UNASSIGNED: The prevalence and incidence of Nonalcoholic fatty liver disease (NAFLD) are increasing worldwide, and NAFLD has emerged as a prominent global health concern. The link between serum alanine aminotransferase (ALT) to aspartate aminotransferase (AST) ratio and NAFLD remains unclear. This study investigated the association between the ALT/AST ratio and NAFLD prevalence, including liver steatosis and fibrosis levels in the population.
UNASSIGNED: We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018, including 4753 participants. Subgroup analyses, stratified by age, gender, and body mass index (BMI), were performed, along with adjusted multivariable logistic regression analyses to evaluate the relationship between ALT/AST levels and the likelihood of NAFLD, liver steatosis, and hepatic fibrosis stage. A generalized additive model examined the non-linear relationship between ALT/AST and the probability of developing NAFLD.
UNASSIGNED: Among 4753 participants, 1508 (31.73%) were diagnosed with NAFLD. Significant positive correlations between ALT/AST and NAFLD risk were found across all models. In addition, the subgroup analysis by gender, age, and BMI suggested that ALT/AST showed a positive correlation with NAFLD. The ALT/AST ratio was positively correlated with the degree of liver steatosis and liver fibrosis. The correlation between ALT/AST and the incidence of NAFLD showed a non-linear pattern. In women, the non-linear trend is particularly evident, showing an inverted U-shaped curve with an inflection point of 1.302. A receiver operating characteristic (ROC) analysis showed that the predictive value of ALT/AST for NAFLD was better than that of traditional liver enzyme parameters.
UNASSIGNED: A higher ALT/AST ratio was independently associated with a significantly higher risk of NAFLD and liver fibrosis within American cohorts. This link is robust among females, children, and adolescents. ALT/AST ratio can be used as a simple and effective noninvasive biomarker to identify individuals with high risk of NAFLD.

OBJECTIVE: This study sought to examine the association between antipsychotic drug use and hepatobiliary health based on serum markers and ultrasound observations on a sample of patients with schizophrenia compared to age and gender matched healthy controls.
METHODS: The 120 patients with schizophrenia and 60 control subjects had their blood drawn to measure liver function tests and underwent hepatobiliary ultrasonography to determine hepatobiliary lesions. Liver function tests included total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Standardized cross-sectional images of the liver and kidneys were obtained from patients and controls, and analyses were stratified by length of taking psychotropic medication among those with schizophrenia. Liver echo attenuation coefficients, liver-kidney ratios, and liver fat content were determined.
RESULTS: Psychotropic drug use was associated with greater liver burden and liver lesions in patients with schizophrenia compared to controls. The levels of TC, TG, ALT and AST in patients with schizophrenia were also all significantly higher among patients with schizophrenia. Long-term psychotropic medication was associated with increased levels of fatty liver in patients compared with controls. Levels of TC, TG, ALT and AST were all significantly higher in the long-term psychotropic medication use group than in the short-term group. Liver echo attenuation coefficient, liver-kidney ratio, and liver fat content were also higher in the long-term medication use group compared to the short-term group.
CONCLUSIONS: Antipsychotic drug use, particularly long-term use, is associated with increased liver burden in patients with schizophrenia, impaired lipid metabolism, increased liver lesions and fat content.

Metabolic dysfunction associated fatty liver disease (MAFLD) is a common cause of liver disease in children and adolescents. The relationship between insulin resistance (IR) and MAFLD in children with short stature remains largely unknown. The present study was to investigate the relationship between the triglyceride-glucose (TyG) index and alanine aminotransferase (ALT) levels in children with short stature. A total of 1754 children with short stature were enrolled. Anthropometric, biochemical and hormonal indexes were collected through physical measurement examinations and laboratory tests. A nonlinear association was found between the TyG index and ALT. The inflection point of the curve was at a TyG index of 8.24. In multivariate piecewise linear regression, only when the TyG index was greater than 8.24 was there a significant positive association between the TyG index and ALT (β 5.75, 95% CI 3.30, 8.19; P < 0.001). However, when the TyG index was less than 8.24, there was no significant association between the TyG index and ALT (β -0.57, 95% CI -1.84, 0.71; P = 0.382). This study demonstrated a nonlinear relationship between TyG index and ALT in children with short stature. This finding suggests that a high TyG index is associated with elevated ALT in children with short stature.

