Higher Serum Alanine Aminotransferase Research Articles

EEF1A2 identified as a hub gene associated with the severity of metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disease that ranges from metabolic dysfunction-associated steatotic liver (MASL) to metabolic dysfunction-associated steatohepatitis (MASH), and may eventually progress to cirrhosis and hepatocellular carcinoma (HCC). The underlying mechanism of MASLD remains incompletely understood. This study aimed to identify key gene implicated in MASLD pathogenesis and validate its correlation with disease severity through an integration of bioinformatics and experimental approaches. Liver transcriptome data from MASLD patients were obtained from the Gene Expression Omnibus (GEO) database. A diet-induced MASLD mouse model was developed, and liver RNA-sequencing was performed. Liver specimens and clinical data from patients were collected for further analysis. A total of 120 differentially expressed genes (DEGs) were shared between datasets GSE89632 and GSE213621, with functional enrichment in inflammatory, metabolic, and cell cycle-related pathways. Protein-protein interaction (PPI) network analysis identified three modules associated with MASLD, with the cell cycle-related module being the most notable. EEF1A2 was identified as a novel hub gene and revealed to be elevated with MASLD progression through dataset analysis. EEF1A2 was confirmed to be highly expressed in the livers of both MASLD mouse models and patients. Moreover, the increased expression of EEF1A2 in MASH was positively correlated with higher serum alanine aminotransferase (ALT), alanine aminotransferase (AST), total cholesterol (TC), and body mass index (BMI). In conclusion, EEF1A2 is a novel hub gene significantly associated with MASLD severity and is a promising biomarker and therapeutic target for MASLD.

Efficacy of steroid therapy for improving native liver survival after pediatric acute liver failure with immune activation.

Recent evidence suggests that acute liver failure (ALF) in some patients may reflect a dysregulated immune response, and that corticosteroids improve survival of the native liver in ALF patients with high serum alanine aminotransferase levels, which are an indication of liver inflammation. However, it is unclear whether steroids are effective for pediatric acute liver failure (PALF). The aim of this retrospective case-control study is to examine whether steroid therapy for PALF accompanied by immune activation improves the survival of native liver and to identify factors that predict responses to steroid treatment. Of 38 patients with PALF treated at Kyoto University Hospital from February 2006 to August 2022, 19 receiving steroids who met the specific criteria for identifying the pathophysiology of immune activity in the liver (the "Steroid group"), and seven steroid-free patients who also met the criteria ("Nonsteroid group") were enrolled. Patients in the "Steroid group" were categorized as "responders" or "nonresponders" according to treatment outcome. Clinical and histological data were analyzed. Survival of the native liver in the Steroid group was significantly higher than that in the Nonsteroid group (68% vs. 0%, respectively; p=0.0052). Nonresponders were significantly younger, with higher Model for End-stage Liver Disease and pediatric end-stage liver disease scores, higher prothrombin time - international normalized ratio, and higher serum ferritin levels than responders. Massive hepatic necrosis was more common in nonresponders. Steroid therapy is effective for PALF patients with liver inflammation; however, liver transplantation should be prioritized for young children with ALF accompanied by severe coagulopathy or massive hepatic necrosis.

The distinct hepatic metabolic profile and relation with impaired liver function in congenital isolated growth hormone-deficient rats.

Patients with growth hormone deficiency (GHD) with inadequate growth hormone levels are often correlated with nonalcoholic fatty liver disease (NAFLD). However, the potential mechanism of how GHD influences liver function remains obscure. In the present study, we aim to perform hepatic metabolomics in Lewis dwarf rats, which were the standard congenital isolated GH-deficient rat, to evaluate the characterizations of hepatic metabolic profiles and explore their relations with liver functions. Lewis dwarf homozygous (dw/dw) rats at 37 weeks (five females and five males), and Lewis dwarf heterozygous (dw/+) rats at 37 weeks (five females and five males) were analyzed in our study. Body lengths and weights, liver weights, serum alanine transaminase (ALT), and serum aspartate transaminase (AST) were measured. ELISA and RT-qPCR were used to assess IGF-1 levels in serum and liver, respectively. The non-targeted metabolomics was performed in the livers of dw/+ and dw/dw rats. Differential metabolites were selected according to the coefficient of variation (CV), variable importance in the projection (VIP) > 1, and P < 0.05. Hierarchical clustering of differential metabolites was conducted, and the KEGG database was used for metabolic pathway analysis. The body weights, body lengths, liver weights, and IGF-1 levels in the serum and liver of dw/dw rats were significantly decreased compared with dw/+ rats. Dw/dw rats exhibited more obvious hepatic steatosis accompanied by higher serum ALT and AST levels. Hepatic metabolomics showed that a total of 88 differential metabolites in positive ion mode, and 51 metabolites in negative ion mode were identified. Among them, lysophosphatidylcholine (LPC) 16:2, LPC 18:3, LPC 22:6, fatty acid esters of hydroxy fatty acids (FAHFA)18:1 were significantly decreased, while palmitoyl acid, dehydrocholic acid, and 7-ketolithocholic acid were significantly increased in dw/dw rats compared with dw/+ rats. These seven differential metabolites were significantly associated with phenotypes of rats. Finally, KEGG pathway analysis showed that the arginine and proline metabolism pathway and bile secretion pathway were mainly clustered. Lewis dw/dw rats with congenital isolated growth hormone deficiency (IGHD) showed liver steatosis and abnormal liver function, which could be potentially associated with the distinctive hepatic metabolic profiles.

