Aspartate Aminotransferase/alanine Aminotransferase Research Articles

A machine learning-based predictive model discriminates nonalcoholic steatohepatitis from nonalcoholic fatty liver disease

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a leading cause of liver-related morbidity and mortality. The diagnosis of non-alcoholic steatohepatitis (NASH) plays a crucial role in the management of NAFLD patients. ObjectiveThe aim of our observational study was to build a machine learning model to identify NASH in NAFLD patients. MethodsThe clinical characteristics of 259 NAFLD patients and their initial laboratory data (Cohort 1) were collected to train the model and carry out internal validation. We compared the models built by five machine learning algorithms and screened out the best models. Receiver operating characteristic (ROC) curves, sensitivity, specificity, and accuracy were used to evaluate the performance of the model. In addition, the NAFLD patients in Cohort 2 (n = 181) were externally verified. ResultsWe finally identified six independent risk factors for predicting NASH, including neutrophil percentage (NEU%), aspartate aminotransferase/alanine aminotransferase (AST/ALT), hematocrit (HCT), creatinine (CREA), uric acid (UA), and prealbumin (PA). The NASH-XGB6 model built using the XGBoost algorithm showed sufficient prediction accuracy, with ROC values of 0.95 (95 % CI, 0.91–0.98) and 0.90 (95 % CI, 0.88–0.93) in Cohort 1 and Cohort 2, respectively. ConclusionsNASH-XGB6 can serve as an effective tool for distinguishing NASH patients from NAFLD patients.

Alcoholic Liver Disease/Nonalcoholic Fatty Liver Disease Index for Classification of Patients with Steatotic Liver Disease.

Steatotic liver disease (SLD) encompasses metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (AALD) at extremes as well as an overlap group termed MASLD with increased alcohol intake (MetALD). The Alcoholic Liver Disease/Nonalcoholic Fatty Liver Disease Index (ANI) was proposed to differentiate ALD from nonalcoholic fatty liver disease (NAFLD). We analysed the performance of the ANI in differentiating within the SLD spectrum. In a cross-sectional study at a tertiary care center, 202 adults (>18 years) who were prospectively diagnosed with SLD defined by magnetic resonance imaging-proton density fat fraction >6.4% were enrolled. Alcohol consumption (AC) was recorded according to thresholds for significant AC: 140-350 g/week (or 20-50 g/day) for females and 210-420 g/week (or 30-60 g/day) for males. The ANI was calculated, and area under the receiver operating characteristic curve (AUROC) was generated. Of 202 patients (47 years [interquartile range, IQR, 38 to 55], 23.75% females, 77% obese, 42.1% with diabetes, 38.1% hypertensive, 28.7% statin use), 40.5% were ever-alcohol consumers; 120 (59%), 50 (24.7%), and 32 (15.8%) were MASLD (ANI, -3.7 [IQR, -7 to -1.6]; MetALD, - 1.45 [IQR, -2.4 to 0.28]; and AALD, 0.71 [IQR, -1.3 to 4.8], respectively; P<0.05 for all). The AUROC of the ANI for MASLD and AALD was 0.79 (IQR, 0.72 to 0.84; cut-off <-3.5) and 0.80 (IQR, 0.74 to 0.86; cut-off >-1.49), respectively. The ANI outperformed aspartate transaminase/alanine transaminase (AST/ALT) ratio (AUROC=0.75 [IQR, 0.69 to 0.81]) and gamma glutamyl transpeptidase (GGT) (AUROC=0.74 [IQR, 0.67 to 0.80]). Addition of GGT did not improve model performance (AUCdiff=0.004; P=0.33). AC is common in MASLD. The ANI distinguishes MASLD and AALD, with individual cut-offs within the intermediate zone indicating MetALD. ANI also outperforms AST/ALT ratio or GGT.

Clinical and virological characteristics of coexistent hepatitis B surface antigen and antibody in treatment-naive children with chronic hepatitis B virus infection.

