Association of perfluoroalkyl substances (PFAS) with liver function biomarkers in the highly exposed population of the Veneto Region.

INTRODUCTION: Epidemiological studies highlight the presence of associations between per- and polyfluoroalkyl substances (PFAS) exposure with liver damage. In 2013, PFAS contamination was discovered in Veneto (Italy), leading to the implementation of a Surveillance Program (SP). Our objective is to investigate the association between PFAS exposure and biomarkers of liver function using single-pollutant and mixture approaches, while exploring the sex-specific differences and the mediating role of obesity in the association. METHODS: The study included 42,094 subjects aged ≥20 years participating in the SP. We used generalized additive models to investigate the association between several PFAS and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, adjusting for possible confounders and stratifying by sex. Results were back-transformed to show predicted percentage changes in outcomes per ln-unit increase in PFAS levels; furthermore, we explored the role of BMI in the abovementioned causal pathway, considering it as a potential confounder or mediator PFAS joint effect was investigated using Quantile G-computation. RESULTS: One ln-unit increase in PFHxS concentrations was associated with a 1.49% (95%CI: 0.87, 2.12) and a 0.84% (95% CI: 0.27, 1.40) increase in ALT levels, in males and females respectively; one ln-unit increase in PFOA concentrations was associated with a 1.03% (95%CI: 0.50, 1.55) increase in ALT levels in males, and a 0.52% (95% CI: 0.22, 0.82) and a 0.60% (95% CI: 0.25, 0.96) increase in AST levels in females and males. PFOS showed no association with ALT and AST levels. Quantile G-computation revealed that an interquartile increase in the PFAS mixture was associated with a 3.02% increase (95% CI: 1.65, 4.43) and a 1.65% (95% CI: 0.77, 2.5) increase in ALT levels, in females and males. Mediation analysis suggested that BMI suppressed the association between PFAS and ALT levels, with positive direct effects higher than the total effects. CONCLUSION: Our findings suggest sex-specific associations between PFAS exposure and liver function biomarkers and underscore the need for additional studies on potential mediators.

Absence of Survival Impact from Hepatitis During Immunotherapy in 193 Patients with Advanced Hepatocellular Carcinoma - An Observational Study from Taiwan.

Background: Hepatitis often occurs after initiating immune checkpoint inhibitor (ICI) treatment. The time and grade of hepatitis after ICI starts and the prognostic role of immune-related hepatitis in patients with advanced hepatocellular carcinoma (aHCC) remain unclear. Methods: In this real-world analysis, we enrolled aHCC patients receiving ICIs, documented the highest level of liver enzymes during/after ICIs, and analyzed the survival impact of different hepatitis patterns. Results: One hundred and ninety-three aHCC patients receiving ICIs were recruited. During ICIs, 88.6% of patients experienced aspartate transaminase (AST) elevations (Grade III/IV: 7.8%). For alanine transaminase (ALT), 81.3% had elevated levels (Grade III/IV: 3.6%), and 41.5% of patients had elevated bilirubin levels (Grade 3/4: 6.7%). The median AST, ALT, and total bilirubin values significantly increased after ICI treatment initiated (all p < 0.001) and, similarly, after excluding progressive disease (p = 0.014, p = 0.002, p < 0.001). The median time of hepatitis occurrence is from the 4.0th to 15.9th weeks. Multivariable analysis showed that patterns of liver enzyme change of AST and total bilirubin in patients receiving ICIs significantly correlate to overall survival (OS, p = 0.009 and 0.001, respectively). After ICI termination, patients with elevated bilirubin (p = 0.003) and AST (p = 0.005) would indicate poor survival, with adjustment of viral hepatitis and ICI responses. Conclusion: Hepatitis emerges between the 4th and 20th weeks post-ICI initiation. Changes in liver enzymes during ICI therapy do not directly affect OS, implying the safety of ICI use when corticosteroids are promptly administered if clinically indicated.

Investigation the effect of the aqueous extract of Chara vulgaris (L.) on visceral leishmaniasis.

