Differences in liver and mortality outcomes of non-alcoholic fatty liver disease by race and ethnicity: A longitudinal real-world study.

BACKGROUND/AIMS: Understanding of nonalcoholic fatty liver disease (NAFLD) continues to expand, but the relationship between race and ethnicity and NAFLD outside the use of cross-sectional data is lacking. Using longitudinal data, we investigated the role of race and ethnicity in adverse outcomes in NAFLD patients. METHODS: Patients with NAFLD confirmed by imaging via manual chart review from any clinics at Stanford University Medical Center (1995-2021) were included. Primary study outcomes were incidence of liver events and mortality (overall and non-liver related). RESULTS: The study included 9,340 NAFLD patients: White (44.1%), Black (2.29%), Hispanic (27.9%), and Asian (25.7%) patients. For liver events, the cumulative 5-year incidence was highest among White (19.1%) patients, lowest among Black (7.9%) patients, and similar among Asian and Hispanic patients (~15%). The 5-year and 10-year cumulative overall mortality was highest for Black patients (9.2% and 15.0%, respectively, vs. 2.5-3.5% and 4.3-7.3% in other groups) as well as for non-liver mortality. On multivariable regression analysis, compared to White patients, only Asian group was associated with lower liver-related outcomes (aHR: 0.83, P=0.027), while Black patients were at more than two times higher risk of both non-liver related (aHR: 2.35, P=0.010) and overall mortality (aHR: 2.13, P=0.022) as well as Hispanic patients (overall mortality: aHR: 1.44, P=0.022). CONCLUSION: Compared to White patients, Black patients with NAFLD were at the highest risk for overall and non-liver-related mortality, followed by Hispanic patients with Asian patients at the lowest risk for all adverse outcomes. Culturally sensitive and appropriate programs may be needed for more successful interventions.

Increasing nonalcoholic fatty liver disease-related mortality rates in the United States from 1999 to 2022.

BACKGROUND: We examined trends in NAFLD-related mortality in the United States from 1999 to 2022, focusing on sex, racial differences, and specific age groups. METHODS: We analyzed age-adjusted mortality rates (AAMRs) for NAFLD-related deaths using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database and assessed differences between sex and racial groups. RESULTS: Between 1999 and 2022, NAFLD-related mortality rose from an age-adjusted mortality rate (AAMR) of 0.2 to 1.7 per 100,000, with an average annual percent change (AAPC) of 10.0% (p < 0.001). In all, 85.4% of the cases were reported after 2008. Females (0.2-2 per 100,000, AAPC: 11.7%, p < 0.001) saw a steeper increase than males (0.2-1.3 per 100,000, AAPC: 9.3%, p < 0.001). White individuals' AAMR rose from 0.2 to 1.9 per 100,000 (AAPC: 10.8%, p < 0.001). Asian or Pacific Islanders (AAPI) increased from 0.2 in 2013 to 0.5 in 2022 (AAPC: 12.13%, p = 0.002), and American Indians or Alaska Natives (AI/AN) from 1 in 2013 to 2.2 in 2022 (AAPC: 7.9%, p = 0.001). African Americans (AA) showed an insignificant change (0.3-0.5 per 100,000, AAPC: 0.7%, p = 0.498). Regarding age, individuals 45-64 saw AAMR rise from 0.3 to 1.2 per 100,000 (AAPC: 6.5%, p < 0.001), and those 65+ from 0.2 to 6 per 100,000 (AAPC: 16.5%, p < 0.001). No change was observed in the 25-44 age group (AAMR: 0.2 per 100,000, AAPC: 0.0%, p = 0.008). CONCLUSION: We report increased NAFLD-related mortality among both sexes and certain racial groups. The mortality rate increased for older populations, emphasizing the need for targeted public health measures and evidence-based interventions.

Association between Dietary Fatty Acid Intake and Liver Steatosis and Fibrosis in a Sample of Mexican-Origin Hispanic Adults with Overweight or Obesity.