Serological pattern of simultaneous positivity for hepatitis B surface antigen (HBsAg) and antibody against HBsAg (anti-HBs) is considered a specific and atypical phenomenon among patients with chronic hepatitis B virus (HBV) infection, especially in pediatric patients. Unfortunately, there is limited understanding of the clinical and virological characteristics among children having chronic HBV infection and the coexistence of HBsAg and anti-HBs. Hence, our objective was to determine the prevalence of coexistent HBsAg and anti-HBs and to explore the associated clinical and virological features in this patient population. The researchers conducted a retrospective cohort study on the 413 pediatric patients with chronic HBV infection from December 2011 to June 2022. The patients were stratified into two groups based on their anti-HBs status. Demographic, serum biochemical and virological parameters of two group were compared. Of the total 413 enrolled subjects, 94 (22.8%) were tested positive for both HBsAg and anti-HBs. Patients with anti-HBs were younger and demonstrated significantly higher ratio of albumin to globulin (A/G), elevated serum levels of alanine transaminase (ALT), lower ratio of aspartate transaminase (AST)/ALT (AST/ALT) and reduced serum levels of globulin, HBsAg and HBV DNA, Additionally, these patients were more likely to show coexistent HBeAg and anti-HBe when compared to patients without anti-HBs. The results of multivariate logistical analysis revealed that AST/ALT, serum levels of globulin and HBsAg were negatively associated with coexistence of HBsAg and anti-HBs. Our data demonstrated a considerable prevalence of coexisting HBsAg and anti-HBs in pediatric patients. Children with this specific serological pattern were commonly of a younger age, seemly predisposing them to early liver impairment and lower HBV replication activity.

Predicting 1year readmission for heart failure: A comparative study of machine learning and the LACE index.

There is a lack of tools for accurately identifying the risk of readmission for heart failure in elderly patients with arrhythmia. The aim of this study was to establish and compare the performance of the LACE [length of stay ('L'), acute (emergent) admission ('A'), Charlson comorbidity index ('C') and visits to the emergency department during the previous 6months ('E')] index and machine learning in predicting 1 year readmission for heart failure in elderly patients with arrhythmia. Elderly patients with arrhythmia who were hospitalized at Sichuan Provincial People's Hospital between 1 June 2018 and 31 May 2020 were enrolled. The LACE index was calculated for each patient, and the area under the receiver operating characteristic curve (AUROC) was calculated. Six machine learning algorithms, combined with three variable selection methods and clinically relevant features available at the time of hospital discharge, were used to develop machine learning models. AUROC and area under the precision-recall curve (AUPRC) were used to assess discrimination. Shapley additive explanations (SHAP) analysis was used to explain the contributions of the features. A total of 523 patients were enrolled, and 108 patients experienced 1year hospital readmission for heart failure. The AUROC of the LACE index was 0.5886. The complete machine learning model had the best predictive performance, with an AUROC of 0.7571 and an AUPRC of 0.4096. The most important predictors for 1year readmission were educational level, total triiodothyronine (TT3), aspartate aminotransferase/alanine aminotransferase (AST/ALT), number of medications (NOM) and triglyceride (TG) level. Compared with the LACE index, the machine learning model can accurately identify the risk of 1year readmission for heart failure in elderly patients with arrhythmia.

De Ritis Ratio to Predict Clinical Outcomes of Intermediate- and High-Risk Pulmonary Embolisms.

Background: Abnormal liver function tests can identify severe cardiopulmonary failure. The aspartate transaminase/alanine transaminase (AST/ALT) ratio, or the De Ritis ratio, is commonly used to evaluate acute liver damage. However, its prognostic value in pulmonary embolism (PE) is unknown. Methods: Two cohorts, including patients with intermediate- and high-risk PEs, were established: one with an abnormal baseline AST/ALT ratio (>1) and another with a normal baseline AST/ALT ratio (<1). The primary outcome was a 60-day mortality. Secondary outcomes included peak N-terminal pro-brain-natriuretic-peptide (NT-proBNP) levels, complications, and the need for critical care treatment. To assess the effect of abnormal AST/ALT ratios, inverse probability weighted (IPW) analyses were performed. Results: In total, 230 patients were included in the analysis, and 52 (23%) had an abnormal AST/ALT ratio. After the IPW correction, patients with an abnormal AST/ALT ratio had a significantly higher mortality rate and peak NT-proBNP levels. The relative risks of 60-day mortality, shock development, use of inotropes/vasopressors, mechanical ventilation, and extracorporeal life support were 9.2 (95% confidence interval: 3.3-25.3), 10.1 (4.3-24), 2.7 (1.4-5.2), 2.3 (1.4-3.7), and 5.7 (1.4-23.1), respectively. Conclusions: The baseline AST/ALT ratio can be a predictor of shock, multiorgan failure, and mortality in patients with a pulmonary embolism.

Association of AST/ALT ratio with 90-day outcomes in patients with acute exacerbation of chronic liver disease: a prospective multicenter cohort study in China.