Background: Visceral leishmaniasis (VL) is a parasitic disease that affects public health. It is described by weight reduction, irregular fever bouts, anemia, and amplification of the spleen and liver. Materials and Methods: Three concentrations (15.6, 31.2, and 62.5 µg/mL) were used to find the potency of an aqueous extract of Chara vulgaris algae in the treatment of VL. A cytotoxicity assay was performed to show the cytotoxic effect of this extract on human cells. High-performance liquid chromatography (HPLC) test was done to determine the active compounds in the extract. Histopathological sections for infected liver and spleen were performed, as were liver function tests (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase), which were assessed after 1 month of treatment. Results: As cytotoxicity assay, results showed that there were no significant differences between the cells treated and those not treated with the extract. HPLC test demonstrated that phenolic and terpene compounds are the main active compounds in the extract. P-coumaric acid and ursolic acid present the highest percent among other phenolic and terpene compounds (21.84%, 17.82%), respectively. Histopathological sections showed that this extract had a significant effect in the treatment of infected tissues, and this effect was very clear after the end of the treatment period. As for the liver function tests, a significant increase (P < 0.01) in the studied liver enzymes was found in the infected group of mice compared to the healthy group, whereas in the infected and treated groups, a clear and gradual decrease in the level of enzymes was observed.

Metformin: Beyond Type 2 Diabetes Mellitus.

Metformin was developed from an offshoot of Guanidine. It is known to be the first-line medication for type 2 diabetes mellitus, polycystic ovarian syndrome, and weight reduction. Metformin has also been shown to have effectiveness in the management of non-alcoholic fatty liver disease (NAFLD), liver cirrhosis, and various carcinomas like hepatocellular, colorectal, prostate, breast, urinary bladder, blood, melanoma, bone, skin, lung and so on. This narrative review focuses on the effect of metformin on non-alcoholic fatty liver disease, liver cirrhosis, and hepatocellular carcinoma. The search platforms for the topic were PubMed, Scopus, and Google search engine. Critical words for searching included 'Metformin,' AND 'Indications of Metformin,' AND 'Non-Alcoholic Fatty Liver Disease,' AND 'Metformin mechanism of action,' AND 'NAFLD management,' AND 'NAFLD and inflammation,' AND 'Metformin and insulin,' AND 'Metformin and inflammation,' AND 'Liver cirrhosis,' AND 'Hepatocellular carcinoma.' Lifestyle modification and the use of hypoglycemic agents can help improve liver conditions. Metformin has several mechanisms that enhance liver health, including reducing reactive oxygen species, nuclear factor kappa beta (NF-κB), liver enzymes, improving insulin sensitivity, and improving hepatic cell lipophagy. Long-term use of metformin may cause some adverse effects like lactic acidosis and gastrointestinal disturbance. Metformin long-term overdose may lead to a rise in hydrogen sulfide in liver cells, which calls for pharmacovigilance. Drug regulating authorities should provide approval for further research, and national and international guidelines need to be developed for liver diseases, perhaps with the inclusion of metformin as part of the management regime.

Blood cell counts and nonalcoholic fatty liver disease: Evidence from Mendelian randomization analysis.

BACKGROUND: Previous research has highlighted correlations between blood cell counts and chronic liver disease. Nonetheless, the causal relationships remain unknown. AIM: To evaluate the causal effect of blood cell traits on liver enzymes and nonalcoholic fatty liver disease (NAFLD) risk. METHODS: Independent genetic variants strongly associated with blood cell traits were extracted from a genome-wide association study (GWAS) conducted by the Blood Cell Consortium. Summary-level data for liver enzymes were obtained from the United Kingdom Biobank. NAFLD data were obtained from a GWAS meta-analysis (8434 cases and 770180 controls, discovery dataset) and the Fingen GWAS (2275 cases and 372727 controls, replication dataset). This analysis was conducted using the inverse-variance weighted method, followed by various sensitivity analyses. RESULTS: One SD increase in the genetically predicted haemoglobin concentration (HGB) was associated with a ß of 0.0078 (95%CI: 0.0059-0.0096), 0.0108 (95%CI: 0.0080-0.0136), 0.0361 (95%CI: 0.0156-0.0567), and 0.0083 (95%CI: 00046-0.0121) for alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase, and gamma-glutamyl transferase, respectively. Genetically predicted haematocrit was associated with ALP (ß = 0.0078, 95%CI: 0.0052-0.0104) and ALT (ß = 0.0057, 95%CI: 0.0039-0.0075). Genetically determined HGB and the reticulocyte fraction of red blood cells increased the risk of NAFLD [odds ratio (OR) = 1.199, 95%CI: 1.087-1.322] and (OR = 1.157, 95%CI: 1.071-1.250). The results of the sensitivity analyses remained significant. CONCLUSION: Novel causal blood cell traits related to liver enzymes and NAFLD development were revealed through Mendelian randomization analysis, which may facilitate the diagnosis and prevention of NAFLD.