Rates of non-alcoholic fatty liver disease (NAFLD) vary dramatically among Hispanic subpopulations, with Mexican-origin (MO) Hispanics experiencing a disproportionate burden. This study examined dietary fatty acid (FA) intake among overweight and obese MO Hispanic adults in the United States (US) and evaluated its association with liver steatosis and fibrosis. Participants (N = 285, MO Hispanic adults) completed 24-h dietary recalls to assess dietary FA exposure. Liver steatosis and fibrosis were estimated using transient elastography (FibroScan®). Multiple regression analysis tested relationships between FA intakes and liver steatosis or fibrosis, adjusting for age, sex, body mass index (BMI) and total energy. A total of 51% (n = 145) of participants were suspected to have NAFLD and 20% self-reported a type 2 diabetes diagnosis. No significant association was observed between Linoleic Acid and α-Linolenic Acid (LA:ALA) ratio, or omega-6 to omega-3 (n-6:n-3) ratio and liver steatosis. However, a one-point increase in the LA:ALA ratio resulted in a 1.01% increase in the liver fibrosis scores (95% CI: [1.00, 1.03]; p = 0.03), and a one-point increase in the n-6:n-3 ratio resulted in a 1.02% increase in liver fibrosis score (95% CI: [1.01, 1.03]; p = 0.01). Further research is needed to determine if modulation of FA intake could reduce NAFLD risk in this high-risk population.

Obesity among Latinx people in the United States: A review.

Obesity is a serious, chronic disease that is associated with a range of adiposity-based comorbidities, including cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver disease. In the United States, obesity is a public health crisis, affecting more than 40% of the population. Obesity disproportionately affects Latinx people, who have a higher prevalence of obesity and related comorbidities (such as cardiovascular disease, type 2 diabetes, and nonalcoholic fatty liver disease) compared with the general population. Many factors, including genetic predisposition, environmental factors, traditional calorie-dense Latinx diets, family dynamics, and differences in socioeconomic status, contribute to the increased prevalence and complexity of treating obesity in the Latinx population. Additionally, significant heterogeneity within the Latinx population and disparities in health care access and utilization between Latinx people and the general population add to the challenge of obesity management. Culturally tailored interventions have been successful for managing obesity and related comorbidities in Latinx people. Antiobesity medications and bariatric surgery are also important options for obesity treatment in Latinx people. As highlighted in this review, when managing obesity in the Latinx population, it is critical to consider the impact of genetic, dietary, cultural, and socioeconomic factors, in order to implement an individualized treatment strategy.

African genetic ancestry is associated with lower frequency of PNPLA3 G allele in non-alcoholic fatty liver in an admixed population.

INTRODUCTION AND OBJECTIVES: PNPLA3 (rs738409) and TM6SF2 (rs58542926) variants, interindividual and ethnic differences may be risk factors for non-alcoholic fatty liver disease (NAFLD). The PNPLA3 G allele is associated with worse NAFLD evolution in Hispanics and Caucasians. TM6SF2 is associated with hypertriglyceridemia, NAFLD, and cardiovascular disease. We aimed to evaluate the association between genetic ancestry by Ancestry Informative Markers (AIM), PNPLA3 and TM6SF2 polymorphisms in patients with biopsy-proven NAFLD in an admixed population. METHODS: We included adults with biopsy-proven NAFLD and excluded patients with the presence of other chronic liver disease, alcohol intake >100g/week, HIV, drug-induced fatty liver disease, or liver transplantation. We classified NAFLD using the Non-Alcoholic Steatohepatitis Clinical Research Network (NASH-CRN) histological scoring system. The PNPLA3 (rs738409 c.444C>G) and TM6SF2 (rs58542926 c.449C>T) genotyping were performed by RT-PCR. Genetic ancestry was determined using 46 insertion-deletion AIM; α<0.05 was considered significant. RESULTS: A total of 248 patients with NAFLD were enrolled [34 with simple steatosis (NAFL); 214 with NASH]. Overall, we detected a greater European ancestry contribution (0.645), followed by African (0.173), Amerindian (0.095), and East Asian (0.087) ancestry contribution, without differences between NAFL and NASH patients. However, we found a higher African genetic ancestry contribution among patients with NAFL who had the PNPLA3 C/C genotype than those with the G allele (0.216 ± 0.205 versus 0.105 ± 0.101, respectively; p=0.047). Ancestry contributions did not differ among TM6SF2 genotypes. CONCLUSION: Among NAFL patients, greater African genetic ancestry was associated to a lower frequency of the PNPLA3 G allele, demonstrating a possible NASH ancestry-related protective factor.

