Non-alcoholic fatty liver disease in lean individuals.
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ABSTRACT:
SUBMITTER: Albhaisi S
PROVIDER: S-EPMC7001558 | biostudies-literature | 2019 Oct
REPOSITORIES: biostudies-literature
Publications
Non-alcoholic fatty liver disease in lean individuals.
Albhaisi Somaya S Chowdhury Abhijit A Sanyal Arun J AJ
JHEP reports : innovation in hepatology 20190830 4
Non-alcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease, encompassing a spectrum from non-alcoholic fatty liver to non-alcoholic steatohepatitis, which can progress to cirrhosis. It has recently been recognised that NAFLD also occurs in individuals who are not obese, especially in Asian populations. In these patients, NAFLD manifests at lower overall body mass index thresholds in the presence of increased visceral adipose tissue. Currently, the principles of clinical ...[more]
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Project description:Non-alcoholic fatty liver disease (NAFLD), which approximately affects a quarter of the world's population, has become a major public health concern. Although usually associated with excess body weight, it may also affect normal-weight individuals, a condition termed as lean/non-obese NAFLD. The prevalence of lean/non-obese NAFLD is around 20% within the NAFLD population, and 5% within the general population. Recent data suggest that individuals with lean NAFLD, despite the absence of obesity, exhibit similar cardiovascular- and cancer-related mortality compared to obese NAFLD individuals and increased all-cause mortality risk. Lean and obese NAFLD individuals share several metabolic abnormalities, but present dissimilarities in genetic predisposition, body composition, gut microbiota, and susceptibility to environmental factors. Current treatment of lean NAFLD is aimed at improving overall fitness and decreasing visceral adiposity, with weight loss strategies being the cornerstone of treatment. Moreover, several drugs including PPAR agonists, SGLT2 inhibitors, or GLP-1 receptor agonists could also be useful in the management of lean NAFLD. Although there has been an increase in research regarding lean NAFLD, there are still more questions than answers. There are several potential drugs for NAFLD therapy, but clinical trials are needed to evaluate their efficacy in lean individuals.
| S-EPMC8533092 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) has become a significant public health burden affecting not only obese individuals but also people with normal weight. As opposed to previous beliefs, this particular subset of patients has an increased risk of all-cause mortality and worse outcomes than their obese counterparts. The development of NAFLD in lean subjects seems to be interconnected with metabolic phenotype, precisely visceral fat tissue, sarcopenia, and insulin resistance. Here, we summarize available data focusing on the co-dependent relationship between metabolic phenotype, insulin resistance, and development of NAFLD in lean individuals, suggesting more appropriate tools for measuring body fat distribution for the screening of patients at risk.
| S-EPMC7856866 | biostudies-literature
Project description:Background & aimsAround 20% of patients with non-alcoholic fatty liver disease (NAFLD) are lean. Increasing evidence suggests that lean NAFLD is a unique subtype of the disease. We aimed to explore the metabolic profile, genetic basis, causal risk factors, and clinical sequelae underlying lean NAFLD.MethodsNAFLD was diagnosed by whole liver proton density fat fraction ≥5%. Whole liver proton density fat fraction and hepatic iron were quantified using magnetic resonance imaging in the UK Biobank. Individuals in this study were stratified according to the World Health Organization criteria of obesity, into lean, overweight, and obese. Mediation analysis, Mendelian randomisation analysis, and Bayesian networks were used to identify a risk factor or a clinical sequela of lean/obese NAFLD.ResultsLean NAFLD manifested a distinct metabolic profile, featured by elevated hepatic iron and fasting glucose. Four loci, namely, HFE rs1800562, SLC17A3-SLC17A2-TRIM38 rs9348697, PNPLA3 rs738409, and TM6SF2 rs58542926, were associated with lean NAFLD (p <5 × 10-8). HFE rs1800562 was specifically associated with lean NAFLD and demonstrated a significant mediation effect through elevating hepatic iron. Type 2 diabetes was the most pronounced clinical sequela of lean NAFLD, followed by liver cirrhosis.ConclusionsOur study suggested that HFE plays a potential steatogenic role rather than regulating iron homoeostasis in patients with lean NAFLD. The increased liver iron deposition is associated with lean NAFLD, whereas obese NAFLD is not related to hepatic iron. The clinical management of patients with lean NAFLD shall be concerned with the prevention and treatment of type 2 diabetes and liver cirrhosis.Impact and implicationsLean NAFLD has a distinct natural history from obese NAFLD. This study underscored liver iron content and the genetic variant of the iron homoeostasis gene HFE as major risks of lean NAFLD, in addition to the unique metabolic profile. The development of type 2 diabetes or liver cirrhosis shall be closely monitored and prevented in patients with lean NAFLD.