Impact of Isotretinoin on Blood Lipids and Liver Enzymes: A Retrospective Cohort Study in Saudi Arabia.

Background: Isotretinoin is an effective treatment for acne but can cause side effects such as changes in blood lipids and liver enzymes. Laboratory monitoring is essential during treatment, but there is variation in monitoring practices. Aim: This study aims to investigate the relationship between isotretinoin therapy and its effects on complete blood count in Saudi Arabia to improve patient outcomes. Methods: The study was a retrospective cohort study conducted at King Khalid University Hospital in Riyadh, Saudi Arabia, between January 2016 and December 2020. Following the inclusion and exclusion criteria, 515 patients were randomly selected for the study. The data was analyzed using SPSS, and descriptive statistics and paired samples t-tests were employed to analyze the data. Results: In this study, 515 patients were enrolled. Of these participants, 76.7% (n=395) were females and 23.3% (n=120) were males. The mean age of the study participants was 23.98±7.4 years and ranged between 16 and 65 years. The mean dose of Isotretinoin administered was 27.65±9.6 mg/day, with a range of 10-60 mg/day. The mean BMI of the study participants was 24.3±4.1 kg/m2, ranging from 14.3 to 44.8 kg/m2. Regarding the effect of Isotretinoin on laboratory measures, significant statistical differences were found in hemoglobin measurements (t=-3.379, p=0.001), platelets (t=-3.169, p=0.002), neutrophils (%) (t=3.107, p=0.002), total cholesterol (t=-13.017, p=0.000), AST (t=-6.353, p=0.000), ALT (t=-4.352, p=0.000), HDL (t=2.446, p=0.015), and LDL (t=-12.943, p=0.000). However, there were no significant statistical differences in the measurements of WBC, neutrophils (count), or triglycerides. In the Chi-square analysis and Fisher's Exact test to identify the interaction between BMI, dose, and gender on abnormal lab results, significant interaction was found between participants' BMI and abnormal HDL measurements (p=0.006). Furthermore, there were significant interactions between Isotretinoin dose (either less than 30 mg/day or 30 mg/day or more) and abnormal neutrophil count (p=0.04), abnormal HDL measurements (p=0.010), and abnormal triglycerides measurements (p=0.020). Moreover, a statistically significant interaction was found between participants' gender and abnormal hemoglobin measurements (p=0.006), abnormal total cholesterol (p=0.016), abnormal AST measurements (p=0.001), abnormal ALT measurements (p=0.000), abnormal HDL measurements (p=0.000), and abnormal triglycerides measurements (p=0.007). Conclusion: In conclusion, the study found that isotretinoin therapy has significant effects on several laboratory measures, including hemoglobin, platelets, neutrophils, total cholesterol, AST, ALT, HDL, and LDL. The study also revealed significant interactions between BMI, dose, gender, and abnormal lab results.

Synergistic effects of dietary selenium nanoparticles and vitamin C improve growth performance, immune response, and antioxidant status of juvenile common carp (Cyprinus carpio).

INTRODUCTION: This study aimed to investigate the synergistic effects of dietary selenium nanoparticles (Se-NPs) and vitamin C (VC) on growth, body composition, antioxidant defense, immunity, and serum biochemical indexes of common carp (Cyprinus carp) juveniles. METHODOLOGY: The test diets were supplemented with three levels of Se-NPs (0, 0.5, and 1 mg/Kg) and three levels of VC (0, 500, and 1000 mg/Kg): the basal diet without supplemental Se-NPs and VC (VC0SeNPs0; control), 0.5 mg Se-NPs /Kg (VC0SeNPs0.5), 1 mg Se-NPs /Kg (VC0SeNPs1), 500 mg VC/Kg (VC500SeNPs0), 1000 mg VC/Kg (VC1000SeNPs0), 500 mg VC/Kg and 0.5 mg Se-NPs (VC500SeNPs0.5), 1000 mg VC/Kg and 0.5 mg Se-NPs (VC1000SeNPs0.5), 500 mg VC/Kg and 1 mg Se-NPs (VC500SeNPs1), 1000 mg VC/Kg and 1 mg Se-NPs (VC1000SeNPs1). The fish were randomly divided into nine experimental groups in triplicate tanks per treatment and fed on their respective diets for 60 days. RESULTS: The findings displayed that fish fed with VC500SeNPs1 and VC500SeNPs0.5 diets had significantly (P < 0.05) higher specific growth rates when compared to other groups. The lowest feed conversion ratio was detected in the VC1000SeNPs1 group and the highest in the control group (P < 0.05). VC, Se-NPs, and their interaction had no significant effect on serum malondialdehyde, ACH50, and IgM (P > 0.05). However, the best parameters associated with antioxidant capacity (higher serum levels of superoxide dismutase and total reduced glutathione) and physiological status (higher concentration of serum globulin and lower amounts of aspartate aminotransferase and lactate dehydrogenase) belonged to the VC1000SeNPs1 and VC500SeNPs1 groups. The results suggest that the Se-NPs and VC combination more efficiently influence the common carp's growth performance, antioxidant status, immunity, and physiological parameters. CONCLUSION: Overall, the diet enriched with 500 mg VC and 1 mg Se-NPs /Kg (VC500SeNPs1) is suitable for boosting the growth and immunity of common carp.