Hepatic steatosis is associated with anthropometry, cardio-metabolic disease risk, sex, age and urbanisation, but not with ethnicity in adult Kenyans.

OBJECTIVE: We aimed to determine the associations of non-alcoholic fatty liver disease (NAFLD) with cardio-metabolic risk factors for diabetes in adult Kenyans. METHODS: A cross-sectional study was undertaken among rural and urban Kenyans of different ethnic origin. Ultrasonography scanning (USS) methods were used for the assessment of hepatic fat accumulation for NAFLD assessment and abdominal fat distribution, and simple anthropometry measurements were performed. All participants underwent a 2-h oral glucose tolerance test, and biochemical, haemodynamic and lifestyle data were obtained. Multivariate logistic regression analyses were used to assess sex, age, residency and ethnic differences in the association between NAFLD and various metabolic parameters. RESULTS: In total, 743 individuals (59.1% women) with a mean age of 38.0 (range 18-68) years participated in the study. Overall, 118 individuals (15.9%) had NAFLD, of whom 94.1% had mild steatosis. Age >40 years was significantly associated with having NAFLD compared with <30 years of age with no difference found in NAFLD between ethnic groups (Luo, Kamba, Maasai). All body composition and clinical measurements were associated with NAFLD (p < 0.045 for OR). CONCLUSION: Finding lower odds for NAFLD in men was unexpected, as was the lack of differences in NAFLD among the ethnic groups, while higher odds for NAFLD with increasing age and in urban vs. rural populations was expected. Especially the sex-specific results warrant further studies in black African populations on biology of body composition for having NAFLD, and whether this translates into insulin resistance and higher risk of diabetes and consequently cardiovascular disease in black African women.

Asian perspective on NAFLD-associated HCC.

Recent data suggest that non-alcoholic fatty liver disease (NAFLD) has become a major public health problem in Asia, with an updated population prevalence of 34%. In parallel, NAFLD-associated hepatocellular carcinoma (HCC) is also on the rise. In this review, we describe the changing epidemiology of HCC in Asia over the past 30 years. While traditional risk factors for HCC (older age, male sex and metabolic factors) are also important in Asia, the PNPLA3 gene polymorphism is particularly prevalent in East Asia and may increase the risk of HCC. NAFLD among non-obese individuals is also commonly described in Asia. Because NAFLD is often undiagnosed, few patients receive HCC surveillance, and the target surveillance population beyond patients with cirrhosis remains poorly defined. As a result, NAFLD-associated HCC is often diagnosed at an advanced stage, rendering curative treatment impossible. Finally, despite around 20-30 years of universal vaccination, chronic HBV infection remains prevalent in Asia, and emerging evidence highlights the importance of metabolic factors and concomitant hepatic steatosis on HCC development in infected patients. Future studies should explore the role of metabolic treatments in HCC prevention among patients with hepatic steatosis and concomitant liver diseases.

Reduced Rank Regression-Derived Dietary Patterns Related to the Fatty Liver Index and Associations with Type 2 Diabetes Mellitus among Ghanaian Populations under Transition: The RODAM Study.

The Fatty Liver Index (FLI) is a proxy for the steatotic component of non-alcoholic fatty liver disease (NAFLD). For sub-Saharan African populations, the contribution of dietary factors to the development of NAFLD in the etiology of type 2 diabetes mellitus (T2DM) remains to be clarified. We identified sex-specific dietary patterns (DPs) related to the FLI using reduced ranked regression (RRR) and evaluated the associations of these DPs with T2DM. This analysis used data from the RODAM, a multi-center cross-sectional study of Ghanaian populations living in Ghana and Europe. The daily intake frequencies of 30 food groups served as the predictor variables, while the FLI was the response variable. The odds ratios and 95% confidence intervals for T2DM were calculated per one standard deviation increase in the DP score using logistic regression. In males, the DP score explained 9.9% of the variation in their food intake and 16.0% of the variation in the FLI. This DP was characterized by high intakes of poultry, whole-grain cereals, coffee and tea, condiments, and potatoes, and the chance of T2DM was 45% higher per 1 DP score-SD (Model 2). Our results indicate that the intake of modernized foods was associated with proxies of NAFLD, possibly underlying the metabolic pathways to developing T2DM.

