Prospective Evaluation of Raised Liver Transaminases in Asymptomatic Patients Attending OPD in a Tertiary Care Hospital

Background: Liver diseases are a cause of worldwide morbidity .The course is usually long and has no signs before the development of late stage disease. The only indicative markers are liver enzymes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT) during asymptomatic period. There is a paucity of data from our subcontinent regarding the prevalence, risk factors and etiology of asymptomatic chronically raised liver enzymes.The aim of the study was to determine the prevalence, risk factors and etiology associated with unexplained chronically raised liver transaminases in patients attending OPD in a tertiary care hospital.Methods:This was a prospective study conducted in the Department of Gastroenterology, MMIMSR, Mullana from July 2019-Dec 2020 in 50 patients who presented with chronically raised liver enzymes. Detailed comprehensive history, physical examination and investigation was done to identify etiology and risk factors associated with raised liver enzymes.Results:566 patients were screenedfor inclusion in the study. The prevalence of raised transaminases in asymptomatic patients was 9.4%. NAFLD was the most common etiology of raised liver transaminases, seen in 70 % of patients followed by Hepatitis C and Hepatitis B. Dyslipidemia was the most important risk factor associated with NAFLD.Conclusion:NAFLD should be kept in mind while dealing patients with unexplained transaminitis. Earlier detection could help halt the progression to chronic liver disease.

Application of a Machine Learning Technology in the Definition of Metabolically Healthy and Unhealthy Status: A Retrospective Study of 2567 Subjects Suffering from Obesity with or without Metabolic Syndrome

The key factors playing a role in the pathogenesis of metabolic alterations observed in many patients with obesity have not been fully characterized. Their identification is crucial, and it would represent a fundamental step towards better management of this urgent public health issue. This aim could be accomplished by exploiting the potential of machine learning (ML) technology. In a single-centre study (n = 2567), we used an ML analysis to cluster patients with metabolically healthy (MHO) or metabolically unhealthy (MUO) obesity, based on several clinical and biochemical variables. The first model provided by ML was able to predict the presence/absence of MHO with an accuracy of 66.67% and 72.15%, respectively, and included the following parameters: HOMA-IR, upper body fat/lower body fat, glycosylated haemoglobin, red blood cells, age, alanine aminotransferase, uric acid, white blood cells, insulin-like growth factor 1 (IGF-1) and gamma-glutamyl transferase. For each of these parameters, ML provided threshold values identifying either MUO or MHO. A second model including IGF-1 zSDS, a surrogate marker of IGF-1 normalized by age and sex, was even more accurate with a 71.84% and 72.3% precision, respectively. Our results demonstrated high IGF-1 levels in MHO patients, thus highlighting a possible role of IGF-1 as a novel metabolic health parameter to effectively predict the development of MUO using ML technology.

Sigma metrics in quality control- An innovative tool

The clinical laboratory in today’s world is a rapidly evolving field which faces a constant pressure to produce quick and reliable results. Sigma metric is a new tool which helps to reduce process variability, quantitate the approximate number of analytical errors, and evaluate and guide for better quality control (QC) practices.To analyze sigma metrics of 16 biochemistry analytes using ERBA XL 200 Biochemistry analyzer, interpret parameter performance, compare analyzer performance with other Middle East studies and modify existing QC practices.This study was undertaken at a clinical laboratory for a period of 12 months from January to December 2020 for the following analytes: albumin (ALB), alanine amino transferase (SGPT), aspartate amino transferase (SGOT), alkaline phosphatase (ALKP), bilirubin total (BIL T), bilirubin direct (BIL D), calcium (CAL), cholesterol (CHOL), creatinine (CREAT), gamma glutamyl transferase (GGT), glucose (GLUC), high density lipoprotein (HDL), triglyceride (TG), total protein (PROT), uric acid (UA) and urea. The Coefficient of variance (CV%) and Bias % were calculated from internal quality control (IQC) and external quality assurance scheme (EQAS) records respectively. Total allowable error (TEa) was obtained using guidelines Clinical Laboratories Improvement Act guidelines (CLIA). Sigma metrics was calculated using CV%, Bias% and TEa for the above parameters. It was found that 5 analytes in level 1 and 8 analytes in level 2 had greater than 6 sigma performance indicating world class quality. Cholesterol, glucose (level 1 and 2) and creatinine level 1 showed >4 sigma performance i.e acceptable performance. Urea (both levels) and GGT (level 1) showed <3 sigma and were therefore identified as the problem analytes. Sigma metrics helps to assess analytic methodologies and can serve as an important self assessment tool for quality assurance in the clinical laboratory. Sigma metric evaluation in this study helped to evaluate the quality of several analytes and also categorize them from high performing to problematic analytes, indicating the utility of this tool. In conclusion, parameters showing lesser than 3 sigma need strict monitoring and modification of quality control procedure with change in method if necessary.