Partial Replacement of Fishmeal with Poultry By-Product Meal in Diets for Coho Salmon (Oncorhynchus kisutch) Post-Smolts.

The present study evaluated the effects of partially substituting fish meal (FM) with poultry by-product meal (PBPM) on the growth, muscle composition, and tissue biochemical parameters of coho salmon (Oncorhynchus kisutch) post-smolts. Five isonitrogenous (7.45% nitrogen) and isoenergetic (18.61 MJ/kg gross energy) experimental diets were made by substituting 0%, 10%, 20%, 40%, and 60% FM protein with PBPM protein, which were designated accordingly as PBPM0 (the control), PBPM10, PBPM20, PBPM40, and PBPM60, respectively. Each diet was fed to triplicates of ten post-smolts (initial individual body weight, 180.13 ± 1.32 g) in three floating cages three times daily (6:50, 11:50, and 16:50) to apparent satiation for 84 days. Both specific growth rate (SGR) and protein efficiency ratio did not differ significantly (p > 0.05) among the control, PBPM10, and PBPM20 groups, which were remarkably (p < 0.05) higher than those of the PBPM40 and PBPM60 groups. Feed conversion ratio varied inversely with SGR. The PBPM replacement had no remarkable effects on the morphological indices and proximal muscle components. The control and PBPM10 groups led to significantly higher muscle contents of leucine, lysine, and methionine than groups of higher PBPM inclusion. The groups of PBPM40 and PBPM60 obtained significantly (p < 0.05) higher serum alanine aminotransferase and aspartate aminotransferase activities than the control and low PBPM inclusion groups. The control group had significantly higher albumin and total cholesterol contents than the groups with PBPM inclusion. The control group had significantly higher triglycerides content than the PBPM60 group. The PBPM60 group had significantly lower contents of high-density lipoprotein, low-density lipoprotein, and total protein than the control and PBPM10 groups. The high PBPM replacement level up to 40% and 60% had adverse effects on hepatic malondialdehyde levels. The catalase and superoxide dismutase activities were not affected by low PBPM inclusion, but significantly decreased in high-PBPM-inclusion groups. Based on broken-line regression analysis of SGR and PER, the optimum dietary PBPM replacing level was evaluated to be 16.63-17.50% of FM protein for coho salmon post-smolts.

Propafenone-induced liver injury in an elderly patient with paroxysmal atrial fibrillation--a new case report and literature review

Antiarrhythmic drugs are used more and more often, which is related to the aging of the population and the growing number of arrhythmias, especially atrial fibrillation (AF). One of the drugs used in AF is propafenone, considered a relatively safe drug in people without heart disease. Nevertheless, it can cause severe damage to the liver if one ignores the subtle symptoms that indicate an incipient problem. We present the case of an 82-year-old woman diagnosed with paroxysmal AF who developed acute liver injury during treatment with propafenone. On the fifth day of her hospitalization, we observed nausea and vomiting after introducing regular treatment with propafenone. Similar symptoms occurred before hospitalization when propafenone was taken ad hoc in the event of an AF attack. They were treated as dyspeptics in a patient who underwent cholecystectomy. Laboratory tests showed high serum alanine transaminase, gamma-glutamyltranspeptidase, C-reactive protein, total bilirubin, and a slight increase in aspartate transaminase. Infection with hepatic viruses, alcohol abuse, other drugs toxicity, and intrahepatic cholangitis due to cholelithiasis were excluded as a cause of liver damage. With the discontinuation of propafenone, the patient's clinical condition and laboratory test results improved. Similar cases published in the literature are discussed in the paper. It also draws attention to the need to report adverse drug reactions to the appropriate authorities and discusses the reasons for under-reporting in Poland.

