Serum Liver Enzyme Activities Research Articles

The ameliorating effect of Rutin on hepatotoxicity and inflammation induced by the daily administration of vortioxetine in rats

BackgroundVortioxetine (VORTX) is a potent and selective type of selective serotonin reuptake inhibitor (SSRI) that is mainly prescribed for treating major depression along with mood disorders as the first drug of choice. Limited previous findings have indicated evidence of liver injury and hepatotoxicity associated with daily VORTX treatment. Rutin (RUT), which is known for its antioxidant properties, has demonstrated several beneficial health actions, including hepatoprotection. Therefore the current study aimed to evaluate and assess the ameliorative effect of RUT against the hepatotoxic actions of daily low and high-dose VORTX administration.MethodsThe experimental design included six groups of rats, each divided equally. Control, rats exposed to RUT (25 mg/kg), rats exposed to VORTX (28 mg/kg), rats exposed to VORTX (28 mg/kg) + RUT (25 mg/kg), rats exposed to VORTX (80 mg/kg), and rats exposed to VORTX (80 mg/kg) + RUT (25 mg/kg). After 30 days from the daily exposure period, assessments were conducted for serum liver enzyme activities, hepatotoxicity biomarkers, liver antioxidant endogenous enzymes, DNA fragmentation, and histopathological studies of liver tissue.ResultsInterestingly, the risk of liver damage and hepatotoxicity related to VORTX was attenuated by the daily co-administration of RUT. Significant improvements were observed among all detected liver functions, oxidative stress, and inflammatory biomarkers including aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), albumin, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), glutathione S-transferase (GST), total protein, acid phosphatase, N-Acetyl-/β-glucosaminidase (β-NAG), β-Galactosidase (β-Gal), alpha-fetoprotein (AFP), caspase 3, and cytochrom-C along with histopathological studies, compared to the control and sole RUT group.ConclusionThus, RUT can be considered a potential and effective complementary therapy in preventing hepatotoxicity and liver injury induced by the daily or prolonged administration of VORTX.

Efficacy and Safety of Bempedoic Acid in Patients with High Cardiovascular Risk: An Update.

Statins play a significant role in the prevention of cardiovascular (CV) diseases (CVDs); however, non-adherence with statin treatment or statin intolerance (mainly attributed to muscleassociated side effects) is not uncommon. New agents such as bempedoic acid (BA) can provide more treatment options. BA is administered orally, once daily, at a dose of 180 mg in current clinical practice. It can decrease circulating low-density lipoprotein cholesterol (LDL-C) levels by nearly 30% as monotherapy or by 20% as an add-on to statins. CV outcome studies have shown that BA decreases major adverse CV event risk in patients with established CVD or high CV risk by 13%. When patients with high CV risk were analyzed alone, the risk reduction was 30%. Its side effects include a rise in serum uric acid levels and liver enzyme activity, whereas it does not increase diabetes risk as statins do. BA can be used as adjunctive therapy to statins in patients at high CV risk in whom lipid targets cannot be achieved or as an alternative to statins in patients with statin intolerance.

Sulforaphane Is Protective against Warm Ischemia/Reperfusion Injury and Partial Hepatectomy in Rats.

Sulforaphane (SFN) has various beneficial effects on organ metabolism. However, whether SFN affects inflammatory mediators induced by warm hepatic ischemia/reperfusion injury (HIRI) is unclear. To investigate the hepatoprotective effects of SFN using an in vivo model of HIRI and partial hepatectomy (HIRI + PH), rats were subjected to 15 min of hepatic ischemia with blood inflow occlusion, followed by 70% hepatectomy and release of the inflow occlusion. SFN (5 mg/kg) or saline was randomly injected intraperitoneally 1 and 24 h before ischemia. Alternatively, ischemia was prolonged for 30 min to evaluate the effect on mortality. The influence of SFN on the associated signaling pathways was analyzed using the interleukin 1β (IL-1β)-treated primary cultured rat hepatocytes. In the HIRI + PH-treated rats, SFN reduced serum liver enzyme activities and the frequency of pathological liver injury, such as apoptosis and neutrophil infiltration. SFN suppressed tumor necrosis factor-alpha (TNF-α) mRNA expression and inhibited nuclear factor-kappa B (NF-κB) activation by HIRI + PH. Mortality was significantly reduced by SFN. In IL-1β-treated hepatocytes, SFN suppressed the expression of inflammatory cytokines and NF-κB activation. Taken together, SFN may have hepatoprotective effects in HIRI + PH in part by inhibiting the induction of inflammatory mediators, such as TNF-α, via the suppression of NF-κB in hepatocytes.