Hematological and Serum Biochemical Changes and Their Prognostic Value in Horses Spontaneously Poisoned by Crotalaria spectabilis

Determining the prognosis of poisoning by plants containing pyrrolizidine alkaloids is usually challenging. This study aimed to identify important prognostic parameters that can determine the severity of spontaneous poisoning by Crotalaria spectabilis in horses. Blood samples from 42 horses spontaneously poisoned by oats contaminated with C. spectabilis seeds were evaluated. Complete blood counts (CBC) and serum biochemical tests [urea, creatinine, total protein, albumin, total and direct bilirubin concentrations, aspartate aminotransferase (AST), γ-glutamyl transferase (GGT), and creatine kinase (CK) activities] were performed. Horses were followed up for 12 months to determine the long-term survival rate; after 12 months, they were divided into two groups: survivors (n = 30) and non-survivors (n = 12). Horses spontaneously poisoned with C. spectabilis had higher levels of urea, globulin, bilirubin (total, direct, and indirect), AST, GGT, and CK than the reference values. Non-survivor horses showed significantly higher (p < 0.05) values of hemoglobin, GGT, and direct bilirubin than the survivor horses. Horses with serum GGT activity higher than 95 U/l had 14.0 times the risk of death compared to animals showing activities equal to or lower than this value, whereas horses with serum direct bilirubin concentration higher than 0.6 mg/dl (10.26 μmol/L) had 5.78 times the risk of death compared to the others. In summary, serum GGT activity and direct bilirubin concentration may be useful prognostic indicators for assessing the severity of C. spectabilis-poisoned horses.

The short-term effect of vitamin D supplementation on the response to muscle and liver damages indices by exhaustive aerobic exercise in untrained men: a quasi-experimental study

Background Exercise-induced muscle damage typically caused by unaccustomed exercise results in pain, soreness, inflammation, and muscle and liver damages. Antioxidant supplementation might be a useful approach to reduce myocytes and hepatocytes damages. Therefore, the present study was conducted to investigate the effect of short-term vitamin D (Vit D) supplementation on the response to muscle and liver damages indices by Exhaustive Aerobic Exercise (EAE) in untrained men. Methods In this clinical trial, 24 untrained men were randomly divided into experimental (Exp; n = 12) and control (C; n = 12) groups. Exp received 2000 IU of Vit D daily for six weeks (42 days), while C daily received a lactose placebo with the same color, shape, and warmth percentage. Two bouts of EAE were performed on a treadmill before and after six weeks of supplementation. Anthropometric characteristics (Bodyweight (BW), height, Body Fat Percentage (BFP), Body Mass Index (BMI), waist to hip ratio (WHR)) were measured at the Pre 1 and Pre 2. Blood samples were taken to measure the Creatine Kinase (CK), Lactate Dehydrogenase (LDH), Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-Glutamyl Transferase (GGT), Alkaline Phosphatase (ALP), and Vit D levels at four stages: Pre 1 (before the first EE session), Post 1 (after the first EE session), Pre 2 (before the second EE session), and Post 2 (after the second EE session). The data were analyzed using repeated-measures ANOVA, Bonferroni's post hoc test, independent t test, and dependent t-test at the significant level of P < 0.05 using SPSS version 26. Results The results show significant differences between Exp and C in alterations of BW (P = 0.039), BMI (P = 0.025), BFP (P = 0.043), and WHR (P = 0.035). The results showed that EAE increased muscle and liver damage indices and Vit D (P < 0.05). Compared with C, the results of the independent t-test showed significantly lower ALT (P = 0.001; P = 0.001), AST (P = 0.011; P = 0.001), GGT (P = 0.018; P = 0.001), and ALP (P = 0.001; P = 0.001); while significantly higher Vit D (P = 0.001, P = 0.001) in the Exp in both Pre 2 and Post 2; receptivity. The independent t test showed significantly lower ALT (P = 0.001; P = 0.001), AST (P = 0.011; P = 0.001), GGT (P = 0.018; P = 0.001), and ALP (P = 0.001; P = 0.001) and considerably greater Vit D (P = 0.001, P = 0.001) in the Exp in both Pre 2 and Post 2 compared to C. The results of an independent t test showed that LDH and CK levels in the Exp were significantly lower than those in the Post 2 (P = 0.001). Conclusions Short-term Vit D supplementation could prevent myocytes and hepatocytes damage induced by EAE.

Clinical, histological and molecular profiling of different stages of alcohol-related liver disease

