Suspected Nonalcoholic Fatty Liver Disease Research Articles

Nonalcoholic Fatty Liver Disease in Young Children with Obesity.

Background: To evaluate the prevalence of suspected nonalcoholic fatty liver disease (NAFLD) in young children with obesity and determine associated risk factors. Methods: Retrospective single-center study of children with obesity, ages 2-6 years. Suspected NAFLD was defined as an alanine aminotransferase (ALT) >30 U/L. Multivariable analyses were performed to determine predictors of elevated ALT. Results: Among 237 children 2-6 years old, 35% had elevated ALT. Multivariable analysis showed that higher BMI z score [odds ratio (OR): 1.5 confidence interval (95% CI: 1.04-1.92)] and higher gamma-glutamyl transferase (GGT) [OR: 21.3 (95% CI: 3.7-121.1)] predicted elevated ALT. Of those with ≥2 ALT levels, 38% (n = 33/86) had a persistently elevated ALT (median ALT >30 U/L). Only 7% of patients with ALT >30 U/L underwent further testing to evaluate for alternative causes of liver disease. Conclusion: Suspected NAFLD is common in young children with obesity and predicted by obesity severity and GGT. Other cardiometabolic markers were equivalent between those with normal vs. elevated ALT, suggesting NAFLD onset may precede development of comorbidities. Earlier screening will enable prompt diagnosis and intervention, which may prevent or delay the onset of cardiometabolic diseases commonly associated with NAFLD in adolescence and adulthood.

Abstract P148: Modifiable Obesogenic Behaviors Among Latino Adolescents With Suspected Non-alcoholic Fatty Liver Disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) disproportionally affects US children of Latino descent, who also have a higher burden of obesity and type 2 diabetes. We previously found significant associations between diet and sedentary behaviors and weight status, but it is unclear if these measured behaviors are associated with suspected NAFLD among Latino adolescents with obesity, which was the objective of this study. We used cross-sectional data from 10,087 Latino adolescents ages 13-17 years in northern California with a well-child visit in 2016-2019, health behavior assessment, and BMI ≥95th percentile. Adolescents self-reported on 4 daily obesogenic behaviors at the visit: 1) consuming <5 servings of fruits/vegetables; 2) drinking ≥1 juice/soda (12oz); 3) exercising/playing sports for <60 minutes; and 4) >2 hours of screen time. Suspected NAFLD was classified by serum alanine transaminase level ≥44 U/L (girls) and ≥52 U/L (boys). We used logistic regression to examine the associations of obesogenic behaviors with NAFLD, adjusting for age, gender, household language preference (English/Spanish), neighborhood deprivation index (quartiles), and Class 1, 2, and 3 obesity. Among 10,087 Latino adolescents with obesity, 88% (8,877) had ≥1 obesogenic behaviors and 10% (1012) had suspected NAFLD. None of the obesogenic behaviors were associated with NAFLD in unadjusted or adjusted models. Boys (vs girls) had higher odds of NAFLD (OR 2.2; 95% CI: 1.9-2.5), as did older adolescents (ages 16-17 vs 13-15, OR 1.7; 1.5-1.9) and those with more severe obesity (OR 2.2; 1.9-2.5, and OR 3.0; 2.5-3.6 for Class 2 and 3 (vs Class 1) obesity, respectively). In summary, older age, male gender and severe obesity were risk factors for suspected NAFLD while binary assessment of diet and sedentary behaviors were not, suggesting that more precise diet and exercise assessment tools are needed. The high burden of obesogenic behaviors and strong association of severe obesity with NAFLD point to important actionable targets for pediatric primary care.

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

BackgroundPrevious 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.MethodsData 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.ResultsMean (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.ConclusionsIn this sample of diverse U.S. Hispanic Latino adults, elevated serum aminotransferase levels were not independently associated with measures of CKD.