Liver enzyme levels in adolescents with obesity and insulin resistance: a propensity score matching analysis.

BACKGROUND: Elevated liver enzyme levels have been associated with metabolic syndrome in both obese and non-obese pediatric populations. This study aims to compare the serum liver enzyme levels in obese adolescents with and without insulin resistance (IR). METHODS: A cross-sectional analysis was conducted involving obese adolescents aged 10-18. We assessed somatometry, serum insulin levels, lipid profiles, and liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and gamma-glutamyl transferase [GGT]). Statistical differences between groups were evaluated using Student's t-test or the Chi-squared test, with IR (wIR) status matched by propensity scores based on body mass index (BMI) z-scores. RESULTS: The study included 365 adolescents with obesity, 229 wIR, and 136 without (woIR). Before matching, the wIR group had a significantly higher BMI z-score (2.21 vs. 2.14, p = 0.032). After matching for BMI z-scores (n = 122 each group), the wIR group displayed significantly higher levels of AST (32.3 vs. 24.7, p < 0.001) and ALT (42.4 vs. 30.9, p < 0.001), but no significant differences were observed in GGT levels (37.4 vs. 32.5, p = 0.855). CONCLUSION: Obese adolescent's wIR exhibit higher serum ALT and AST levels, suggesting that altered AST is a potential risk factor for IR.

INTRODUCCIÓN: Se ha observado asociación entre niveles elevados de enzimas hepáticas y síndrome metabólico en población pediátrica con y sin obesidad. El objetivo del estudio fue comparar los niveles séricos de enzimas hepáticas entre adolescentes con obesidad con y sin resistencia a la insulina (RI). MÉTODOS: Se realizó un estudio transversal en adolescentes con obesidad entre 10 y 18 años. Se analizaron los datos somatometricos, insulina sérica, perfil lipídico y niveles de enzimas hepáticas (aspartato aminotransferasa [AST], alanina aminotransferasa [ALT] y gamma-glutamil transferasa [GGT]). Análisis estadístico: se utilizó t de Student o la prueba de Chi-cuadrado para evaluar diferencias entre grupos. Los pacientes con RI se emparejaron con pacientes sin RI utilizando puntuaciones de propensión basadas en la puntuación z del IMC. RESULTADOS: Se incluyeron un total de 365 adolescentes con obesidad (229 con RI y 136 sin RI). El grupo con RI tuvo un IMC mayor (con RI 2.21 vs sin RI 2.14 p = 0.032). Después de emparejar los grupos según el IMCz (n = 122 por grupo), el grupo con RI tuvo niveles de AST (24.7 vs., 32.3, p < 0.001) y ALT (30.9 vs., 42.4, p < 0.001) significativamente más altos en comparación al grupo sin RI. Sin embargo, no hubo diferencia en los niveles de GTT (37.4 vs 32.5, p = 0.855). CONCLUSIONES: Los niveles séricos de ALT y AST en adolescents con obesidad y RI fueron mayores. La AST alterada fue un factor de riesgo para presentar RI.

Factors Influencing Liver Abnormalities in Psoriatic Arthritis Patients: A Comprehensive Study.