First report of splenic myelolipoma in a Schnauzer in Colombia: a case report

Splenic myelolipoma is a rare tumor in dogs with an unclear origin. A male 13-year-old Schnauzer dog was presented because of a bump on the left side of the abdomen. Clinical examination and abdominal ultrasound revealed a mass in the spleen. A total splenectomy was carried out, and histopathology revealed a splenic myelolipoma. Before surgery, the patient showed high serum alanine aminotransferase levels, which returned to normal eight months after the resection. Unfortunately, the postoperative follow-up showed increased serum cholesterol and triglyceride levels, suggesting liver compromise. This is the first report of a splenic myelolipoma in Colombia.

Lifestyle habits to prevent the development of benign prostatic hyperplasia: Analysis of Japanese nationwide datasets.

Benign prostatic hyperplasia (BPH) refers to nonmalignant hyperplasia of prostate tissue, which causes lower urinary tract symptoms and has become a global public health concern in the aging population. The purpose of this study is to identify modifiable factors, which would prevent or delay BPH development. The association between BPH marker drugs and climate-, socioeconomic-, health condition-, and lifestyle habits-related variables was investigated by analyzing nationwide datasets which were collected in 2018, aggregated by prefecture (administrative unit), and published by Japanese ministries. Uroselective α1 receptor blockers and dutasteride were used as marker drugs referring to BPH prevalence. Correlation analysis, multiple linear regression analysis, and binomial logistic regression analysis were conducted with 47 Japanese prefectures as the unit. The variables which showed |r| > 0.5 by correlation analysis were exercise habits (r=-0.5696), smoking habits (r=0.6116), and daily drinking (r=0.6001) for uroselective α1 receptor blockers, and antihypertensive medication (r=0.5971), smoking habits (r=0.6598), a small amount of drinking (r=-0.5292), and serum alanine aminotransferase (r=0.6814) for dutasteride. Multiple linear regression equations were constructed by including these variables (R 2 =0.5453 for uroselective α1 receptor blockers and R 2 =0.5673 for dutasteride). Binomial logistic regression analysis found a significant association between climate in the resident area and BPH development. This ecological study, analyzing Japanese nationwide datasets, demonstrates that healthy lifestyle habits, especially avoidance of smoking, implementation of exercise in daily life, and a small amount of alcohol consumption, are important to prevent or delay BPH development. High blood pressure and high serum alanine aminotransferase are suggested as risk factors of BPH development.

The Adaptive Characteristics of Cholesterol and Bile Acid Metabolism in Nile Tilapia Fed a High-Fat Diet.

Since high-fat diet (HFD) intake elevates liver cholesterol and enhanced cholesterol-bile acid flux alleviates its lipid deposition, we assumed that the promoted cholesterol-bile acid flux is an adaptive metabolism in fish when fed an HFD. The present study investigated the characteristic of cholesterol and fatty acid metabolism in Nile tilapia (Oreochromis niloticus) after feeding an HFD (13% lipid level) for four and eight weeks. Visually healthy Nile tilapia fingerlings (average weight 3.50 ± 0.05 g) were randomly distributed into four treatments (4-week control diet or HFD and 8-week control diet or HFD). The liver lipid deposition and health statue, cholesterol/bile acid, and fatty acid metabolism were analyzed in fish after short-term and long-term HFD intake. The results showed that 4-week HFD feeding did not change serum alanine transaminase (ALT) and aspartate transferase (AST) enzyme activities, along with comparable liver malondialdehyde (MDA) content. But higher serum ALT and AST enzyme activities and liver MDA content were observed in fish fed 8-week HFD. Intriguingly, remarkably accumulated total cholesterol (mainly cholesterol ester, CE) was observed in the liver of fish fed 4-week HFD, along with slightly elevated free fatty acids (FFAs) and comparable TG contents. Further molecular analysis in the liver showed that obvious accumulation of CE and total bile acids (TBAs) in fish fed 4-week HFD was mainly attributed to the enhancement of cholesterol synthesis, esterification, and bile acid synthesis. Furthermore, the increased protein expressions of acyl-CoA oxidase 1/2 (Acox1 and Acox2), which serve as peroxisomal fatty acid β-oxidation (FAO) rate-limiting enzymes and play key roles in the transformation of cholesterol into bile acids, were found in fish after 4-week HFD intake. Notably, 8-week HFD intake remarkably elevated FFA content (about 1.7-fold increase), and unaltered TBAs were found in fish liver, accompanied by suppressed Acox2 protein level and cholesterol/bile acid synthesis. Therefore, the robust cholesterol-bile acid flux serves as an adaptive metabolism in Nile tilapia when fed a short-term HFD and is possibly via stimulating peroxisomal FAO. This finding enlightens our understanding on the adaptive characteristics of cholesterol metabolism in fish fed an HFD and provides a new possible treatment strategy against metabolic disease induced by HFD in aquatic animals.

