Alanine aminotransferase predicts incident steatotic liver disease of metabolic etiology: Long life to the old biomarker!

Alanine aminotransferase (ALT) serum levels increase because of hepatocellular damage. Metabolic dysfunction-associated fatty liver disease (MAFLD), which identifies steatotic liver disease (SLD) associated with ≥ 2 metabolic abnormalities, has prominent sexual differences. The Metabolic Syndrome defines a cluster comprising abdominal obesity, altered glucose metabolism, dyslipidemia, and hypertension. Male sex, body mass index, glucose, lipids, ferritin, hypertension, and age independently predict ALT levels among blood donors. Over the last few decades, the reference range of ALT levels has been animatedly debated owing to attempts to update sex-specific reference ranges. With this backset, Chen et al have recently published a study which has two main findings. First, > 80% of individuals with MAFLD had normal ALT levels. Second, there was a linear increasing trend in the association between cumulative excess high-normal ALT levels and the rate of incident MAFLD. This study has biologically credible findings. However, it inaccurately considered sex differences in the MAFLD arena. Therefore, future studies on SLD owing to metabolic dysfunction should adopt locally determined and prospectively validated reference ranges of ALT and carefully consider sex differences in liver enzymes and MAFLD pathobiology.

The ratio of alanine aminotransferase to high-density lipoprotein cholesterol is positively correlated with the insulin resistance in American adults: a population-based cohort study.

Introduction: Previous studies have demonstrated a correlation between the ratio of alanine aminotransferase to high-density lipoprotein cholesterol (ALT/HDL-C) in the serum and the risk of diabetes. However, no existing study has investigated the association between insulin resistance (IR) and ALT/HDL-C. Therefore, this study aims to explore the association between ALT/HDL-C and IR in American adults. Methods: A total of 7,599 adults selected from the National Health and Nutrition Examination Survey (NHANES) in 2013 to 2020 were studied. IR was assessed based on the homeostatic model assessment of insulin resistance (HOMA-IR). And the association between IR and ALT/HDL-C was assessed through multiple logistic regression, generalized smooth curve fitting and subgroup analyses. Results: Multiple logistic regression analysis indicated a significant correlation between IR and ALT/HDL-C, with odds ratios (OR) of 1.04 (95% CI = 1.02-1.05) in males and 1.04 (95% CI = 1.02-1.07) in females. A non-linear association and saturation effect between ALT/HDL-C and IR risk were identified, with an inverted L shaped curve and an inflection point at 33.62. The area under the ROC curve (AUC) of ALT/HDL-C was significantly larger (AUC = 0.725 for males and 0.696 for females, all p < 0.01) compared with the use of ALT, HDL-C, AST and AST/ALT. Subgroup analysis showed a significantly higher independent association in obese individuals and individuals aged ≥50 years (All P interaction <0.05). Conclusion: Elevated ALT/HDL-C demonstrates a significant correlation with IR, which can be used as a potential indicator of IR in American adults.

Screening for metabolic dysfunction-associated fatty liver disease: Time to discard the emperor's clothes of normal liver enzymes?

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most prevalent chronic liver condition worldwide. Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays. Regarding Chen et al, the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range. Therefore, there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention. This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD: Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.

A combined association of obesity, alanine aminotransferase and creatinine with hyperuricemia in youth aged 13-20 years.