A high aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio is associated with liver injury in liver disease; however, no data exist regarding its relationship with 90-day prognosis in patients with acute exacerbation of chronic liver disease. In this study, 3,758 participants (955 with advanced fibrosis and 2,803 with cirrhosis) from the CATCH-LIFE cohort in China were included. The relationships between different AST/ALT ratios and the risk of adverse 90-day outcomes (death or liver transplantation) were determined in patients with cirrhosis or hepatitis B virus (HBV)-associated advanced fibrosis, respectively. In the patients with HBV-associated advanced fibrosis, the risk of 90-day adverse outcomes increased with AST/ALT ratio; after adjusting for all confounding factors, the risk of adverse 90-day outcomes was the highest when AST/ALT ratio was more than 1.08 (OR = 6.91 [95% CI = 1.789-26.721], p = 0.005), and the AST/ALT ratio of >1.9 accelerated the development of adverse outcomes. In patients with cirrhosis, an AST/ALT ratio > 1.38 increased the risk of adverse 90-day outcomes in all univariables (OR = 1.551 [95% CI = 1.216-1.983], p < 0.001) and multivariable-adjusted analyses (OR = 1.847 [95% CI = 1.361-2.514], p < 0.001), and an elevated AST/ALT ratio (<2.65) accelerated the incidence of 90-day adverse outcomes. An AST/ALT ratio of >1.38 corresponded with a more than 20% incidence of adverse outcomes in patients with cirrhosis. The AST/ALT ratio is an independent risk factor for adverse 90-day outcomes in patients with cirrhosis and HBV-associated advanced fibrosis. The cutoff values of the AST/ALT ratio could help clinicians monitor the condition of patients when making clinical decisions.

What Laboratory Examinations for Open-angle Glaucoma Risk Stratification

Purpose: We analyzed the laboratory examinations associated with open-angle glaucoma (OAG) using data from the Korea National Health and Nutrition Examination Survey (KNHANES) to enhance our understanding of OAG risk factors.Methods: We categorized participants in KNHANES between 2008 and 2012 into OAG and non-glaucomatous groups. Next, we conducted a multivariate analysis, adjusting for age, sex, education level, and survey year.Results: Significant differences were observed in age, sex, and educational levels between the two groups. After propensity score matching, the OAG group demonstrated a significantly elevated intraocular pressure (IOP), myopia prevalence, systolic blood pressure (SBP), and diastolic blood pressure (DBP). In addition, that group exhibited a significantly increased prevalence of hypertension and melancholic mood disorders and aspartate transaminase/alanine transaminase (AST/ALT) ratio. Multiple logistic regression revealed elevated IOP, SBP, DBP, AST/ALT ratio, and prevalence of hypertension, melancholic mood, and myopia as OAG risk factors.Conclusions: Our study revealed several risk factors for OAG, including elevated IOP, SBP, DBP, AST/ALT ratio, and prevalence of hypertension, melancholic mood, and myopia. However, the mechanism underlying OAG remains uncertain. Notably, a positive correlation was observed between the AST/ALT ratio and OAG risk. Further studies are needed to evaluate this association.

Prognostic value of aspartate aminotransferase/alanine aminotransferase ratio in hepatocellular carcinoma after hepatectomy.

The prognostic significance of the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio in hepatocellular carcinoma remains uncertain. The aim of the current study was to evaluate the association between the AST/ALT ratio and prognosis in patients with hepatocellular carcinoma after hepatectomy, and to explore the role of underlying liver diseases as mediators. This retrospective study included patients with hepatocellular carcinoma who underwent hepatectomy between January 2014 and January 2018 at two Chinese hospitals. The maximally selected rank statistic and g-computation approach were used to quantify and visualize the association between the AST/ALT ratio and overall survival or recurrence-free survival. The role of mediators (chronic hepatitis B, hepatic steatosis and liver cirrhosis) was analysed. Among the 1519 patients (mean(s.d.) age at baseline, 50.5(11.3) years), 1309 (86.2%) were male. During a median follow-up of 46.0 months, 514 (33.8%) patients died and 358 (23.6%) patients experienced recurrence. The optimal cut-off value for the AST/ALT ratio was 1.4, and the AST/ALT ratio greater than or equal to 1.4 was independently associated with a 39.0% increased risk of death and a 30.0% increased risk of recurrence (overall survival: hazard ratio (HR), 1.39; 95% c.i. 1.15 to 1.68; recurrence-free survival: HR, 1.30; 95% c.i. 1.12 to 1.52) after adjusting for confounders. Chronic hepatitis B significantly mediated the association of the ratio of AST/ALT with both overall survival and recurrence-free survival (20.3% for overall survival; 20.1% for recurrence-free survival). The AST/ALT ratio greater than or equal to 1.4 was associated with shorter overall survival and recurrence-free survival in patients with hepatocellular carcinoma after hepatectomy, and chronic hepatitis B may play a role in their association.

Systemic Inflammation Score Using Pretherapeutic Inflammatory Markers to Predict Prognosis for Hepatocellular Carcinoma Patients After Hepatic Arterial Infusion Chemotherapy.