Evaluation of biochemical parameters in operating room staff exposed to radiation and anesthetic gases.

Exposure to ionizing radiations and other hazardous agents such as anesthetic gases pose serious risks to the health of healthcare workers. This study aimed to evaluate the changes in blood and biochemical parameters of the operating room staff exposed to ionizing radiations and remnants of anesthetic gas. This cross-sectional study was performed at (Ayatollah Taleghani Hospital). The control group was selected from different parts of the hospital that were not exposed to ionizing radiations and anesthetics, including the office, services, and treatment. The case group included all operating room personnel. Hematopoietic parameters such as complete blood count and WBC differential, and parameters of liver function such as serum activity of liver enzymes (ALT, AST, ALP, LDH) and serum bilirubin levels, fasting blood sugar, serum lipid profile, level of vitamin D and magnesium were measured for the exposed and referent subjects. Additionally, a checklist was used to gather data regarding the occupational variables and medical histories of the studied subjects. The mean values of Hb, Hct, Vitamin D, and MCHC, as well as the RBC count, were significantly lower in the exposed individuals than in the referent subjects. In contrast, the proportion of smokers was significantly higher in the exposed group than in the referent group. No significant differences were noted between exposed and unexposed groups as far as other parameters were concerned. However, no significant differences were noted between the case and control groups as far as other measured parameters were concerned. Likewise, no significant differences were noted between exposed and referent groups as far as blood types, history of underlying diseases, work history, working hours per month, number of morning and evening shift hours, type of diet, consumption of a high-fat diet a day before blood sampling, X-ray in the recent year, history of radiotherapy, and therapeutic agents use was concerned. Exposure of operating room staff to ionizing radiations and waste anesthetics gases is associated with subtle, subclinical prepathologic decreases in some hematopoietic parameters such as hemoglobin, hematocrit and MCHC levels, RBC count as well as vitamin D levels.

Serum Bile Acids Concentrations and Liver Enzyme Activities after Low-Dose Trilostane in Dogs with Hyperadrenocorticism.

Hyperadrenocorticism (HAC) often leads to vacuolar hepatopathy. The impact of trilostane treatment on serum total bile acids (SBAs) concentrations in dogs with HAC remains unknown. This study investigated SBAs concentrations in healthy dogs and those with HAC following trilostane therapy. Ten healthy dogs and fifteen dogs with HAC were prospectively enrolled. A biochemistry profile and pre- and post-prandial SBAs concentrations were determined in each dog. Dogs with HAC were reassessed at 1 and 3 months after the initiation of trilostane treatment. Dogs with HAC had significantly higher serum ALT, ALP, and GGT activities, and cholesterol, triglyceride, and pre-prandial SBAs concentrations compared to healthy dogs. After 3 months of trilostane treatment, polyuria/polydipsia and polyphagia were completely resolved in 42.8% and 35.7%, respectively. Significant improvements in serum ALT and ALP activities and cholesterol concentrations were observed within 1-3 months of trilostane treatment. However, pre- and post-prandial SBAs concentrations did not significantly decrease. These findings suggest that treatment with low-dose trilostane for 3 months appears to reduce serum liver enzyme activities, but not SBAs concentrations. Further investigation is warranted to explore the effects of low-dose trilostane treatment on SBAs concentrations for a longer duration or after achieving appropriate post-ACTH cortisol levels.

Lutein Modulates Oxidative Stress, Inflammatory and Apoptotic Biomarkers Related to Di-(2-Ethylhexyl) Phthalate (DEHP) Hepato-Nephrotoxicity in Male Rats: Role of Nuclear Factor Kappa B.