Background: Despite extensive research on hyperuricemia (HUA) in adults, there remains a dearth of studies examining this condition in youth. Consequently, our objective was to investigate the prevalence of HUA among youth in the United States, as well as identify the corresponding risk factors. Methods: This study employed a nationally representative subsample of 1,051 youth aged 13-20 from the US National Health and Nutrition Examination Survey (NHANES) conducted between January 2017 and March 2020. Univariate and multivariate techniques were utilized to examine the association between HUA and obesity, dietary nutrients, liver and kidney function, glucose and lipid metabolism, inflammation, and other indicators in the adolescent population. Results: The study encompassed a cohort of 1,051 youth aged 13-20 years, comprising 538 boys and 513 girls. The overall prevalence of HUA was found to be 7% (74 out of 1,051). Univariate analysis revealed that the HUA group exhibited greater age, body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR). Additionally, the prevalence of obesity was significantly higher in the HUA group compared to the non- HUA group (all p < 0.05). Regarding biochemical indicators, the levels of urea nitrogen, creatinine (Cr), alanine aminotransferase (ALT), glutamic oxalic aminotransferase (AST), gamma-glutamyl transferase (GGT), total cholesterol (TC), triglyceride (TG), and HS C reactive protein (Hs CRP) were found to be significantly higher in the HUA group compared to the non-HUA group (all p < 0.05). Further analysis using binary logistics regression showed that BMI (p = 0.024, OR1.158, 95%CI1.019-1.316), ALT (p = 0.020, OR1.032, 95%CI1.005-1.059), and Cr (p = 0.016, OR1.028, 95%CI1.005-1.051) were identified as risk factors for HUA, after controlling for age, gender, BMI, WC, HC, WHR, ALT, AST, GGT, TG, TC, Cr, Hs CRP, and other indicators. Interestingly, neither univariate nor multivariate analysis found any association between dietary nutrients and the risk of HUA (all p > 0.05). Conclusion: High BMI remains a major risk factor for HUA in US youth aged 13-20 years, and ALT and Cr levels should be closely monitored along with serum uric acid.

AST/ALT Ratio as an indicator of functional severity in chronic heart failure with reduced left ventricular ejection fraction: A prospective cross-sectional study.

OBJECTIVE: The study was carried out to evaluate the role of the AST (Aspartate transaminase)/ALT (Alanine transaminase) ratio as an indicator of the functional severity in people with chronic heart failure (CHF) with reduced left ventricular ejection fraction. METHODS: A prospective cross-sectional study was conducted in a tertiary care centre in South India among the individuals who had left ventricular ejection fraction (LVEF) of ≤40 %. The study period was between January 2021 and December 2021. Consecutive patients with the criteria were enrolled in the study. Study participants were grouped based on their AST/ALT ratio value (ratio<1 and ratio≥1). RESULTS: In present study of 100 participants, there was a statistically significant difference between two groups with respect to ALT, AST/ALT ratio, and ALP (Alkaline phosphatase). There was a significant correlation between the APRI (AST to platelet ratio index) and FIB-4 (Fibrosis-4) with AST/ALT ratio. Diagnostic analysis of AST/ALT ratio to predict the severity of CHF with reduced EF, the area under the curve (AUC) was 0.547 (p-value = 0.5654) with a 95 % confidence interval of 0.299-0.795 with an optimal cut-off value of 0.6, sensitivity of 96.70 %, and specificity of 33.33 %. CONCLUSION: The AST/ALT ratio is increased in patients with CHF patients with reduced left ventricular ejection fraction. It is a simple predictor of left ventricular dysfunction in patients with heart failure with reduced ejection fraction.

Serum Gamma Glutamyltransferase: A Biomarker for Identifying Postprandial Hypertriglyceridemia.

Purpose: Elevated serum gamma-glutamyltranspeptidase (GGT) is an independent marker of the activation of systemic inflammation, while conditions associated with elevated triglyceride (TG) levels, such as type 2 diabetes, non-alcoholic fatty liver disease, obesity, and metabolic syndrome, are associated with an increased inflammatory burden. Moreover, serum liver enzymes (GGT, alanine aminotransferase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase [ALP]) are associated with metabolic syndrome and its components, including hypertriglyceridemia. However, the relationship between liver enzymes and postprandial hypertriglyceridemia (PHTG) remains unclear. Therefore, in this study we conducted oral fat tolerance tests (OFTTs) to understand the differences in serum liver enzyme levels among individuals with different lipid tolerance levels and their correlation with PHTG. Patients and Methods:  For the OFTT, we enrolled 202 non-diabetic volunteers whose fasting triglyceride (TG) levels were less than 1.7 mmol/L in this case-control study. The participants were categorized into two groups according to the TG levels at the 0- and 4-h OFTT: a postprandial normal TG (PNTG) group and a PHTG group. Routine fasting serum biochemical indices, liver enzyme (GGT, ALT, AST, and ALP) levels, and 0- and 4-h OFTT lipid levels were assessed. Results: The PHTG group had significantly higher serum GGT and ALT levels and a lower AST/ALT ratio than those in the PNTG group. However, no significant difference was observed in AST and ALP levels compared with the PNTG group. After adjusting for major confounders, logistic regression analysis indicated a significant correlation between serum GGT and PHTG (odds ratio = 1.168, P < 0.001), but not with ALT level, AST level, AST/ALT ratio, and ALP level. The receiver operating characteristic curve analysis demonstrated that the serum GGT level was an effective predictor of PHTG. Conclusion: Serum GGT levels are significantly associated with PHTG risk and serve as an effective biomarker for early identification.

