The current definition of lean is based on body mass index (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 nonalcoholic fatty liver disease (NAFLD) with and without CO.

One hundred seventy 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). Noninvasive 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.

Of 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 the 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 metabolic dysfunction associated steatotic liver disease (MASLD) criteria. CO was also an independent risk factor for advanced fibrosis in MASLD (3.32 (1.23-8.5), P = 0.02).

Lean patients with NAFLD or MASLD and CO have more severe liver disease compared to those without CO.

Background and aim Non-alcoholic fatty liver disease (NAFLD), now known as metabolic dysfunction-associated steatotic liver disease (MASLD), is more common in people with type-2 diabetes mellitus (T2DM) than in people without diabetes mellitus (non-DM). This disease can lead to cirrhosis or hepatic cancer. There is limited data on NAFLD prevalence and the level of risk of fibrosis in Bangladeshi individuals. This study aimed to assess NAFLD prevalence and compare the proportion of NAFLD and the level of risk of fibrosis between T2DM and non-DM Bangladeshi individuals. Methods A cross-sectional analytical study was conducted for six months in 2024 in the outpatient section of the Department of Medicine at Holy Family Red Crescent Medical College, Dhaka, Bangladesh. Among the patients seeking outpatient care, a total of 179 male and non-pregnant female participants aged 18 years and older were selected using a purposive sampling technique. Individuals with a history of alcohol use, diagnosed cases of chronic liver diseases, prior use of hepatotoxic drugs, and primary biliary cholangitis were excluded from the study. Detailed demographic characteristics, comorbidities, family history of diabetes and liver disease, physical measurements, and biochemical tests were done. Ultrasonography (USG) of the hepatobiliary system was employed to ascertain the existence of NAFLD. The presence or absence of T2DM was evaluated through prior medical documents, corroborated by laboratory analyses of random blood glucose (RBS) and glycosylated hemoglobin (HbA1c) levels. The Fibrosis-4 (FIB-4) index score was utilized to evaluate the risk of liver fibrosis. Results The mean age of the participants was 49.11±12.25 years and 107 (59.8%) of participants were female. Almost two-thirds of the participants were suffering from T2DM. About 17 (9.5%) of the study participants were suffering from NAFLD, which was much higher among T2DM (15 (12.5%)) than non-DM individuals (two (3.3%)). T2DM and family history of liver disease were found to significantly increase the risk of suffering from NAFLD by 5.247 times (95% CI: 1.081-25.468) and 4.202 times (95% CI: 1.249-14.135), respectively. About one (6.7%) of T2DM individuals with NAFLD were at high risk for fibrosis. Conclusion Almost one in 10 people had NAFLD, and it was way more common among those with T2DM, who also exhibit a higher risk of hepatic fibrosis. Moreover, T2DM and a family history of liver disease can independently increase the risk of NAFLD.

Metabolic-associated fatty liver disease (MAFLD) was proposed in 2020 to replace the original term nonalcoholic fatty liver disease (NAFLD) with new diagnostic criteria. The disease risks of lean and overweight/obese MAFLD patients remain controversial.

The participants from the Taiwan biobank cohort were included. Advanced liver fibrosis is defined as NAFLD fibrosis score (NFS) >0.675. We use carotid plaques of duplex ultrasounds to diagnose atherosclerosis.

A total of 20,058 participants (age 55.67 ± 10.32; males 37.6%) were included in the final analysis. Seven thousand eight hundred and forty-three (39.1%) participants were diagnosed with MAFLD. Of them, 965 (12.3%) were lean MAFLD patients. Among lean MAFLD patients, 25.6% were comorbid with diabetes mellitus (DM). Lean MAFLD patients were older and had higher percentages of females and DM than overweight/obese MAFLD patients. After propensity score matching for age and sex, they had lower levels of NFS but a higher percentage of carotid plaques. Among four subtypes of MAFLD including "lean with DM," "lean without DM," "overweight/obese with DM," and "overweight/obese without DM," logistic regression showed that "lean with DM" subjects had the highest risk of atherosclerosis and "overweight/obese with DM" subjects had the highest risk of advanced liver fibrosis in MAFLD patients.

The population-based study revealed that lean MAFLD patients make up 12.3% of all MAFLD patients, and they have a higher proportion of coexisting diabetes. Among lean MAFLD patients concurrent with diabetes, they have the highest risk of atherosclerosis and should receive special attention clinically.

A new nomenclature consensus has emerged for liver diseases that were previously known as non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD). They are now defined as metabolic dysfunction-associated steatotic liver disease (MASLD), which includes cardiometabolic criteria in adults. This condition, extensively studied in obese or overweight patients, constitutes around 30% of the population, with a steady increase worldwide. Lean patients account for approximately 10%-15% of the MASLD population. However, the pathogenesis is complex and is not well understood.

To systematically review the literature on the diagnosis, pathogenesis, characteristics, and prognosis in lean MASLD patients and provide an interpretation of these new criteria.

We conducted a comprehensive database search on PubMed and Google Scholar between January 2012 and September 2023, specifically focusing on lean NAFLD, MAFLD, or MASLD patients. We include original articles with patients aged 18 years or older, with a lean body mass index categorized according to the World Health Organization criteria, using a cutoff of 25 kg/m2 for the general population and 23 kg/m2 for the Asian population.

We include 85 studies in our analysis. Our findings revealed that, for lean NAFLD patients, the prevalence rate varied widely, ranging from 3.8% to 34.1%. The precise pathogenesis mechanism remained elusive, with associations found in genetic variants, epigenetic modifications, and adaptative metabolic response. Common risk factors included metabolic syndrome, hypertension, and type 2 diabetes mellitus, but their prevalence varied based on the comparison group involving lean patients. Regarding non-invasive tools, Fibrosis-4 index outperformed the NAFLD fibrosis score in lean patients. Lifestyle modifications aided in reducing hepatic steatosis and improving cardiometabolic profiles, with some medications showing efficacy to a lesser extent. However, lean NAFLD patients exhibited a worse prognosis compared to the obese or overweight counterpart.

MASLD is a complex disease comprising epigenetic, genetic, and metabolic factors in its pathogenesis. Results vary across populations, gender, and age. Limited data exists on clinical practice guidelines for lean patients. Future studies employing this new nomenclature can contribute to standardizing and generalizing results among lean patients with steatotic liver disease.

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.

Non-alcoholic fatty liver disease (NAFLD) is a growing concern, affecting about 45 million of the Bangladeshi population. There is a paucity of research on the economic burden of NAFLD. The study aims to estimate the cost of illness of NAFLD in Bangladesh.

In this prospective, cross-sectional study, a total of 250 patients of NAFLD, non-alcoholic steatohepatitis (NASH), and NASH cirrhosis were included from public and private hospitals. Costs of hospitalization, physician fees, investigation costs, expenditures on medical procedures, drugs; and nonmedical costs such as transport expenses and other informal payments (tips) were estimated.

The overall cost per patient per evaluation was (16.90-46 942.00) USD. The cost in public and private hospitals was 384.76 and 1146.93 USD, respectively. The cost per patient of NAFLD was 157.91 (16.90-955.08) USD, and for NASH cirrhosis was 1783.80 (422.48-46 942) USD. The cost of illness increased to USD 281.18 for diabetics and 254.52 USD for hypertensive. If all the NAFLD patients are evaluated once in healthcare settings, the projected cost will be 7.11 billion USD. In NAFLD, cost for investigations, medicines, transportation, and consultation of physicians was 49.08%, 32.41%, 11.11%, and 6.67%, respectively.

NAFLD is causing a huge economic burden to the healthcare system. The cost of illness is increased with NASH cirrhosis. Overall, this study provides valuable insights into the economic burden of NAFLD in Bangladesh and emphasizes the several ways of intervention to reduce the cost by preventive measures and accessible healthcare for affected individuals.

Abnormal liver function tests (LFTs) can indicate cirrhosis or liver cancer leading to mortality among systemic sclerosis (SSc) patients. No recent studies have investigated the clinical predictors of an abnormal LFT in SSc. We aimed to determine the incidence of abnormal LFT (including from hepatitis and cholestasis) and to identify its clinical predictors in SSc patients.