To assess the clinical value of the pretherapeutic systemic inflammation score (SIS) in predicting the prognosis of hepatocellular carcinoma (HCC) after hepatic arterial infusion chemotherapy (HAIC). From February 2016 to April 2021, 415 advanced HCC patients who underwent HAIC at Sun Yat-sen University Cancer Center were randomly divided into training (n = 277) and validation cohorts (n = 138) and analyzed. The aspartate aminotransferase-alanine aminotransferase ratio (AAR), lymphocyte × albumin (L × A), and neutrophil × monocyte (N × M) were used to construct the SIS score based on a multivariate Cox analysis in the training cohort. A nomogram consisting of the SIS score was created and evaluated by calibration plot, areas under the receiver operating characteristic (AUC) curve, and decision curve analysis (DCA). Univariate and multivariate Cox analyses revealed that the SIS score was an independent predictor of OS. A high SIS score was associated with large tumor size (P < 0.05), multiple lesions (P < 0.01), high AFP level (P < 0.01), extrahepatic metastasis (P < 0.05), and advanced BCLC stage (P < 0.01). Kaplan-Meier analysis showed that the patients with a high SIS had shorter OS than those with a low SIS in both the non-PD (p = 0.015) and PD group (p = 0.023). The calibration plots showed good concordance between the nomogram's prediction and the actual observations in both the training and validation cohorts. In the training cohort, the AUCs of the nomogram predicting the 2-year and 3-year survival rates were 0.749 and 0.739, respectively; in the validation cohort, they were 0.760 and 0.681, respectively. Based on the AUC and DCA, the nomogram showed better predictive ability than other predictors. The pretherapeutic SIS score is a potential prognostic predictor for HCC patients undergoing HAIC.

Association of AST/ALT (De Ritis) ratio with sarcopenia in a Chinese population of community-dwelling elderly

BackgroundThe aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, also known as De Ritis ratio, has been reportedly associated with malnutrition which plays a crucial role in sarcopenia. The aim of this study was to examine the relationship between AST/ALT ratio and sarcopenia in the Chinese community-dwelling elderly. MethodsA cross-sectional study with 2751 participants (1343 men and 1408 women) aged ≥60 years was performed. Appendicular skeletal muscle mass index (ASMI), grip strength, and gait speed were measured to diagnose sarcopenia according to the latest Asian Working Group for Sarcopenia (AWGS) consensus. The association of AST/ALT ratio with sarcopenia was examined using logistic regression analysis. ResultsThe prevalence of sarcopenia in the present study was 4.4%. AST/ALT ratio was higher in the sarcopenia group than in the non-sarcopenia group (1.30 ± 0.33 vs. 1.16 ± 0.62, P = 0.010). AST/ALT ratio was negatively correlated with the components of sarcopenia, including ASMI, grip strength, and gait speed. Logistic regression analysis indicated that high AST/ALT ratio (>1.20) was associated with increased risk of sarcopenia even after adjustment for potential confounders (adjusted OR = 2.33, 95%CI = 1.48–3.68, P < 0.001). Stratification analyses indicated that the association of high AST/ALT ratio with high risk of sarcopenia was more significant in males and the elderly with ≥70 years. ConclusionsOur findings demonstrate that high AST/ALT ratio is associated with increased risk of sarcopenia in a Chinese population of community-dwelling elderly.

The Effects of a Low Linoleic Acid/α-Linolenic Acid Ratio on Lipid Metabolism and Endogenous Fatty Acid Distribution in Obese Mice.

A reduced risk of obesity and metabolic syndrome has been observed in individuals with a low intake ratio of linoleic acid/α-linolenic acid (LA/ALA). However, the influence of a low ratio of LA/ALA intake on lipid metabolism and endogenous fatty acid distribution in obese patients remains elusive. In this investigation, 8-week-old C57BL/6J mice were randomly assigned to four groups: low-fat diet (LFD) as a control, high-fat diet (HFD), high-fat diet with a low LA/ALA ratio (HFD+H3L6), and high-fat diet with a high LA/ALA ratio (HFD+L3H6) for 16 weeks. Our results show that the HFD+H3L6 diet significantly decreased the liver index of HFD mice by 3.51%, as well as the levels of triacylglycerols (TGs) and low-density lipoprotein cholesterol (LDL-C) by 15.67% and 10.02%, respectively. Moreover, the HFD+H3L6 diet reduced the pro-inflammatory cytokines interleukin-6 (IL-6) level and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio and elevated the level of superoxide dismutase (SOD) in the liver. The HFD+H3L6 diet also resulted in the downregulation of fatty acid synthetase (FAS) and sterol regulatory element binding proteins-1c (SREBP-1c) expression and the upregulation of peroxisome proliferator-activated receptor-α (PPAR-α) and acyl-CoA oxidase 1 (ACOX1) gene expression in the liver. The low LA/ALA ratio diet led to a notable increase in the levels of ALA and its downstream derivative docosahexaenoic acid (DHA) in the erythrocyte, liver, perienteric fat, epididymal fat, perirenal fat, spleen, brain, heart, and gastrocnemius, with a strong positive correlation. Conversely, the accumulation of LA in abdominal fat was more prominent, and a high LA/ALA ratio diet exacerbated the deposition effect of LA. In conclusion, the low LA/ALA ratio not only regulated endogenous fatty acid levels but also upregulated PPAR-α and ACOX1 and downregulated SREBP-1c and FAS gene expression levels, thus maintaining lipid homeostasis. Optimizing dietary fat intake is important in studying lipid nutrition. These research findings emphasize the significance of understanding and optimizing dietary fat intake.