Neurological prognostic factors for human herpes virus 6/7-associated acute encephalopathy in children: A single-center study

AimTo identify prognostic factors for severe neurological sequelae and epileptic seizures in children with human herpes virus (HHV) 6/7-associated acute encephalopathy (AE). MethodsWe retrospectively studied pediatric cases of HHV6/7-associated AE between April 2011 and March 2021. Neurological sequelae were assessed using the Pediatric Cerebral Performance Category scale (PCPC) and the presence of epileptic seizures 1 year after onset. We investigated the prognostic factors between the non-severe sequelae group (PCPC scores ≤ 2) and severe sequelae group (PCPC scores ≥ 3) in patients without severe neurological complications before onset. ResultsForty patients, ranging from 4 to 95 months old, were included. AE with biphasic seizures and late reduced diffusion were the most common types of encephalopathy (n = 28). Among the 36 patients evaluated neurological sequelae, 17, nine, eight, and two were categorized as PCPC 1, 2, 3 and 4, respectively. Epileptic seizures were observed in nine patients. In the severe sequelae group, significantly more cases with coma in the acute phase and thalamic lesions on MRI and higher serum aspartate aminotransferase, alanine aminotransferase (ALT), and lactate dehydrogenase levels were observed. Multivariate analysis showed a significant between-group difference in the rate of coma (p = 0.0405). Patients with epileptic seizures had a higher rate of coma and thalamic lesions and higher serum ALT and urinary beta 2-microglobulin levels, but there was no significant difference in the multivariate analysis. ConclusionsIn HHV6/7-associated AE, coma was a significant prognostic factor for severe neurological sequelae.

Virus Elimination by Direct-Acting Antiviral Agents Impacts Glucose Homeostasis in Chronic Hepatitis C Patients.

Background and AimsChronic hepatitis C virus (HCV) infection is associated with dysregulation of glucose homeostasis, including insulin resistance (IR) and type 2 diabetes. However, independent risk factors associated with IR in chronic HCV-infected patients have not been detailly elucidated. Previous data regarding the impact of HCV elimination by direct-acting antiviral agents (DAAs) on glucose homeostasis is insufficient and controversial. This study aimed to analyze the independent factors associated with IR and to evaluate the changes in glucose homeostasis in chronic HCV-infected patients treated with DAAs therapies.MethodsWe screened 704 patients with chronic HCV infection who underwent treatment with interferon-free DAAs. Patients’ baseline characteristics, biochemical and virological data were collected. The outcome measurements were their IR and β-cell function assessed by the homeostasis model assessment (HOMA) method at baseline and 12-weeks post-treatment.ResultsHigh IR (HOMA-IR ≥ 2.5) was observed in 35.1% of the patients. Multivariable logistic regression analysis revealed that body mass index (BMI) >25 kg/m2, treatment experience, elevated baseline levels of alanine aminotransferase (ALT) and triglyceride, as well as Fibrosis-4 score >3.25 were independently associated with high IR. In patients who achieved sustained virological response (SVR), no significant change in mean HOMA-IR was observed from baseline to 12-weeks post-treatment (2.74 ± 2.78 to 2.54 ± 2.20, p = 0.128). We observed a significant improvement in β-cell secretion stress from 121.0 ± 110.1 to 107.6 ± 93.0 (p = 0.015). Subgroup analysis revealed that SVR was associated with a significant reduction in mean HOMA-IR in patients with baseline HOMA-IR ≥ 2.5 (5.31 ± 3.39 to 3.68 ± 2.57, p < 0.001), HCV genotype 1 (3.05 ± 3.11 to 2.62 ± 2.05, p = 0.027), and treatment experience (4.00 ± 3.37 to 3.01 ± 2.49, p = 0.039).ConclusionsThere were several independent factors associated with IR in patients with chronic HCV infection, including obesity, treatment experience, high serum ALT and triglyceride levels, as well as advanced hepatic fibrosis. After viral elimination by DAAs, we observed a significant reduction in mean HOMA-IR in patients with baseline high IR, HCV genotype 1, and treatment experience.