An historical cohort was conducted on 674 adult SSc patients who attended the Scleroderma Clinic, Khon Kaen University, between January 2012 and November 2019 and who underwent routine screening for LFT. A Cox regression was used to analyze the clinical predictors of abnormal LFT.

Four hundred and thirty cases, representing 4190 person-years, had abnormal LFTs (viz, from hepatitis, cholestasis, and cholestatic hepatitis) for an incidence rate of 10.2 per 100 person-years. The respective incidence of hepatitis, cholestasis, and cholestatic hepatitis was 20.5, 12.9, and 20.4 per 100 person-years. The respective median first-time detection of hepatitis, cholestasis, and cholestatic hepatitis was 3.0, 5.9, and 2.8 years, and none had signs or symptoms suggestive of liver disease. According to the Cox regression analysis, the predictors of an abnormal LFT in SSc were elderly onset of SSc (hazard ratio (HR) 1.02), alcoholic drinking (HR 1.74), high modified Rodnan Skin Score (mRSS) (HR 1.03), edematous skin (HR 2.94), Raynaud's phenomenon (HR 1.39), hyperCKaemia (HR 1.88), and methotrexate use (HR 1.55). In contrast, current sildenafil treatment (HR 0.63) and high serum albumin (HR 0.70) were protective factors.

Occult hepatitis, cholestasis, and cholestatic hepatitis can be detected in SSc patients using LFT screening, especially in cases of early disease onset. The long-term outcome is uncertain, and more longitudinal research is required.

Nonalcoholic fatty liver disease (NAFLD) is strongly associated with obesity but around 10% to 20% of patients with NAFLD have normal body mass index, a condition referred to as lean or nonobese NAFLD. Although lean patients more often have milder liver disease, a proportion may nonetheless develop steatohepatitis and advanced liver fibrosis. Both genetic and environmental factors contribute to the development of NAFLD. Noninvasive tests have similarly good accuracy as initial assessments for lean NAFLD. Future studies should determine the most appropriate treatment in this special population.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, with an estimated prevalence of 25% globally. NAFLD is closely associated with metabolic syndrome, which are both becoming increasingly more common with increasing rates of insulin resistance, dyslipidemia, and hypertension. Although NAFLD is strongly associated with obesity, lean or nonobese NAFLD is a relatively new phenotype and occurs in patients without increased waist circumference and with or without visceral fat. Currently, there is limited literature comparing and illustrating the differences between lean/nonobese and obese NAFLD patients with regard to risk factors, pathophysiology, and clinical outcomes. In this review, we aim to define and further delineate different phenotypes of NAFLD and present a comprehensive review on the prevalence, incidence, risk factors, genetic predisposition, and pathophysiology. Furthermore, we discuss and compare the clinical outcomes, such as insulin resistance, dyslipidemia, hypertension, coronary artery disease, mortality, and progression to nonalcoholic steatohepatitis, among lean/nonobese and obese NAFLD patients. Finally, we summarize the most up to date current management of NAFLD, including lifestyle interventions, pharmacologic therapies, and surgical options.

Non-alcoholic fatty liver disease is one of the most common causes of chronic liver diseases and occurs even in lean individuals having normal or low body mass index (BMI). Crucial issue is understanding the clinical, pathobiologic and metabolic characteristics in comparison to obese patients. Very few studies have compared clinicopathological characteristics between lean and obese. Published literature is generally in a small cohort of patients, rarely included over-weight as separate category, and most often had non-standardized use of BMI criteria with discordant conclusions. There is very sparse published literature on liver biopsy-confirmed cohort and that to from Asia; also, none had explored the role of mediators such as stellate cells, progenitor cells and macrophages.

To evaluate the prevalence of NAFLD in lean patients in a large cohort of histology-confirmed NAFLD, and explore clinico-pathological spectrum of lean NAFLD in comparison to over-weight and obese. Also, to investigate role of hepatic stellate cells, macrophage polarization and their relation to hepatic progenitor cells, in particular the relation to fibrosis and to different BMI categories.

Prospective analysis of eleven-year retrospective cross-sectional data of all consecutive patients of NAFLD diagnosed in the period between the year 2011 and 2021. All histologically confirmed cases of NAFLD fulfilling inclusion and exclusion criteria were stratified to three groups according to BMI based on Asian criteria. Demographic, lab, metabolic, and histological comparisons between lean and overweight-obese patients were performed. Histological grading and staging of NAFLD components were performed by NAS-CRN score. Immunohistochemical and image analysis-based assessment and quantification of stellate cells, progenitor cells, and macrophage polarization was performed. Appropriate statistical methods were applied, and study was approved by the Institutional ethics committee.

Lean patients with biopsy-proven diagnosis constituted 21 % (n = 267) of total NAFLD (n = 1273). Other groups were-over-weight patients (232;18.2 %), and the highest were obese patients (774; 60.8 %). 13.9 % of the lean patients with NAFLD were under-weight with BMI<18.5 kg/m2. Lean patients had significantly lower BMI and waist circumference along with lesser fasting glucose levels in comparison to the other groups. Rest of the metabolic parameters were nearly similar. Lean patients showed higher serum ALT levels, and histological characteristics such as ballooning of hepatocytes and steatosis were also more marked in comparison to other groups. Lobular inflammation and advanced fibrosis were significantly less common in lean patients with NASH related cirrhosis found in only 20.9 % of them. Immunophenotypic studies revealed the inter-relationship of HPCs, HSCs, and macrophages was influenced by the stage of fibrosis and not by the BMI.

Prevalence of NAFLD in lean individuals in a histological-confirmed patient cohort was 21 %. (n = 267/1273). Major strengths of this study are large cohort of lean individuals from a single center, inclusion of only histology-confirmed cases, Asia specific BMI criteria usage, comparative clinical, metabolic, immune-morphologic and image analysis-based characterization, inclusion of over-weight in addition to obese patients, and investigating cross-talk of principal patho-physiologic markers.

Whether adiposity and muscle function are associated with mortality risk in patients with non-alcoholic fatty liver disease (NAFLD) remains unknown. We examine the independent and combined associations of body mass index (BMI) and muscle strength with overall mortality in individuals with NAFLD.

We analysed data from 7083 participants with NAFLD in the Thai National Health Examination Survey and their linked mortality. NAFLD was defined using a lipid accumulation product in participants without significant alcohol intake. Poor muscle strength was defined by handgrip strength of <28 kg for men and <18 kg for women, according to the Asian Working Group on Sarcopenia. The Cox proportional-hazards model was constructed to estimate the adjusted hazard ratio (aHR) for overall mortality.

The mean age was 49.3 ± 13.2 years, and 69.4% of subjects were women. According to the Asian-specific criteria, 1276 individuals (18.0%) were classified as lean NAFLD (BMI 18.5-22.9 kg/m2 ), 1465 (20.7%) were overweight NAFLD (BMI 23-24.9 kg/m2 ), and 4342 (61.3%) were obese NAFLD (BMI ≥ 25 kg/m2 ). Over 60 432 person-years, 843 participants died. In Cox models adjusted for physiologic, lifestyle, and comorbid factors, individuals with lean NAFLD [aHR 1.18, 95% confidence interval (CI): 0.95-1.48; P = 0.138] and subjects with overweight NAFLD (aHR 1.28, 95% CI: 0.89-1.84; P = 0.158) had mortality risk estimates similar to their obese counterparts, whereas participants with lower handgrip strength had significantly higher mortality risk than those with higher handgrip strength in men and women. Compared with obese individuals with the highest handgrip strength, elevated mortality risk was observed among men (aHR 3.21, 95% CI: 1.35-7.62, P = 0.011) and women (aHR 2.22, 95% CI, 1.25-3.93, P = 0.009) with poor muscle strength. Among men, poor muscle strength was associated with increased risk of mortality with obese NAFLD (aHR 3.94, 95% CI, 1.38-11.3, P = 0.013), overweight NAFLD (aHR 2.93, 95% CI, 1.19-7.19, P = 0.021), and lean NAFLD (aHR 2.78, 95% CI, 0.93-8.32, P = 0.065). Among women, poor muscle strength was associated with increased mortality risk with obese NAFLD (aHR 2.25, 95% CI, 1.06-4.76, P = 0.036), overweight NAFLD (aHR 1.69, 95% CI, 0.81-3.51, P = 0.153), and lean NAFLD (aHR 2.47, 95% CI, 1.06-5.73, P = 0.037).