Effect of Intermittent Fasting on Liver Function Tests: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

CONTEXT: Intermittent fasting (IF) is a diet strategy with alternate intervals of calorie reduction and normal eating. Despite its beneficial effects on weight loss and cardiometabolic risk factors, the effect of IF on liver function tests (LFTs) remains unclear. OBJECTIVE: This study aimed to investigate the effect of IF on LFTs through a systematic review and meta-analysis of randomized clinical trials. DATA SOURCES: An electronic search was performed using predefined search terms in databases including PubMed, Scopus, and ISI Web of Science until February 2023. DATA EXTRACTION: The studies were selected according to PRISMA guidelines, and the risk of bias was assessed for the randomized controlled trials. DATA ANALYSIS: The results of this study are reported as weighted mean differences (WMDs) with 95% CIs. Fourteen RCTs were included in the meta-analysis, with a total sample size of 908. IF significantly reduced alanine aminotransferase (ALT) (WMD: -2.88, 95% CI: -4.72 to -1.04, P-value = .002) and aspartate aminotransferase (AST) levels (WMD: -1.67, 95% CI: -3.12 to -0.22, P-value = .024). The results of the subgroup analysis showed that the impact of IF was significant in both the nonalcoholic fatty liver disease and the healthy groups for ALT. The effects of IF on the serum gamma-glutamyl transpeptidase (GGT) level were significant (WMD: -3.19, 95% CI: -6.00 to -0.39, P-value = .026), but there were no significant changes in the alkaline phosphatase (ALP) level (WMD: 1.06, 95% CI: -0.23 to 2.34, P-value = .106). Furthermore, no substantial heterogeneity between studies was reported. CONCLUSION: IF can improve ALT, AST, and GGT levels but not ALP enzyme levels and may have a benefit on liver function. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42023396211.

Evaluation of alanine aminotransferase/aspartate aminotransferase ratio and high-density lipoprotein for predicting neonatal adverse outcomes associated with intrahepatic cholestasis of pregnancy.

Background: To determine the association between lipid metabolism and intrahepatic cholestasis of pregnancy (ICP), and explore the value of maternal alanine aminotransferase/aspartate aminotransferase (ALT/AST) and high-density lipoprotein (HDL) in predicting adverse neonatal outcomes in women with ICP. Methods: A total of 147 pregnant women with ICP admitted to The Fourth Hospital of Shijiazhuang and 120 normal pregnant women in the same period were selected in this study. The Mann-Whitney U test and Chi-square tests were used to compare the differences in clinical data. Multivariate logistic regression was used to analyze the relationship between ALT/AST and the occurrence of adverse pregnancy outcomes in patients with ICP. The combined predictive value of ALT/AST and HDL was determined by receiver operating characteristic (ROC) curve analysis. Results: Among 147 women with ICP, 122 women had total bile acid (TBA) levels of 10-39.9 µmol/L, and 25 had TBA ≥ 40 µmol/L. There was significantly lower gestational age in patients with severe ICP than in those with mild and control groups (all p < 0.05), and the weight of newborns in the maternal ICP group was significantly lower than in the control group (p < 0.05). Increasing TBA levels was associated with higher AST, ALT, ALT/AST, and lower HDL level (all p < 0.05). Meanwhile, higher levels of ALT/AST was positively associated with neonatal hyperbilirubinemia [adjusted odds ratio (AOR) = 4.019, 95% CI [1.757-9.194, p = 0.001] and cardiac injury [AOR = 3.500, 95% CI [1.535-7.987], p = 0.003]. HDL was a significant protective factor for neonatal hyperbilirubinemia and cardiac injury [AOR = 0.315, 95% CI [0.126-0.788], p = 0.014; AOR = 0.134 (0.039-0.461), p = 0.001]. The area under the ROC curve (AUC) for prediction of neonatal hyperbilirubinemia by ALT/AST combined with HDL was 0.668 [95% CI [56.3-77.3%], p = 0.002], and the sensitivity and specificity were 47.1% and 84.0%, respectively. To predict neonatal cardiac injury, the AUC value was 0.668 [95% CI [56.4-77.1%], p = 0.002], with sensitivity and specificity were 41.2% and 87.1%, respectively. Conclusions: The levels of higher ALT/AST and lower HDL were significantly associated with the risk of ICP-related adverse neonatal outcomes. Moreover, ALT/AST combined with HDL has moderate clinical value in predicting the adverse outcomes of neonatal hyperbilirubinemia and cardiac injury.