Associations of the gut microbiome with hepatic adiposity in the Multiethnic Cohort Adiposity Phenotype Study.

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for liver cancer and prevalence varies by ethnicity. Along with genetic and lifestyle factors, the gut microbiome (GM) may contribute to NAFLD and its progression to advanced liver disease. Our cross-sectional analysis assessed the association of the GM with hepatic adiposity among African American, Japanese American, White, Latino, and Native Hawaiian participants in the Multiethnic Cohort. We used MRI to measure liver fat and determine nonalcoholic fatty liver disease (NAFLD) status (n = 511 cases) in 1,544 participants, aged 60-77 years, with 12-53% overall adiposity (BMI of 17.8-46.2 kg/m2). The GM was measured by 16S rRNA gene sequencing and, on a subset, by metagenomic sequencing. Alpha diversity was lower overall with NAFLD and in certain ethnicities (African Americans, Whites, and Latinos). In models regressing genus on NAFLD status, 62 of 149 genera (40%) exhibited a significant interaction between NAFLD and ethnicity stratified analysis found 69 genera significantly associated with NAFLD in at least one ethnic group. No single genus was significantly associated with NAFLD across all ethnicities. In contrast, the same bacterial metabolic pathways were over-represented in participants with NAFLD regardless of ethnicity. Imputed secondary bile acid and carbohydrate pathways were associated with NAFLD, the latter of which was corroborated by metagenomics, although different genera in different ethnicities were associated with these pathways. Overall, we found that NAFLD was associated with altered bacterial composition and metabolism, and that bacterial endotoxin, assessed by plasma lipopolysaccharide binding protein (LBP), may mediate liver fat-associated systemic inflammation in a manner that seems to vary by ethnicity.

Association of elevated serum aminotransferase levels with chronic kidney disease measures: hispanic community health study/study of latinos.

BACKGROUND: Previous studies have shown an association between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD), but it is unclear whether the association is independent of metabolic syndrome. METHODS: Data from 13,006 participants aged 18 to 74 years in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) without viral hepatitis, excessive alcohol consumption, or high transferrin saturation levels were analyzed. Suspected NAFLD was defined as presence of sex-specific elevations in serum aminotransferase levels (aspartate aminotransferase (AST) > 37 U/L or alanine aminotransferase (ALT) > 40 U/L for men and AST or ALT > 31 U/L for women). Logistic regression was used to examine cross-sectional associations of elevated serum aminotransferase levels with low estimated glomerular filtration rate (eGFR < 60 ml/min/1.73 m2 based on cystatin C), and with high urinary albumin-to-creatinine ratio (UACR) (> 17 mg/g in men and > 25 mg/ g in women) in separate models adjusting for demographic characteristics and metabolic syndrome. RESULTS: Mean (SD) age was 41 (0.27) years, and 45 % were male. Elevated serum aminotransferase levels were noted in 18.8 % of the population and were associated with greater odds of high UACR (OR = 1.31; 95 % CI = 1.10, 1.56) after adjusting for demographic characteristics; this association became non-significant after adjustment for metabolic syndrome (OR = 1.11, 95 % CI = 0.92, 1.33). In contrast, elevated serum aminotransferase levels were not associated with low eGFR (odds ratio (OR) = 0.73; 95 % confidence interval (CI) = 0.45, 1.18) after adjusting for covariates. CONCLUSIONS: In this sample of diverse U.S. Hispanic Latino adults, elevated serum aminotransferase levels were not independently associated with measures of CKD.

Association of Genetic Risk Score With NAFLD in An Ethnically Diverse Cohort.