In this nationwide cohort of individuals with NAFLD, muscle strength, but not BMI, was independently associated with long-term overall mortality. Measuring handgrip strength can be a simple, non-invasive risk stratification approach for overall mortality in patients with NAFLD.

NAFLD can occur in non-obese individuals with BMI < 25 kg/m2. Our goal was to examine the prevalence and clinical factors associated with non-obese NAFLD using vibration-controlled transient elastography (VCTE) with controlled attenuation parameter which estimates steatosis and fibrosis among US adults. We aggregated data from the 2017−2018 cycle of NHANES and included adults (age ≥ 20 years) with BMI < 25 kg/m2 with complete data for the survey, medical examination, and VCTE along with controlled attenuation parameter (CAP). We excluded participants with risks of other liver diseases. We considered patients to have non-obese NAFLD if CAP was >285 dB/m, or non-obese NAFLD fibrosis if this CAP criteria was met and liver stiffness was >8.6 kPa. We calculated the adjusted OR and 95% CI for associations with non-obese NAFLD using multivariable logistic regression. The prevalence of non-obese NAFLD was 6.2% and Asian Americans (12.2%) had the highest non-obese NAFLD prevalence. Clinical factors associated with non-obese NAFLD were advanced age and metabolic syndrome (ORadjusted = 6.8, 95% CI 3.0−15.5). In a separate model, we found elevated glucose (ORadjusted = 4.1, 95% CI 2.1−7.9), triglycerides (ORadjusted = 3.8, 95% CI 1.7−8.5), and truncal fat (100-unit increase ORadjusted = 1.07, 95% CI: 1.04−1.10) were associated with higher odds of non-obese NAFLD. Meanwhile, low physical activity (ORadjusted = 2.9, 95% CI 1.2−7.1) was also positively associated with non-obese NAFLD. Non-obese NAFLD is prevalent in the US and is highly associated with metabolic conditions and syndrome. Our results support the importance of considering racial/ethnic differences when investigating NAFLD in a clinical setting.

Nonalcoholic fatty liver disease (NAFLD) is traditionally associated with obesity. However, there is a subtype of NAFLD, namely NAFLD in lean, that occurs without obesity. However, a recent call to redefine NAFLD to metabolic-associated fatty liver disease focuses on obesity and metabolic dysfunction. Criticism has arisen from the perceived over emphasis on systemic comorbidities, which may disadvantage the lean. The current analysis seeks to quantify the degree of metabolic dysfunction in NAFLD in lean and compare with NAFLD in overweight and obese and non-NAFLD.

Medline and Embase databases were searched from inception to March 3, 2022. The inclusion criteria were articles with NAFLD in lean patients presenting with baseline metabolic parameters. Comparisons were conducted with subgroup analysis.

Eighty-five articles were included in the meta-analysis. NAFLD in lean accounted for 13.11% (95% confidence interval [CI], 10.26%-16.62%) of the global population and 14.55% (95% CI, 11.32%-18.51%) in Asia. The degree of metabolic dysfunction was weight dependent with significantly less metabolic dysfunction in NAFLD in lean subjects as compared with NAFLD in overweight counterparts. For NAFLD in lean, only 19.56% (95% CI, 15.28%-24.69%) of the subjects were diabetic, whereas 45.70% (95% CI, 35.01%-56.80%) of obese subjects with NAFLD had diabetes (P < .01). Fasting blood glucose and systolic and diastolic blood pressure values were significantly lower in subjects with NAFLD in lean than in overweight and obese.

The current analysis highlights the weight-dependent nature of metabolic dysfunction in NAFLD. Lean subjects with NAFLD were significantly less metabolically unhealthy than were obese and overweight persons with NAFLD. An overreliance on metabolic dysfunction in defining fatty liver will be a flaw in potentially excluding previously characterized NAFLD.

The natural history of lean nonalcoholic fatty liver disease (NAFLD) is not well-understood. Consequently, patient counseling and disease management are limited. We aimed to compare the natural history of lean, overweight, and obese NAFLD in a U.S. population with long-term follow-up.

All adults diagnosed with NAFLD in Olmsted County, MN between 1996 and 2016 were identified, and all subsequent medical events were ascertained using a medical record linkage system. Subjects were divided on the basis of body mass index (BMI) at NAFLD diagnosis into 3 groups: normal, overweight, and obese. The probability to develop cirrhosis, decompensation, malignancies, cardiovascular events, or death among the 3 groups was estimated by using the Aalen-Johansen method, treating death as a competing risk. The impact of BMI categories on these outcomes was explored by using Cox proportional hazards regression analysis.

A total of 4834 NAFLD individuals were identified: 414 normal BMI, 1189 overweight, and 3231 obese. Normal BMI NAFLD individuals were characterized by a higher proportion of women (66% vs 47%) and lower prevalence of metabolic comorbidities than the other 2 groups. In reference to obese, those with normal BMI NAFLD had a nonsignificant trend toward lower risk of cirrhosis (hazard ratio [HR], 0.33, 95% confidence interval [CI], 0.1-1.05). There were no significant differences in the risk of decompensation (HR, 0.79; 95% CI, 0.11-5.79), cardiovascular events (HR, 1.05; 95% CI, 0.73-1.51), or malignancy (HR, 0.87; 95% CI, 0.51-1.48). Compared with obese, normal BMI NAFLD had higher risk of all-cause mortality (HR, 1.96; 95% CI, 1.52-2.51).

NAFLD with normal BMI is associated with a healthier metabolic profile and possibly a lower risk of liver disease progression but similar risk of cardiovascular disease and malignancy than obese NAFLD.

A significant proportion of the non-alcoholic fatty liver disease (NAFLD) population is non-obese. Prior studies reporting the severity of NAFLD amongst non-obese patients were heterogenous. Our study, using data from the largest biopsy-proven NAFLD international registry within Asia, aims to characterize the demographic, metabolic and histological differences between non-obese and obese NAFLD patients.

1812 biopsy-proven NAFLD patients across nine countries in Asia assessed between 2006 and 2019 were pooled into a curated clinical registry. Demographic, metabolic and histological differences between non-obese and obese NAFLD patients were evaluated. The performance of Fibrosis-4 index for liver fibrosis (FIB-4) and NAFLD fibrosis score (NFS) to identify advanced liver disease across the varying obesity subgroups was compared. A random forest analysis was performed to identify novel predictors of fibrosis and steatohepatitis in non-obese patients.

One-fifth (21.6%) of NAFLD patients were non-obese. Non-obese NAFLD patients had lower proportions of NASH (50.5% vs 56.5%, p = 0.033) and advanced fibrosis (14.0% vs 18.7%, p = 0.033). Metabolic syndrome in non-obese individuals was associated with NASH (OR 1.59, 95% CI 1.01-2.54, p = 0.047) and advanced fibrosis (OR 1.88, 95% CI 0.99-3.54, p = 0.051). FIB-4 performed better than the NFS score (AUROC 81.5% vs 73.7%, p < 0.001) when classifying patients with F2-4 fibrosis amongst non-obese NAFLD patients. Haemoglobin, GGT, waist circumference and cholesterol are additional variables found on random forest analysis useful for identifying non-obese NAFLD patients with advanced liver disease.

A substantial proportion of non-obese NAFLD patients has NASH or advanced fibrosis. FIB-4, compared to NFS better identifies non-obese NAFLD patients with advanced liver disease. Serum GGT, cholesterol, haemoglobin and waist circumference, which are neither components of NFS nor FIB-4, are important biomarkers for advanced liver disease in non-obese patients.