Serum selenium and non-alcoholic fatty liver disease (NAFLD) in U.S. adults: National Health and Nutrition Examination Survey (NHANES) 2011-2016

BACKGROUND AND AIM: Selenium is an essential trace element that shows beneficial or adverse health effects depending on the dose. Laboratory studies suggest that high selenium may contribute to the development of non-alcoholic fatty liver disease (NAFLD). However, human evidence is limited. We evaluated the associations of serum selenium level with serum alanine aminotransferase (ALT) activity and suspected NAFLD prevalence in U.S. adults. METHODS: We conducted the cross-sectional analysis in 3,827 adults aged 20 years and older without viral hepatitis, hemochromatosis, or alcoholic liver disease who participated in the National Health and Nutrition Examination Survey (NHANES) 2011-2012, 2013-2014, and 2015-2016. Serum selenium was measured using inductively coupled plasma dynamic reaction cell mass spectrometry. Suspected NAFLD cases were defined in the presence of serum ALT 30 IU/L in men and 19 IU/L in women in the absence of other identifiable causes of liver disease. RESULTS:The median (interquartile range) of serum selenium level was 127.9 (117.9, 139.4) µg/L. Non-linear associations of serum selenium with NAFLD prevalence and serum ALT activity were observed in the generalized additive models with penalized splines. After adjustment for sociodemographic variables, lifestyle factors, body mass index, and NHANES survey cycles, positive associations were found at ~130 µg/L serum selenium with both NAFLD and ALT, whereas the associations were flattened at ~130 µg/L. CONCLUSIONS:Our findings provide evidence of non-linear associations of serum selenium with ALT activity and NAFLD prevalence. In particular, positive associations were found above serum selenium level of 130 µg/L, whereas no association was observed below this value. This finding requires confirmation in future prospective cohort studies. KEYWORDS: selenium, NAFLD, alanine aminotransferase, nutrients.

Inverse Association between Serum 25-hydroxyvitamin D Levels and Risk of Suspected Non-Alcoholic Fatty Liver Disease in Obese Population

Background: Worldwide, vitamin D deficiency is a public health issue and the prevalence of obesity and non-alcoholic fatty liver disease (NAFLD) are rapidly increasing. There are a limited number of studies assessing the association between serum levels of 25-hydroxyvitamin D (25(OH)D) and NAFLD risk in obese population. Objective: We evaluated the associations between serum 25(OH)D levels and risk of suspected NAFLD after stratification by obesity using data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2008–2014. Methods: This study included 25,755 subjects without significant alcohol consumption for the serum alanine aminotransferase (ALT) and hepatic steatosis index (HSI) analyses (8922 subjects for the serum gamma-glutamyl transferase (GGT) and fatty liver index (FLI) analyses), based on a cross-sectional study design. Serum 25(OH)D levels were measured using a Gamma counter with radioimmunoassay. A survey logistic regression model was applied to estimate ORs and 95% CIs. Restricted cubic smoothing splines were applied to evaluate nonlinear associations. Results: The risk of suspected NAFLD was reduced per unit of natural log-transformed serum 25(OH)D concentration in obese individuals (OR [95% (CI)]; for ALT, 0.80 [0.67, 0.96]; for GGT, 0.70 [0.49, 0.99; for FLI, 0.68 [0.47, 1.01]; for HSI, 0.70 [0.56, 0.87]). The ORs [95% CI] of suspected NAFLD changed across the quartiles: for serum ALT, from 1.02 [0.85, 1.23] to 0.72 [0.59, 0.87]; for serum GGT, from 0.79 [0.56, 1.13] to 0.64 [0.44, 0.92]; for FLI, from 0.98 [0.67, 1.44] to 0.70 [0.48, 1.02]; and for HSI, from 0.91 [0.73, 1.14] to 0.65 [0.52, 0.81] with dose–response relationships (all p for trend < 0.01). Conclusions: This study suggests that vitamin D sufficiency for public health should be emphasized in order to prevent adverse health effects in obese populations.

Association between Visceral Adipose Tissue and Non-Alcoholic Steatohepatitis Histology in Patients with Known or Suspected Non-Alcoholic Fatty Liver Disease.