Phthalates are widely distributed in our environment due to their usage in many industries, especially in plastic production, which has become an essential part of daily life. This investigation aimed to assess the potential remedial influence of lutein, a naturally occurring carotenoid, on phthalate-triggered damage to the liver and kidneys. When di-(2-ethylhexyl) phthalate (DEHP) was administered to male albino rats over sixty straight days at a dosage of 200 mg/kg body weight, it resulted in a significant increase in the serum activity of liver enzymes (AST, ALT, and GGT), alpha-fetoprotein, creatinine, and cystatin-C, as well as disruptions in the serum protein profile. In addition, intoxication with DEHP affected hepato-renal tissues' redox balance. It increased the content of some proinflammatory cytokines, nuclear factor kappa B (Nf-κB), and apoptotic marker (caspase-3); likewise, DEHP-induced toxicity and decreased the level of anti-apoptotic protein (Bcl-2) in these tissues. Lutein administration at a dose level of 40 mg/kg b.w efficiently facilitated the changes in serum biochemical constituents, hepato-renal oxidative disturbance, and inflammatory, apoptotic, and histopathological alterations induced by DEHP intoxication. In conclusion, it can be presumed that lutein is protective as a natural carotenoid against DEHP toxicity.

Candida albicans cholecystitis in a dog with diabetes mellitus

AbstractA 10‐year‐old, 8.9‐kg, spayed, female Jack Russell Terrier, with previously well‐controlled diabetes mellitus, presented with hyporexia of 2‐day duration. Cranial abdominal pain and weight loss were detected on clinical examination. Blood tests, urinalysis, urine protein:creatinine ratio, blood pressure, abdominal ultrasound and liver aspirate cytology revealed hyperglycaemia, elevated serum liver enzyme activities, glucosuria, proteinuria, hypertension, rounded liver edges, irregular hyperechoic gall bladder wall thickening, irregular hyperechoic gall bladder content and vacuolar hepatopathy. Bile cytological examination demonstrated fungal organisms, which were identified as Candida albicans on bile fungal culture. No bacteria were detected on bile cytological examination or bile bacterial aerobic and anaerobic culture. The dog was diagnosed with Candida albicans cholecystitis and recovered after a 12‐week course of oral ketoconazole. This case report highlights the value of performing bile cytology in suspect canine cholecystitis cases and is the first to describe Candida albicans fungal cholecystitis without bacterial coinfection in dogs.

In-vitro and in-vivo antibacterial activity of potential probiotic Lactobacillus paracasei against Staphylococcus aureus and Escherichia coli

Previous studies documented that Lactobacillus paracasei has obvious in vitro cholesterol-lowering abilities. In this study, initially, L. paracasei was tested in terms of antibacterial properties as well as antibiogram profile. Then, the safety of the mentioned strain was evaluated in rats. Evaluation of antibiotic susceptibility revealed that the L. paracasei strain had high antibiotic resistance to several antibiotics as well as a great ability to autoaggregation. After identification of the probiotic aptitude, six groups of six rats from both sexes were used (three groups of each sex). L. paracasei was administered to the experimental groups via drinking water for 28 days (1 × 108 and 1 × 109, respectively). The negative control group received only tap water during this period. Hematological indicators, serum liver enzyme activity including (alanine transaminase (ALT), alkaline phosphatase (ALP), and aspartate transaminase (AST)) as well as serum creatinine and urea were evaluated at the end of 28 days. The blood and serum factors were not changed significantly during the 28 days. The only noticeable difference was the increase of blood urea in both sexes which was in a normal range. Furthermore, the evaluation of antagonistic properties revealed that L. paracasei had antibacterial aptitude against Escherichia coli and Staphylococcus aureus. In conclusion, this strain has good cholesterol-lowering and antibacterial properties and is a safe supplement in Wistar rats.

Supplementation with sesame oil suppresses genotoxicity, hepatotoxicity and enterotoxicity induced by sodium arsenite in rats

BackgroundSesame oil, an edible essential oil, is known to be rich in unsaturated fatty acids, vitamins and lignans with several reported health-promoting benefits. Acute arsenic poisoning produces toxic hepatitis, bone marrow depression and adverse gastrointestinal responses. In this study, we investigated the protective effect of sesame seed oil (SSO) against genotoxicity, hepatotoxicity and colonic toxicity induced by sodium arsenite (SA) in Wistar rats.MethodsTwenty-eight male Wistar albino rats were randomly allocated into four groups: control, SA only (2.5 mg/kg), SA + SSO (4 ml/kg) and SSO alone for eight consecutive days. Liver function and morphology, bone marrow micronuclei induction, colonic histopathology, mucus production and immune expression of Bcl-2, carcinoembryonic antigen (CEA), MUC1 and cytokeratins AE1/AE3 were evaluated.ResultsSA provoked increased serum activities of liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and caused severely altered morphology of hepatic and colonic tissues with increased frequency of micronucleated polychromatic erythrocytes (MnPCEs/1000PCE) in the bone marrow. In addition, SA triggered increased expression of colonic CEA and MUC1 but weak Bcl-2 immunoexpression. However, cotreatment with SSO demonstrated protective activities against SA-induced damage, as indicated by significantly reduced serum ALT and AST, fewer micronucleated bone marrow erythrocytes and well-preserved hepatic and colonic morphologies compared to the SA-treated rats. Furthermore, SSO protected the colonic mucosa by boosting mucus production, elevating anti-apoptotic Bcl-2 expression and reducing CEA expression. GC–MS analysis of SSO revealed that it was predominated by linoleic acid, an omega-3 fatty acid, and tocopherols.ConclusionsOur data indicated that SSO protected the liver, colon and bone marrow potentially via anti-inflammatory and anti-apoptotic activities. The data suggest that sesame oil has potential therapeutic applications against chemical toxicities induced by arsenic.