The protective effect of boric acid on cholestatic rat liver ischemia reperfusion injury.

Background/aim To evaluate the potential protective effects of boric acid (BA) in experimental cholestatic liver ischemia reperfusion (IR) injury model.Materials and methods The study included 24 female rats which were divided into 3 groups each containing 8 rats. The control group (Group 1) only received laparotomy. In the IR group (Group 2) biliary tract ligation was applied and 1 week later 45 min ischemia and 1 h reperfusion with relaparotomy without any treatment was implemented. In the treatment BA+IR group (Group 3). 1 week after the biliary ligation intraperitoneal administration of 200 mg/kg BA was given 10 min before the ischemia for 45 min and reperfusion for 1 h with relaparotomy. Liver tissue and blood samples were taken for histopathological and biochemical examination. Ischemia modified albumin (IMA), SCUBE1, total antioxidant status (TAS), and total oxidant status (TOS) levels were also examined.Results Compared to control, groups IR and BA+IR had higher serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total, and direct bilirubin levels. Albumin value was high in the control group and low in the other groups. In terms of IMA levels there was no significant difference between groups (p > 0.05). When SCUBE-1 levels were examined groups IR and BA+IR were significantly higher than the group 1. TAS was highest in the group BA+IR whereas TOS was highest in the group IR and lower in the group BA+IR. In histopathological analysis, loss of intercellular border loss in hepatocytes, diffuse nuclear pycnosis and mild to moderate neutrophilic cell infiltration were observed in the IR group. Statistically significant dissociation, hemorrhage and severe neutrophilic cell infiltration were seen in hepatocytes of rats with IR (p < 0.05). Conclusion BA has promising results in the treatment of experimental IR injury of the cholestatic liver because of its antioxidant effects. It may be used in clinical practice after more extensive studies about the effects of BA on IR injury of the cholestatic liver.

Higher hemoglobin levels are an independent risk factor for adverse metabolism and higher mortality in a 20-year follow-up

The aim of this study was to cross-sectionally and longitudinally examine whether higher hemoglobin (Hb) levels within the normal variation associate with key components of metabolic syndrome and total and cardiovascular mortality. The study included 967 Finnish subjects (age 40–59 years) followed for ≥ 20 years. The focus was on Hb levels, cardiovascular diseases (CVDs) and mortality rates. Higher Hb levels associated positively with key anthropometric and metabolic parameters at baseline. At the follow-up similar associations were seen in men. The highest Hb quartile showed higher leptin levels and lower adiponectin levels at baseline and follow-up (p < 0.05) and lower plasma ghrelin levels at baseline (p < 0.05). Higher baseline Hb levels associated independently with prevalence of type 2 diabetes at follow-up (p < 0.01). The highest Hb quartile associated with higher serum alanine aminotransferase levels (p < 0.001) and independently with increased risk for liver fat accumulation (OR 1.63 [1.03; 2.57]) at baseline. The highest Hb quartile showed increased risk for total (HR = 1.48 [1.01; 2.16]) and CVD-related mortality (HR = 2.08 [1.01; 4.29]). Higher Hb levels associated with an adverse metabolic profile, increased prevalence of key components of metabolic syndrome and higher risk for CVD-related and total mortality.

Allele-specific variation at APOE increases nonalcoholic fatty liver disease and obesity but decreases risk of Alzheimer's disease and myocardial infarction.

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is highly correlated with metabolic disease. NAFLD results from environmental exposures acting on a susceptible polygenic background. This study performed the largest multiethnic investigation of exonic variation associated with NAFLD and correlated metabolic traits and diseases. An exome array meta-analysis was carried out among eight multiethnic population-based cohorts (n = 16 492) with computed tomography (CT) measured hepatic steatosis. A fixed effects meta-analysis identified five exome-wide significant loci (P < 5.30 × 10-7); including a novel signal near TOMM40/APOE. Joint analysis of TOMM40/APOE variants revealed the TOMM40 signal was attributed to APOE rs429358-T; APOE rs7412 was not associated with liver attenuation. Moreover, rs429358-T was associated with higher serum alanine aminotransferase, liver steatosis, cirrhosis, triglycerides and obesity; as well as, lower cholesterol and decreased risk of myocardial infarction and Alzheimer's disease (AD) in phenome-wide association analyses in the Michigan Genomics Initiative, United Kingdom Biobank and/or public datasets. These results implicate APOE in imaging-based identification of NAFLD. This association may or may not translate to nonalcoholic steatohepatitis; however, these results indicate a significant association with advanced liver disease and hepatic cirrhosis. These findings highlight allelic heterogeneity at the APOE locus and demonstrate an inverse link between NAFLD and AD at the exome level in the largest analysis to date.

