Zinc (Zn) is an essential trace element that is required for various biological functions, but excessive exposure to Zn is associated with many disorders and even diseases. However, the health effects and underlying mechanisms of long-term and high concentration exposure of Zn remain to be unclear. In the present study, we investigated the association between occupational exposure to Zn and liver function indicators (like alanine aminotransferase (ALT)) in workers. We found a positive association between Zn exposure and ALT level in workers. Workers having higher blood Zn (7735.65 (1159.15) μg/L) shows a 30.4 % increase in ALT level compared to those with lower blood Zn (5969.30 (989.26) μg/L). Furthermore, we explored the effects of phospholipids (PLs) and their metabolism on ALT level and discovered that Zn exposure in workers was associated with changes in PL levels and metabolism, which had further effects on increased ALT levels in workers. The study provides insights into the relationship between occupational Zn exposure and liver function, highlights the risk of long-term exposure to high concentrations of Zn, and paves the way for understanding the underlying mechanisms of Zn exposure on human health.

UNASSIGNED: Disease progression of chronic hepatitis B virus (HBV) infection is driven by the interactions between viral replication and the host immune response against the infection. This study aimed to clarify the relationship between HBV replication and hepatic inflammation during disease progression.
UNASSIGNED: Two cross-sectional, one validation cohort, and meta-analyses were used to explore the relationship between HBV replication and liver inflammation. Spearman analysis, multiple linear regression, and logistic regression were used to explore the relationship between variables.
UNASSIGNED: In the cross-sectional cohorts A and B including 1,350 chronic hepatitis B patients, Spearman analysis revealed a negative relationship between HBV replication (such as HBV DNA) and liver inflammation (such as ALT) in HBeAg-positive patients with higher HBV DNA >2×106 IU/mL (rho=-0.160 and -0.042) which turned to be positive in HBeAg-positive patients with HBV DNA ≤2×106 IU/mL (rho=0.278 and 0.260) and HBeAg-negative patients (rho=0.450 and 0.363). After adjustment for sex, age, and anti-HBe, results from logistic regression and multiple linear regression showed the opposite relationship still existed in HBeAg-positive patients with different DNA levels; the opposite relationship in HBeAg-positive patients with different DNA levels was validated in a third cohort; the opposite relationship in patients with different HBeAg status was partially confirmed by meta-analysis (overall R: -0.004 vs 0.481).
UNASSIGNED: These results suggested a negative relationship between viral replication and liver inflammation in HBeAg-positive patients with high HBV DNA, which changed to a positive relationship for those HBeAg-positive patients with DNA less than 2×106 IU/mL and HBeAg-negative patients.

Observational studies have shown an association between liver dysfunction and hepatocellular carcinoma (HCC), but the causality relationship between them is unclear. We aimed to determine whether there is a bidirectional causal relationship between liver function indicators (alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; γ-glutamyltransferase, GGT) and HCC. Our two-sample Mendelian randomization (MR) study acquired single nucleotide polymorphisms (SNPs) associated with liver function indicators (ALT, n = 134,182; AST, n = 134,154; GGT, n = 118,309; ALP, n = 105,030) and with HCC (n = 197,611) from publicly available genome-wide association studies (GWAS) of East Asian ancestry in Japan (BioBank Japan, BBJ). Univariable MR analyses were performed to identify whether the genetic evidence of exposure was significantly associated with outcome. Multivariable MR analysis was conducted to estimate the independent effects of exposures on outcome. Univariable MR analysis indicated that the level of ALT, AST, and GGT was the risk factor for HCC incidence. Meanwhile, multivariable MR analysis revealed that AST was an independent risk factor for HCC. The hazard ratio (HR) of the probability of HCC was 3.045 [95% confidence interval (95%CI), 1.697-5.463, p = 0.003] for AST. The results of reverse MR analyses showed that gene-predictive HCC incidence could increase the levels of AST (HR = 1.031, 95%CI: 1.009-1.054, p = 2.52 × 10-4) and ALT (HR = 1.040, 95%CI: 1.019-1.063, p = 0.005). Meanwhile, HCC may be negatively correlated with ALP levels (HR = 0.971, 95%CI: 0.947-0.995, p = 0.018). This study provides evidence to support that genetically predicted higher levels of AST are related to increased risk of HCC, with no strong evidence of a causal effect of genetically predicted ALP, ALP, and GGT on HCC. In addition, genetic predisposition to HCC could influence blood concentration of ALT, AST, and ALP. Thus, this may create a vicious cycle.