Assessment of the diagnostic accuracy of noninvasive scoring tools in predicting moderate-to-severe steatohepatitis via ultrasonography in asymptomatic healthy subjects admitted to family medicine outpatient clinics.

Efficacies of the noninvasive scoring tools in screening and diagnosing nonalcoholic fatty liver disease (NAFLD) remain controversial. Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, AST-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) index are the most frequently used parameters for differentiating moderate and severe steatohepatitis. In this context, the objective of this study is to evaluate the diagnostic accuracy of noninvasive tools in predicting moderate-to-severe steatohepatitis via ultrasonography in asymptomatic healthy subjects admitted to family medicine outpatient clinics. The population of this retrospective study consisted of healthy individuals tested within the scope of a medical check-up program between January and July 2021. All participants included in the study underwent relevant laboratory tests and liver ultrasonography (US). Steatohepatitis was graded using the US images as normal (grade 0), mild (grade 1), moderate (grade 2), and severe (grade 3). The participants with grade 0 and 1 steatohepatitis were categorized as Group 1, whereas those with grade 2 and 3 steatohepatitis (NAFLD) were categorized as Group 2. Any relationship between the aminotransferase/alanine aminotransferase (AST/ALT), AST-to-platelet ratio index (APRI), and fibrosis-4 index (FIB-4) parameters and the diagnostic powers thereof were analyzed based on the collected data. The mean age of the study sample (n=408) was 46.1±12.7 years. There were 352 (86.3%) and 56 individuals in Groups 1 and 2, respectively. Platelet-to-lymphocyte ratio (PLR) and AST/ALT values were significantly higher, whereas APRI values were significantly lower in Group 1 than in Group 2 (p=0.004, p<0.001, and p<0.001, respectively). There were significant correlations between the presence of NAFLD and PLR values of ≤90.78 [area under the curve (AUC)=0.619, 95% confidence interval (CI): 0.570-0.666, p=0.007], AST/ALT values of ≤0.91 (AUC=0.802, 95% CI: 0.760-0.840, p<0.001), and APRI values of >0.22 (AUC=0.687, 95% CI: 0.640-0.732, p<0.001). The composite noninvasive indices, including PLR, AST/ALT, and APRI, can be beneficial in predicting NAFLD in healthy individuals.

Persistent organic pollutants associate with liver disease in a Finnish general population sample.

Persistent organic pollutants (POPs) have multiple adverse effects on human health. Recent studies show a possible association with liver disease, but population-based data are scarce. In this population-based study, we studied the associations between POPs and biomarkers of liver disease and incident liver disease. This study consisted of 2789 adults that participated in the environmental toxin subset of the Finnish health-examination survey, FINRISK 2007. Toxins were measured from serum samples, and standard liver tests and dynamic aspartate aminotransferase-alanine aminotransferase ratio (dAAR) were measured as biomarkers of liver function. Associations between POPs and the biomarkers were then analysed using linear regression. Associations between POPs and incident liver disease (n = 36) were analysed by Cox regression. Organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and several perfluorinated alkyl substances exhibited statistically significant positive associations with several biomarkers of liver injury (betacoefficient per SD 0.04-0.14, p < 0.05). These associations were stronger in subgroups of individuals with obesity or non-alcoholic fatty liver disease. OCPs, PCBs and perfluoro-octanoic acid also had significant positive associations with dAAR, which can be used to predict risk of incident severe liver outcomes (beta coefficient per SD 0.05-0.08, p < 0.05). OCPs and PCBs were also significantly and positively associated with incident liver disease (hazard ratio per SD 1.82 95% CI 1.21-2.73, p < 0.01 and hazard ratio per SD 1.69, 95% CI 1.07-2.68, p < 0.05 respectively). Several POPs show positive associations with markers of liver injury and incident liver disease, suggesting that environmental toxins are important risk factors for chronic liver disease.