(1) Purpose: To determine the association between visceral adipose tissue (VAT) and proton density fat fraction (PDFF) with magnetic resonance imaging (MRI), and hepatic steatosis (HS), non-alcoholic steatohepatitis (NASH) and hepatic fibrosis (HF) in patients with known or suspected non-alcoholic fatty liver disease (NAFLD). (2) Methods: 135 subjects that had a liver biopsy performed within 3 months (bariatric cohort) or 1 month (NAFLD cohort) of an MRI exam formed the study group. VAT volume was quantified at L2-L3 level on opposed-phase images with signal intensity-based painting using a semi-quantitative software. Liver PDFF and pancreas PDFF were calculated on fat fraction maps. Liver volume (Lvol) and spleen volume (Svol) were also calculated using a semi-automated 3D volume tool available on PACS. A histological analysis was performed by an expert hepatopathologist blinded to imaging findings. (3) Results: The mean Lvol, Svol, liver PDFF, pancreas PDFF and VAT of the study population were 2492.2 mL, 381.6 mL, 13.2%, 12.7% and 120.6 mL, respectively. VAT showed moderate correlation with liver PDFF (r = 0.41, p < 0.001) and weak correlation with Lvol (r = 0.38, p < 0.001), Svol (r = 0.20, p = 0.025) and pancreas PDFF (rs = 0.29, p = 0.001). VAT, Lvol and liver PDFF were significantly higher in patients with HS (p < 0.001), NASH (p < 0.05) and HF (p < 0.05). VAT was also significantly higher in the presence of lobular inflammation (p = 0.019) and hepatocyte ballooning (p = 0.001). The cut-off VAT volumes for predicting HS, NASH and HF were 101.8 mL (AUC, 0.7), 111.8 mL (AUC, 0.64) and 111.6 mL (AUC, 0.66), respectively. (4) Conclusion: The MRI determined VAT can be used for predicting the presence of HS, NASH and HF in patients with known or suspected NAFLD.

699 Pre-Operative Screening and Investigation of Patients with Suspected Non-Alcoholic Fatty Liver Disease Among Bariatric Surgery Patients

Abstract Introduction Non-alcoholic fatty liver disease (NAFLD) is becoming more prevalent. The investigations used to diagnose NAFLD include FIB-4 score, NAFLD score and AST/ALT ratio (AAR). Gold-standard for diagnosis is liver biopsy. Bariatric surgery reduces steatosis and fibrosis in NAFLD patients. However, in undiagnosed NAFLD, it can lead to worsening fibrosis and decompensation of cirrhosis, causing complications. The aim is to identify how well bariatric patients are being screened for NAFLD pre-operatively. Method Database analysis was conducted in the bariatric clinics at Royal Derby Hospital and analysed using SPSS. Results 392 patients’ data (Overall group) were analysed and compared with those who had an AAR&amp;gt;1 (Abnormal group). Abnormal group had a higher mean AAR, NAFLD and FIB-4 scores. Surprisingly, ALT and AST levels were higher in Overall group compared to Abnormal. Generally, patients were not pre-operatively checked sufficiently (81.9% LFTs, 62.2% ASTs). Conclusions A large number of patients could have undiagnosed NAFLD due to the lack of LFT/AST checks as ALT scores alone would miss fibrosis. Using AAR&amp;gt;1 and FIB-4 would allow clinicians to detect fibrosis earlier to carry out non-invasive diagnostic measures, avoiding unnecessary biopsies. Early diagnosis means patients undergoing bariatric surgery with possible cirrhosis will not experience decompensation and associated complications.

Serum selenium and non-alcoholic fatty liver disease (NAFLD) in U.S. adults: National Health and Nutrition Examination Survey (NHANES) 2011–2016