Most genetic studies of nonalcoholic fatty liver disease (NAFLD) have been conducted in Whites. In this large and ethnically diverse cohort, we assessed the transportability of previously identified genetic variants for NAFLD, built a genetic risk score (GRS), and examined its association with NAFLD risk in multiple ethnic groups. Thirty previously identified genome-wide association studies (GWAS) variants (P < 5 × 10-8 ) and 17 other variants associated with NAFLD were examined in a nested case-control study of NAFLD (1,448 cases/8,444 controls) in this multi-ethnic cohort study. We then built a GRS using 11 independent single-nucleotide polymorphisms from these prior studies and examined its association with NAFLD by cirrhosis status across multiple ethnic groups. Of the 30 GWAS SNPs, 20 (67%) were replicated (P < 0.05) in the pooled multi-ethnic population. The highest percentage of replication was seen in Latinos (43%), followed by Japanese Americans (37%), Whites (17%), and Native Hawaiians and African Americans (≤10%). Several genetic variants, including those in PNPLA3 (patatin-like phospholipase domain containing 3), HSD17B13 (hydroxysteroid 17-beta dehydrogenase 13), TM6SF2 (transmembrane 6 superfamily member 2), GATAD2A (GATA zinc finger domain containing 2A), GCKR (glucokinase regulator), SUGP1 (SURP and G-patch domain containing 1), MBOAT7 (membrane bound O-acyltransferase domain containing 7), TRIB1 (tribbles pseudokinase 1), SAMM50 (sorting and assembly machinery component), and ERLIN1 (ER lipid raft associated 1)-CHUK (component of inhibitor of nuclear factor kappa B kinase complex)-CWF19L1 (CWF19 like cell cycle control factor 1) gene cluster, were replicated in at least two ethnic groups. An 11-SNP weighted GRS was associated with NAFLD risk in the multi-ethnic population (odds ratio [OR] per SD increase = 1.41; 95% confidence interval [CI] = 1.32-1.50), as well as in each ethnic group (OR ranged from 1.30 in African Americans to 1.52 in Latinos). The GRS-NAFLD association was stronger for NAFLD with cirrhosis (OR = 1.67; 95% CI = 1.46-1.92) compared to NAFLD without cirrhosis (OR = 1.37; 95% CI = 1.28-1.46) (P heterogeneity = 0.003). Conclusion: In this ethnically diverse cohort, we replicated several key genetic variants for NAFLD and showed the utility of GRS based on the risk alleles for NAFLD risk stratification in multiple ethnic groups.

Cross-sectional pilot study to assess primary healthcare workers' knowledge of nonalcoholic fatty liver disease in a marginalized community in Mexico.

The registered incidence of nonalcoholic fatty liver disease (NAFLD) in primary healthcare centers is lower than expected, suggesting a lack of awareness by primary care healthcare professionals. The implementation of educational tools for healthcare workers has been found to increase timely referral and treatment of patients. We aimed to determine healthcare workers' knowledge of NAFLD to identify their educational needs in one marginalized region. We performed a cross-sectional survey of 261 healthcare professionals in Tlapa de Comonfort, Guerrero, Mexico from October 2019 to December 2019. We created a questionnaire that assessed domains most relevant to NAFLD knowledge. Two hundred and forty-six questionnaires were completed. Of the respondents, 38.3% were nurses and 63.4% were women. Most nurses identified NAFLD as a prevalent (89%) and preventable (93%) disease. Hypertension (33%) and obesity (84%) were recognized as risk factors. The associations between NAFLD and cancer, cirrhosis and cardiovascular disease were identified by 53%, 67% and 72% of respondents, respectively. The largest gaps were found in diagnostic workup, therapeutic approach and the current treatments. We identify modifiable knowledge gaps in NAFLD. Educational strategies for primary care workers could enhance the identification of patients with NAFLD and prevent complications.

The albumin-to-alkaline phosphatase ratio as an independent predictor of future non-alcoholic fatty liver disease in a 5-year longitudinal cohort study of a non-obese Chinese population.