In-vivo Ameliorative Potential Effect of N-Acetylcysteine and Gallic Acid against Hepatotoxicity Induced by Mercuric Chloride in Wistar Rats

Mercury is a highly toxic metal induces oxidative stress in the body and results in a variety of adverse health effects including liver damage. In the present experimental study was to investigate the hepatoprotective effect of some phytochemical on Mercury intoxicated rats. During treatment periods, a sub-lethal dose of mercuric chloride (1.29 mg/kg body weight) treated rat liver tissue shows hepatic injury is mainly associated with distortion of the metabolic function of the liver in rats, it is Hepatic damage can be evaluated by biochemical analysis of the serum tests, includes levels of serum Alanine and Aspartate aminotransferases, alkaline phosphatase, lactic dehydrogenase of liver marker enzymes. In the present experimental study, drastically altered in the level of Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), Lactic dehyrogenase (LDH) and Bilirubin levels were observed in the blood serum of mercuric chloride intoxicated Wistar rats. The activity of liver marker enzymes such as ALT AST, ALP and LDH were significantly increased. In addition, lipid peroxidation (LPO) were significantly increased while the activities of the levels of non enzymatic antioxidants (reduced glutathione (GSH)) and enzymatic antioxidants (glutathione peroxidase (GPx) superoxide dismutase (SOD) and catalase (CAT)) were significantly decreased in liver tissues and the toxicity with mercury is associated with oxidative stress in which mercury induces the formation of free radicals including ROS. It alters the antioxidant capacity of the cells to promote cellular damages. During the recovery period, the hepatic marker enzymes, enzymatic antioxidant and non-enzymatic antioxidant are restored to near normal level in liver tissues. Our experimental studies indicate that treatment for N-Acetylcysteine and Gallic acid exhibited the strong hepatoprotective activity against mercuric chloride induced liver damage in Wistar rat.

AST/ALT ratio, APRI, and FIB-4 compared to FibroScan for the assessment of liver fibrosis in patients with chronic hepatitis B in Bandar Abbas, Hormozgan, Iran

BackgroundChronic hepatitis B (CHB) is a significant risk factor for liver-related disorders. Hepatic fibrosis staging by liver biopsy in these patients can lead to complications. This study aimed to compare aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, AST to platelet ratio index (APRI), and fibrosis-4 (FIB-4) with FibroScan results for the evaluation of hepatic fibrosis in CHB patients.MethodsThis cross-sectional study included patients with CHB referred to the outpatient clinics of Bandar Abbas, Hormozgan, Iran, in 2021. The age and sex of the participants were noted. FibroScan evaluation was done for all subjects. Moreover, AST, ALT, and platelet counts were measured in their blood samples within one month of the FibroScan evaluation.ResultsOf the 267 CHB patients evaluated in the present study (mean age: 45.45 ± 18.16 years), 173 (64.8%) were male. According to FibroScan results, 65 CHB patients (24.3%) had F1, 53 (19.9%) F2, 38 (14.2%) F3, and 20 (7.5%) F4 liver fibrosis. There was a significant correlation between FibroScan results and the three indices of AST/ALT ratio, APRI, and FIB-4 (P < 0.001), with the strongest correlation between FibroScan results and APRI (r = 0.682). With an area under the receiver operating characteristic (AUROC) curve of 0.852 (95% confidence interval [CI] 0.807; 0.897, P < 0.001), APRI ≥ 0.527 had the best diagnostic accuracy (77.15%) for the detection of any grade of liver fibrosis. Although the AUROC curve of APRI and FIB-4 was similar (0.864) for distinguishing between F3/F4 and F0-F2 of liver fibrosis, FIB-4 had the best diagnostic accuracy (82.02%).ConclusionsAPRI can rule out 95.4% of F3/F4 of liver fibrosis and rule in any grade of liver fibrosis in CHB patients by 90.78%. Therefore, APRI appears to be the best substitute for FibroScan in the assessment of liver fibrosis in patients with CHB.

The effect of postoperative hepatic fibrosis factors on morbidity in mitral valve replacement surgery: A single center ten years' experience.