The Impact of Chitosan on Oxidative Stress in Liver of Rats Loaded With Lead Acetate

This study was conducted to determine the impact of chitosan on lead (Pb)-induced hepatotoxicity. Thus, lead acetate was administered intraperitoneally (50 mg/kg for 5 days) and chitosan was given as 200 mg/kg via oral gavage for 28 days. When the trial was terminated, it was determined that aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities in serum as well as Pb, 8-hydroxy-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) levels and catalase (CAT) activity in liver tissue significantly increased, however reduced glutathione (GSH) and ceruloplasmin (Cp) levels in liver and high density lipoproteins (HDL) in serum had a significant decrease in the Pb group when compared to the control group. The administration of chitosan significantly prevented Pb-induced changes in serum liver enzyme activities, 8-OHdG and MDA levels. In addition, chitosan showed a statistically insignificant effect on reduced GSH, Cp, HDL levels and CAT activity. Accordingly, administration of chitosan can strengthen the antioxidant defence system of liver tissue and may decrease oxidative stress.

Ethanolic leaf extract ofDatura stramoniumattenuates methotrexate-induced biochemical alterations in Wistar Albino rats

AbstractObjectivesMethotrexate (MTX) is a commonly used anti-cancer drug. However, its usage could lead to various biochemical dysregulations culminating in organ toxicity. Globally, most plant products have been used for the treatment of several diseases. Thus, we investigated the effect of Datura stramonium ethanolic leaf extract (DSELE) supplementation in MXT-induced biochemical alterations in rats.MethodsRats were divided into four groups: Group 1 received normal saline (5 mg/kg b. w), Group 2 received DSELE (200 mg/kg), Group 3 received 20 mg/kg MXT while rats in Group 4 received 200 mg/kg + MTX 20 mg/kg. Normal saline and DSELE were administered per os for 21 days while MXT single injection was given intraperitoneally on day 18 and the rats were sacrificed after 3 days. Thereafter, biochemical parameters were evaluated.Key findingsMTX caused a significant (P < 0.05) increase in serum activities of liver enzymes (AST, ALT and ALP) and levels of total cholesterol and low-density lipoprotein while the levels of total protein and albumin decreased significantly relative to the normal control. Interestingly, DSELE administration favourably modulated MXT-induced biochemical alterations to levels comparable to normal control.ConclusionsDSELE can be a useful combinatorial natural product in MTX chemotherapy since it mitigates MXT-induced biochemical alterations in rats.

Nutritional Components, Biochemical Characteristics, Enzyme Activities, and Growth Differences of Five Freshwater Fish Species?