Objective: The aim of this study was to establish the incidence of liver abnormalities in psoriatic arthritis patients and identify the factors that contributed to this condition. Methods: This is a longitudinal cohort study. Psoriatic arthritis (PsA) patients with liver enzymes abnormalities were identified. Our control group consisted of PsA patient from the same cohort who had no history of liver abnormalities. Factors associated with liver abnormalities were identified using univariate and multivariate analysis. Results: A total of 247 of PsA patients were included and out of those, 99 developed liver enzymes abnormalities. The mean age of the patients was 56 years old (±13.5) with 56.1% female and 39.4% Indian descendants. The univariate logistic regression demonstrated that disease duration of PsA (OR=1.06, 95% CI=1.01 - 1.10, p=0.012), diabetes mellitus (OR=2.16, 95% CI=1.26 - 3.70, 0.005) and non-alcoholic fatty liver disease (NAFLD) (OR=3.90, 95% CI = 1.44 - 10.53, p=0.007) were associated with abnormal liver function in PsA patients. No association was found with both conventional synthetic disease-modifying antirheumatic drugs or biologics. Conclusion: Liver enzymes abnormalities in PsA patients were linked to disease duration, diabetes mellitus and NAFLD. For these high-risk populations, vigilant monitoring of liver function tests is vital for early detection and intervention.

Efficacy of probiotics on improvement of health outcomes in cirrhotic liver disease patients: A systematic review and meta-analysis of randomised controlled trials.

Liver cirrhosis is a chronic condition of the liver and is the 14th most common cause of death around the world; yet it remains an incurable disease. Probiotics have gained significant popularity as a potential treatment option for liver cirrhosis. METHODS: A systematic review and meta-analysis was conducted to assess the effects of probiotics on liver cirrhosis. PubMed, Scopus, Cochrane Central Register for Controlled Trials (CENTRAL) and ProQuest Dissertation and Thesis were searched from 2000 to January 2024 for studies that evaluated the effects of probiotics on a variety of outcomes of liver disease. RESULTS: A total of 22 randomised controlled trial studies were included in the meta-analysis. Probiotics significantly decreased Gamma-glutamyl transferase (effect size: 0.307, p = 0.024, 95% CI [-0.572, -0.040]) and Aspartate aminotransferase (p = 0.013, 95% CI [-17.927, -2.128]). Significant reduction in serum ammonia levels (effect size = -1.093, p = 0.000, 95% CI [-1.764, -0.423]) and endotoxin levels (effect size = -0.961, p = 0.000, 95% CI [-1.537, -0.385]) were also found. SUMMARY: Overall probiotics could be recommended as a potential adjunct therapy for patients with cirrhosis, as they appear to have some benefit in improving liver function, and are well tolerated with minimal adverse effects. More comprehensive research with larger sample sizes is recommended to understand more about the widespread effects of probiotic use.

Effects of Propolis Consumption on Glycemic Indices and Liver Enzymes in Adults: A Grading of Recommendations Assessment, Development, and Valuation-assessed Systematic Review and Dose-Response Meta-analysis.

PURPOSE: Even though various randomized controlled trials (RCTs) have assessed the effect of propolis on glycemic indices and liver enzyme concentrations in adults, results have been inconsistent, without conclusive evidence. This systematic review and meta-analysis of RCTs sought to evaluate the effects of propolis consumption on glycemic indices and liver enzymes, fasting blood glucose, insulin, homeostatic model assessment of insulin resistance, glycosylated hemoglobin, alanine transaminase, aspartate aminotransferase, and gamma-glutamyl transferase in adults. METHODS: Two independent researchers systematically searched PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library for English-language RCTs published up to April 2024. The results were generated through a random-effects model and presented as the weighted mean difference (WMD) with a 95% CI. The Cochrane Risk of Bias Tool for RCTs and Grading of Recommendations Assessment, Development, and Evaluation assessment were used to evaluate quality assessment and certainty of evidence. FINDINGS: A total of 21 RCTs were included. A pooled analysis of 24 trials reported that propolis consumption led to a significant reduction in fasting blood glucose (WMD, -9.75 mg/dL; 95% CI, -16.14 to -3.35), insulin (WMD, -1.64 µU/mL; 95% CI, -2.61 to -0.68), glycosylated hemoglobin (WMD, -0.46%; 95% CI, -0.71 to -0.21), homeostatic model assessment of insulin resistance (WMD, -0.54; 95% CI, -0.98 to -0.09), alanine transaminase (WMD, -2.60 IU/L; 95% CI, -4.58 to -0.61), and aspartate aminotransferase (WMD, -2.07 IU/L; 95% CI, -3.05 to -1.09). However, there were no significant effects on gamma-glutamyl transferase in comparison with the control group. IMPLICATIONS: This meta-analysis has shown that propolis supplementation may have beneficial effects on glycemic indices and liver enzymes. Future high-quality, long-term RCTs are needed to confirm our results. CLINICALTRIALS: gov identifiers: CRD42024524763. (Clin Ther. 2024;46:XXX-XXX) © 2024 Elsevier HS Journals, Inc.