The pathophysiology and risk factors of nonalcoholic fatty liver disease (NAFLD) among lean patients is poorly understood and therefore investigated. We performed a meta-analysis of observational studies. Of 1175 articles found through searching from Medline/PubMed, Banglajol, and Google Scholar by two independent investigators, 22 were selected. Data from lean (n = 6768) and obese (n = 9253) patients with NAFLD were analyzed; lean (n = 43 398) and obese (n = 9619) subjects without NAFLD served as controls. Age, body mass index, waist circumference, systolic blood pressure, and diastolic blood pressure (DBP) had significantly higher estimates in lean NAFLD patients than in lean non-NAFLD controls. Fasting blood sugar [MD(mean difference) 5.17 mg/dl, 95% CI(confidence interval) 4.14-6.16], HbA1c [MD 0.29%, 95% CI 0.11-0.48], and insulin resistance [HOMA-IR] [MD 0.49 U, 95% CI 0.29-0.68]) were higher in lean NAFLD patients than in lean non-NAFLD controls. All components of the lipid profile were raised significantly in the former group except high-density lipoprotein. An increased uric acid (UA) level was found to be associated with the presence of NAFLD among lean. Cardio-metabolic profiles of nonlean NAFLD patients significantly differs from the counter group. However, the magnitude of the difference of lipid and glycemic profile barely reached statistical significance when subjects were grouped according to lean and nonlean NAFLD. But DBP (slope: 0.19, P < 0.037), HOMA-IR (slope: 0.58, P < 0.001), and UA (slope: 0.36, P = 0.022) were significantly higher if NAFLD was present compared to that of non-NAFLD group. Lean and nonlean NAFLD patients are metabolically similar and share common risk factors.

Metabolic associated fatty liver disease (MAFLD) is the commonest cause of chronic liver disease, which is associated with obesity and diabetes. However, it also occurs in lean individuals especially in Asian populations.

The participants of Tzu Chi MAFLD cohort (TCMC) including health controls or MAFLD patients were enrolled. MAFLD was defined as fatty liver in imaging without hepatitis B virus, hepatitis C virus infection, drug, alcohol or other known causes of chronic liver disease. Lean MAFLD was defined as MAFLD in lean subjects (BMI < 23 kg/m²).

A total of 880 subjects were included for final analysis. Of 394 MAFLD patients, 65 (16.5%) patients were diagnosed as lean MAFLD. Lean MAFLD patients were elder, higher percentage of female gender, lower ALT, diastolic blood pressure, triglyceride, and waist circumference but higher HDL than non-lean MAFLD patients. Using binary regression analysis, elder age and lower waist circumference were associated with lean MAFLD. Compared with lean healthy controls, lean MAFLD patients had higher BMI, waist circumference, and percentage of hypertension. In body composition, fatty tissue index (FTI), lean tissue index (LTI) ,and total body water (TBW) were lower in lean MAFLD than non-lean MAFLD patients; but they were comparable with lean healthy controls.

The prevalence of lean MAFLD was 16.5% in this study population and it was higher in elder age, especially of female subjects. Lean MAFLD patients had different metabolic profiles compared with lean healthy controls, but different body composition compared with non-lean MAFLD patients.

Non-alcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome. Worryingly, it has been increasingly reported among nonobese patients. This study aims to analyse patient characteristics of biopsy-proven NAFLD in an Asian cohort and explore differences stratified by body mass index (BMI).

Clinical, laboratory, and histological data were collected from 263 adults with biopsy-proven NAFLD. Patients with and without obesity (BMI cut-off 25) were compared. The ability to predict advanced liver fibrosis with three non-invasive scores, the NAFLD Fibrosis score (NFS), Fibrosis-4 (FIB4), and the aspartate aminotransferase to platelet ratio index (APRI), was compared.

Obese subjects had a lower mean age (49.5 ± 12.5 vs 54.0 ± 12.9 years, P = 0.017), a higher prevalence of diabetes (52.4% vs 36.8%, P = 0.037), and a higher waist circumference (113.9 ± 16.0 cm vs 87.0 ± 18.4 cm, P = 0.022). The prevalence of dyslipidaemia (68.0% vs 61.4%, P = 0.353) and hypertension (61.7% vs 49.1%, P = 0.190) was comparable between the two groups. The distribution of non-alcoholic steatohepatitis (NASH) (63.1% versus 61.4%, P = 0.710) and advanced fibrosis (31.6% versus 26.3%, P = 0.447) were also similar in both groups. All three non-invasive scores (NFS, FIB4, and APRI) performed poorly in predicting advanced fibrosis in nonobese patients with NAFLD. The FIB4 was the most accurate non-invasive score in predicting advanced fibrosis in the obese group.

Obese and nonobese patients are equally at risk of NASH and advanced fibrosis. While the FIB4 is the most accurate non-invasive score in predicting advanced fibrosis among obese individuals, further research is warranted to develop a nonobese specific score to correctly identify nonobese NAFLD patients with advanced fibrosis.

Since there is a paucity of data on the epidemiology of the non-alcoholic fatty liver disease (NAFLD), particularly in rural areas in Asia, we undertook such a study among the population of a rural community in Bangladesh with the aims to (1) determine the prevalence of non-obese and obese NAFLD, (2) compare the sociodemographic clinical and metabolic characteristics between non-obese and obese NAFLD subjects, and (3) determine the risk factors of NAFLD and no-nobese NAFLD.

In this door-to-door survey, clinical examination, anthropometric measurements, biochemical tests and ultrasonography were performed on the adult population (≥18 years) of three villages in Bangladesh.

Of 1682, 1353 (80.44%) responded. After the exclusion of 48 subjects for alcohol consumption, HBsAg or anti-hepatitis C virus positivity, 1305 ((mean age 41.28±15.10 years, female 908 (69.6%)) were included in the final analysis. On ultrasonography, among the study population, 57 (4.4%) non-obese, 185 (14.2%) obese and, overall, 242 (18.5 %, (male 23.40%, female 16.4%, p=0. 003)) participants had NAFLD. NAFLD was detected in 57/804 (7.1%) of non-obese and 185/501 (36.93%) obese participants. Among the lean subjects, 24/592 (4.1%) had NAFLD. Among NAFLD subjects, 57 (23.55%) were non-obese, and 53 (22%) had raised alanine aminotransferase. On multivariate analysis, age >40 years, male gender, metabolic syndrome (MS), diabetes mellitus (DM), abdominal obesity, hypertension, dyslipidaemia and obesity were found as the risk factors for NAFLD. There were no differences in sociodemographic characteristics, DM, MS, abdominal obesity, hypertension and dyslipidaemia between non-obese and obese NAFLD (all p>0.05).

In this community study in Bangladesh, NAFLD was present in 18.5% participants, one-quarter of whom were non-obese. Apart from body mass index, the metabolic profile was comparable between obese and non-obese NAFLD. Public health measures are needed to control and prevent NAFLD and MS and their adverse health consequences.

Nonalcoholic fatty liver disease (NAFLD) accounts for most cases of chronic liver disease worldwide, with an estimated global prevalence of approximately 25% and ranges from simple steatosis to nonalcoholic steatohepatitis and cirrhosis. NAFLD is strongly connected to metabolic syndrome, and for many years, fatty liver was considered to be an exclusive feature of obese patients. However, recent studies have highlighted the presence of NAFLD in non-obese subjects, with or without increased visceral fat or even in lean subjects without increased waist circumference. "Lean NAFLD" is a relatively new concept and there is significant scientific interest in understanding the differences in pathophysiology, prognosis and management compared with NAFLD in overweight/obese patients. In the present editorial, we discuss the clinical and metabolic profiles and outcomes of lean NAFLD compared with both obese NAFLD and lean healthy individuals from Asian and Western countries. Moreover, we shed light to the challenging topic of management of NAFLD in lean subjects since there are no specific guidelines for this population. Finally, we discuss open questions and issues to be addressed in the future in order to categorize NAFLD patients into lean and non-lean cohorts.