Previous studies have shown that hepatic fibrosis indices and rates can be used to predict cardiovascular mortality and morbidity. Our aim with this study was to investigate the effect of aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio and fibrosis-4 (FIB-4) index calculated with ALT, AST, and platelet biomarkers, which are simple, fast, and relatively inexpensive and were used in previous studies to predict cardiovascular disease prognosis, on the prediction of postoperative morbidity and early mortality after mitral valve replacement (MVR) surgery. By scanning the hospital electronic health record system, 116 patients who underwent isolated MVR or MVR + tricuspid valve intervention were identified from 178 patients who underwent MVR with the standard sternotomy procedure between 2011 and 2021. The study was completed with 81 of these patients. Patients were divided into AST/ALT <2 (Group 1) and >2 (Group 2). In addition, the same patients were divided into FIB-4 index <3.25 (Group 3) and >3.25 (Group 4), and a total of four groups were formed. The mean age of Group 2 was significantly higher than Group 1 (P = 0.049). In addition, the mean age of Group 4 was significantly higher than Group 3 (P = 0.003). Postoperative complications did not differ between Groups 1 and 2 (P > 0.05). While noninvasive mechanincal ventilation (NIMV) requirements did not differ between Groups 3 and 4 (P > 0.05), MV duration and intensive care unit stay were significantly longer in Group 4 (P < 0.05). The AST/ALT ratio, which has been shown to be a predictor of cardiovascular mortality in various studies, was not useful in predicting mortality and morbidity in our study. However, a high FIB-4 index, another hepatic fibrosis index, was found to be associated with increased perioperative bleeding, duration of mechanical ventilation, and cardiac intensive care unit stay, which are important criteria in the prediction of morbidity in cardiovascular surgery.

CD4+ T Cell NRF2 Signaling Improves Liver Transplantation Outcomes by Modulating T Cell Activation and Differentiation.

Aims: Innate and adaptive immune responses regulate hepatic ischemia-reperfusion injury (IRI) in orthotopic liver transplantation (OLT). While the mechanism of how nuclear factor erythroid 2-related factor 2 (NRF2) plays a role in liver IRI has been studied, the contribution of T cell-specific NRF2 in OLT remains unknown. In the current translational study, we investigated whether and how CD4+ T cell-specific NRF2 signaling affects liver transplant outcomes in mice and humans. Results: In the experimental arm, cold-stored (4°C/18 h) wild-type (WT) mouse livers transplanted to NRF2-deficient (NRF2-knockout [NRF2-KO]) recipients experienced greater hepatocellular damage than those in Nrf2-proficient (WT) counterparts, evidenced by Suzuki's histological scores, frequency of TdT-mediated dUTP nick end labeling (TUNEL)+ cells, and elevated serum aspartate aminotransferase/alanine aminotransferase (AST/ALT) levels. In vitro studies showed that NRF2 signaling suppressed CD4+ T cell differentiation to a proinflammatory phenotype (Th1, Th17) while promoting the regulatory (Foxp3+) T cell lineage. Furthermore, OLT injury deteriorated in immune-compromised RAG2-KO test recipients repopulated with CD4+ T cells from NRF2-KO compared with WT donor mice. In the clinical arm of 45 human liver transplant patients, the perioperative increase of NRF2 expression in donor livers negatively regulated innate and adaptive immune activation, resulting in reduced hepatocellular injury in NRF2-proficient OLT. Innovation and Conclusion: CD4+ T cell population expressing NRF2 attenuated ischemia and reperfusion (IR)-triggered hepatocellular damage in a clinically relevant mouse model of extended donor liver cold storage, followed by OLT, whereas the perioperative increase of NRF2 expression reduced hepatic injury in human liver transplant recipients. Thus, CD4+ T cell NRF2 may be a novel cytoprotective sentinel against IR stress in OLT recipients. Antioxid. Redox Signal. 38, 670-683.

Clinical muscle mass-related biomarkers that predict mortality in older patients with community-acquired pneumonia

ObjectiveCommunity-acquired pneumonia (CAP) is associated with elevated morbidity and mortality, and it usually occurs in older adults. Our goal here was to assess the efficacies of muscle mass-related biomarkers, such as, aspartate transaminase/alanine transaminase (AST/ALT) and creatinine/cystatin C*100 (Cr/CysC*100), in predicting 1-, 2-, and 3-year mortalities of older CAP patients.MethodsDesign: Retrospective cohort study. Setting and Participants: A teaching hospital in western China. Hospitalized CAP patients, aged≥60 years. We separated patients into a high or low muscle mass group, according to the median AST/ALT and Cr/CysC*100, respectively. We acquired data from medical records and local government mortality databases, as well as telephonic interviews. We analyzed the association between low muscle mass (AST/ALT and Cr/CysC*100) and all-cause mortality at 1, 2, and 3 years in older patients with CAP.ResultsWe enrolled 606 patients (58.58% male; median age: 81 years) for analysis. The 1-, 2-, and 3-year mortality in older patients with CAP in the low muscle mass group (AST/ALT) was higher than in the high muscle mass group (AST/ALT) (1-year: 51.16% vs. 36.96%, p < 0.001; 2-year: 54.46% vs. 41.25%, p = 0.001; 3-year: 54.79% vs. 42.9%, p = 0.003). Upon adjustment of potential confounding factors, we revealed, using cox regression analysis, that the low muscle mass group (AST/ALT) experienced enhanced mortality risk at the 1-, 2-, and 3-year follow-ups, compared to the high muscle mass group (AST/ALT) (1-year: hazard ratios (HR) = 1.46, 95% confidence interval (CI): 1.13–1.88; 2-year: HR = 1.39, 95% CI: 1.09–1.77; 3-year: HR = 1.35, 95% CI: 1.06–1.72). The 1-, 2-, and 3-year mortality of older CAP patients in the low muscle mass group (Cr/CysC*100) was also higher than the high muscle mass group (Cr/CysC*100) (1-year: 56.29% vs. 31.91%, p < 0.001; 2-year: 60.26% vs. 35.53%, p < 0.001; 3-year: 61.26% vs. 36.51%, p < 0.001). Compared to the high muscle mass group (Cr/CysC*100), the low muscle mass group (Cr/CysC*100) experienced enhanced mortality risk at the 1-, 2-, and 3-year follow ups (1-year: HR = 1.9, 95% CI: 1.46–2.48; 2-year: HR = 1.85, 95% CI: 1.44–2.39; 3-year: HR = 1.85, 95% CI: 1.44–2.37).ConclusionsLow muscle mass (AST/ALT and Cr/CysC*100) were associated with enhanced 1-, 2-, and 3-year mortality risk in older patients with CAP.