The association between frailty biomarkers and 20-year all-cause and cardiovascular mortality among community-dwelling older adults.

OBJECTIVES: While several biomarkers were previously associated with frailty and mortality, data are still contradicting. We aimed to evaluate the association between novel biomarkers and frailty among community-dwelling older adults to enhance understanding of the pathophysiology of frailty. METHODS: Nine hundred and sixty-three older adults were screened during the third phase (1999-2008) of the Israel study on Glucose Intolerance, Obesity, and Hypertension (GOH). Frailty was defined as sedentary individuals, past 10 years hospitalizations, or at least one of the following: body mass index (BMI) <21 kg/m2; albumin <3.2 g/dl; ≥2 major baseline diseases. Biomarkers were evaluated for their association with frailty, all-cause, and cardiovascular mortality. RESULTS: Mean baseline age was 72 ± 7 years, 471 (49%) were women, and 195 (20%) were classified as frail. Median follow-up for cardiovascular and all-cause mortality was 11 and 13 years, with 179 (18.6%) and 466 (48.4%) deaths recorded, respectively. Multivariable logistic regression showed greater odds for frailty with lower quartile of alanine aminotransferase (ALT) (OR = 1.8, 95%CI: 1.2-2.8, p = 0.01), and for each 5 µmol/L increment in homocysteine levels (OR = 1.3, 95%CI: 1.1-1.5, p = 0.001). Multivariate Cox regression showed greater all-cause and cardiovascular mortality risk for individuals with low ALT (HR = 1.6, 95%CI: 1.3-2.0, p < 0.001 and HR = 1.5, 95% CI: 1.0-2.2, p = 0.03, respectively), and high homocysteine (HR = 1.1, 95%CI: 1.1-1.3, p = 0.003 and HR = 1.2, 95%CI: 1.0-1.3, p = 0.04, respectively). Homocysteine association with mortality was more pronounced in those with baseline ischemic heart disease (IHD) compared with subjects free of IHD (P for interaction = 0.01). CONCLUSIONS: Lower ALT and higher homocysteine were associated with frailty, all-cause and cardiovascular mortality. These available and low-cost biomarkers underscore the nutritional and metabolic aspects of frailty when screening high-risk older adults, especially those with IHD, and may be considered as preferable screening biomarkers to be tested among these individuals for frailty and mortality risk.

Changes in alanine aminotransferase and body composition and metabolic factors among individuals receiving medical health checkups.

AIM: To examine the relationship between changes in alanine aminotransferase (ALT) and those in body composition and metabolic factors in participants receiving medical health checkups (4350 men [mean age 52.5 years] and 5398 women [mean age 50.5 years]) METHODS: We divided the participants into four types based on their ALT value at baseline and 1 year: A, ALT ≤30 (baseline) and ≤30 (1 year); B, ALT ≥31 (baseline) and ≤30 (1 year); C, ALT ≤30 (baseline) and ≥31 (1 year); and D, ALT ≥31 (baseline) and ≥31 (1 year). The change in each body composition-related parameter (waist circumference, fat mass, fat-free mass, fat mass to fat-free mass ratio, etc.) after 1-year was defined as Δ. RESULTS: The mean changes in waist circumference (cm) in the four types (A, B, C, and D) were -0.33, -1.54, 0.66, and -0.29 (overall p < 0.0001) in men, and -0.19, -0.90, 0.30, and 0.090 (overall p < 0.0001) in women. The mean changes in fat mass (kg) in the four types were -0.027, -0.86, 0.62, and 0.092 (overall p < 0.0001) in men, and 0.0067, -0.48, 0.39, and 0.063 (overall p < 0.0001) in women. The mean changes in fat-free mass (kg) in the four types were -0.028, -0.55, 0.42, and -0.034 (overall p < 0.0001) in men, and -0.0091, -0.34, 0.12, and -0.045 (overall p = 0.0012) in women. The mean changes in fat mass to fat-free mass ratio in the four types were -0.00042, -0.0120, 0.00837, and 0.00171 (overall p < 0.0001) in men, and -0.00013, -0.00817, 0.00730, and 0.00628 (overall p < 0.0001) in women. CONCLUSION: A decrease in ALT to ≤30 IU/L may be associated with improved body composition balance, but caution should be exercised for the decrease in muscle mass.