Common carp (Cyprinus carpio) is an economically important fish worldwide, with many of its species bred for consumption. However, there are few reports on the comprehensive comparative analysis of the muscle nutritional quality and stress resistance characteristics of different common carp species. In this study, after 15 months of feeding in the same environment, the nutritional components, serum biochemical indices, liver antioxidant and intestinal digestive enzyme activities, and muscle growth-related gene expression were determined in Songpu mirror carp (SPM; Cyprinus carpio Songpumirror), Heilongjiang wild carp (HLJ; Cyprinus carpio haematopirus), cold-resistant strain of purse red carp (CPR; Cyprinus carpio ‘Red purse cold-resistant’), Songhe carp (SH; Cyprinus carpio ‘Songhe’), and Songpu carp (SP; Cyprinus carpio Songpu). Muscle nutrient composition showed that HLJ had a significantly lower crude fat content and higher docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) proportion than the other four common carp species (p < 0.05). The contents of lysine (Lys) and aspargine (Asp) were significantly higher in the CPR than in other species (p < 0.05). Serum biochemical parameters showed that total protein (TP), total cholesterol (T-CHO), triglycerides (TG), and low-density lipoprotein (LDL) were significantly lower in SPM than in the other species (p < 0.05). The results of tissue enzyme activity showed that the activities of superoxide dismutase (SOD) and catalase from Micrococcus lysodeikticus (CAT) in the liver were significantly higher, while the activities of lipase (LPS), trypsin (TRS), and α-amylase (α-AMS) in the intestine were significantly the lower in HLJ than in the other species (p < 0.05). In addition, the relative expression levels of growth hormone (GH), growth hormone receptor (GHR), insulin-like growth factor 1 (IGF1), insulin-like growth factor receptor (IGF1R), and myoblast determination factor (MyoD) in SP and SH were significantly higher than those in the other species, while the relative expression of myostatin (MSTN) in HLJ was significantly higher (p < 0.05). Therefore, there were significant differences in muscle nutritional quality, serum biochemical indices, liver, and intestinal enzyme activities, and muscle growth potential among the five species of common carp. This study could provide a theoretical basis for the germplasm evaluation and variety improvement of common carp.

Correlations between Cytokine Levels, Liver Function Markers, and Neuropilin-1 Expression in Patients with COVID-19.

Aim: The study evaluated the correlations between cytokine levels, liver function markers, and neuropilin-1 (NRP-1) expression in patients with COVID-19 in Egypt. The study also aimed to evaluate the accuracy sensitivity, specificity, and area under the curve (AUC) of the tested laboratory parameters in identifying COVID-19 infection and its severity. Patients and Methods: Fifty healthy subjects and 100 confirmed patients with COVID-19 were included in this study. COVID-19 patients were separated into two groups based on the severity of their symptoms. Serum ALT, AST, albumin, C-reactive protein (CRP), interleukin (IL)-1β, IL-4, IL-6, IL-18, IL-35, prostaglandin E2 (PGE2), and thromboxane A2 (TXA2) were estimated. We measured the gene expression for nuclear factor-kappa B p50 (NF-κB p50) and nuclear factor-kappa B p65 (NF-κB p65) and NRP-1 in blood samples using quantitative real-time polymerase chain reaction (qRT-PCR). AUC and sensitivity and specificity for cytokine levels and NF-κB p50 and NF-κB p65 and NRP-1 in identifying COVID-19 infection were also determined in both moderate and severe patient groups using receiver-operating characteristic curve (ROC) analysis. Results: All patients with COVID-19 showed higher serum activities of liver enzymes, levels of CRP, IL-1β, IL-4, IL-6, IL-18, IL-35 PGE2, and TXA2, and mRNA expression of NF-κB p50, NF-κB p65, and NRP-1 than healthy subjects. The severe group exhibited a significant increase in serum ALT, AST and IL-6 and a significant decrease in albumin, IL-1β, TXA2, and NF-κB p65 levels compared to the moderate group. In all patients (moderate and severe), all cytokines were positively correlated with NF-κB p50, NF-κB p65 and NRP-1 expression levels. Serum ALT and AST were positively correlated with CRP, cytokines (IL-4, IL-6, IL-18, IL-35 and TXA2), and NF-κB p50 and NF-κB p65 expression levels in both moderate and severe groups. They were also positively correlated with serum IL-1β level in the severe COVID-19 patient group and with NRP-1 expression in the moderate group. Using the logistic regression analysis, the most important four statistically significant predictors associated with COVID-19 infection in the study were found to be IL-6, TAX2, NF-κB p50 and NF-κB p65. ROC analysis of these variables revealed that three of them had AUC > 0.8. In moderate cases, AUC of the serum TXA2 level and NF-κB p65 expression were 0.843 (95% CI 0.517–0.742, p < 0.001) and 0.806 (95% CI 0.739–0.874, p < 0.001), respectively. In the severe group, AUC of serum IL-6 level was 0.844 (95% CI 0.783–0.904, p < 0.001). Moreover, Il-6 had a sensitivity of 100% in both moderate and severe groups. Conclusions: This study concluded that liver injury in patients with COVID-19 may be strongly attributed to the cytokines storm, especially IL-6, which was positively correlated to NF-κB p50, NF-κB p65 and NRP-1 mRNA expression levels. Moreover, ROC analysis revealed that IL-6, TXA2, and NF-κB p65 could be useful in predicting the possibility of infection with COVID-19, and IL-6 could be of possible significance as a good predictor of the severity and disease progress. However, RT-qPCR for SARS-CoV-2 detection is essential to confirm infection and further clinical studies are required to confirm this elucidation.