UNASSIGNED: The liver plays an important role in gonadal steroid hormone metabolism, which can affect reproductive health, including the menstrual cycle. However, evidence from large population-based studies is limited. Therefore, this study aimed to investigate the association between liver function markers and menstrual cycle irregularities in premenopausal Korean women using nationwide data.
UNASSIGNED: This study analyzed Data from the Korea National Health and Nutrition Examination Survey 2010-2011. We investigated 3,045 premenopausal women aged 19-59 years. Liver function markers including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase, and fatty liver index were analyzed. Multivariable logistic regression analysis was performed to investigate the association between liver function markers and menstrual cycle irregularity while adjusting for confounding factors. Values were presented as odds ratios (ORs) with 95% confidence intervals (CIs). Subgroup analysis was also performed.
UNASSIGNED: Baseline characteristic analysis showed that approximately 14.4% of the study population experienced menstrual cycle irregularity. The mean age was 34.5±0.7 years. The highest quartile of serum ALT and AST levels showed significantly higher ORs for menstrual cycle irregularity (adjusted OR, 1.83; 95% CI, 1.26-2.64 and adjusted OR, 1.67; 95% CI, 1.17-2.39, respectively). A similar result was observed in the subgroup analysis.
UNASSIGNED: Liver function markers were positively associated with menstrual cycle irregularities. In clinical settings, women of reproductive age with relatively decreased liver function should be considered for regular followup of their reproductive health status.

BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) keeps increasing annually worldwide. Non-invasive assessment tools for evaluating the risk and severity of the disease are still limited. Insulin resistance (IR) and abdominal obesity (ABO) are closely related to NAFLD.
METHODS: A retrospective large-scale, population-based study was conducted based on the data from the 2017-2018 cycle of the National Health and Nutrition Examination Survey (NHANES). Three ABO indices, namely lipid accumulation product (LAP), visceral obesity index (VAI), waist circumference-triglyceride index (WTI), and three IR indices, including triglyceride glucose index (TyG), homeostasis model assessment of insulin resistance (HOMA-IR) and metabolic score for insulin resistance (METS-IR), were analyzed and compared for their relationships with NAFLD based on weighted multivariable logistic regression, spearman correlation heatmap, smooth curve fittings. The area under the curve (AUC) of receiver-operating characteristic (ROC) curve was used to evaluate the diagnostic capability of these indices for NAFLD. Differences among the AUCs were calculated and compared by Delong test.
RESULTS: In total, 3095 participants were included in our study among which 1368 adults were diagnosed with NAFLD. All six indices presented positive associations with NAFLD. There was a claw-shaped curve between HOMA-IR, VAI, LAP and NAFLD while a smooth semi-bell curve was observed in TyG, METS-IR and WTI. LAP and HOMA-IR had the best diagnostic capability for NAFLD (LAP: AUC = 0.8, Youden index = 0.48; HOMA-IR: AUC = 0.798, Youden index = 0.472) while VAI (AUC = 0.728, Youden index = 0.361) showed the lowest predictive value. The correlation heat map indicated positive correlations between all six indices and liver function, hepatic steatosis and fibrosis severity. In the NAFLD group, IR indicators presented a stronger association with alanine aminotransferase (ALT) compared with ABO indices.
CONCLUSIONS: All six indices can screen NAFLD withLAP and HOMA-IR being possibly optimal predictors. IR indices may be more sensitive to identify acute hepatic injury in NAFLD patients than ABO indices.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver ailment worldwide, in which nonpharmacological strategies have a considerable role in the treatment. Probiotic supplementation as well as physical exercise can improve cardiometabolic parameters, but further research is needed to determine the effects of combined treatment versus exercise alone in managing NAFLD-associated biomarkers, primarily liver enzymes, lipid markers, and insulin resistance.
OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the effects of probiotic supplementation, combined with exercise versus exercise alone, on liver enzymes and cardiometabolic markers in patients with NAFLD.
METHODS: A systematic review and meta-analysis of randomized clinical trials was performed by searching PubMed, Scopus, and Web of Science databases up to April 2024. The search was restricted to articles published in the English language and human studies. Random effects models were used to calculate weighted mean differences (WMD).
RESULTS: Pooled estimates (9 studies, 615 patients, intervention durations ranging from 8 to 48 weeks) revealed that probiotics plus exercise decreased aspartate transaminase (AST) [WMD=-5.64 U/L, p = 0.02], gamma-glutamyl transferase (GGT) [WMD=-7.09 U/L, p = 0.004], low-density lipoprotein (LDL) [WMD=-8.98 mg/dL, p = 0.03], total cholesterol (TC) [WMD=-16.97 mg/dL, p = 0.01], and homeostatic model assessment for insulin resistance (HOMA-IR) [WMD=-0.94, p = 0.005] significantly more than exercise only. However, probiotics plus exercise did not significantly change high-density lipoprotein (HDL) [WMD = 0.07 mg/dL, p = 0.9], fasting insulin [WMD=-1.47 µIU/mL, p = 0.4] or fasting blood glucose (FBG) [WMD=-1.57 mg/dL, p = 0.3] compared with exercise only. While not statistically significant, there were clinically relevant reductions in alanine aminotransferase (ALT) [WMD=-6.78 U/L, p = 0.1], triglycerides (TG) [WMD=-21.84 mg/dL, p = 0.1], and body weight (BW) [WMD=-1.45 kg, p = 0.5] for probiotics plus exercise compared with exercise only. The included studies exhibited significant heterogeneity for AST (I2 = 78.99%, p = 0.001), GGT (I2 = 73.87%, p = 0.004), LDL (I2 = 62.78%, p = 0.02), TC (I2 = 72.41%, p = 0.003), HOMA-IR (I2 = 93.86%, p = 0.001), HDL (I2 = 0.00%, p = 0.9), FBG (I2 = 66.30%, p = 0.01), ALT (I2 = 88.08%, p = 0.001), and TG (I2 = 85.46%, p = 0.001). There was no significant heterogeneity among the included studies for BW (I2 = 0.00%, p = 0.9).
CONCLUSIONS: Probiotic supplementation combined with exercise training elicited better results compared to exercise alone on liver enzymes, lipid profile, and insulin resistance in patients with NAFLD.
BACKGROUND: PROSPERO registration number CRD42023424290.