Circulating metabolites are associated with persistent elevations of ALT in patients with chronic hepatitis B with complete viral suppression.

Hepatitis B virus (HBV) can be completely suppressed after antiviral treatment; however, some patients with chronic hepatitis B (CHB) exhibit elevated alanine aminotransferase (ALT) levels and sustained disease progression. This study provides novel insights into the mechanism and potential predictive biomarkers of persistently elevated ALT (PeALT) in patients with CHB after complete viral inhibition. Patients having CHB with undetectable HBV DNA at least 12 months after antiviral treatment were enrolled from a prospective, observational cohort. Patients with PeALT and persistently normal ALT (PnALT) were matched 1:1 using propensity score matching. Correlations between plasma metabolites and the risk of elevated ALT were examined using multivariate logistic regression. A mouse model of carbon tetrachloride-induced liver injury was established to validate the effect of key differential metabolites on liver injury. Of the 1238 patients with CHB who achieved complete viral suppression, 40 (3.23%) had PeALT levels during follow-up (median follow-up: 2.42 years). Additionally, 40 patients with PnALT levels were matched as controls. Ser-Phe-Ala, Lys-Ala-Leu-Glu, 3-methylhippuric acid, 3-methylxanthine, and 7-methylxanthine were identified as critical differential metabolites between the two groups and independently associated with PeALT risk. Ser-Phe-Ala and Lys-Ala-Leu-Glu levels could be used to discriminate patients with PeALT from those with PnALT. Furthermore, N-acetyl- l-methionine (NALM) demonstrated the strongest negative correlation with ALT levels. NALM supplementation alleviated liver injury and hepatic necrosis induced by carbon tetrachloride in mice. Changes in circulating metabolites may contribute to PeALT levels in patients with CHB who have achieved complete viral suppression after antiviral treatment.

Correlation of alanine aminotransferase levels and a histological diagnosis of steatohepatitis with ultrasound-diagnosed metabolic-associated fatty liver disease in patients from a centre in Nigeria.

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is defined as the occurrence of hepatic fat accumulation in patients with negligible alcohol consumption or any other cause of hepatic steatosis. This study aimed to correlate the ultrasound-based diagnosis of MAFLD with the histological diagnosis of nonalcoholic steatohepatitis (NASH) and alanine aminotransferase (ALT) levels in patients with MAFLD. METHODS: This was a hospital-based cross-sectional study of 71 patients with MAFLD diagnosed by ultrasound. Percutaneous liver biopsy was performed for histological evidence of NASH in all patients, regardless of liver function test (LFT) values, provided that they had no contraindications. Liver histology was graded using the NASH Clinical Research Network MAFLD Activity Score. The data obtained were entered into SPSS version 21 and analysed using descriptive and inferential statistics. The significance level was set at < 0.05. RESULTS: A total of 71 patients (26 males and 45 females) with MAFLD were included. Thirty-nine (76.5%) patients with MAFLD and normal ALT levels had NASH, while 14 (82.4%) had elevated ALT levels. There was no statistically significant difference in the histological grade of NASH between patients with normal and elevated ALT levels. A weak correlation was found between the severity of steatosis on ultrasound scan and NASH incidence (p = 0.026). The sensitivity and specificity of ALT levels for predicting NASH according to the area under the receiver operating characteristics (AUROC 0.590) at an ALT cut-off value of 27.5 IU/L were 55.8% and 64.7%, respectively. CONCLUSION: NASH can occur in patients with MAFLD, irrespective of alanine transaminase (ALT) levels, and ultrasound grading of the severity of steatosis cannot accurately predict NASH. Liver biopsy remains the investigation of choice.