BackgroundSelenium is an essential trace element that shows beneficial or adverse health effects depending on the dose. Laboratory studies suggest that high selenium may contribute to the development of non-alcoholic fatty liver disease (NAFLD). However, human evidence is limited. We evaluated the associations of serum selenium level with serum alanine aminotransferase (ALT) activity and suspected NAFLD prevalence in U.S. adults. MethodsWe conducted the cross-sectional analysis in 3827 adults aged 20 years and older without viral hepatitis, hemochromatosis, or alcoholic liver disease who participated in the National Health and Nutrition Examination Survey (NHANES) 2011–2012, 2013–2014, and 2015–2016. Serum selenium was measured using inductively coupled plasma dynamic reaction cell mass spectrometry. Suspected NAFLD cases were defined in the presence of serum ALT >30 international units (IU)/L in men and >19 I.U./L in women in the absence of other identifiable causes of liver disease. ResultsThe median (interquartile range) of serum selenium level was 127.9 (117.9, 139.4) μg/L. Non-linear associations of serum selenium with NAFLD prevalence and serum ALT activity were observed in the generalized additive models with penalized splines. After adjustment for sociodemographic variables, lifestyle factors, body mass index, and NHANES survey cycles, positive associations were found at > ~130 μg/L serum selenium with both NAFLD and ALT, whereas the associations were flattened at < ~130 μg/L. ConclusionsOur findings provide evidence of non-linear associations of serum selenium with ALT activity and NAFLD prevalence. In particular, positive associations were found above serum selenium level of 130 μg/L, whereas no association was observed below this value. This finding requires confirmation in future prospective cohort studies.

Quantification of Liver Fat by MRI-PDFF Imaging in Patients with Suspected Non-alcoholic Fatty Liver Disease and Its Correlation with Metabolic Syndrome, Liver Function Test and Ultrasonography

Magnetic resonance imaging (MRI)-estimated proton density fat fraction (PDFF) has emerged to be a promising tool in quantification of liver fat. Aim of this study was to quantify liver fat using MRI-PDFF in patients with suspected non-alcoholic fatty liver disease (NAFLD) and to correlate it with the presence of metabolic syndrome (MetS), ultrasonography (USG) and liver function test (LFT). We included 111 consecutive patients who were suspected to have NAFLD on the basis of clinical, laboratory or USG findings. A 3 Tesla Phillips MRI machine was used with a software named "mDixon Quant" for quantification of the liver fat. MRI-PDFF revealed hepatic steatosis grading as Grade 0 in 31 patients (28%), Grade I in 40 (36%), Grade II in 19 (17.1%) and Grade III in 21 patients (18.9%). MetS patients had higher proportion of advanced steatosis (Grades II and III) as compared to those without MetS (P< 0.001). ALT (alanine transaminase) was found to be significantly elevated (>1.5 times) in the patients with advanced steatosis as compared to patients with Grades I and 0 fatty liver on MRI-PDFF (P< 0.001). The Kappa measure of agreement between USG and MRI-PDFF was found to be 0.2, which suggests a low level of agreement between the two tests. MetS patients have higher proportion of advanced steatosis (Grades II and III) at MRI-PDFF as compared to those without MetS. Patients with advanced steatosis at MRI-PDFF had higher proportion of abnormal LFTs as compared to those with Grades 0 and I hepatic steatosis. There was a dis-correlation between MRI-PDFF and USG in the evaluation of NAFLD.

Oxidative stress is associated with suspected non-alcoholic fatty liver disease and all-cause mortality in the general population.

Background & AimsNon‐alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation, inflammation and an imbalanced redox homeostasis. We hypothesized that systemic free thiol levels, as a proxy of systemic oxidative stress, are associated with NAFLD.MethodsProtein‐adjusted serum free thiol concentrations were determined in participants from the Prevention of Renal and Vascular End‐Stage Disease (PREVEND) cohort study (n = 5562). Suspected NAFLD was defined by the Fatty Liver Index (FLI ≥ 60) and Hepatic Steatosis Index (HSI > 36).ResultsProtein‐adjusted serum free thiols were significantly reduced in subjects with FLI ≥ 60 (n = 1651). In multivariable logistic regression analyses, protein‐adjusted serum free thiols were associated with NAFLD (FLI ≥ 60) (OR per doubling of concentration: 0.78 [95% CI 0.64‐0.96], P = .016) even when adjusted for potential confounding factors, including systolic blood pressure, diabetes, current smoking, use of alcohol and total cholesterol (OR 0.80 [95% CI 0.65‐0.99], P = .04). This association lost its significance (OR 0.94 [95% CI 0.73‐1.21], P = .65) after additional adjustment for high‐sensitive C‐reactive protein. Stratified analyses showed significantly differential associations of protein‐adjusted serum free thiol concentrations with suspected NAFLD for gender (P < .02), hypertension (P < .001) and hypercholesterolemia (P < .003). Longitudinally, protein‐adjusted serum free thiols were significantly associated with the risk of all‐cause mortality in subjects with NAFLD (FLI ≥ 60) (HR 0.27 [95% CI 0.17‐0.45], P < .001).ConclusionProtein‐adjusted serum free thiol levels are reduced and significantly associated with all‐cause mortality in subjects with suspected NAFLD. Quantification of free thiols may be a promising, minimally invasive strategy to improve detection of NAFLD and associated risk of all‐cause mortality in the general population.