In this editorial, we comment on the article by Chen et al recently published in 2024. We focus the debate on whether reducing the upper limit of normal of alanine aminotransferase (ALT) would effectively identify cases of fibrosis in metabolic-dysfunction associated fatty liver disease (MAFLD). This is important given the increasing prevalence of MAFLD and obesity globally. Currently, a suitable screening test to identify patients in the general population does not exist and most patients are screened after the finding of an abnormal ALT. The authors of this paper challenge the idea of what a normal ALT is and whether that threshold should be lowered, particularly as their study found that 83.12% of their study population with a diagnosis of MAFLD had a normal ALT. The main advantages of screening would be to identify patients and provide intervention early, the mainstay of this being changing modifiable risk factors and monitoring for liver fibrosis. However, there is not enough suitable therapeutic options available as of yet although this is likely to change in the coming years with more targets for therapy being discovered. Semaglutide is one example of this which has demonstrated benefit with an acceptable side effect profile for those patients with MAFLD and obesity, although studies have not yet shown a significant improvement in fibrosis regression. It would also require a huge amount of resource if a reduced ALT level alone was used as criteria; it is more likely that current scoring systems such as fibrosis-4 may be amended to represent this additional risk. Currently, there is not a good argument to recommend widespread screening with a reduced ALT level as this is unlikely to be cost-effective. This is compounded by the fact that there is a significant heterogeneity in what is considered a normal ALT between laboratories. Although studies previously have suggested a more pragmatic approach in screening those over the age of 60, this is likely to change with the increasing incidence of obesity within the younger age groups. The main message from this study is that those who have hypercholesterolemia and high body metabolic index should have these risk factors modified to maintain a lower level of ALT to reduce the risk of progression to fibrosis and cirrhosis.