Updated Reference Intervals for Alanine Aminotransferase in a Metabolically and Histologically Normal Population.

BACKGROUND & AIMS: This study aims to reevaluate upper reference limit (URL) for alanine aminotransferase (ALT) by considering the changing epidemiology of major liver diseases. We employed histological and metabolic parameters in Asian living liver donors. METHODS: We performed a retrospective analysis of 5455 potential living liver donors from 2005 to 2019. Participants were screened for hepatitis B, C, HIV, and alcohol use. Histologically and metabolically healthy participants were assessed using the Prati criteria (body mass index <23 kg/m2, triglyceride ≤200 mg/dL, fasting glucose ≤105 mg/dL, total cholesterol ≤220 mg/dL). The updated ALT-URL was determined as the 95th percentile among participants without hepatic steatosis and who met the Prati criteria. RESULTS: The median age was 30 years, with a male predominance (66.2%). Among 5455 participants, 3162 (58.0%) showed no hepatic steatosis, with 1553 (49.1%) meeting both the criteria for no steatosis and the Prati criteria for metabolic health. The updated URL for ALT in these participants was 34 U/L for males and 22 U/L for females, which was significantly lower than conventionally accepted values. Using this revised ALT-URL, 72.8% of males with ALT levels ≥34 U/L and 55.0% of females with ALT levels ≥22 U/L showed signs of steatosis, whereas 32.7% of males and 22.2% of females met the criteria for metabolic syndrome. CONCLUSIONS: Our study provided the newly established reference intervals for ALT levels in a metabolically and histologically verified Asian population. The proposed URL for ALT are 34 U/L and 22 U/L for males and females, respectively.

[New progress on diagnosis and treatment for indeterminate-phase chronic hepatitis B virus-infected patients].

Authoritative guidelines at home and abroad typically classify chronic hepatitis B virus (HBV) infection into four stages. However, in clinical practice, a considerable number of patients do not meet the guidelines for staging and are called "indeterminate phase" chronic HBV- infected patients. Studies have shown that patients in the indeterminate phase account for about 30%-50% of chronic HBV infection, have significant liver histological changes or even cirrhosis in a large proportion, and are at a higher risk of HCC and death if they do not receive antiviral therapy. Preliminary research shows that patients in the indeterminate phase who receive antiviral treatment have a good virological response and a remarkable reduced HCC risk. To this end, the 2022 publication "Expert Opinions on Expanding Antiviral Treatment for Chronic Hepatitis B" recommends aggressive treatment for patients with an indeterminate phase who have undergone more than a year of follow-up. However, there is still a lack of unified standards to refine the classification, as well as a lack of effective and rapid non-invasive diagnostic methods to identify patients in the indeterminate phase who are at risk for disease progression. This article aims to review the researches on the proportion, clinical characteristics, disease progression, and treatment benefits to further explore how to better manage indeterminate-phase chronic HBV-infected patients.

A retrospective study to determine the correlation among HBV PreS1 antigen, HBV e antigen, alanine aminotransferase, and HBV DNA.