The Pediatric Obesity Microbiome and Metabolism Study (POMMS): Methods, Baseline Data, and Early Insights.

The purpose of this study was to establish a biorepository of clinical, metabolomic, and microbiome samples from adolescents with obesity as they undergo lifestyle modification. A total of 223 adolescents aged 10 to 18 years with BMI ≥95th percentile were enrolled, along with 71 healthy weight participants. Clinical data, fasting serum, and fecal samples were collected at repeated intervals over 6 months. Herein, the study design, data collection methods, and interim analysis-including targeted serum metabolite measurements and fecal 16S ribosomal RNA gene amplicon sequencing among adolescents with obesity (n = 27) and healthy weight controls (n = 27)-are presented. Adolescents with obesity have higher serum alanine aminotransferase, C-reactive protein, and glycated hemoglobin, and they have lower high-density lipoprotein cholesterol when compared with healthy weight controls. Metabolomics revealed differences in branched-chain amino acid-related metabolites. Also observed was a differential abundance of specific microbial taxa and lower species diversity among adolescents with obesity when compared with the healthy weight group. The Pediatric Metabolism and Microbiome Study (POMMS) biorepository is available as a shared resource. Early findings suggest evidence of a metabolic signature of obesity unique to adolescents, along with confirmation of previously reported findings that describe metabolic and microbiome markers of obesity.

Stress responses of Indian major carps cultured in the East Kolkata Wetland, West Bengal, India

Fish are continuously exposed to multiple environmental stressors that work cumulatively and synergistically. This study assessed the stress responses of Indian major carps (IMCs) cultured in a sewage-fed pond (SP) in the East Kolkata Wetland (EKW), India and compared with the normal carps in situ. The experiment was conducted in two farms that cultured Labeo rohita, Catla catla and Cirrhinus mrigala for seven months, covering the summer and winter periods. Serum biomarkers of primary (cortisol) and secondary (glucose, total protein, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH)) stress responses, and oxidative stress (superoxide dismutase (SOD)) were quantified using standard kits. The health status of carps was evaluated as a tertiary response. The biological oxygen demand, hardness, total dissolved solids, ammonia and phosphate levels of both ponds exhibited marked variations. The SP carps had significantly low haemoglobin and total protein, and high serum glucose, creatinine, ALT, AST and LDH levels. The SOD and cortisol levels were comparatively low in SP carps. The winter temperature had a significant effect on serum glucose, cortisol, SOD, creatinine, ALT and AST. Carps had a high degree of ectoparasitic infestation during the winter. Cirrhinus mrigala of the SP had significantly high serum creatinine levels. The increasing levels of serum glucose, creatinine, ALT and AST suggested that these indices, which were more pronounced in the carps of EKW in conjunction with winter temperature, could be useful biomarkers of stress, kidney and liver functioning in carps, respectively.

Profiles of liver function abnormalities in elderly patients with Coronavirus Disease 2019.

BackgroundThe profiles of liver function abnormalities in COVID‐19 patients need to be clarified.MethodsIn this retrospective study, consecutive COVID‐19 patients over 60 years old in Renmin Hospital of Wuhan University from January 1 to February 6 were included. Data of demographics, clinical characteristics, comorbidities, laboratory tests, medications and outcomes were collected and analysed. Sequential alterations of serum alanine aminotransferase (ALT) were monitored.ResultsA total of 330 patients were included and classified into two groups with normal (n = 234) or elevated ALT (n = 96). There were fewer females (40.6% vs 54.7%, P = .020) and more critical cases (30.2% vs 19.2%, P = .026) in patients with elevated ALT compared with the normal group. Higher levels of bacterial infection indices (eg, white blood cell count, neutrophil count, C‐reactive protein and procalcitonin) were observed in the elevated group. Spearman correlation showed that both ALT and AST levels were positively correlated with those indices of bacterial infection. No obvious effects of medications on ALT abnormalities were found. In patients with elevated ALT, most ALT elevations were mild and transient. 59.4% of the patients had ALT concentrations of 41‐100 U/L, while only a few patients (5.2%) had high serum ALT concentrations above 300 U/L. ALT elevations occurred at 13 (10‐17) days and recovered at 28 (18‐35) days from disease onset. For most patients, the elevation of serum ALT levels occurred at 6‐20 days after disease onset and reached their peak values within a similar time frame. The recovery of serum ALT levels to normal frequently occurred at 16‐20 days or 31‐35 days after disease onset.ConclusionsLiver function abnormalities were observed in 29.1% of elderly people COVID‐19 patients, which were slightly and transient in most cases. Liver function abnormalities in COVID‐19 may be correlated with bacterial infection.