This review provides an update on the characteristics of nonalcoholic fatty liver disease (NAFLD), with a focus on the effects of age, sex, and body mass index. Age is a risk factor for NAFLD progression; however, extremely old patients have unique features, namely, the associations between metabolic comorbidities and NAFLD are weaker and NAFLD is not a risk factor for mortality. The prevalence of NAFLD is higher in men than in premenopausal women, whereas the reverse is true after menopause. Thus, before menopause, estrogen may have protective effects against NAFLD. Our hospital data showed that over 25% of male patients with NAFLD and almost 40% of female patients with NAFLD, especially elderly patients, were nonobese. Although histological steatosis and activity were associated with body mass index, the prevalence of nonalcoholic steatohepatitis was not. The prevalence of advanced fibrosis showed a significant sex difference. Advanced fibrosis was significantly more frequent among severely obese men but the prevalence was lower among severely obese women. This difference could be because a substantial proportion of severely obese women were premenopausal; thus, estrogen may have much stronger effects on the development of fibrosis than on obesity. Further studies are required to develop tailored management strategies.

Although non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, it is increasingly being identified in non-obese individuals. We aimed to characterise the prevalence, incidence, and long-term outcomes of non-obese or lean NAFLD at a global level.

For this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and the Cochrane Library from inception to May 1, 2019, for relevant original research articles without any language restrictions. The literature search and data extraction were done independently by two investigators. Primary outcomes were the prevalence of non-obese or lean people within the NAFLD group and the prevalence of non-obese or lean NAFLD in the general, non-obese, and lean populations; the incidence of NAFLD among non-obese and lean populations; and long-term outcomes of non-obese people with NAFLD. We also aimed to characterise the demographic, clinical, and histological characteristics of individuals with non-obese NAFLD.

We identified 93 studies (n=10 576 383) from 24 countries or areas: 84 studies (n=10 530 308) were used for the prevalence analysis, five (n=9121) were used for the incidence analysis, and eight (n=36 954) were used for the outcomes analysis. Within the NAFLD population, 19·2% (95% CI 15·9-23·0) of people were lean and 40·8% (36·6-45·1) were non-obese. The prevalence of non-obese NAFLD in the general population varied from 25% or lower in some countries (eg, Malaysia and Pakistan) to higher than 50% in others (eg, Austria, Mexico, and Sweden). In the general population (comprising individuals with and without NAFLD), 12·1% (95% CI 9·3-15·6) of people had non-obese NAFLD and 5·1% (3·7-7·0) had lean NAFLD. The incidence of NAFLD in the non-obese population (without NAFLD at baseline) was 24·6 (95% CI 13·4-39·2) per 1000 person-years. Among people with non-obese or lean NALFD, 39·0% (95% CI 24·1-56·3) had non-alcoholic steatohepatitis, 29·2% (21·9-37·9) had significant fibrosis (stage ≥2), and 3·2% (1·5-5·7) had cirrhosis. Among the non-obese or lean NAFLD population, the incidence of all-cause mortality was 12·1 (95% CI 0·5-38·8) per 1000 person-years, that for liver-related mortality was 4·1 (1·9-7·1) per 1000 person-years, cardiovascular-related mortality was 4·0 (0·1-14·9) per 1000 person-years, new-onset diabetes was 12·6 (8·0-18·3) per 1000 person-years, new-onset cardiovascular disease was 18·7 (9·2-31·2) per 1000 person-years, and new-onset hypertension was 56·1 (38·5-77·0) per 1000 person-years. Most analyses were characterised by high heterogeneity.

Overall, around 40% of the global NAFLD population was classified as non-obese and almost a fifth was lean. Both non-obese and lean groups had substantial long-term liver and non-liver comorbidities. These findings suggest that obesity should not be the sole criterion for NAFLD screening. Moreover, clinical trials of treatments for NAFLD should include participants across all body-mass index ranges.

None.

Data on prevalence and profile of nonalcoholic fatty liver disease (NAFLD) among individuals who are lean (normal body mass index) is unclear. Published data from studies comparing lean with obese NAFLD or with healthy subjects on prevalence, comorbidities, liver chemistry and histology, and metabolic/inflammatory markers were analyzed. Data were reported as odds ratio and 95% confidence interval for categorical variables and difference of means for continuous variables. Analysis of 53 studies on 65,029 subjects with NAFLD (38,084 lean) and 249,544 healthy subjects showed a prevalence of lean NAFLD at 11.2% in the general population. Among individuals with NAFLD, the prevalence of lean NAFLD was 25.3%. Lean NAFLD versus healthy subjects had higher odds for abnormalities on metabolic profile, including metabolic syndrome and its components, renal and liver function, and patatin-like phospholipase domain-containing protein 3 (PNPLA3) G allele; and inflammatory profile, including uric acid and C-reactive protein. The abnormalities were less severe among lean versus obese NAFLD on metabolic syndrome with its components, renal and liver chemistry, liver stiffness measurement, PNPLA3 and transmembrane 6 superfamily member 2 polymorphisms, and uric acid levels as markers of inflammation. Lean NAFLD had less severe histologic findings, including hepatocyte ballooning, lobular inflammation, NAFLD activity score, and fibrosis stage. Limited data also showed worse outcomes between obese versus lean NAFLD. Conclusion: Lean NAFLD is a distinct entity with metabolic, biochemical, and inflammatory abnormalities compared to healthy subjects and a more favorable profile, including liver histology of steatohepatitis and fibrosis stage, compared to obese NAFLD. We suggest that prospective multicenter studies examine long-term hepatic and extrahepatic outcomes in individuals with lean NAFLD.

As a subgroup of nonalcoholic fatty liver disease (NAFLD), patients with non-obese NAFLD may also have an increased risk of adverse hepatic and metabolic outcomes. We aimed to estimate the prevalence and incidence of non-obese NAFLD and to describe its clinical characteristics in this systematic review and meta-analysis.

We performed a systematic search of 1235 citations published up to Mar 2020. Meta-analyses, stratified analyses and meta-regression were all performed.

Of the 46 studies included, 28 cross-sectional and longitudinal studies of 155 846 non-obese participants reported a pooled NAFLD prevalence of 14.5% (95% confidence interval [CI] 12.3%-17.1%). A multivariate meta-regression analysis showed the trend that the prevalence varied by their geographical location. Further stratified analyses showed that NAFLD was relatively prevalent among people aged ≥45 years (16.2%; 95% CI 10.8-23.4) and those in South America (25.7%; 95% CI 24.4-27.0). The PNPLA3 rs738409 gene polymorphism was more frequently observed in non-obese NAFLD than in both obese NAFLD and non-obese controls, while the metabolic profiles of non-obese NAFLD were less severe than those of the obese NAFLD group. Patients with non-obese NAFLD had 4.81-fold and 5.43-fold higher risk of diabetes mellitus and metabolic syndrome, respectively, than the non-obese controls.

Non-obese NAFLD is common, particularly in South America and among people aged ≥45 years. Metabolic diseases and PNPLA3 rs738409 gene polymorphism are more frequent in the non-obese NAFLD group than in non-obese controls.

Non-alcoholic fatty liver disease (NAFLD) has become a major health concern. Focal fat deposition frequently seems to involve segment IV b. This indicates a consistent pattern of fat deposition in the liver. The present study evaluates the pattern of fat distribution in the liver using computed tomogram (CT) attenuation index.

Two radiologists evaluated 517 non-contrast CT scan images of the abdomen and pelvis. Two 40-mm² regions of interest (ROIs) were selected from each segment. The hepatic segmental densities (HSDs) were obtained by calculating the mean densities of areas of corresponding liver segments. The mean hepatic attenuation (MHA) was quantified by obtaining the mean segmental densities. Densities were compared between the segments and with the MHA.

The mean age (SD) of the patients was 55.5 year (15.6), and 276 (53.4%) were males. The overall mean hepatic density was 53.05 (95% CI, 52.95-53.15) Hounsfield units (HU). The lowest mean HSD was observed in segment IV b and the highest mean HSD was observed in segment V. Segments I, IV a and IV b showed significantly lower mean HSDs and segments V, VI and VIII showed significantly higher mean HSDs compared with the overall mean MHA/mean hepatic density (MHD), whereas mean HSDs of segments II, III and VII were not significantly different from the overall mean MHA/MHD.

Segment IV b seems to be the most vulnerable site for fat deposition; focal lesions here should be carefully evaluated. Segments II, III and VII seem to closely represent MHD.