Effect of COVID-19 on Serum Activity of Liver Enzymes: Is This Associated with Severity and Mortality Rate?

Abstract Introduction Coronavirus disease 2019 (COVID-19) is a viral infection caused by a novel coronavirus known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease raises an enormous public health challenge for the international community. Liver enzymes have been reported to be frequently elevated in hospitalized patients with severe COVID-19 disease. Materials and Methods This article is a narrative review of abnormal liver tests and liver injury as a manifestation of progression to severe pneumonia. We collected data from the PubMed database (National Library of Medicine, Bethesda, Maryland, United States). We used the search term “abnormal liver test” and relevant records were measured. The review article was organized thematically. Results This narrative review aims to summarize the available clinical data on abnormal liver enzymes in coronavirus infection and its association with the risk of mortality, severer pneumonia, and systemic inflammation. Some clinical studies refer to abnormal liver tests and liver injury as a manifestation of progression to severe pneumonia. Recent research verified the relationship between hepatic liver enzyme activities and liver damage in patients with COVID-19, which suggested that it might reflect the infection severity and the mortality risk. Thus, this review investigated the correlation between liver serum enzymes level and the severity of COVID-19 patients, by reviewing investigating the relationship between the illness severity in COVID-19 patients with abnormal liver tests, liver pathology, and markers of inflammation. Conclusion In the current pandemic of SARS-CoV-2, abnormalities of liver enzyme tests were commonly observed in patients with COVID-19. However, because of multiorgan damages that observed in COVID-19 patients, various issues should be considered such as the pathology and pathophysiology of the liver tissue, especially on the activation process of the immune response and cytokine storm to prevent the severity of the disease.

PNPLA3 and TM6SF2 genetic variants and hepatic fibrosis and cirrhosis in Pakistani chronic hepatitis C patients: a genetic association study

BackgroundThe present study investigates if common missense functional variants p.I148M and p.E167K in PNPLA3 and TM6SF2 genes, respectively, associate with development of hepatic fibrosis and cirrhosis in a geographically novel cohort of Pakistani chronic hepatitis C (CHC) patients.MethodsIn total, 502 Pakistani CHC patients [242 males, median age 40 years, 220 with significant hepatic fibrosis, including 114 with cirrhosis] were genotyped for PNPLA3 and TM6SF2 variants using TaqMan genotyping assays. Associations between genotypes, biochemical and clinical parameters were evaluated.ResultsGenotypic distributions for PNPLA3 and TM6SF2 polymorphisms conformed to Hardy–Weinberg equilibrium and did not associate with fibrosis grades ≥ F2 or cirrhosis in any of the genetic models tested (all p = > 0.05). PNPLA3 and TM6SF2 variants did not modulate baseline characteristics and serum markers of liver injury in CHC patients. Similarly, increasing number of risk alleles of PNPLA3 and TM6SF2 polymorphisms had no trend effect on serum liver enzyme activities or proportion of CHC patients with significant or advanced fibrosis or cirrhosis (p = > 0.05). The same trend of no association with hepatic fibrosis or cirrhosis persisted in the multivariate logistic regression models adjusting for age, gender, body mass index and HCV viral load (p = > 0.05).ConclusionsPNPLA3 and TM6SF2 variants do not appear to modulate development of hepatic fibrosis or cirrhosis in present CHC patients of Pakistani origin, and may be of more relevance in liver pathology involving abnormalities in hepatic fat accumulation. These results also reflect the divergent associations observed for different genetic modifiers of hepatic fibrosis and cirrhosis in distinct ethnicities.

Domestic cat hepadnavirus associated with hepatopathy in cats: A retrospective study.