The change in prevalence of suspected non-alcoholic fatty liver disease in Korean adolescents from 2001 to 2017

ABSTRACT Aim Data on trends in the prevalence of suspected non-alcoholic fatty liver disease (NAFLD) in adolescents are scarce, especially in the Asia-Pacific region. The purpose of this study was to determine whether the prevalence of suspected NAFLD changed between 2001–2005 and 2015–2017. Methods Data were extracted from the Korea National Health and Nutrition Examination Survey (2001–2005 to 2015–2017, n = 4448). Suspected NAFLD was defined by an elevated alanine aminotransferase (ALT) level of >26 IU/L in boys and >22 IU/L in girls. In addition, the analysis was repeated using the Korean cut-off levels for ALT of 33 IU/L for boys and 25 IU/L for girls. Results The prevalence of suspected NAFLD increased, with a relative increase of 44% from 7.8% (95% CI 6.6–9.2%) in 2001–2005 to 11.2% (95% CI 9.7–12.9%) in 2015–2017 (p = 0.001). This increase was evident in both boys (10.6 vs 14.7%, p = 0.01) and girls (4.6 vs 7.4%, p = 0.02). Increases were also observed in obesity (7.3 vs 10.6%), central obesity (10.0 vs 12.8%) and ALT level (14.9 vs 16.7 IU/L). The prevalence of suspected NAFLD was approximately 40–45% in obese/central obese adolescents in 2015–2017. Using the Korean cut-off levels, the prevalence of suspected NAFLD has increased, with a relative increase of 55%, from 4.6% (95% CI 3.7–5.7%) in 2001–2005 to 7.2% (95% CI 6.1–8.5%) in 2015–2017 (p = 0.01). Conclusions The prevalence of suspected NAFLD continues to increase in Korean adolescents. Abbreviations ALT, alanine aminotransferase; BMI, body mass index; KNHANES, Korea National Health and Nutrition Examination Survey; NAFLD, non-alcoholic fatty liver disease.

Trends in pioglitazone use among U.S. adults with type 2 diabetes and suspected nonalcoholic fatty liver disease

ABSTRACTBackground: We aimed to estimate population-based trends in the prevalence of coexisting type 2 diabetes (T2D) and suspected nonalcoholic fatty liver disease (NAFLD) and pioglitazone use among U.S. adults.Research design and methods: We conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey from 2003 to 2016. We included people aged ≥18 years who had HbA1C >6.4%, fasting plasma glucose >125 mg/dL, or were told they had diabetes by a doctor. Suspected NAFLD was defined using a hepatic steatosis index of >36. Prevalence was estimated for each 2-year survey cycle. Trends were analyzed using logistic regression, accounting for the complex survey design.Results: Total sample size was 40,323 U.S. adults, of which 5690 had T2D. Age-adjusted prevalence of T2D with NAFLD increased from 5.6% in 2003–2004 to 6.8% in 2015–2016 (p-value <0.001). Pioglitazone use peaked at 20% in 2005–2006 and then declined to 4.1% in 2013–2014. Patients with suspected NAFLD were not more likely to receive pioglitazone; 3.8% of patients received the drug in 2015–2016.Conclusions: The prevalence of T2D with suspected NALFD increased among U.S. adults, but pioglitazone use decreased significantly over 2003–2016. Our study suggested a missed opportunity to prevent a future epidemic of cirrhosis due to NAFLD in patients with T2D.