Non-alcoholic fatty liver disease (NAFLD) is associated with obesity, which is known to be associated with metabolic syndrome (MS). However, the risk factors for NAFLD in absence of obesity (leanness) is not well-studied. This study aimed to investigate and compare the clinical characteristics, metabolic associations, and cardiovascular risk factors among patients having NAFLD with (body mass index [BMI] ≥ 23 kg/m²) or without obesity (BMI < 23 kg/m²).

The cross-sectional study was conducted among the outdoor and indoor patients diagnosed as NAFLD by ultrasonography in a tertiary care teaching hospital in eastern India. Relevant anthropometric measurements, laboratory investigations, and imaging were performed. Metabolic syndrome was classified by the "International Diabetes Federation, 2005" criteria.

Among 120 NAFLD patients, 37 (30.8%) were lean, while 83 (69.2%) were obese. The components of MS such as systolic blood pressure (lean, 138.0 ± 17.6 mmHg; obese, 137.9 ± 15.3 mmHg), diastolic blood pressure (lean, 88.9 ± 6.5 mmHg; obese, 87.3 ± 6.1 mmHg), fasting blood sugar (lean, 127.8 ± 30.8 mg/dL; obese, 135.1 ± 29.5 mg/dL), and serum triglyceride (lean, 170.5 ± 34.2 mg/dL; obese, 186.4 ± 43.8 mg/dL) were comparable among patients with obese and lean NAFLD and were more often abnormal among both the groups of NAFLD as compared with controls.

The overall prevalence of MS among NAFLD study population was 64.2%. Lean NAFLD was also associated with the component of MS like obese NAFLD.

Insulin resistance (IR) plays a central role in pathogenesis of nonalcoholic steatohepatitis (NASH). The aim of this study was to correlate histopathological grading and IR in overweight/obese patients with NASH as compared with lean NASH.

Patients with NASH who underwent liver biopsy between January 2012 and December 2012 were included. Anthropometric, clinical, and biochemical features, necro-inflammatory grades, and fibrosis stage on liver biopsies were scored according to Brunt and non-alcoholic fatty liver disease (NAFLD) activity score (NAS).

Of 42 patients, 33 (78.6%) had body mass index (BMI) ≥ 23 kg/m² (overweight/obese) while 9 had BMI < 23 kg/m² (lean). Mean fasting blood sugar (FBS) and HbA1c levels in overweight/obese patients with NASH were higher than in lean NASH (p < 0.05). The median homeostatic model assessment-estimated insulin resistance (HOMA-IR) among NASH patients with BMI ≥ 23 kg/m² was higher than among those with BMI < 23 kg/m² (3.02 [0.34-17.22] vs. 2 [0.52-5.26]; p = 0.045). However, fasting insulin levels were comparable among lean and overweight/obese patients with NASH. Metabolic syndrome could be predicted with 75% sensitivity and 85.3% specificity at a HOMA-IR cutoff value of 3.9. No significant difference was observed with regard to HOMA-IR levels with Brunt grades, Brunt staging, Brunt grades 1 and 2, Brunt scores < 2 and > 2, and NAS scores, and NAS scores < 4 and > 4.

Although IR was significantly higher in overweight/obese patients with NASH as compared with that in lean patients with NASH, there was no difference in the correlation of HOMA-IR with histology between these groups.

Nonalcoholic fatty liver disease (NAFLD) is considered the most common liver disorder worldwide, affecting 25.2% of the general population. In fact, NAFLD is among the most common etiologies for hepatocellular carcinoma (HCC). The burden of NAFLD is primarily driven by the epidemic of obesity and type 2 diabetes which are expected to worsen throughout the world. In this context, the burden of NAFLD and associated HCC and cirrhosis are also expected to increase. Despite its growing disease burden, diagnostic tools and treatment modalities remain very limited. This conundrum of increasing prevalence and limited treatment options will be reflected as increasing number of NAFLD-related cirrhosis and HCC cases. This article reviews the most updated information about NAFLD-related HCC and provides some insight into strategies that must be considered to reduce its potential disease burden.

Weight reduction has evidenced benefit on attenuation of histological activity and fibrosis of nonalcoholic steatohepatitis (NASH), but there is scarcity of data for lean NASH subgroup. We have designed this study to compare the effects of weight reduction on histological activity and fibrosis of lean and non-lean NASH.

We have included 20 lean and 20 non-lean histologically proven NASH patients. BMI < 25 kg/m2 was defined as non-lean. Informed consent was taken from each subject. All methods were carried out in accordance with the Declaration of Helsinki. Moderate exercise along with dietary restriction was advised for both groups for weight reduction. After 1 year, 16 non-lean and 15 lean had completed second liver biopsy.

Age, sex, alanine transaminase (ALT), aspartate aminotransferase (AST), gamma-glutamyltrasferase (GGT), Homeostasis model assessment insulin resistance (HOMA-IR), triglyceride and high density lipoprotein (HDL) was similar in both groups. Steatosis, ballooning, lobular inflammation, nonalcoholic fatty liver disease activity score (NAS) and fibrosis was similar in the two groups. In lean/non-lean group, any amount of weight reduction, ≥ 5% weight reduction and ≥ 7% weight reduction was found in respectively 8/11, 5/6 and 2/6 patients. In both lean and non-lean groups, weight reduction of any amount was associated with significant reduction of steatosis, ballooning and NAS, except lobular inflammation and fibrosis. In both groups, weight reduction of ≥ 5% was associated with significant reduction in NAS only. However, significant improvement in NAS was noted with ≥ 7% weight reduction in non-lean group only.

Smaller amount of weight reduction had the good benefit of improvement in all the segments of histological activity in both lean and non-lean NASH.

To elucidate features of nonobese non-alcoholic fatty liver disease (NAFLD), we assessed Japanese patients with NAFLD stratified by body mass index (BMI) and by sex.

Biopsy-proven 762 NAFLD patients (404 men) were classified into three groups by the Japanese criteria: nonobese group (BMI < 25 kg/m² ), obese group (25 to 30), and severely obese group (≥ 30). Clinicopathological features and single nucleotide polymorphism of patatin-like phospholipase 3 (PNPLA3) rs738409 were investigated, and body composition analysis was performed by bioelectrical impedance analysis and computed tomography.

Over 25% of men and almost 40% of women were nonobese, but most of them had visceral fat obesity and/or insulin resistance. The median age (years) of the nonobese, obese, and severely obese men was 49.9, 46.8, and 40.5 (P < 0.01), respectively, while those of women was 60.2, 59.6, and 48.5 (P < 0.01), respectively. The prevalence of metabolic comorbidities and PNPLA3 risk alleles did not differ among these groups in both sexes. Also, the prevalence of non-alcoholic steatohepatitis was not significantly different in both sexes, although nonobese patients had a higher prevalence of mild steatosis. Advanced fibrosis showed a marked difference between men and women. Advanced fibrosis was significantly more frequent among severely obese men (nonobese: 31.0%, obese: 41.6%, severely obese: 60.9%; P < 0.01), but it was lower among severely obese women (51.4%, 62.9%, 33.7%; P < 0.01). Skeletal muscle mass was significantly lower in nonobese patients.

Non-alcoholic fatty liver disease was not milder in nonobese patients. Histological steatosis was associated with BMI, but advanced fibrosis was not and showed a significant sex difference.

It is not known whether non alcoholic fatty liver disease (NAFLD) is a risk factor for diabetes in non obese, non centrally-obese subjects. Our aim was to investigate relationships between fatty liver, insulin resistance and a biomarker score for liver fibrosis with incident diabetes at follow up, in subjects who were neither obese nor centrally-obese.

