Erratum: Pilot trials of oral betaine in participants with non-alcoholic fatty liver disease and elevated alanine aminotransferase.

Abnormal aminotransferase activity in women with polycystic ovary syndrome

This Month in Gastroenterology

Evaluation and management of non-alcoholic steatohepatitis

Implications of Elevated Serum Alanine Aminotransferase Levels: Think Outside the Liver

BackgroundThe prevalence of nonalcoholic fatty liver disease (NAFLD) in the non-obese population has increased and NAFLD is not always recognized in individuals with metabolic syndrome (MS). The risk of cirrhosis is higher in patients having NAFLD with elevated alanine aminotransferase (ALT) levels than in those having NAFLD with normal ALT levels.ObjectiveTo measure the differences in clinical factors associated with NAFLD having elevation of ALT among subjects with Non-MS, Pre-MS, and MS, and to measure differences in metabolites between MS subjects with and without NAFLD having elevation of ALT.MethodsAmong 7,054 persons undergoing health check-ups, we included 3,025 subjects who met the selection criteria. We measured differences in clinical factors for NAFLD having elevation of ALT among subjects with Non-MS, Pre-MS, and MS, and compared metabolites between subjects with and without NAFLD having elevation of ALT in 32 subjects with MS.ResultsThe prevalence of NAFLD and NAFLD having elevation of ALT was significantly progressively greater in subjects with Non-MS, Pre-MS, and MS (p <0.001, respectively). In the Non-MS group, there were significant differences between subjects with and without NAFLD having elevation of ALT with respect to body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, hemoglobin A1c, uric acid, aspartate aminotransferase (AST); In the Pre-MS group, there were significant differences in BMI, hypertension, AST, and gamma-glutamyl transpeptidase (GGT); In the MS group, there were significant differences in HDL-C, impaired glucose tolerance, AST, and GGT. There were significant differences in levels of metabolites of nicotinamide, inosine, and acetyl-L-carnitine between MS subjects with and without NAFLD having elevation of ALT (all p <0.05).ConclusionsAlthough NAFLD having elevation of ALT is important for development of NAFLD, differences in factors associated with NAFLD having elevation of ALT at various stages of MS should be considered. Additionally, several metabolites may play roles in the identification of risk for NAFLD in individuals with MS.

Elevated alanine aminotransferase (ALT) and non-alcoholic fatty liver disease (NAFLD) have been associated with insulin resistance (IR). The objective of this study was to determine whether elevated ALT and NAFLD were useful for early and definitive determination of IR and to compare their coexistence with conventional risk factors in young Han males. Anthropometric and metabolic measurements were assessed in 216 young Han males (19.3 ± 0.8 years). NAFLD was diagnosed using ultrasonography, and the homeostasis model assessment of insulin resistance (HOMA-IR) served as an index of IR. Subjects in the fourth HOMA-IR quartile had a significantly higher frequency of abdominal obesity, elevated blood pressure and ALT, and NAFLD compared to subjects in quartiles 1-3 (P < 0.05). Using multivariate logistic regression analysis, risk of IR increased by 2.33-fold (95% CI: 1.00-5.42, P = 0.050) in participants with NAFLD. In addition, the coexistence of NAFLD and elevated ALT were significantly associated with HOMA-IR and participants with both elevated ALT and NAFLD had a 4.65-fold (95% CI: 1.55-13.97, P = 0.006) increased risk of IR. Coexistence of NAFLD and elevated ALT are associated with IR in young Han males and might be useful for early detection of IR as compared to conventional risk factors.

Assessing causal relationship between non-alcoholic fatty liver disease and risk of atrial fibrillation

Prevalence of Elevated Alanine Aminotransferase Among US Adolescents and Associated Factors: NHANES 1999–2004

Referral pathways for NAFLD fibrosis in primary care – No longer a ‘needle in a haystack’

Contribution of metabolic factors to alanine aminotransferase activity in persons with other causes of liver disease