BACKGROUND: The albumin-to-alkaline phosphatase ratio (AAPR) is a newly developed index of liver function, but its association in patients with non-alcoholic fatty liver disease (NAFLD) has not been established. The aim of this study was to investigate the association between the AAPR and NAFLD in a non-obese Chinese population. METHODS: The study included 10,749 non-obese subjects without NAFLD at baseline and divided them into quintiles according to the AAPR. A Cox multiple regression model was used to examine the association between the AAPR and its quintiles and the incidence of NAFLD. RESULTS: The average age of the study population was 43.65 ± 15.15 years old. During the 5-year follow-up, 1860 non-obese subjects had NAFLD events. In the Cox multiple regression model, after adjusting the model according to important risk factors, the AAPR and NAFLD risk were independently correlated, and with a gradual increase in the AAPR, the NAFLD risk decreased gradually (HR: 0.61, 95% CI: 0.47, 0.81; P-trend< 0.0001). Additionally, there were significant interactions between the AAPR and BMI, blood pressure and lipids (P-interaction < 0.05). Stratified analysis showed that the risk of AAPR-related NAFLD decreased in people with normal blood pressure and lipid levels, while the risk of AAPR-related NAFLD increased abnormally in people who were underweight. CONCLUSIONS: This longitudinal cohort study provides the first evidence that the AAPR is an independent predictor of future NAFLD events in non-obese people. For non-obese people with a low AAPR, especially those with BMI < 18.5 kg/m2, more attention should be given to the management of risk factors for NAFLD to prevent future NAFLD.

A correlation study of the relationships between nonalcoholic fatty liver disease and serum triglyceride concentration after an oral fat tolerance test.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases worldwide. Triglyceride (TG) accumulation is central to NAFLD development. People now spend most of their day in the postprandial state, and the measurement of postprandial blood lipid concentration can make up for the lack of simple detection of fasting blood lipids. Postprandial triglyceride (PTG) is commonly used as a surrogate for postprandial blood lipid concentrations, and many studies have shown that PTG is a risk factor for NAFLD. The aim of the present study was to investigate the relationship between PTG concentration during oral fat tolerance testing (OFTT) and NAFLD. METHODS: A total of 472 Chinese adults, aged 25 to 65 years, were enrolled in the study. All the participants underwent OFTT. The serum concentrations of TG and other lipids were measured, and their relationships with NAFLD were analyzed. RESULTS: Of the 472 participants, 155 were diagnosed with NAFLD. The fasting and postprandial TG concentrations of the participants with NAFLD were higher than those of healthy participants (P < 0.05). The TG concentrations of the healthy participants peaked 4 h postprandially, whereas those of the participants with NAFLD peaked 6 h postprandially and reached higher peak values. Postprandial TG concentration was significantly associated with a higher risk of NAFLD. CONCLUSIONS: High PTG is positively related to a higher risk of NAFLD, and the PTG concentrations of patients with NAFLD are higher than in healthy individuals, with a delayed peak. Therefore, 4-h PTG may represent a potential marker of NAFLD. TRIAL REGISTRATION: ChiCTR1800019514 .

Liver Fibrosis is Associated with Ischemic Stroke Risk in Women but not Men: The REGARDS Study.

BACKGROUND: Nonalcoholic fatty liver disease is inconsistently associated with ischemic stroke, with one study suggesting an association in women and not men. The relative importance of liver fibrosis, as opposed to fatty liver, for cardiovascular risk is increasingly appreciated. We hypothesized that advanced liver fibrosis is associated with incident ischemic stroke risk, and especially in women. METHODS: We performed a case-cohort study in the REasons for Geographic and Racial Differences in Stroke cohort. Black and white individuals aged 45 and older were recruited between 2003 and 2007 and followed for ischemic stroke. The Fibrosis-4 (FIB-4) score and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS) were calculated using baseline data for stroke cases and a cohort random sample; advanced liver fibrosis was classified using validated cutoffs. Cox proportional hazards models were used to estimate hazard ratios (HR) of stroke after adjusting for potential confounders. Sex differences were assessed. RESULTS: There were 572 incident ischemic strokes (285 in women) over 5.4 (SD, 2.2) years. Advanced liver fibrosis was not significantly associated with ischemic stroke overall using the FIB-4 (HR 1.44; 95% CI 0.49-4.28) or NFS (HR 1.76; 95% CI 0.67-4.61). However, liver fibrosis was associated with stroke in women (HR 3.51; 95% CI 1.00-12.34) but not men (HR 0.70, 95% CI 0.16-3.16) (P = 0.098 for interaction) when using FIB-4. A similar but non-significant sex difference was seen for NFS. CONCLUSION: Advanced liver fibrosis may be associated with a higher risk of ischemic stroke in women but not men.