As many as 70,303 subjects with a body mass index (BMI) < 25 kg/m2 and without diabetes were followed up for a maximum of 7.9 years. At baseline, fatty liver was identified by liver ultrasound, insulin resistance (IR) by homeostatic model assessment of insulin resistance (HOMA-IR) ≥2.0, and central obesity by waist circumference (waist circumference ≥90 cm (men) and ≥85 cm (women). The Fibrosis-4 (FIB-4 score) was used to estimate extent of liver fibrosis. Cox proportional hazards models adjusted for confounders were used to estimate hazard ratios (aHRs) for incident diabetes. As many as 852 incident cases of diabetes occurred during follow up (median [IQR] 3.71 [2.03] years). Mean ± SD BMI was 22.8 ± 1.8 and 21.7 ± 2.0 kg/m2 in subjects with and without diabetes at follow up. In subjects without central obesity and with fatty liver, aHRs (95% CI) for incident diabetes at follow up were 2.17 (1.56, 3.03) for men, and 2.86 (1.50,5.46) for women. Similar aHRs for incident diabetes occurred with fatty liver, IR and the highest quartile of FIB-4 combined, in men; and there was a non significant trend toward increased risk in women.

In normal weight, non-centrally obese subjects NAFLD is an independent risk factor for incident diabetes.

Nonalcoholic Fatty Liver Disease (NAFLD) is thought to be a hepatic manifestation of Metabolic Syndrome (MS) or Insulin Resistance (IR). The aim of the study was to explore the clinical, anthropometric, metabolic, biochemical and histological profile of NAFLD patients without IR by comparing it with NAFLD with IR.

Total 851 patients with sonographic evidence of fatty liver were included. These patients underwent clinical, anthropometric, biochemical and histological evaluation. IR was calculated using the homeostatic model assessment. Liver biopsy done in 285 patients who consented for the procedure and who had MS or raised ALT.

Among 851 NAFLD patients, 561(65.9%) patients were without IR and 290 (34.1%) patients were with IR. The proportion of male sex [230 (41.0%) vs. 89 (30.7%); P = 0.046] were higher but diabetes [19.10% vs. 39.0%; P = 0.000] and MS were [58.80%vs. 78.10%; P = 0.014] significantly lower in non IR group. Body Mass Index (BMI) kg/m2 and Waist Circumference (WC) in cm were also lower in non IR group: [26.6 ± 3.5 vs. 27.9 ± 4.3; P = 0.002] and [93.3 ± 8.4 vs. 95.9 ± 8.4; P = .003]. Lipid profile, ALT, AST and ALP were not differed between the groups. Histopathology reports revealed that lobular inflammation, ballooning and fibrosis were similar in two groups, only steatosis score was higher in IR group [2.0 ± 0.7 vs. 1.8 ± 0.8; P = 0.007].

There are significant proportion of NAFLD patients without IR in Bangladesh. NAFLD patients without IR predominantly male, had lower BMI, WC, MS and diabetes. Histologically NAFLD without IR equally severe with ballooning, lobular inflammation and fibrosis except steatosis. Insulin resistance is the principal but not the sole factor for NAFLD in our population.

Non-alcoholic fatty liver disease (NAFLD), with its increasing prevalence and association with various co-morbidities, such as diabetes, cardiovascular disease and metabolic syndrome, is a growing concern. Previously thought to predominantly affect obese individuals, NAFLD has been shown to occur in non-obese subjects. This subset of individuals, known to have 'lean NAFLD' or 'non-obese NAFLD', is also growing increasingly prevalent. We summarize the clinical manifestations, pathophysiology and management of lean NAFLD in both adult and pediatric populations.

Two reviewers performed an independent, formal review and analysis of the literature (PubMed and EMBASE search until April 2018).

Patients with lean NAFLD share metabolic features of insulin resistance and dyslipidemia, similar to obese patients with NAFLD. Genetic predisposition, dietary and environmental factors may play a role in the pathogenesis of lean NAFLD. Genetic and metabolic conditions should be considered as well. Currently, there are no formal recommendations for the treatment of adult or pediatric lean NAFLD; however, lifestyle changes aimed at improving overall fitness are likely to have a favorable impact.

Nonalcoholic fatty liver disease (NAFLD) can develop in lean subjects referred to as lean NAFLD. We aim to evaluate the prevalence and risk factors of NAFLD in lean adolescents in the United States (US).

Cross sectional data from 1482 lean subjects (body mass index <85th percentile) ages between 12 and 18 years, who were enrolled in the National Health and Examination Survey during the 2005 to 2014 cycles were included. We defined suspected NAFLD as alanine aminotransferase >25.8 U/L for boys and >22.1 U/L for girls; hypertriglyceridemia as triglycerides ≥150 mg/dL; low HDL as HDL <40 mg/dL and insulin resistance (IR) as homeostatic model assessment of IR ≥3.

The mean weighted prevalence of suspected NAFLD among lean adolescents during 2005 to 2014 cycles was 8% (95% CI 6.2-9.9). Lean subjects with suspected NAFLD were significantly older compared with lean non-NAFLD subjects (15.5 vs 15 years, P value <0.05). Low HDL (15.5% vs 6.8%; P value 0.016) and hypertriglyceridemia (10% vs 3.9%; P value 0.028) were also found to be more common among lean NAFLD subjects compared with their non-NAFLD counterparts. Presence of IR increased the risk of having suspected NAFLD by 4-fold among lean adolescents. Non-Hispanic black lean adolescents were less likely to have suspected NAFLD compared with non-Hispanic white lean adolescents.

The estimated prevalence of suspected NAFLD among lean adolescents in the US was found to be 8% with evidence of metabolic derangements such as low HDL, hypertriglyceridemia, and IR.

A number of researches have explored the association between obesity and nonalcoholic fatty liver disease (NAFLD) liver function, histopathology, complications, genetic factors and prognosis, but the results were conflicting and inconclusive. Areas covered: In this meta-analysis, the liver function, histopathology, metabolic complications, patatin-like phospholipase domain-containing protein 3 (PNPLA3) genetic polymorphism and prognosis were compared between non-obese and obese NAFLD. Pubmed, EMBASE, Cochrane databases were searched to identify eligible studies. The odds ratio (OR) or standardized mean difference (SMD) with 95% confidence intervals (CI) were pooled using fixed- or random-effects models. Expert commentary: This meta-analysis indicated that for NAFLD patients, obesity (according to ethnic-specific BMI cut-off points to define obesity) could predict a worse long-term prognosis. However, obesity may not be an independent factor for the development of NASH or advanced fibrosis in NAFLD patients and NAFLD should be considered as potential population for pharmacologic treatment regardless of obesity. In addition, PNPLA3 rs738409 may be more relevant to the progression of non-obese NAFLD when compared to obese NAFLD. Importantly, large-sample, long-term follow-up cohort studies based on liver biopsy are highly needed due to limited liver pathology and long-term follow-up data at present.

Non-alcoholic fatty liver disease (NAFLD) is a significant cause of hepatic dysfunction and liver-related mortality. As there is a lack of population-based prevalence data in a representative sample of general population, we aimed to estimate the prevalence and risk factors of NAFLD in Bangladesh.

A cross-sectional study was conducted both in urban and rural areas of Bangladesh from December 2015 to January 2017. Data were collected using a pretested structured questionnaire followed by ultrasonography of hepatobiliary system for screening of NAFLD. Multivariate logistic regression was used to estimate the risk factors of NAFLD.

A total of 2782 (1694 men and 1088 women) participants were included in the study, with a mean age of 34.21 (±12.66) years. The overall prevalence of NAFLD was 33.86% (95% confidence interval [CI]: 32.12, 35.64). Females living in the rural areas and midlife adults (45-54 years) had the highest prevalence of NAFLD (P < 0.05). Multivariable logistic regression model demonstrated that increasing age, diabetes, elevated body mass index, and married individuals are significantly associated with NAFLD. Individuals with diabetes (adjusted odds ratio: 2.71, 95% CI: 1.85, 3.97) and hypertension were at a higher risk of having NAFLD. The odds of having NAFLD were 4.51 (95% CI: 3.47, 5.86) and 10.71 (95% CI: 7.80, 14.70) times higher among overweight and obese participants, respectively, as compared to normal-weight participants.

About one-third of the population of Bangladesh is affected by NAFLD. Individuals with higher body mass index (overweight and obese), diabetics, midlife adults, married individuals, and rural women were more at risk of having NAFLD than others.