BACKGROUND AND AIM: Hepatitis B virus (HBV) infection presents with indicators of varying clinical significance. We aimed to evaluate the correlation among HBV Pre-S1 antigen (HBV PreS1-Ag), HBV e antigen (HBeAg), HBV DNA, and alanine aminotransferase (ALT) levels. METHODS: We retrospectively analyzed 6180 serum samples collected between 2020 and 2022 at the Shanghai General Hospital, China. Data regarding PreS1-Ag, HBeAg, ALT, and HBV DNA were compiled. Correlation analyses and cross-tabulations were employed to explore the diagnostic indicators. RESULTS: The detection rates of both antigen indicators showed a proportional increase with HBV DNA loads. The correlation between PreS1-Ag and HBV DNA (r = 0.616) was stronger than that between HBeAg and HBV DNA (r = 0.391). The specificity of PreS1-Ag (84.30 %) was lower than that of HBeAg (97.44 %), whereas the sensitivity of HBeAg (91.13 %) significantly surpassed that of PreS1-Ag (29.56 %). Among the HBV DNA positive patients, 92.04 % tested positive for at least one indicator, which exceeded the rate of PreS1+HBeAg- and PreS1-HBeAg+ (52. 28 % and 68. 56 %, respectively). Only 1.75 % of the patients exhibited double negativity, which was lower than the percentage of patients with single negativity (1.95 % and 12.00 % for PreS1-Ag and HBeAg, respectively). The PreS1 levels correlated with ALT levels (r = 0.317); patients with PreS1-positive status had higher ALT levels than patients with PreS1-negative status. CONCLUSION: PreS1-Ag is a more robust HBV replication indicator than HBeAg. PreS1-Ag displayed high sensitivity, whereas HBeAg demonstrated high specificity. Moreover, PreS1-Ag levels correlated with ALT levels. A combination of these indicators demonstrated dependable clinical value for detecting HBV infection and evaluating liver function.

Clinicopathologic findings of splenic marginal zone lymphoma with gallbladder involvement that progressed to diffuse large B-cell lymphoma in a dog.

A 12-year-old spayed female Dalmatian presented with acute vomiting and anorexia. The clinicopathological and imaging abnormalities included icterus, biliary obstruction, and multiple diffuse splenic hypoechogenic nodules. Cholecystectomy was performed to remove the obstruction, followed by liver biopsy and splenectomy. Histopathological and immunohistology evaluation of the spleen, liver, and gallbladder revealed splenic marginal zone lymphoma (MZL) with gallbladder and hepatic infiltration of neoplastic CD20/CD79α-positive cells. Moreover, we observed clonal rearrangements of the immunoglobulin heavy-chain (IgH) gene in all three tissues. The dog was in good condition without chemotherapy. However, there was progressive elevation of liver enzymes, which could be attributed to neoplastic hepatic infiltration. Chlorambucil and prednisolone were administered until day 108, when the liver enzyme levels normalized. On day 156, the dog developed diffuse large B-cell lymphoma (DLBCL) of the peripheral lymph nodes. Sequence analysis of the clonally rearranged IgH gene revealed that all neoplastic cells in the spleen, gallbladder, and liver at initial presentation, as well as lymph nodes on day 156, possessed the same sequence identity of the amplified IgH fragments. This demonstrated that all neoplastic cells were derived from the same B-lymphocyte clone. The DLBCL was considered to have transformed from the splenic MZL, with gallbladder involvement. In cases of splenic MZL, it is important to consider gallbladder involvement and transformation to DLBCL. Moreover, gallbladder lymphoma should be included in the differential diagnosis of dogs with gallbladder abnormalities. Further studies are warranted to investigate the prognosis of splenic MZL.

Effect of grape-derived products on the serum levels of enzymes mainly produced by the liver: A systematic review and meta-analysis of parallel randomized controlled trials.

In recent years, an increase in the incidence of liver diseases has been reported all over the world. This study aims to comprehensively summarize and quantitatively analyze the existing evidence concerning the effectiveness of grape-derived products on liver enzymes through a systematic review and meta-analytic approach. PubMed, Scopus, Cochrane Library, and ISI Web of Science were comprehensively searched until January 2024. Articles that reported the effect of grape-derived products on serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels were included. Weighted mean differences (WMDs) were pooled using a random-effects model. Nine studies were included in the meta-analysis. The results revealed that grape-derived products did not significantly change the concentrations of ALT (WMD: -2.70 IU/L, 95% CI: -6.14 to 0.75, p = 0.12), and AST (WMD: -1.42 IU/L, 95% CI: -3.54 to 0.70, p = 0.18). However, a significant reduction was observed in serum ALP levels (WMD: -5.49 IU/L, 95% CI: -9.57 to -1.4, p = 0.008). The present findings suggest that grape-derived products positively influence serum ALP levels among adults. However, a more comprehensive decision necessitates additional studies.

Serum Biochemical Parameters of Broilers Affected by Wooden Breast Myopathy.