Prescription of statins in suspected non-alcoholic fatty liver disease and high cardiovascular risk, a population-based study.

Background & AimsThe prevalence of non‐alcoholic fatty liver disease (NAFLD) is increasing, with concomitant high incidence of lipoprotein abnormalities. Cardiovascular disease (CVD) is the main cause of death in subjects with NAFLD and management of dyslipidaemia is pivotal for prevention. We aimed to determine cardiovascular risk and indication for statin therapy in subjects with NAFLD.MethodsA cross‐sectional analysis of the population‐based Lifelines Cohort Study of 34 240 adult individuals. Subjects with reported use of lipid‐lowering drugs were excluded. Suspected NAFLD was defined as Fatty Liver Index (FLI) ≥60 and advanced hepatic fibrosis as NAFLD fibrosis score (NFS) >0.676. Cardiovascular risk and indication for statin therapy were defined according to the European Society of Cardiology and European Atherosclerosis Society Guideline for the Management of Dyslipidaemias.ResultsFLI ≥ 60 was present in 7067 (20.6%) participants and coincided with increased prevalence of type 2 diabetes mellitus, metabolic syndrome, CVD and impaired renal function (all P < 0.001). 10‐year predicted cardiovascular risk was significantly increased in subjects with elevated FLI and NFS (both P < 0.001). Indication for statin use was significantly increased in subjects with FLI ≥ 60 (31.0% vs 15.6%, P < 0.001) and NFS > 0.676 (73.2% vs 30.6%, P < 0.001). In multivariable analyses, FLI ≥ 60 (OR 1.26, 95%CI: 1.13‐1.41, P < 0.001) and NFS > 0.676 (OR 5.03, 95%CI: 2.76‐9.17, P < 0.001) were independent predictors for indication regarding statin therapy.ConclusionsBecause of increased cardiovascular risk, substantial proportions of subjects with suspected NAFLD and/or fibrosis have an indication for lipid‐lowering treatment and could benefit from statin therapy.

American Ancestry Is a Risk Factor for Suspected Nonalcoholic Fatty Liver Disease in Hispanic/Latino Adults

Nonalcoholic fatty liver disease (NAFLD) disproportionally affects Hispanic/Latino populations. However, the magnitude varies among Hispanic/Latino ethnic groups. We investigated the mechanisms of these disparities. We examined associations of NAFLD-associated genetic variants and continental ancestry with suspected NAFLD, levels of alanine aminotransferase (ALT), and liver fibrosis using data fromthe Hispanic Community Health Study/Study of Latinos-a population-based study of Hispanic/Latino adults in the United States. We evaluated data from 16,415 Hispanic/Latino adults in 4 cities from 2008 through 2011. Subjects suspected of having NAFLD or liver fibrosis were identified based on unexplained increases in levels of aminotransferases and FIB-4 score, respectively. Among the 9342 participants with available genetic and aminotransferase data, the PNPLA3 G allele (odds ratio [OR], 1.53; 95% CI, 1.41-1.66), TM6SF2 T allele (OR, 1.41; 95% CI, 1.20-1.67), and PPP1R3B G allele (OR, 1.16; 95% CI, 1.06-1.28) were associated with suspected NAFLD. PNPLA3 G was also associated with increased levels of ALT, except in participants with Dominican and South American backgrounds, and with liver fibrosis. The frequency of PNPLA3 G was high (41%) and TM6SF2 T (5%) was low in Hispanic/Latinos. PNPLA3 G frequency differed among Hispanic background groups with the highest proportion in Mexicans (52%) and the lowest proportion in Dominicans (23%). After adjustment for demographic, clinical, and behavioral factors, as well as PNPLA3 G, TM6SF2 T, and PPP1R3B G, American ancestry hada positive association with level of ALT (r= 6.61%; P < .001), whereas African (r= -3.84%; P < .001) and European (r= -4.31%; P < .001) ancestry were inversely associated with level of ALT. American ancestry and PNPLA3 G are independent predictors of ALT levels in US Hispanic/Latinos and may in part explain NAFLD disparities in US Hispanic/Latinos.

Prevalence of Suspected Nonalcoholic Fatty Liver Disease in Lean Adolescents in the United States.