BACKGROUND: This study aimed to investigate the role of immunocompetence in chronic hepatitis B (CHB) patients with normal alanine transaminase (ALT) levels and negative hepatitis B e antigen (HBeAg) in the risk assessments of the progression of liver fibrosis.
METHODS: We collected the clinical data of 57 patients with CHB, with normal ALT levels and negative HBeAg from December 2020 to December 2022. With hepatitis B virus (HBV) DNA > 20 IU/mL and ALT ≤ 40 U/L, these patients had never undergone antiviral therapy. The levels of CD4+ , CD4+ CD25+ , CD8+ , and CD4+ CD25+ CD127LOW regulatory T cells (Tregs) in the patients were detected using flow cytometry; the liver stiffness measurement (LSM) values of the patients were detected using Fibroscan.
RESULTS: There was a statistically significant difference between the levels of fibrosis-4 (FIB-4) and hepatitis B surface antigen (HBsAg) when the cutoff point was HBsAg ≥ 1500 (p < .001). FIB-4 was negatively correlated with HBsAg (R = -0.291, p = .028) and positively correlated with age (R = 0.787, p < .001). LSM was negatively correlated with Treg but this correlation was not statistically significant (p > .05). Findings based on the analysis using logistic regression were as follows: (i) age was the independent risk factor when FIB-4 was used as the indicator for assessing liver fibrosis; (ii) Treg was the independent risk factor when LSM was used as the indicator for assessing liver fibrosis. When Treg was used to predict liver fibrosis, the cutoff value, diagnostic efficacy, area under the receiver operating characteristic (ROC) curve, and p value of the ROC curve were 6.875, 0.641, 0.84, and .027, respectively.
CONCLUSIONS: Age and Treg are independent risk factors for progressive liver fibrosis. The cutoff value of Treg > 6.81 indicates the need for timely antiviral treatment and can serve as an indicator for evaluating liver fibrosis.

Every distinct liver enzyme biomarker exhibits a strong correlation with non-alcoholic fatty liver disease (NAFLD). This study aims to comprehensively analyze and compare the associations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) with NAFLD from a gender perspective.
This study was conducted on 6,840 females and 7,411 males from the NAGALA cohort. Multivariable logistic regression analysis was used to compare the associations between liver enzyme markers and NAFLD in both genders, recording the corresponding adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Receiver operating characteristic (ROC) curves were used to evaluate the accuracy of individual liver enzyme markers and different combinations of them in identifying NAFLD.
Liver enzyme markers ALT, AST, and GGT were all independently associated with NAFLD and exhibited significant gender differences (All P-interaction<0.05). In both genders, ALT exhibited the most significant association with NAFLD, with adjusted standardized ORs of 2.19 (95% CI: 2.01-2.39) in males and 1.60 (95% CI: 1.35-1.89) in females. Additionally, ROC analysis showed that ALT had significantly higher accuracy in identifying NAFLD than AST and GGT in both genders (Delong P-value < 0.05), and the accuracy of ALT in identifying NAFLD in males was higher than that in females [Area under the ROC curve (AUC): male 0.79, female 0.77]. Furthermore, out of the various combinations of liver enzymes, ALT+GGT showed the highest accuracy in identifying NAFLD in both genders, with AUCs of 0.77 (95% CI: 0.75-0.79) in females and 0.79 (95% CI: 0.78-0.81) in males.
Our study revealed significant gender differences in the associations of the three commonly used liver enzyme markers with NAFLD. In both genders, the use of ALT alone may be the simplest and most effective tool for screening NAFLD, especially in males.

Alternative lengthening of telomeres (ALTs) mechanism is activated in some somatic, germ cells, and human cancer cells. However, the key regulators and mechanisms of the ALT pathway remain elusive. Here we demonstrated that ZBTB40 is a novel telomere-associated protein and binds to telomeric dsDNA through its N-terminal BTB (BR-C, ttk and bab) or POZ (Pox virus and Zinc finger) domain in ALT cells. Notably, the knockout or knockdown of ZBTB40 resulted in the telomere dysfunction-induced foci and telomere lengthening in the ALT cells. The results also show that ZBTB40 is associated with ALT-associated promyelocytic leukemia nuclear bodies, and the loss of ZBTB40 induces the accumulation of the ALT-associated promyelocytic leukemia nuclear bodies in U2OS cells. Taken together, our results implicate that ZBTB40 is a key player of telomere protection and telomere lengthening regulation in human ALT cells.

UNASSIGNED: To discuss the clinical value of hepatic and portal vein Doppler ultrasounds in assessing liver inflammation and fibrosis in patients with chronic hepatitis B virus (HBV) infection, and a normal alanine transaminase (ALT) level.
UNASSIGNED: 94 patients with chronic HBV infections who had undergone ultrasound-guided liver biopsies were enrolled and grouped by the liver tissue pathological results. Analyzed the differences and correlation between parameters of the hepatic and portal vein Doppler ultrasounds are discussed across different degrees of liver inflammation and fibrosis.
UNASSIGNED: There were 27 patients with no significant liver damage and 67 patients with significant liver damage, there were significant differences in the parameters of the hepatic and portal vein Doppler ultrasounds between them (p < 0.05). As liver inflammation was aggravated, the inner diameter of the portal vein increased, and the blood flow velocities of the portal and superior mesenteric veins decreased (p < 0.05). When liver fibrosis became more severe, the inner diameter of the portal vein increased, while the blood flow velocities of the portal, superior mesenteric, and splenic veins decreased, and the Doppler waveforms of hepatic veins became unidirectional or flat (p < 0.05). The receiver operating characteristic (ROC) curve showed the assessment efficacy of hepatic and portal vein Doppler ultrasounds was superior to abdominal Doppler ultrasound alone in assessing liver fibrosis, and the combination of the two examination techniques outperformed any technique used alone.
UNASSIGNED: The hepatic and portal vein Doppler ultrasounds have important clinical value for assessing liver fibrosis in patients with chronic HBV infection, to aid improve the diagnosis of liver fibrosis.