ObjectiveAlcohol-related liver disease (ALD) ranges from never-decompensated ALD (ndALD) to the life-threatening decompensated phenotype, known as alcohol-related hepatitis (AH). A multidimensional study of the clinical, histological and molecular features of these subtypes is lacking.DesignTwo large cohorts of patients were recruited in an international, observational multicentre study: a retrospective cohort of patients with ndALD (n=110) and a prospective cohort of patients with AH (n=225). Clinical, analytical, immunohistochemistry and hepatic RNA microarray analysis of both disease phenotypes were performed.ResultsAge and mean alcohol intake were similar in both groups. AH patients had greater aspartate amino transferase/alanine amino transferase ratio and lower gamma-glutamyl transferase levels than in ndALD patients. Patients with AH demonstrated profound liver failure and increased mortality. One-year mortality was 10% in ndALD and 50% in AH. Histologically, steatosis grade, ballooning and pericellular fibrosis were similar in both groups, while advanced fibrosis, Mallory-Denk bodies, bilirubinostasis, severe neutrophil infiltration and ductular reaction were more frequent among AH patients. Transcriptome analysis revealed a profound gene dysregulation within both phenotypes when compare to controls. While ndALD was characterised by deregulated expression of genes involved in matrisome and immune response, the development of AH resulted in a marked deregulation of genes involved in hepatocyte reprogramming and bile acid metabolism.ConclusionsDespite comparable alcohol intake, AH patients presented with worse liver function compared with ndALD patients. Bilirubinostasis, severe fibrosis and ductular reaction were prominent features of AH. AH patients exhibited a more profound deregulation of gene expression compared with ndALD patients.

Health Risks of Sarcopenic Obesity in Overweight Children and Adolescents: Data from the CHILT III Programme (Cologne)

Sarcopenic obesity is increasingly found in youth, but its health consequences remain unclear. Therefore, we studied the prevalence of sarcopenia and its association with cardiometabolic risk factors as well as muscular and cardiorespiratory fitness using data from the German Children’s Health InterventionaL Trial (CHILT III) programme. In addition to anthropometric data and blood pressure, muscle and fat mass were determined with bioelectrical impedance analysis. Sarcopenia was classified via muscle-to-fat ratio. A fasting blood sample was taken, muscular fitness was determined using the standing long jump, and cardiorespiratory fitness was determined using bicycle ergometry. Of the 119 obese participants included in the analysis (47.1% female, mean age 12.2 years), 83 (69.7%) had sarcopenia. Affected individuals had higher gamma-glutamyl transferase, higher glutamate pyruvate transaminase, higher high-sensitivity C-reactive protein, higher diastolic blood pressure, and lower muscular and cardiorespiratory fitness (each p < 0.05) compared to participants who were ‘only’ obese. No differences were found in other parameters. In our study, sarcopenic obesity was associated with various disorders in children and adolescents. However, the clinical value must be tested with larger samples and reference populations to develop a unique definition and appropriate methods in terms of identification but also related preventive or therapeutic approaches.

Clinicopathologic Features of Lymphoproliferative Neoplasms Involving the Liver

Background and Objectives: Primary hepatic lymphoproliferative neoplasms (PHL) are uncommon. This retrospective study is aimed to present the clinicopathological characteristics of PHL and compare to secondary hepatic lymphoproliferative neoplasms (SHL). Materials and Methods: Patients who were diagnosed with lymphoproliferative neoplasms involving the liver between January 2004 and December 2018 at a tertiary medical center in central Taiwan were included. The demographic and clinical data, radiological results and histopathological findings were reviewed and summarized. Results: We analyzed 36 patients comprising 6 PHL patients and 30 SHL patients. The median age at diagnosis tended to be younger in PHL than in SHL (59 vs. 63 years old, p = 0.349). Both entities had a small male predominance. The PHL patients tended to have higher levels of aspartate aminotransferase, alanine transaminase and serum albumin and lower levels of alkaline phosphatase, total bilirubin, γ-glutamyl transferase and lactate dehydrogenase compared with SHL, but there was no significant difference. Multiple mass lesions were the most common radiological finding in both groups. Diffuse large B-cell lymphoma was the predominant subtype in both groups (67% in PHL and 40% in SHL). The PHL patients had a longer median survival than the SHL patients (not reached vs. 3 months, p = 0.003). Conclusions: Although there was no significant difference between PHL and SHL in clinical, laboratory and radiological features, the SHL patients had very poor outcomes with a median survival time of 3 months. Effective therapies are urgently required for these patients.

The Glutathione Metabolite γ-Glutamyl-Glutamate Partially Activates Glutamate NMDA Receptors in Central Neurons With Higher Efficacy for GluN2B-Containing Receptors

Gamma-L-glutamyl-L-glutamate (γ-Glu-Glu) was synthetized and further characterized for its activity on cultured neurons. We observed that γ-Glu-Glu elicited excitatory effects on neurons likely by activating mainly the N-methyl-D-aspartate (NMDA) receptors. These effects were dependent on the integrity of synaptic transmission as they were blocked by tetrodotoxin (TTX). We next evaluated its activity on NMDA receptors by testing it on cells expressing these receptors. We observed that γ-Glu-Glu partially activated NMDA receptors and exhibited better efficacy for NMDA receptors containing the GluN2B subunit. Moreover, at low concentration, γ-Glu-Glu potentiated the responses of glutamate on NMDA receptors. Finally, the endogenous production of γ-Glu-Glu was measured by LC-MS on the extracellular medium of C6 rat astroglioma cells. We found that extracellular γ-Glu-Glu concentration was, to some extent, directly linked to GSH metabolism as γ-Glu-Glu can be a by-product of glutathione (GSH) breakdown after γ-glutamyl transferase action. Therefore, γ-Glu-Glu could exert excitatory effects by activating neuronal NMDA receptors when GSH production is enhanced.