Relation between GSTP1 polymorphism and oxidative stress in patients with hepatocellular carcinoma

BackgroundGlutathione can reduce the oxidative stress by converting the unstable to stable molecules and its status in hepatocellular carcinoma (HCC) is correlated with tumor growth and metastasis.Glutathione S-transferase Pi (GSTP1) is reported to detoxify the xenobiotic substrates by catalyzing their conjugation to reduced glutathione (GSH) and its over-expression was demonstrated in the early stages of HCC, while loss of GSTP1 has been suggested to increase the risk of deoxyribonucleic acid (DNA) damage and mutation.The aim of this study is to assess the relationship of GSTP1 polymorphism Ile105Val (rs1695 A > G) with HCC risk, and to investigate the oxidative stress status of HCC patients by measuring the antioxidant glutathione (GSH) levels.This study was conducted on 99 newly diagnosed HCC patients and 80 apparently healthy individuals as a normal control group.All participants were subjected to the measurement of plasma GSH levels according to Ellman’s method, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the detection of GSTP1 polymorphismIle105Val (rs1695 A > G).ResultsThe occurrence of either the mutant homozygous or the mutant heterozygous genotype of GSTP1 was significantly higher in HCC patients, while the occurrence of the wild genotype was significantly higher among the normal control subjects.Mutant GSTP1 genotype, older age, male gender, and high serum alanine aminotransferase (ALT) were associated with increased risk of development of HCC.The best sensitivity, specificity, PPV (positive predictive value), NPV (negative predictive value), and overall diagnostic performance for plasma GSH at a cutoff level of 2003.5 μM/mg were 57.6%, 52.5%, 60%, and 40%. The area under the curve for GSH was 0.562.ConclusionMutant GSTP1 genotype was an independent prognostic factor for increased HCC risk which can be used in a risk assessment model for HCC.Plasma GSH presents insufficient sensitivity and specificity for HCC.

Inhibition of Carnitine Palmitoyltransferase 1A Aggravates Fatty Liver Graft Injury via Promoting Mitochondrial Permeability Transition.

Hepatic steatosis is a major risk factor for graft failure due to increased susceptibility of fatty liver to ischemia-reperfusion injury (IRI) during transplantation. Here, we aimed to investigate the role of carnitine palmitoyltransferase 1A (CPT1A) in fatty liver graft injury and to explore the underlying mechanism and therapeutic potential on attenuating hepatic IRI. Intragraft CPT1A expression profile and the association with fatty graft injury were investigated in human and rat liver transplantation samples. The underlying mechanism and therapeutic potential of CPT1A activator against IRI were also explored in mouse hepatic ischemia-reperfusion plus major hepatectomy model and in in vitro. CPT1A expression was significantly reduced (P = 0.0019; n = 96) in human fatty liver graft compared with normal one at early phase after transplantation. Low expression of CPT1A was significantly associated with high serum alanine aminotransferase (P = 0.0144) and aspartate aminotransferase (P = 0.0060) levels. The inhibited CPT1A and poor liver function were consistently observed in rat and mouse models with fatty livers. Furthermore, inhibition of CPT1A significantly promoted the translocation of chloride intracellular channel 1 to form chloride ion channel. The dysregulation of chloride ion channel activity subsequently triggered mitochondrial permeability transition (MPT) pore opening, exacerbated cellular oxidative stress, and energy depletion. Importantly, our intravital confocal imaging showed that CPT1A activation attenuated hepatic injury through preventing MPT after reperfusion in fatty mice. CPT1A inhibition triggered MPT contributed to severe IRI in fatty liver graft. CPT1A restoration may offer therapeutic potential on attenuating hepatic IRI.