Wooden breast (WB) myopathy is a pathology of the pectoralis major muscle. Wooden breast is caused by multiple factors. The exact etiopathogenesis of this myodegenerative pathology is still unclear. Fast-growing commercial lines of broilers that are selected for high breast muscle yields are more susceptible to this myopathy. The biochemical analysis of blood is used to diagnose pathologies and understand disease processes. Therefore, the objective of this research was to determine and compare the changes in the blood serum biochemical parameters of Ross 308 chicken broilers without myopathy and those affected by WB myopathy. Blood samples were collected from male and female Ross 308 broilers that were 43 days old, with an average live weight of 2.98-3.09 kg. Representative blood samples were selected from broilers with WB (n = 33) and without WB (n = 33). In the laboratory, the blood was centrifugated, and biochemical tests were performed with an automated computerized biochemistry analyzer. The research results showed that broilers with WB had elevated blood serum levels of creatine kinase (CK) (p = 0.018), potassium (p = 0.010), and alanine aminotransferase (ALT) (p = 0.012). In conclusion, elevated serum levels of CK and potassium indicated that skeletal muscle cells were damaged. Moreover, increased ALT levels suggested a possible association between WB myopathy and liver damage. Additionally, these research findings underscore the diagnostic significance of CK and hint at its potential as a WB biomarker.

The ratio of high aspartate aminotransferase to alanine aminotransferase: an independent risk factor associated with poor prognosis in IgA nephropathy.

OBJECTIVE: To investigate the relationship between the aspartate aminotransferase to alanine aminotransferase ratio (AAR) and the prognosis of IgA nephropathy (IgAN). METHODS: Clinical, pathological and follow-up data of 271 patients with IgAN from January 1, 2013, to July 31, 2023, were collected. A 50% decrease in estimated glomerular filtration rate (eGFR) or end-stage renal disease (ESRD) was used as renal composite end point events. A receiver operating characteristic (ROC) curve was plotted to predict the composite end point events by AAR. The optimal cutoff value of 1.24 was determined, and patients were allocated to high AAR and low AAR groups. Kaplan‒Meier (K‒M) curves and Cox proportional hazard models were used to evaluate the predictive effect of AAR on renal composite end point events. RESULTS: After a mean follow-up of 29 months, 39 patients achieved renal composite end point events. Among them, 9 and 30 patients in the low and high AAR groups achieved renal composite end point events, respectively, with a significant difference (P < 0.001). After adjustment for confounding factors, AAR was found to be an independent prognostic factor for renal composite end point events (HR = 3.283, 95% CI: 1.489-7.238, P = 0.003). Kaplan‒Meier analysis showed that high AAR was associated with achieving renal composite end point events in patients with IgAN. Moreover, the clinical features in the high AAR group were more severe. Further subgroup analysis showed that high AAR had a better predictive effect in patients with more severe clinicopathological manifestations. CONCLUSION: AAR is an independent prognostic factor in patients with IgAN.

A potential new way to facilitate HCV elimination: The prediction of viremia in anti-HCV seropositive patients using machine learning algorithms.

BACKGROUND AND STUDY AIMS: The present study was undertaken to design a new machine learning (ML) model that can predict the presence of viremia in hepatitis C virus (HCV) antibody (anti-HCV) seropositive cases. PATIENTS AND METHODS: This retrospective study was conducted between January 2012-January 2022 with 812 patients who were referred for anti-HCV positivity and were examined for HCV ribonucleic acid (HCV RNA). Models were constructed with 11 features with a predictor (presence and absence of viremia) to predict HCV viremia. To build an optimal model, this current study also examined and compared the three classifier data mining approaches: RF, SVM and XGBoost. RESULTS: The highest performance was achieved with XGBoost (90%), which was followed by RF (89%), SVM Linear (85%) and SVM Radial (83%) algorithms, respectively. The four most important key features contributing to the models were: alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB) and anti-HCV levels, respectively, while "ALB" was replaced by the "AGE" only in the XGBoost model. CONCLUSION: This study has shown that XGBoost and RF based ML models, incorporating anti-HCV levels and routine laboratory tests (ALT, AST, ALB), and age are capable of providing HCV viremia diagnosis with 90% and 89% accuracy, respectively. These findings highlight the potential of ML models in the early diagnosis of HCV viremia, which may be helpful in optimizing HCV elimination programs.