Efficacy of the Mediterranean Diet Containing Different Macronutrients on Non-Alcoholic Fatty Liver Disease.

This study aimed to investigate the effects of the typical Mediterranean diet (TMD), low-carbohydrate Mediterranean diet (LCMD), and low-fat Mediterranean diet (LFMD) on biochemical findings, fatty liver index (FLI), anthropometric measurements, and body composition in individuals with obesity with non-alcoholic fatty liver disease (NAFLD) and insulin resistance. This study included 63 participants with obesity with insulin resistance diagnosed with NAFLD by ultrasonography to investigate the effects of an 8-week energy-restricted TMD, LCMD, and LFMD on biochemical findings, FLI, fibrosis-4 index (FIB-4), anthropometric measurements, and body composition. Patients were randomized into three groups and were interviewed face-to-face every week. According to the food consumption records (baseline end), the difference in the amount of sucrose and total fat consumed in the TMD group; the difference in energy intake from sucrose, monounsaturated fatty acids, and oleic acid in the LCMD group; and the difference in energy intake from fiber, sucrose, monounsaturated and polyunsaturated fatty acids, and cholesterol in the LFMD group showed significant correlations with liver enzymes and FLI (p < 0.05). In conclusion, although it has a different macronutrient composition, the Mediterranean diet may positively affect biochemical parameters and FLI in individuals with NAFLD, albeit in different ways.

Evaluation of lipid profile, liver function enzymes, and trace elements in Iraqi diabetic nephropathy patients.

Diabetic nephropathy, a common complication of type 2 diabetes (T2DM), is associated with abnormal lipid profiles, liver dysfunction, and kidney impairment. However, research on its association with trace elements in Iraqi patients is limited. The objective of the present study is to evaluate the association between lipid profile, liver function, and trace elements in diabetic nephropathy (DN) patients. In this study, 120 individuals were selected. Sixty of these individuals were labeled as the DN patient group, and 60 individuals were labeled as the healthy control group. A flame atomic absorption spectrophotometer (FAAS) was utilized to assess the levels of zinc (Zn), copper (Cu), and magnesium (Mg), whereas a flameless atomic absorption (FAA) was used to assess manganese (Mn). A colorimetric method was used based on the protocols included in the leaflets by Spinreact kits to determine the levels of lipid profiles and liver function enzymes in the serum. The mean value of high-density lipoprotein (HDL) decreased significantly in the DN patient group compared to the control group (p < 0.001) while cholesterol and low-density lipoprotein (LDL) decreased insignificantly. Conversely, the mean value of triglycerides (TGs) increased significantly in patient group ((p < 0.001) while very low-density lipoprotein (VLDL) increased insignificantly. On the other hand, the mean values of aspartate aminotransferase (AST), alanine transferase (ALT), alkaline phosphatase (ALP), and γ- glutamyl transferase (GGT) were significantly greater in DN patients compared to the healthy controls. Conversely, the mean values of total protein (TP) and albumin (Alb) were significantly lower in the DN patient group. In terms of trace elements, the mean values of Zn, Mg, and Mn were significantly lower in each of the patient groups compared to the healthy group. Conversely, a significant elevation in the means of Cu and Fe was observed in patients compared to the healthy group. Additionally, the findings revealed no association between BMI and lipid profile, liver enzymes, or trace elements. However, an association with age was limited to TGs, ALP, and GGT. The study's results show that the DN patients have abnormalities in their serum trace element levels. This means that these elements could be valuable indicators for monitoring and assessing the progression of DN. Understanding the correlation between lipid profile, liver function, and trace elements could offer valuable insights for managing and preventing diabetic nephropathy. More extensive studies, including an additional group of DM patients without nephropathy complications, are required, and could be used in practice due to the progression of the disease.

Association of liver function markers and apolipoprotein E ε4 with pathogenesis and cognitive decline in Alzheimer's disease.

Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder influenced by various factors, including liver function, which may impact the clearance of amyloid-ß (Aß) in the brain. This study aimed to explore how the apolipoprotein E (APOE) ε4 allele affects the relationship of liver function markers with AD pathology and cognition. Methods: We analyzed data from two independent cohorts, including 732 participants from the Hallym University Medical Center and 483 from the Alzheimer's Disease Neuroimaging Initiative, each group consisting of individuals with and without the APOE ε4 allele. Cross-sectional analyses evaluated the associations of liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, total bilirubin, and albumin) with AD diagnosis, amyloid positron emission tomography (PET) burden, and cerebrospinal fluid biomarkers for AD (Aß42, total tau, and phosphorylated tau181) at baseline. Longitudinally, we investigated the associations between these liver enzymes and changes in cognitive performance over the course of a year. Logistic and linear regression models were used to analyze these associations and mediation analyses were conducted to assess whether age and amyloid PET burden mediated these associations. Results: Only in the APOE ε4 carrier group, a high AST to ALT ratio and low ALT levels were significantly associated with AD diagnosis, increased amyloid PET burden, and faster longitudinal decline in cognitive function in both cohorts. In particular, the AST to ALT ratio was associated with cerebrospinal fluid Aß42 levels exclusively in the APOE ε4 carrier group in the Alzheimer's Disease Neuroimaging Initiative cohort but not with phosphorylated tau181 or total tau levels. Moreover, mediation analyses from both cohorts revealed that in the APOE ε4 carriers group, age did not mediate the associations between liver enzymes and AD diagnosis or amyloid PET burden. However, amyloid PET burden partially mediated the association between liver enzymes and AD diagnosis exclusively in the APOE ε4 carriers group. Conclusion: This study provides valuable insights into the significant association of the APOE ε4 allele with liver enzymes and their potential role in Aß-related pathogenesis and cognition in AD. Further research is required to elucidate the underlying mechanisms and potential therapeutic implications of these findings.

New biomarkers for liver involvement by dengue infection in adult Vietnamese patients: a case-control study.

Liver injury with marked elevation of aspartate aminotransferase enzyme (AST) is commonly observed in dengue infection. To understand the pathogenesis of this liver damage, we compared the plasma levels of hepatic specific, centrilobular predominant enzymes (glutamate dehydrogenase, GLDH; glutathione S transferase-α, αGST), periportal enriched 4-hydroxyphenylpyruvate dioxygenase (HPPD), periportal predominant arginase-1 (ARG-1), and other non-specific biomarkers (paraoxonase-1, PON-1) in patients with different outcomes of dengue infection. This hospital-based study enrolled 87 adult dengue patients, stratified into three groups based on plasma AST levels (< 80, 80-400, > 400 U/L) in a 1:1:1 ratio (n = 40, n = 40, n = 40, respectively. The new liver enzymes in the blood samples from the 4th to 6th days of their illness were measured by commercial enzyme-linked immunosorbent assay (ELISA) or colorimetric kits. Based on the diagnosis at discharge days, our patients were classified as 40 (46%) dengue without warning signs (D), 35 (40.2%) dengue with warning signs (DWS), and 11 (12.6%) severe dengue (SD) with either shock (two patients) or AST level over 1000 U/L (nine patients), using the 2009 WHO classification. The group of high AST (> 400 U/L) also had higher ALT, GLDH, ARG-1, and HPPD than the other groups, while the high (> 400 U/L) and moderate (80-400 U/L) AST groups had higher ALT, αGST, ARG-1, and HPPD than the low AST group (< 80 U/L). There was a good correlation between AST, alanine aminotransferase enzyme (ALT), and the new liver biomarkers such as GLDH, αGST, ARG-1, and HPPD. Our findings suggest that dengue-induced liver damage initiates predominantly in the centrilobular area toward the portal area during the dengue progression. Moreover, these new biomarkers should be investigated further to explain the pathogenesis of dengue and to validate their prognostic utility.

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.

Effect of Diets with the Addition of Edible Insects on the Development of Atherosclerotic Lesions in ApoE/LDLR-/- Mice.

Foods enriched with insects can potentially prevent several health disorders, including cardiovascular diseases, by reducing inflammation and improving antioxidant status. In this study, Tenebrio molitor and Gryllus assimilis were selected to determine the effect on the development of atherosclerosis in ApoE/LDLR-/- mice. Animals were fed AIN-93G-based diets (control) with 10% Tenebrio molitor (TM) and 10% Gryllus assimilis (GA) for 8 weeks. The nutritional value as well as antioxidant activity of selected insects were determined. The lipid profile, liver enzyme activity, and the fatty acid composition of liver and adipose tissue of model mice were evaluated. Quantitative analysis of atherosclerotic lesions in the entire aorta was performed using the en face method, and for aortic roots, the cross-section method was used. The antioxidant status of the GA cricket was significantly higher compared to the TM larvae. The results showed that the area of atherosclerosis (en face method) was not significantly different between groups. Dietary GA reduced plaque formation in the aortic root; additionally, significant differences were observed in sections at 200 and 300 µm compared to other groups. Furthermore, liver enzyme ALT activity was lower in insect-fed groups compared to the control group. The finding suggests that a diet containing edible insect GA potentially prevents atherosclerotic plaque development in the aortic root, due to its high antioxidant activity.