| S-EPMC10206181 | biostudies-literature
Project description:BackgroundThere is limited knowledge about the risk of non-alcoholic fatty liver disease (NAFLD) associated with cardiometabolic disorders in lean persons. This study examines the contribution of cardiometabolic disorders to NAFLD risk among lean individuals and compares to non-lean individuals.MethodsWe analyzed longitudinal data from 6,513 participants of a yearly voluntary routine health testing conducted at the Hospital Israelita Albert Einstein, Brazil. NAFLD was defined as hepatic ultrasound diagnosed fatty liver in individuals scoring below 8 on the alcohol use disorders identification test. Our main exposure variables were elevated blood glucose, elevated blood pressure (BP), presence of atherogenic dyslipidemia (AD, defined as the combination of elevated triglycerides and low HDL cholesterol) and physical inactivity (<150 minutes/week of moderate activity). We further assessed the risk of NAFLD with elevations in waist circumference and high sensitivity C-reactive protein (HsCRP).ResultsOver 15,580 person-years (PY) of follow-up, the incidence rate of NAFLD was 7.7 per 100 PY. In multivariate analysis adjusting for likely confounders, AD was associated with a 72% greater risk of NAFLD (IRR: 1.72 [95% CI:1.32-2.23]). Elevated blood glucose (IRR: 1.71 [95%CI: 1.29-2.28]) and physical inactivity (IRR: 1.46 [95%CI: 1.28-1.66]) were also independently associated with increased risk of NAFLD. In lean individuals, AD, elevated blood glucose and elevated BP were significantly associated with NAFLD although for elevated blood glucose, statistical significance was lost after adjusting for possible confounders. Physical inactivity and elevations in HsCRP were not associated with the risk of NAFLD in lean individuals only. Among lean (and non-lean) individuals, there was an independent association between progressively increasing waist circumference and NAFLD.ConclusionCardiometabolic risk factors are independently associated with NAFLD. However, there are significant differences in the metabolic risk predictors of NAFLD between lean and non-lean individuals. Personalized cardiovascular disease risk stratification and appropriate preventive measures should be considered in both lean and non-lean individuals to prevent the development of NAFLD.
| S-EPMC8985996 | biostudies-literature
Project description: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.
| S-EPMC5606968 | biostudies-literature
Project description:BackgroundNon-alcoholic fatty liver disease (NAFLD) is common in obese individuals, but its occurrence in lean individuals and the underlying mechanisms are not well understood. This study aimed to systematically review the literature on the genetic and epigenetic factors influencing NAFLD in lean individuals.MethodsA comprehensive search was conducted on April 2nd, 2023, in seven databases using specific criteria. Only peer-reviewed studies in English, focusing on genetic or epigenetic effects on NAFLD in lean individuals, were included for qualitative synthesis. The Newcastle Ottawa Scale (NOS) was used for quality assessment. This study is registered with PROSPERO (CRD42023413809).ResultsFollowing PRISMA guidelines, 18 studies were included in this review. The studies were conducted globally, with varying sample sizes and study designs. The NOS quality assessment revealed a moderate overall quality with variations in risk of bias and limitations in comparability and ascertainments of exposure among contributing studies. Genetic determinants related to lipid metabolism, inflammation, and oxidative stress pathways were identified, including PNPLA3 and TM6SF2 gene variants associated with increased NAFLD risk in lean individuals. Epigenetic modifications, particularly depletion of histone variants, were also implicated. However, some studies found no significant associations between genetic or clinical characteristics and lean NAFLD. Less frequent genetic risk factors, such as CETP and APOC3 gene variants, were reported.ConclusionsThis systematic review underscores the importance of investigating genetic and epigenetic factors in lean NAFLD. The findings highlight the role of PNPLA3 and TM6SF2 gene variants and suggest potential epigenetic contributions. Further research is needed to fully understand the genetic and epigenetic mechanisms underlying NAFLD in lean individuals.
| S-EPMC10838615 | biostudies-literature
Project description:Lean NAFLD is a special phenotypic closely correlated with metabolic syndrome (MS). The aim of this study is to investigate the MS development and the gender differences in lean NAFLD population. Participants were divided into 4 groups by BMI and NAFLD status. Descriptive analysis was performed to characterize baseline information. A total of 18,395 subjects were participated, and 1524 incident cases of MS were documented. Then, Kaplan-Meier curves were used to present the MS outcomes in different groups, and the NAFLD was found to be a riskier factor than obesity for MS. Subgroup analysis showed significantly higher MS incidence in female than male among lean NAFLD group, which is different from other groups. Although with higher prevalence in male, lean NAFLD seems to be a more harmful phenotype for females according to the TG, ALT and GGT levels. The logistic regressive analysis was performed to show the impact of NAFLD status and BMI changes on MS risk. Lean non-NAFLD subjects merely developed to NAFLD with no BMI status changes exhibited highest MS risk (ORs = 1.879, 95% CI 1.610-2.292) than that with both BMI increase and NAFLD development (ORs = 1.669, 95% CI 1.325-2.104). It also suggests the metabolic specificity of this population.