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.

Leucocyte telomere shortening is associated with nonalcoholic fatty liver disease-related advanced fibrosis.

Telomere length and telomerase have been linked with cirrhosis and hepatocellular carcinoma. However, the impact of telomere length on nonalcoholic fatty liver disease and advanced fibrosis in a large national population sample is not well understood. Cross-sectional data from the National Health and Nutrition Examination Survey 1999-2002 were utilized. Suspected nonalcoholic fatty liver disease was diagnosed if serum alanine aminotransferase was >30IU/L for men and >19IU/L for women in the absence of other causes of chronic liver disease. Presence of advanced fibrosis was determined by the nonalcoholic fatty liver disease fibrosis score, aspartate aminotransferase to platelet ratio index and FIB-4 score. Of the 6738 participants (mean age 46.3years, 48.4% male), suspected nonalcoholic fatty liver disease prevalence was inversely associated with leucocyte telomere length in young adults aged 20-39years, though this was not seen in the overall population. Percentage of participants with advanced fibrosis increased corresponding with leucocyte telomere length (longest to shortest). The shortest quartile of leucocyte telomere length was associated with a significantly higher odds ratio (95% confidence interval) of advanced fibrosis of 2.36 (1.32-4.24) in a univariate model compared to the longest quartile, and 2.01 (1.13-3.58) in a multivariate model adjusted for age, gender, ethnicity, waist circumference, smoking, diabetes, hypertension, total cholesterol and high-density lipoprotein cholesterol (P for trend <.05 respectively). In this large nationally representative sample of American adults, leucocyte telomere shortening was associated with increased risk of advanced fibrosis in the setting of suspected nonalcoholic fatty liver disease independent of other known risk factors.

Prevalence and risk factors of elevated alanine aminotransferase among Korean adolescents: 2001-2014

BackgroundAn elevated alanine aminotransferase (ALT) level is a surrogate marker of non-alcoholic fatty liver disease (NAFLD), the most common liver disorder in adolescents. The majority of previous NAFLD studies in adolescents were performed in selected obese populations or had a cross-sectional design without a time-trend analysis. The purpose of this study was to estimate the prevalence and time trends of elevated ALT levels in a general adolescent population and to identify factors associated with ALT elevation.MethodsWe analysed data of adolescent participants (aged 10–18 years) from the Korean National Health and Nutrition Examination Survey 2001–2014, a representative sample of the general population in South Korea. Suspected NAFLD was defined as ALT elevation (> 30 U/L) without hepatitis B surface antigen. In all statistical analyses, sampling weight- and design-based data were used.ResultsALT was elevated in 5.3% (standard error: 0.3%) of the study population of adolescent participants (N = 8455). No significant trends were found from 2001 to 2014 in the prevalence of elevated ALT among male and female adolescents. In multiple logistic regression analysis, elevated ALT was independently associated with sex (odds ratio [OR] male versus female 4.5; 95% CI, 3.3-6.2), obesity (OR 7.6; 95% CI, 5.3-11.0), and truncal obesity (OR 2.5; 95% CI, 1.8-3.5). Furthermore, male sex, obesity, truncal obesity and high household income level were associated with log-transformed ALT levels in multiple regression analysis.ConclusionsIn Korean adolescents of both genders, the prevalence of elevated ALT levels was stable from 2001 to 2014. This study has revealed that sex, obesity, truncal obesity and household income level are associated with ALT elevation in adolescents.

Serum testosterone and non-alcoholic fatty liver disease in men and women in the US.