Prevalence of non-alcoholic fatty liver disease and factors associated with it in Indian women with a history of gestational diabetes mellitus.

AIMS/INTRODUCTION: This study aims to evaluate the prevalence of and factors associated with non-alcoholic fatty liver disease (NAFLD) in Indian women with prior gestational diabetes mellitus (GDM) diagnosed using International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. MATERIALS AND METHODS: This cross-sectional study (2018-2019) enrolled women with and without prior GDM. Study participants underwent detailed assessments, including relevant medical, obstetric and demographic details; 75-g oral glucose tolerance test with glucose and insulin estimation at 0, 30 and 120 min; and other relevant biochemical and anthropometric measurements. NAFLD status was defined by ultrasonography. RESULTS: We evaluated a total of 309 women (201 and 108 with and without prior GDM, respectively) at a mean age of 31.9 ± 5.0 years and median of 16 months (interquartile range 9-38 months) following the index delivery. The prevalence of NAFLD was significantly higher in women with prior GDM (62.7% vs 50.0%, P = 0.038; grade 2 and 3 disease, 13.9% vs 6.5%). On logistic regression analysis (fully adjusted model), the odds of NAFLD were 2.11-fold higher in women with prior GDM (95% confidence interval 1.16-3.85, P = 0.014). Overweight/obesity, metabolic syndrome, prediabetes and homeostasis model of assessment of insulin resistance (a measure of insulin resistance) were positively associated with NAFLD, whereas the Matsuda index (a measure of insulin sensitivity) showed a negative association with NAFLD. CONCLUSIONS: The prevalence of NAFLD is high in women with prior GDM. Such women also have a high burden of cardiometabolic risk factors. Future studies should evaluate the intermediate and long-term hepatic and cardiovascular risk, and the impact of lifestyle interventions in reducing morbidity in such women.

A nomogram for estimating the probability of nonalcoholic fatty liver disease in a Chinese population: A retrospective cohort study.

Studies have showed that dyslipidemia is closely related to nonalcoholic fatty liver disease (NAFLD). However, less attention has been paid to the relationship between early dyslipidemia and long-term risk of NAFLD. Therefore, we aimed to develop a simple-to-use nomogram to predict early dyslipidemia and long-term risk of NAFLD onset.A retrospective cohort study including 3621 employees (including retirees) from 7 companies was conducted between 2012 and 2019. Anthropometric, potential laboratory parameters and abdominal ultrasound were performed at baseline and after a 5-year follow-up. Cox proportional hazards model was used to determine predictors for NAFLD onset. The effects of lipids, age, body mass index (BMI), and serum uric acid (UA) on NAFLD were evaluated with the use of Kaplan-Meier curves (log-rank test). A nomogram was developed based on the Cox proportional hazard model and a 2-piecewise linear regression model. The accuracy of model was evaluated according to the area under the receiver operating characteristic curves.A total of 1545 subjects were included in the final analysis. The mean follow-up time was 52 ±â€Š6.6 months. Of the total subjects, 77.61% were male and 22.39% were female. The mean age at the time of initial visit was 45.21 ±â€Š11.20 years. Five hundred fifty-five subjects (35.92% of all subjects) were finally diagnosed with NAFLD. Variables in the nomogram included age, BMI, triglycerides, high-density lipoprotein, low-density lipoprotein, and UA. The accuracy of the nomogram for predicting 5-year cumulative occurrence of NAFLD was 0.8135 (95% confidence interval: 0.7921-0.8349), and the sensitivity and specificity were 0.8108 and 0.6960, respectively.The combination of age, BMI, triglycerides, high-density lipoprotein, low-density lipoprotein, and UA translated into a nomogram can reliably estimate the incidence of NAFLD within 5 years. It may serve as a decision support tool to determine whether to intervene at an early stage.