Neonatal Graves Disease Masquerading as Hemochromatosis.

Thyroid autoimmunity is extremely common in the adult population and can affect pregnancy outcomes. Signs in the newborn can range from absent to severe, making the diagnosis easy to miss. We present an interesting case of neonatal Graves disease associated with intrauterine growth restriction, premature delivery, and liver failure with severely high ferritin, thought to be secondary to hemochromatosis. Treatment of the underlying hyperthyroidism caused a rapid resolution of the elevated ferritin and liver failure. This report highlights the importance of considering Graves disease in newborns with liver failure of unknown etiology.

Fetal gender prediction by monitoring circulating steroid hormones and some biochemical parameters in maternal dromedary camels.

To predict the sex of the foetus, healthy pregnant dromedary camels (n = 24) were included. Blood samples were collected for measurements of progesterone, estradiol, testosterone, and cortisol as well as total proteins, albumin, glucose, creatinine, blood urea nitrogen, phosphorus, calcium, creatine kinase, alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), calcium, phosphorus, and magnesium. Statistical analysis revealed differences between pregnant camels and pregnant camels in terms of female or male foetuses depending on the actual sex of the born calf. The results revealed that testosterone and ALP concentrations were significantly (P < 0.001) greater in camels given to males than in those given to calves. There were strong positive correlations between male calf birth and testosterone and ALP concentrations (r = 0.864; P < 0.0001 and r = 0.637; P < 0.001, respectively). On the other hand, the cortisol, glucose and creatinine concentrations were significantly lower (P lower in camel calved males than in females). There were significant negative correlations between male calf birth and the cortisol, glucose and creatinine concentrations (r =-0.401; P = 0.052; r =-0.445; P = 0.029 and r =-0.400; P = 0.053, respectively). The concentrations of calcium, phosphorus, calcium/phosphorus ratio, magnesium, and albumin and the albumin/globulin ratio were not significantly different (P > 0.05) between the two groups. In conclusion, testosterone could be used as a biomarker to determine the sex of foetuses in dromedary camels.

Evaluation of elevated serum liver enzymes and metabolic syndrome in the PERSIAN Guilan cohort study population.

Objective: The purpose of this study is to evaluate the association between elevated serum liver enzymes and Metabolic Syndrome (MetS) in Prospective Epidemiological Research Studies of the Iranian Adults (PERSIAN) Guilan Cohort Study (PGCS) population. Methods: This cross-sectional study involved 10,519 individuals between the ages of 35 and 70 enrolled in the PGCS. The gathered data encompassed demographic information, anthropometric measurements, blood pressure, and biochemical indicators. MetS was defined by the National Cholesterol Education Program-Adult Treatment Panel III criteria (NCEP-ATP III). The associations between elevated liver enzymes and MetS were examined using logistic regression analysis. Odds ratio (OR) and 95 % confidence interval (CI) were calculated. Results: The prevalence of MetS was 41.8 %, and the prevalence of elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) were 19.4, 4.6, 11.6, and 5.1 %, respectively. In the unadjusted model, elevated ALT, AST, and GGT were associated with increased odds of MetS (OR = 1.55, 95 % CI: 1.41-1.71; OR = 1.29, 95 % CI: 1.07-1.55, and OR = 1.90, 95 % CI: 1.69-2.14, respectively). These associations remained significant for ALT and GGT after adjustment for some demographic and clinical characteristics (aOR = 1.31, 95 % CI: 1.17-1.46 and aOR = 1.30, 95 % CI: 1.14-1.49, respectively). In addition, the odds of MetS increased with the number of elevated liver enzymes, up to almost 1.32-fold among subjects with three/four elevated liver enzymes. Conclusion: The higher incidence of elevated liver enzymes was associated with an increased likelihood of MetS. Including liver markers in diagnosing and predicting MetS holds promise and is considered a possible approach.