In this editorial, we offer commentary on the article published by Chen et al in a recent issue of the World Journal of Gastroenterology (2024; 30: 1346-1357). The study highlights a noteworthy association between persistently elevated, yet high-normal levels of alanine transaminase (ALT) and an escalated cumulative risk of developing metabolic dysfunction-associated fatty liver disease (MAFLD). MAFLD has emerged as a globally prevalent chronic liver condition, whose incidence is steadily rising in parallel with improvements in living standards. Left unchecked, MAFLD can progress from hepatic steatosis to liver fibrosis, cirrhosis, and even hepatocellular carcinoma, underscoring the importance of early screening and diagnosis. ALT is widely recognized as a reliable biomarker for assessing the extent of hepatocellular damage. While ALT levels demonstrate a significant correlation with the severity of fatty liver disease, they lack specificity. The article by Chen et al contributes to our understanding of the development of MAFLD by investigating the long-term implications of high-normal ALT levels. Their findings suggest that sustained elevation within the normal range is linked to an increased likelihood of developing MAFLD, emphasizing the need for closer monitoring and potential intervention in such cases.

BACKGROUND: As one of the most requested profiles of blood tests, there is a need for standardization among liver function tests (LFT). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are key markers of hepatocellular injury. ALT and AST are used to calculate a Fibrosis-4 (FIB-4) score for assessing liver fibrosis. Despite recommendations by the International Federation of Clinical Chemistry (IFCC) to include pyridoxal-5-phosphate in ALT and AST assay methodologies, most laboratories continue to omit this.
METHODS: Data from the UK NEQAS for Clinical Chemistry Scheme, Distribution 1160 (November 2023), was reviewed to investigate variation in practice regarding liver blood tests in relation to ALT, AST and FIB-4. In addition, a series of questions audited laboratory practice in relation to liver enzymes.
RESULTS: Wide variation was seen in LFT profiles offered by laboratories, with 32 different combinations of tests used. The IFCC-recommended methods for ALT and AST are used by one-third of laboratories and give significantly higher results than non-IFCC methods. Laboratories using IFCC methods also reported significantly higher FIB-4 scores. Reference ranges and cut-offs for these tests also varied, and did not account for method-related differences in results.
CONCLUSIONS: The lack of standardization of LFTs can have a significant impact on patient care. The difference in results for ALT, AST and FIB-4 in laboratories not using IFCC-recommended methods may lead to misdiagnosis. This issue should be addressed by laboratories using methods including pyridoxal-5-phosphate. Until then, method-related reference ranges and cut-offs for ALT, AST and FIB-4 are required.

Studies have indicated that reduced serum ALT levels are commonly linked to aging and are known to predict poor outcomes in many clinical conditions as potential frailty indicators. There are close connections between the brain and peripheral organs, particularly the liver. In patients with acute ischemic stroke (AIS), the interactive effects may change ALT levels, which in turn influence stroke outcomes. Whether ALT has potential neuroprotective effects or is an indicator of frailty in AIS patients remains unknown. This retrospective analysis examined 572 AIS patients in Beijing Luhe Hospital between August 2020 and June 2021. Patient demographics and laboratory results were assembled. The National Institutes of Health Stroke Scale (NIHSS) was used to analyze stroke severity. Modified Rankin Score (mRS) determined stroke outcome 3 months after AIS, with mRS≤2 indicating a favorable outcome. Based on serum ALT measurements, patients were classified into three tertiles (T1-T3). Binary logistic regression analysis evaluated the correlation between ALT tertiles and AIS outcomes. Of the patients, 66 exhibited unfavorable outcomes. The median ALT level in this group was 13 (IQR: 11-18.25), which was lower than in the favorable outcomes cohort (16; IQR: 11-22). A decline in ALT corresponded with a higher incidence of poor outcomes at 3 months (T1, 15.5 %; T2, 11.4 %; T3, 7.0 %; p = 0.03). The lowest ALT tertile (T1) was independently linked to an adverse 3-month outcome (OR 2.50 95 %CI 1.24-5.07, p = 0.038) compared to the highest tertile. ALT levels demonstrated no correlation with age (T1, 62.59 ± 12.64; T2, 64.01 ± 11.47; T3, 65.12 ± 11.27; p > 0.05). Regardless of age, lower serum ALT levels are independently associated with poorer outcomes in AIS patients. This finding suggests the potential pivotal part of the liver in AIS outcomes, highlighting the need to consider both neurological and liver functions post-stroke.