Nonalcoholic fatty liver disease (NAFLD) encompasses simple steatosis and steatohepatitis (NASH) with or without fibrosis/cirrhosis and hepatocellular carcinoma. NAFLD occurs epidemically in most areas of the world, contributes to cardiovascular events and liver-related mortality and therefore exacts a major economic toll. Areas covered: Here we summarize what clinicians should know about NAFLD histopathology in adults. We report on the individual histological features and scoring systems of NAFLD: the NAFLD activity score (NAS) introduced by the NASH-Clinical Research Network, the 'Fatty Liver Inhibition of Progression' algorithm and Steatosis, Activity, and Fibrosis (SAF) score. Pros and cons of histological classifications in NASH are discussed. Special emphasis is given to liver histopathology in some high-risk patient groups, such as those with severe obesity and type 2 diabetes. Moreover, we also examine the relationship between liver histopathology and clinical features, and the impact of liver histopathology on the long-term prognosis of NAFLD. Finally, we propose an integrated diagnostic approach which utilizes both non-invasive tools and liver biopsy in those individual patients with suspected NAFLD. Expert commentary: Based on expert opinions, we conclude with a research agenda on NAFLD which focuses on the most burning topics to be addressed over the next five years.

Current evidence suggests that lean and obese patients with nonalcoholic fatty liver disease (NAFLD) share an altered metabolic and cardiovascular profile. However, there is an incomplete understanding of the natural history of "lean-NAFLD." Indeed, an unanswered question is whether lean (BMI ≤ 25 Kg/m² ) NAFLD-patients are protected from severe histological outcomes.

To perform a meta-analysis with the goal of providing a quantitative estimation of the magnitude of fibrosis, as well as histological features associated with the disease severity, in lean versus overweight/obese-NAFLD patients.

Through a systematic search up to July 2017, we identified eight studies that compared histological outcomes in lean (n = 493) versus overweight/obese (n = 2209) patients.

Relative to lean-NAFLD, overweight/obese-NAFLD patients showed significantly (P = .032) higher fibrosis scores; the observed difference in means between the two groups, which is the absolute difference between the mean value of fibrosis score [0-4] ± standard error, was 0.28 ± 0.13. The risk of having nonalcoholic steatohepatitis-NASH (OR 0.58 95% CI 0.34-0.97) was significantly lower in lean-NAFLD (n = 322) than in overweight/obese-NAFLD (n = 1357), P = .04. Relative to lean-NAFLD, overweight/obese-NAFLD patients also have significantly greater NAFLD activity (difference in means ± SE: 0.58 ± 0.16, P = .0004) and steatosis (difference in means ± SE: 0.23 ± 0.07, P = .002) scores.

Lean-NAFLD patients tend to show less severe histological features as compared to overweight/obese-NAFLD patients. Subsequent longitudinal assessment is needed to understand the clinical impact of these findings; however, the significant ~ 25% increment of mean fibrosis score in overweight/obese patients suggests that obesity could predict a worse long-term prognosis.

Non-alcoholic fatty liver disease (NAFLD) is commonly diagnosed in obese subjects; however, it is not rare among lean individuals. Given the absence of traditional risk factors, it tends to remain under-recognised. The metabolic profiles of lean NAFLD patients are frequently comparable to those of obese NAFLD patients. Though results from several studies have been mixed, it has been generally revealed that lean subjects with NAFLD have minor insulin resistance compared to that in obese NAFLD. Several genetic variants are associated with NAFLD without insulin resistance. Some data suggest that the prevalence of steatohepatitis and advanced fibrosis do not differ significantly between lean and obese NAFLD; however, the former tend to have less severe disease at presentation. The underlying pathophysiology of lean NAFLD may be quite different. Genetic predispositions, fructose- and cholesterol-rich diet, visceral adiposity and dyslipidaemia have potential roles in the pathogenic underpinnings. Lean NAFLD may pose a risk for metabolic disturbances, cardiovascular morbidity or overall mortality. Secondary causes of hepatic steatosis are also needed to be ruled out in lean subjects with NAFLD. The effectiveness of various treatment modalities, such as exercise and pharmacotherapy, on lean NAFLD is not known. Weight loss is expected to help lean NAFLD patients who have visceral obesity. Further investigation is needed for many aspects of lean NAFLD, including mechanistic pathogenesis, risk assessment, natural history and therapeutic approach.

Nonalcoholic fatty liver disease (NAFLD) is well described as a common cause of chronic liver disease, mostly in the obese population. It refers to a spectrum of chronic liver disease that starts with simple steatosis than progresses to nonalcoholic steatohepatitis and cirrhosis in patients without significant alcohol consumption. NAFLD in the non-obese population has been increasingly reported and studied recently. The pathogenesis of nonobese NAFLD is poorly understood and is related to genetic predisposition, most notably patatin-like phospholipase domain-containing 33 G allele polymorphism that leads to intrahepatic triglyceride accumulation and insulin resistance. Non-obese NAFLD is associated with components of metabolic syndrome and, especially, visceral obesity which seems to be an important etiological factor in this group. Dietary factors and, specifically, a high fructose diet seem to play a role. Cardiovascular events remain the main cause of mortality and morbidity in NAFLD, including in the non-obese population. There is not enough data regarding treatment in non-obese NAFLD patients, but similar to NAFLD in obese subjects, lifestyle changes that include dietary modification, physical activity, and weight loss remain the mainstay of treatment.

The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is closely associated with the co-occurrence of multiple pathological conditions characterising the metabolic syndrome (MetS), obesity in particular. However, NAFLD also develops in lean subjects, whose risk factors remain poorly defined.

We performed a meta-analysis of 15 studies, along with the data pertaining to our own population (n=336 patients). Data from lean (n=1966) and obese (n=5938) patients with NAFLD were analysed; lean (n=9946) and obese (n=6027) subjects without NAFLD served as controls.

Relative to the lean non-NAFLD controls, lean patients with NAFLD were older (3.79±0.72 years, P=1.36×10^-6 ) and exhibited the entire spectrum of the MetS risk factors. Specifically, they had a significant (P=10^-10 ) increase in plasma glucose levels (6.44±1.12 mg/dL) and HOMA-IR (0.52±0.094-unit increment), blood lipids (triglycerides: 48.37±3.6, P=10^-10 and total cholesterol: 7.04±3.8, mg/dL, P=4.2×10^-7 ), systolic (5.64±0.7) and diastolic (3.37±0.9) blood pressure (mm Hg), P=10^-10 , and waist circumference (5.88±0.4 cm, P=10^-10 ); values denote difference in means±SE. Nevertheless, the overall alterations in the obese group were much more severe when compared to lean subjects, regardless of the presence of NAFLD. Meta-regression suggested that NAFLD is a modifier of the level of blood lipids.

Lean and obese patients with NAFLD share a common altered metabolic and cardiovascular profile. The former, while having normal body weight, showed excess of abdominal adipose tissue as well as other MetS features.

Nonalcoholic fatty liver disease (NAFLD) refers to a group of conditions characterized by hepatic steatosis in the absence of significant alcohol consumption. NAFLD is seen commonly in patients with metabolic abnormalities associated with obesity, such as type II diabetes, dyslipidemia, and metabolic syndrome. Evidently, however, not all obese subjects develop NAFLD and, more importantly, NAFLD can be found in nonobese individuals. Although NAFLD occurring in nonobese subjects has been reported in children and adults of all ethnicities, it appears to be recognized more frequently in Asians, even when strict ethnicity-specific body mass index criteria are used to define obesity. Studies based on liver biopsies suggest that the prevalence of nonalcoholic steatohepatitis and fibrosis does not differ significantly between nonobese NAFLD and NAFLD in obese patients. Visceral obesity as opposed to general obesity, high fructose and cholesterol intake, and genetic risk factors (eg, palatin-like phospholipase domain-containing 3) may be associated with nonobese NAFLD. In general, nonalcoholic steatohepatitis is associated with increased mortality, primarily from cardiovascular causes, independent of other metabolic factors. Although data regarding the mortality impact of nonobese NAFLD are not as mature, it may be important to identify high-risk nonobese NAFLD patients and manage their metabolic profile. Currently, lifestyle modification to reduce visceral adiposity, including dietary changes and physical activity, remains the standard of care in patients with nonobese NAFLD.