Alanine transaminase (ALT) is an important amino acid-metabolizing enzyme in silkworm Bombyx mori L., and is mainly involved in transferring glutamate to alanine (serving as an essential precursor in silk protein synthesis) through transamination. Therefore, it is generally believed that silk protein synthesis in the silk gland and the cocoon quantity increase with the increase in ALT activity to a certain extent. Here, a novel analytical method was developed to determine the ALT activity in several key tissues of Bombyx mori L. including the posterior silk gland, midgut, fat body, middle silk gland, trachea and hemolymph, by combining the direct-analysis-in-real-time (DART) ion source with a triple-quadrupole mass spectrometer. In addition, a traditional ALT activity assay, the Reitman-Frankel method, was also used to measure ALT activity for comparison. The ALT activity results obtained via the DART-MS method are in good agreement with those obtained via the Reitman-Frankel method. However, the present DART-MS method provides a more convenient, rapid and environmentally friendly quantitative method for ALT measurement. Especially, this method can also monitor ALT activity in different tissues of Bombyx mori L. in real time.

OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is a highly prevalent liver disease that lacks targeted therapeutic drugs and non-invasive diagnostic methods. Increasing evidence demonstrated that aberrant expression of leucine aminopeptidase 3 (LAP3) is involved in NASH. Herein, we aimed to investigate whether LAP3 can be a promising serum biomarker for NASH diagnosis.
METHODS: Liver tissues and serum from NASH rats, serum from NASH patients, and liver biopsies from chronic hepatitis B (CHB) patients combined with NASH (CHB+NASH) were obtained to evaluate the LAP3 level. Correlation analysis was conducted to evaluate the association between LAP3 expression and clinical indexes in CHB patients and CHB+NASH patients. ROC curve analysis of LAP3 in the serum and liver was applied to assess whether LAP3 can be a promising biomarker for NASH diagnosis.
RESULTS: LAP3 was significantly upregulated in serum and hepatocytes of NASH rats and patients with NASH. Correlation analysis revealed that LAP3 in the liver of CHB patients and CHB+NASH patients showed a strong positive correlation with lipidome indicators total cholesterol (TC) and triglyceride (TG), and liver fibrosis indicator hyaluronic acid (HA), which showed a negative correlation with the international normalized ratio of prothrombin coagulation (INR) and liver injury indicator aspartate aminotransferase (AST). For NASH, the diagnostic accuracy of ALT > LAP3 > AST, the sensitivity LAP3 (0.87) > ALT (0.5957) > AST (0.2941), the specificity AST (0.975) > ALT (0.9) > LAP3 (0.5).
CONCLUSIONS: Our data urge that LAP3 can serve as a promising serum biomarker candidate for NASH diagnosis.

Iron overload has been associated with acute/chronic organ failure, but whether iron overload induces liver injury remains unclear. The objectives of this study were to assess the relationship between urinary iron and serum alanine aminotransferase (ALT, a biomarker for liver injury), and investigate the potential mediating roles of lipid peroxidation and oxidative DNA damage in such association. Levels of urinary iron, serum ALT, and urinary biomarkers of lipid peroxidation (8-iso-prostaglandin-F2α [8-iso-PGF2α]) and oxidative DNA damage (8-hydroxy-deoxyguano-sine [8-OHdG]) were measured among 5386 observations of 4220 participants from the Wuhan-Zhuhai cohort. The relationships of urinary iron with serum ALT and risk of hyperALT were evaluated by linear mixed model and logistic regression model, respectively. The mediating roles of 8-iso-PGF2α and 8-OHdG were assessed by mediation analyses. This cross-sectional analysis found that urinary iron was positively associated with ALT (β = 0.032; 95% CI: 0.020, 0.044) and hyperALT prevalence (OR = 1.127; 95% CI: 1.065, 1.192). After 3 years of follow-up, participants with persistent high iron levels had increased risk of developing hyperALT (RR = 3.800; 95% CI: 1.464, 9.972) when compared with those with persistent low iron levels. In addition, each 1% increase in urinary iron was associated with a 0.146% (95% CI: 0.128%, 0.164%) increase and a 0.192% (95% CI: 0.154%, 0.229%) increase in 8-iso-PGF2α and 8-OHdG, respectively. Urinary 8-iso-PGF2α (β = 0.056; 95% CI: 0.039, 0.074) was positively associated with ALT, while the association between 8-OHdG and ALT was insignificant. Furthermore, increased 8-iso-PGF2α significantly mediated 22.48% of the urinary iron-associated ALT increment. Our study demonstrated that iron overload was significantly associated with liver injury, which was partly mediated by lipid peroxidation. Controlling iron intake and regulating lipid peroxidation may help in preventing liver injury.