Longitudinal changes in insulin resistance in children with epilepsy on ketogenic diet: Prevalence and risk factors

IntroductionThe aim of the study was to evaluate the incidence of insulin resistance (IR) and the associated risk factors in children with epilepsy on a ketogenic diet (KD). MethodsThis longitudinal cohort study analyzed data of children with epilepsy on KD. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). The HOMA-IR value, fasting serum insulin levels, fasting glucose (FG) levels, and lipid profiles were measured before the initiation of the KD and at 6- to 12-month intervals. ResultsA total of 28 children were enrolled. The median age at the initiation of KD was 2.7 ± 2.4 years, and the median follow-up duration was 2.1 ± 1.4 years. The median HOMA-IR (HOMA-IR-1) value before the initiation of KD was 1.2 ± 0.2, which significantly increased to 1.8 ± 0.3 at the last follow-up (HOMA-IR-2; ∆HOMA-IR = 0.6 ± 0.3, p < 0.001). The following factors were associated with patients with higher HOMA-IR-2 values (≥1.9): younger age at seizure onset (0.3 ± 0.2 years, p < 0.001), at the initiation of antiepileptic drugs (AEDs; 0.3 ± 0.3 years, p < 0.001), and at the initiation of KD (1.3 ± 0.5 years, p < 0.001) and higher serum alanine transaminase (ALT; 84.0 ± 17.8 U/L, p = 0.022), total cholesterol (TC; 245.0 ± 20.1 mg/dL, p = 0.001), low-density lipoprotein cholesterol (LDL-C, 103.0 ± 6.7 mg/dL, p = 0.003), and triglyceride (387.0 ± 28.8 mg/dL, p < 0.001) levels. Multivariate regression analysis revealed that the age at seizure onset (p = 0.002), at initiation of AEDs (p = 0.021), and at initiation of KD (p = 0.022) and serum levels of LDL-C (p = 0.012) and triglycerides (p = 0.026) were associated with a significantly high HOMA-IR-2 value. ConclusionClose monitoring of serum lipids levels, especially at younger age, may aid in detecting exacerbation of IR.

Chronic Carbon Tetrachloride Applications Induced Hepatocyte Apoptosis in Lipocalin 2 Null Mice Through Endoplasmic Reticulum Stress and Unfolded Protein Response.

The lack of Lipocalin (LCN2) provokes overwhelming endoplasmic reticulum (ER) stress responses in vitro and in acute toxic liver injury models, resulting in hepatocyte apoptosis. LCN2 is an acute phase protein produced in hepatocytes in response to acute liver injuries. In line with these findings we investigated ER stress responses of Lcn2−/− mice in chronic ER stress using a long-term repetitive carbon tetrachloride (CCl4) injection model. We found chronic CCl4 application to enhance ER stress and unfolded protein responses (UPR), including phosphorylation of eukaryotic initiation factor 2α (eIF2α), increased expression of binding immunoglobulin protein (BiP) and glucose-regulated protein 94 (GRP94). IRE1α/TRAF2/JNK signaling enhanced mitochondrial apoptotic pathways, and showed slightly higher in Lcn2−/− mice compared to the wild type counterparts, leading to increased hepatocyte apoptosis well evidenced by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Hepatocyte injuries were confirmed by significant high serum alanine transaminase (ALT) levels in CCl4-treated Lcn2−/− mice. Lcn2−/− mice furthermore developed mild hepatic steatosis, supporting our finding that ER stress promotes lipogenesis. In a previous report we demonstrated that the pharmacological agent tunicamycin (TM) induced ER stress through altered protein glycosylation and induced high amounts of C/EBP-homologous protein (CHOP), resulting in hepatocyte apoptosis. We compared TM-induced ER stress in wild type, Lcn2−/−, and Chop null (Chop−/−) primary hepatocytes and found Chop−/− hepatocytes to attenuate ER stress responses and resist ER stress-induced hepatocyte apoptosis through canonical eIF2α/GADD34 signaling, inhibiting protein synthesis. Unexpectedly, in later stages of TM incubation, Chop−/− hepatocytes resumed activation of IRE1α/JNK/c-Jun and p38/ATF2 signaling, leading to late hepatocyte apoptosis. This interesting observation indicates Chop−/− mice to be unable to absolutely prevent all types of liver injury, while LCN2 protects the hepatocytes by maintaining homeostasis under ER stress conditions.