Patients with metabolic syndrome (MetS) are likely to have nonalcoholic fatty liver disease (NAFLD), which can progress to advanced fibrosis. Early recognition of those at highest risk may ameliorate outcomes. Noninvasive liver fibrosis assessment through validated scoring systems such as the fibrosis-4 (FIB-4) index is helpful to identify these high-risk patients, with the process ideally beginning in the primary care setting. The primary objective of this study was to determine rates of disease recognition and initial management of patients with NAFLD and advanced fibrosis in a diverse primary care setting. The secondary objective was to define demographic and clinical predictors of NAFLD identification and management in this population. Medical charts from patients seen at three university-based primary care practices in New York City from January 2016 to December 2019 were reviewed. Inclusion criteria consisted of: age 18 years and above, persistent alanine transaminase (ALT) elevation (2 values ≥40IU/mL ≥6mo apart), and body mass index ≥30kg/m 2 . Patients with viral hepatitis or alcohol misuse were excluded. Patients were defined as likely having NAFLD if they met 2 of the following criteria indicating MetS: systolic blood pressure >135mmHg or diastolic blood pressure >85mmHg or active treatment for hypertension; high-density lipoprotein <40g/dL; triglycerides >150mg/dL or active treatment for hyperlipidemia; or hemoglobin A1c ≥5.7% or active treatment for insulin resistance. The primary study endpoints were the frequency of providers' recognition of NAFLD and referral to specialist and/or for imaging based on visit diagnosis codes or chart documentation. The secondary endpoints were frequency of detecting those with NAFLD and advanced fibrosis utilizing previously defined FIB-4 index cutoffs as well as predictors of disease recognition and management. Analysis was completed using descriptive statistics and logistical regression modeling. A total of 295 patients were identified as having persistently elevated ALT, a body mass index ≥30kg/m 2 , and MetS consistent with likely NAFLD diagnosis. In patients meeting these criteria, ALT elevation was documented by primary care providers in 129 patients (43.7%), NAFLD was noted in chart documentation in 76 patients (25.8%), and a NAFLD ICD-10 diagnosis was assigned to 7 patients (2.4%). 50 patients (16.9%) were referred for ultrasound. Among 51 patients (17.2%) at high risk for advanced fibrosis based on FIB-4 >3.25, 23 patients (45.1%) had NAFLD recognized by their provider and 3 (5.9%) were referred to a specialist. On logistic regression, female gender, dyslipidemia, and private insurance were predictors of disease identification by the primary care physician. ALT elevation and NAFLD are under recognized among patients with MetS in the primary care setting. Importantly, while 17.2% of patients with likely NAFLD in our cohort were high risk for advanced fibrosis, less than half of this group had a NAFLD diagnosis recognized by their primary care provider and only three were referred to a liver specialist. Further investigation of disease recognition and management algorithms in the primary care setting are necessary to enhance NAFLD detection, implement clinical care pathways, and reduce disease progression and complications.

We explored the role of the adiponutrin (PNPLA3) nonsynonymous-rs738409 single nucleotide polymorphism (SNP) in genetic susceptibility to nonalcoholic fatty liver disease (NAFLD) and whether this SNP contributes to the severity of histological disease. Two hundred sixty-six individuals were evaluated in a case-control association study, which included 172 patients with features of NAFLD and 94 control subjects. The rs738409 G allele was significantly associated with NAFLD (P < 0.001; OR 2.8 95%, CI 1.5-5.2), independent of age, sex, body mass index (BMI), and Homeostasis Model Assessment (HOMA) index. When we tested the hypothesis of a relation between the SNP and the histological spectrum of NAFLD, a significant association was observed [chi2 19.9, degree of freedom (df): 2, P < 5 x 10(-5), adjusted for HOMA and BMI]. The degree of liver steatosis, as evaluated by liver biopsy, was significantly associated with the rs738409 G allele. Patients with CC genotype showed a lower steatosis score (14.9% +/- 3.9) in comparison with the CG genotype (26.3% +/- 3.5) and GG genotype (33.3% +/- 4.0) (P < 0.005). The proportion of the total variation attributed to rs738409 genotypes was 5.3% (beta 0.23 +/- 0.07; P < 0.002). Our data suggest that the rs738409 G allele is associated not only with fat accumulation in the liver but also with liver injury, possibly triggered by lipotoxicity.

Metabolic Associated Fatty Liver Disease (MAFLD) is the most common cause of liver disease in Australia, but prevalence data are limited. We aimed to describe the frequency of alanine aminotransferase (ALT) elevation, and MAFLD within a large prospective Australian cohort. Cross-sectional analysis of the 2012 survey of the Australian Diabetes, Obesity and Lifestyle (AusDiab) study which included 4747 Australian adults (aged 34–97 yrs) was performed. Frequency of ALT elevation (men ≥ 40 IU/L, women ≥ 30 IU/L) and MAFLD (Fatty Liver Index (FLI) > 60 alongside metabolic risk factors) was determined and risk of advanced fibrosis stratified using the BARD score. Elevated ALT was found in 13% of the cohort, including 22% of people with diabetes, 18% with obesity, and 17% with the metabolic syndrome. 37% of the cohort had MAFLD, and those with MAFLD were more likely to be older (OR 1.01 per 1 year (95% CI 1.00–1.02)), male (OR 1.37 (95% CI 1.17–1.59)), have ALT elevation (OR 3.21 (95% CI 2.59–3.99)), diabetes (OR 3.39 (95% CI 2.61–4.39)), lower HDL-C (OR 0.15 per 1 mmol/L (95% CI 0.12–0.19)), higher diastolic blood pressure (OR 1.05 per 10 mmHg (95% CI 1.05–1.06)), a sedentary lifestyle (OR 1.99 (95% CI 1.59–2.50)) and less likely to have tertiary education (OR 0.81 (95% CI 0.7–0.94) compared to those without MAFLD. Of those with MAFLD, 61% had a BARD score suggesting risk of advanced fibrosis and 22% had an elevated ALT. Over 10% of this Australian cohort had elevated ALT, and 37% had MAFLD, with many at risk for advanced fibrosis.

Epidemiology of non-alcoholic fatty liver disease in China

Nonalcoholic Fatty Liver Disease in Children: Where Are We?