NASH by 2% (95% CI 2–4). ConclusionsWe evaluated the metabolic risk across the entire body mass index spectrum in a Colombian cohort with NAFLD and presented the characteristics of what we believe is the first Latin American lean NAFLD population to be described.

Waist circumference mediates the association between rs1260326 in GCKR gene and the odds of lean NAFLD

While non-alcoholic fatty liver disease (NAFLD) has been widely studied, the pathophysiology of lean NAFLD, the critical NAFLD subgroup, remains elusive. This study aimed to clarify the association between polymorphisms of GCKR, waist circumference, and the odds of lean NAFLD in the elderly Chinese Han population who live in the Zhangjiang community center of Shanghai, China. Three single nucleotide polymorphisms (SNPs), including rs1260326, rs780093, and rs780094, were genotyped in MassARRAY Analyzer. The association between SNPs with waist circumference in five genetic models was analyzed and rechecked by the logistic regression analysis. Mediation models were established to evaluate whether the waist circumstance can mediate the association between SNPs and lean NAFLD. In this study, the frequency of the C allele of rs1260326, rs780093, and rs780094 was significantly lower in lean NAFLD individuals than in lean non-NAFLD ones. The association between rs1260326 in GCKR and the odds of lean NAFLD was mediated via waist circumference after adjusting gender and age in the elderly Chinese Han population (β = 1.196, R2 = 0.043, p = 0.020). For the first time, this study examined the mediating effect of waist circumference on the association between rs1260326 in GCKR and the odds of lean NAFLD (β = 0.0515, 95% CI 0.0107–0.0900, p = 0.004). It may contribute to illustrating the pathogenesis of lean NAFLD and indicate that waist circumference management might improve lean NAFLD control.