Organophosphate pesticide exposure and biomarkers of liver injury/liver function.

There is little epidemiological evidence linking the exposure of organophosphate pesticides (OPs) to liver function or liver injury in the general population. We used data from the National Health and Nutrition Examination Survey 1999-2012 to investigate the relationship of urinary OPs with biomarkers of liver function/liver injury. The exposures were the concentrations of urinary OP metabolites (dimethyl phosphate [DMP], dimethyl thiophosphate [DMTP], diethyl phosphate [DEP] and diethyl thiophosphate [DETP]). The health outcomes were biomarkers of liver function/liver injury. The multivariable linear regression model, restricted cubic splines (RCSs) analysis and weighted quantile sum (WQS) regression were used to evaluate the relationship between individual or overall exposure of OPs and outcomes. Regressions of RCSs suggested linear and positive associations of OP metabolites with aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio (DMP and DEP) and fibrosis-4 (FIB-4) index (DMP, DEP and DMTP) (all p-non-linear values >.05). However, L-shaped relationships were found between OP metabolites (DMTP and DETP) and blood albumin and total protein (TP) concentrations (both p and non-linear values <.05). The positive associations of urinary DMP, DEP and DMTP with AST/ALT ratio, and with FIB-4 score were more pronounced among non-smokers than smokers, among alcohol drinkers than non-drinkers and among those with a body mass index (BMI) of ≥25 than participants with a BMI of <25. However, most of the interaction p values were more than .05, indicating no significant interactions between covariates and OPs on outcomes mainly including AST/ALT, FIB-4, ALB and TP levels. Finally, the WQS indices were positively associated with AST/ALT ratio (p=.014) and FIB-4 score (p=.002). Our study added novel evidence that exposures to OPs might be adversely associated with the biomarkers of liver function/liver injury. These findings indicated the potential toxic effect of OP exposures on the human liver.

Evaluation of Six Noninvasive Methods for the Detection of Fibrosis in Chinese Patients with Obesity and Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and liver fibrosis has been proven to be associated with liver diseaserelated events and total mortality. Several noninvasive methods have been developed, but whether those methods are suitable for the detection of fibrosis in Chinese patients with obesity and NAFLD has not been completely elucidated. This study aimed to compare the efficacy of fibrosis-4 (FIB-4), aspartate transaminase to platelet ratio index (APRI), modified aspartate transaminase to platelet ratio index (m-APRI), BARD (BARD (BMI (body mass index) > 28 = 1 point, AAR (aspartate aminotransferase/alanine aminotransferase) > 0.8 = 2 points, DM (diabetes mellitus) = 1 point)), NAFLD fibrosis score (NFS), and shear wave elastography (SWE) in the evaluation of the degree of liver fibrosis in Chinese patients with obesity and NAFLD. A retrospective study consisted of 100 patients. The accuracy of FIB-4, APRI, m-APRI, BARD, NFS, and SWE in the assessment of significant or advanced liver fibrosis in Chinese patients with obesity and NAFLD was compared. Weight and alanine aminotransferase (ALT) were independent risk factors for liver fibrosis. SWE, APRI, and m-APRI had significant efficiency in the diagnosis of significant fibrosis in patients with obesity and NAFLD. APRI and SWE were superior to the other methods in the diagnosis of significant and advanced liver fibrosis in patients with obesity and NAFLD. APRI and SWE showed no statistically significant difference in diagnostic efficiency. Weight and ALT are independent risk factors for liver fibrosis progression in NAFLD patients. SWE and APRI have predictive value for significant and advanced fibrosis of NAFLD in Chinese patients with obesity.