Testosterone plays a role in predisposing individuals to cardiovascular and metabolic diseases, but its effects differ between men and women. We investigated the association between serum total testosterone and non-alcoholic fatty liver disease in adults in the US. A cross-sectional analysis of data from participants in the 2011-2012 National Health and Nutrition Examination Survey was performed. Subjects with significant alcohol consumption and those with viral hepatitis were excluded. We used the highest sex-specific quartiles of serum total testosterone as references. Suspected non-alcoholic fatty liver disease was diagnosed when serum alanine aminotransferase was >30IU/L for men and >19IU/L for women. Of the 4758 subjects (49.4% men), the prevalence of suspected non-alcoholic fatty liver disease was inversely correlated with the sex-specific quartiles of testosterone in men and women. In a multivariate model, low total testosterone levels were associated with progressively higher odds of suspected non-alcoholic fatty liver disease in men after adjusting for age, obesity and other metabolic risk factors (P values for trends <.01). When the women were divided into 2 groups according to menopausal status, a significant correlation was observed only in the post-menopausal women (P values for trends <.01). The adjusted odds ratios for suspected non-alcoholic fatty liver disease were 1.72-1.99 in men and 2.15-2.26 in post-menopausal women (lowest quartile vs highest quartile). In this nationally representative sample of adults in the US, low total testosterone levels were associated with suspected non-alcoholic fatty liver disease in men and post-menopausal women independent of known risk factors.

Repeatability and Reproducibility of the Ultrasonic Attenuation Coefficient and Backscatter Coefficient Measured in the Right Lobe of the Liver in Adults With Known or Suspected Nonalcoholic Fatty Liver Disease.

To assess the repeatability and reproducibility of the ultrasonic attenuation coefficient (AC) and backscatter coefficient (BSC) measured in the livers of adults with known or suspected nonalcoholic fatty liver disease (NAFLD). The Institutional Review Board approved this Health Insurance Portability and Accountability Act-compliant prospective study; informed consent was obtained. Forty-one research participants with known or suspected NAFLD were recruited and underwent same-day ultrasound examinations of the right liver lobe with a clinical scanner by a clinical sonographer. Each participant underwent 2 scanning trials, with participant repositioning between trials. Two transducers were used in each trial. For each transducer, machine settings were optimized by the sonographer but then kept constant while 3 data acquisitions were obtained from the liver without participant repositioning and then from an external calibrated phantom. Raw RF echo data were recorded. The AC and BSC were measured within 2.6 to 3.0 MHz from a user-defined hepatic field of interest from each acquisition. The repeatability and reproducibility were analyzed by random-effects models. The mean AC and log-transformed BSC (logBSC) were 0.94 dB/cm-MHz and -27.0 dB, respectively. Intraclass correlation coefficients were 0.88 to 0.94 for the AC and 0.87 to 0.95 for the logBSC acquired without participant repositioning. For between-trial repeated scans with participant repositioning, the intraclass correlation coefficients were 0.80 to 0.84 for the AC and 0.69 to 0.82 for the logBSC after averaging results from 3 within-trial images. The variability introduced by the transducer was less than the repeatability error. Hepatic AC and BSC measures using a reference phantom technique on a clinical scanner are repeatable and reproducible between transducers in adults with known or suspected NAFLD.

Prevalence and Correlates of Suspected Nonalcoholic Fatty Liver Disease in Chinese Children.

Nonalcoholic fatty liver disease (NAFLD) has become a serious public health problem worldwide; however, the availability of information on the prevalence of NAFLD in the general pediatric population is still limited. The primary aim of this study was to reveal the prevalence and correlates of suspected NAFLD in Chinese children at the national level. Data from the China Health and Nutrition Surveys (CHNS) was used. Weight, height, waist circumference (WC), blood pressure (BP) were measured for children aged 7–18 years. Blood samples were collected and analyzed. Children were classified as having suspected NAFLD if common causes of liver disease were excluded, and serum alanine aminotransferase (ALT) values were above the established thresholds (>22.1 IU/L for girls and >25.8 IU/L for boys). A percentage of 9.03% (75 out of 831) of Chinese children was found to have suspected NAFLD. Overweight and obesity according to BMI percentiles, abdominal obesity, hyperuricemia (uric acid (UA) > 327 μmol/L), and elevated total cholesterol (TC) were all detected as the correlates of childhood suspected NAFLD when adjusting for other factors. Our study revealed the prevalence of suspected NAFLD in general Chinese children at the national level for the first time. Our findings indicate that suspected NAFLD in children is associated with increasing childhood morbidities, further studies are needed to better understand the prevalence of childhood NAFLD and its correlates, and large-scale programs should be launched to screen NAFLD in the pediatric population in China.