Validating a non-invasive, ALT-based non-alcoholic fatty liver phenotype in the million veteran program.

BACKGROUND & AIMS: Given ongoing challenges in non-invasive non-alcoholic liver disease (NAFLD) diagnosis, we sought to validate an ALT-based NAFLD phenotype using measures readily available in electronic health records (EHRs) and population-based studies by leveraging the clinical and genetic data in the Million Veteran Program (MVP), a multi-ethnic mega-biobank of US Veterans. METHODS: MVP participants with alanine aminotransferases (ALT) >40 units/L for men and >30 units/L for women without other causes of liver disease were compared to controls with normal ALT. Genetic variants spanning eight NAFLD risk or ALT-associated loci (LYPLAL1, GCKR, HSD17B13, TRIB1, PPP1R3B, ERLIN1, TM6SF2, PNPLA3) were tested for NAFLD associations with sensitivity analyses adjusting for metabolic risk factors and alcohol consumption. A manual EHR review assessed performance characteristics of the NAFLD phenotype with imaging and biopsy data as gold standards. Genetic associations with advanced fibrosis were explored using FIB4, NAFLD Fibrosis Score and platelet counts. RESULTS: Among 322,259 MVP participants, 19% met non-invasive criteria for NAFLD. Trans-ethnic meta-analysis replicated associations with previously reported genetic variants in all but LYPLAL1 and GCKR loci (P<6x10-3), without attenuation when adjusted for metabolic risk factors and alcohol consumption. At the previously reported LYPLAL1 locus, the established genetic variant did not appear to be associated with NAFLD, however the regional association plot showed a significant association with NAFLD 279kb downstream. In the EHR validation, the ALT-based NAFLD phenotype yielded a positive predictive value 0.89 and 0.84 for liver biopsy and abdominal imaging, respectively (inter-rater reliability (Cohen's kappa = 0.98)). HSD17B13 and PNPLA3 loci were associated with advanced fibrosis. CONCLUSIONS: We validate a simple, non-invasive ALT-based NAFLD phenotype using EHR data by leveraging previously established NAFLD risk-associated genetic polymorphisms.

Global epidemiology of lean non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: Lean non-alcoholic fatty liver disease (NAFLD) is a potentially metabolically unhealthy state that refers to NAFLD occurring in non-overweight/nonobese subjects. Yet its global epidemiology and metabolic characteristics are not extensively elucidated. METHODS: PubMed, EMBASE, Web of Science and Cochrane databases were searched for eligible studies until January 2020. Random-effects/fixed-effects models were used to estimate the global prevalence of lean NAFLD and to compare clinical characteristics among lean non-NAFLD, lean NAFLD, and overweight/obese NAFLD subjects. "Lean" NAFLD was defined by ethnic-specific body mass index measurements in the normal range. Meta-regression and subgroup analyses were performed to determine potential sources of heterogeneity. RESULTS: A total of 33 observational studies were included with 205 307 individuals from 14 countries. The global prevalence of lean NAFLD was 4.1% (95% confidence interval [CI]: 3.4-4.8%). In lean subjects, the prevalence of NAFLD was 9.7% (95% CI: 7.7-11.8%). The prevalence of lean NAFLD with diabetes, hypertension, metabolic syndrome, dyslipidemia, or central obesity was 0.6% (95% CI: 0.4-0.9%), 1.8% (95% CI: 1.2-2.5%), 1.4% (95% CI: 1.0-1.9%), 2.8% (95% CI: 1.9-3.7%), and 2.0% (95% CI: 1.6-2.4%), respectively. The prevalence of lean NAFLD showed an upward trend between 1988 and 2017. Asian individuals had the highest prevalence of lean NAFLD (4.8%, 95% CI: 4.0-5.6%). Middle-aged people (45-59 years old) had the highest prevalence of lean NAFLD (4.4%, 95% CI: 3.2-5.5%). The prevalence of metabolic complications in lean non-NAFLD, lean NAFLD, and overweight/obese NAFLD groups increased sequentially. CONCLUSIONS: Lean NAFLD occurs with metabolic complications and is not an uncommon condition. The highest prevalence of lean NAFLD occurs in middle-aged individuals of Asian countries.