| S-EPMC9243064 | biostudies-literature
Project description:Non-alcoholic fatty liver disease (NAFLD) has a global prevalence of about 25%. Incidence is increasing with rising levels of obesity, type 2 diabetes and the metabolic syndrome, and NAFLD is predicted to become the leading cause of cirrhosis requiring liver transplantation in the next decade. However, the cardiovascular disease is the most common cause of death and only a minority will develop fibrosis and liver-related complications. Therefore, it is imperative to identify patients with advanced disease using non-invasive markers of fibrosis, which include serology-based tests (eg NAFLD Fibrosis Score and ELF test) and imaging (eg transient elastography). This targets appropriate patients for referral to secondary care for additional investigations such as liver biopsy and specialist care. Lifestyle modification and weight loss remains the cornerstone of management, but we are about to enter a new era of promising pharmacotherapies for NASH and fibrosis.
| S-EPMC6334080 | biostudies-literature
Project description:BACKGROUND & AIMS:Little is known regarding the risk of hepatic steatosis (HS) among adult children of affected parents. We examined the association between parental and offspring HS in the multigenerational Framingham Heart Study, which characterized HS using computed tomography. METHODS:We performed multivariable logistic regression models adjusted for age, sex, alcohol use, and body mass index to generate the odds of HS according to parental HS. We determined the proportion of participants with HS according to parental HS and the presence or absence of hypertension, diabetes, or obesity (BMI ?30 kg/m2 ). After excluding heavy alcohol use (n = 126) and missing covariates (n = 1), 785 offspring with at least one parent were included. RESULTS:Approximately 23% (183/785) had at least one parent with HS and 1.1% had two affected parents (9/785). In adjusted models, participants with at least one parent with HS had a nearly two-fold increased odds of HS compared to participants without a parental history of HS (OR 1.86, 95% confidence interval 1.15-3.03). Among participants without hypertension, diabetes, or obesity, a higher proportion had HS if they had a parental history of HS compared to those without (16.1% vs 5.2%, P < 0.001). However, for participants with cardiometabolic risk factors, we did not observe a difference in HS among those with and without parental HS (30.3% vs 28.5%, P = 0.78). CONCLUSIONS:Individuals with a parental history of HS are at increased risk for HS. Specifically, a parental history of HS may be an important factor among those that are otherwise metabolically healthy.
| S-EPMC6758911 | biostudies-literature
Project description:BackgroundRecent studies suggest that non-alcoholic fatty liver disease (NAFLD) in lean (BMI<25 kg/m2) individuals presents a distinct phenotype. We sought to determine the cardiometabolic consequences of lean NAFLD in a population cohort of relatively young asymptomatic individuals who participated in a voluntary routine health promotion evaluation in Brazil.MethodsWe analyzed data in our population collected from 2004 to 2016. Medical and demographic history, anthropometric measures, and fasting blood samples were obtained. Participants had ultrasonography to assess for fatty liver. We defined NAFLD as fatty liver in individuals scoring below 8 on the alcohol use disorders identification test (AUDIT). We included data from 9137 individuals who had complete data at baseline and at follow-up.ResultsThe prevalence of lean NAFLD in our cohort was 3.8%. Over the median follow-up period of 2.4 years (range 0.5-9.9 years), lean individuals had 74% (HR: 1.74 (1.39-2.18)) and 67% (1.67 (1.29-2.15)) greater risk of developing elevated BP and elevated glucose, and nearly 3 times the risk of atherogenic dyslipidemia (HR: 2.98 (2.10-4.24)) compared to lean individuals without NAFLD. Lean NAFLD individuals also had higher risk of developing elevated glucose (HR: 1.37 (1.07-1.75)) and atherogenic dyslipidemia (1.46 (1.05-2.01)) compared to non-lean individuals without NAFLD. However, there was no significant difference in the risk of elevated BP, elevated glucose or atherogenic dyslipidemia between lean NAFLD and non-lean individuals with NAFLD in fully adjusted models.ConclusionLean NAFLD is not metabolically benign. Further cardiovascular risk stratification and appropriate preventive measures should be considered in lean individuals who present with NAFLD.
| S-EPMC8315654 | biostudies-literature