BackgroundWhether domestic cat hepadnavirus (DCH) infection is associated with clinical disease remains to be determined.ObjectivesTo determine the relationship between DCH detection, hematology, serum bichemistry and liver histology in DCH‐positive cats.AnimalsOne thousand twenty‐two cats in Thailand without concurrent diseases and not undergoing treatments adversely affecting the liver.MethodsRetrospective cross‐sectional study. Samples derived from cats with concurrent virus detection were excluded. DCH detection was determined in blood and fresh‐frozen liver by quantitative polymerase chain reaction (qPCR) and further investigated in liver sections showing histological parenchymal disorders (HPD) and normal liver (HNL) using in situ hybridization (ISH). Proliferative/apoptotic activities were determined using immunohistochemistry and ISH panels. Biochemical variables and risk factors for DCH infection were investigated.ResultsSix hundred sixty‐one (557 blood and 119 liver samples) cats were included. DCH was detected in 18.50% (103/557), 13.85% (9/65), and 3.70% (2/54) of the blood, HPD, and HNL groups, respectively. Cats with DCH revealed abnormally high activity of aspartate aminotransferase (AST) (P = .001) and alanine aminotransferase (ALT) (P < .001). Among DCH‐positive HPD case 2/9 an 7/9 were acute and chronic hepatitis, of which 4/7 had hepatitis. Log viral copy number (LVCN) was positively correlated with ALT (P < .001), triglyceride (P < .001), and gamma‐glutamyl transpeptidase (GGT) (P = .022). The LVCN also had a positive association with degree of hepatitis (P < .05). There was hepatocyte proliferation activity in DHC positive cats.Conclusion and Clinical ImportanceDomestic cat hepadnavirus infection was associated with high serum activity of liver enzymes and chronic lymphoplasmacytic hepatitis (LPH).

Liver Involvement in Acute Respiratory Infections in Children and Adolescents - Results of a Non-interventional Study.

BackgroundIn children and adults with acute respiratory tract infections (ARTI), elevations of serum liver enzyme activities are frequently observed in clinical practice. However, epidemiological data particularly in the pediatric population are very limited. The aim of this study was to assess the incidence of hepatic involvement, to identify the viruses and to analyze risk factors in children and adolescents with ARTI in a real-world setting.MethodsWe report on a prospective, multicenter, non-interventional study with 1,010 consecutive patients aged 1–17 years with ARTI who consulted a physician within 5 days after onset of symptoms. Laboratory blood tests and PCR virus detection in nasopharyngeal lavage were performed at first presentation and after 3–7 days. Patients with elevated activities of serum liver enzymes (ASAT, ALAT, and γ-GT) were determined in local laboratories and values were normalized by dividing by the individual upper limit of the normal range (ULN). The resulting index (<1 means below ULN, >1 means above ULN) allowed to compare results from laboratories with different reference ranges.ResultsLaboratory test results of 987 patients were available at first visit. 11.1% (95% CI: 9.2–13.3%) exhibited an elevation of ASAT, ALAT, and/or γ-GT activities. Virus DNA or RNA was identified in nasopharyngeal lavages of 63% of the patients. 12.2% of patients with positive PCR and 9.7% of those with negative PCR (p = 0.25) had elevated serum liver enzyme activities. The highest rates were observed in patients with a positive result for influenza B virus (24.4%) followed by human metapneumovirus (14.6%), and human coronavirus (others than SARS-CoV-2) (13.6%). The rate of children and adolescents with ARTI and elevation of serum liver enzyme activities correlated with the virus species and with overweight of the patients but did not differ in patients with or without previous medication intake.ConclusionElevated enzyme activities are present in about 10% of children and adolescents with ARTI. In our cohort, these elevations were mild to moderate; probably resulting from an inflammation process with hepatic involvement.

Metabolomic serum abnormalities in dogs with hepatopathies

Hepatopathies can cause major metabolic abnormalities in humans and animals. This study examined differences in serum metabolomic parameters and patterns in left-over serum samples from dogs with either congenital portosystemic shunts (cPSS, n = 24) or high serum liver enzyme activities (HLEA, n = 25) compared to control dogs (n = 64). A validated targeted proton nuclear magnetic resonance spectroscopy platform was used to assess 123 parameters. Principal component analysis of the serum metabolome demonstrated distinct clustering among individuals in each group, with the cluster of HLEA being broader compared to the other groups, presumably due to the wider spectrum of hepatic diseases represented in these samples. While younger and older adult control dogs had very similar metabolomic patterns and clusters, there were changes in many metabolites in the hepatopathy groups. Higher phenylalanine and tyrosine concentrations, lower branched-chained amino acids (BCAAs) concentrations, and altered fatty acid parameters were seen in cPSS dogs compared to controls. In contrast, dogs with HLEA had increased concentrations of BCAAs, phenylalanine, and various lipoproteins. Machine learning based solely on the metabolomics data showed excellent group classification, potentially identifying a novel tool to differentiate hepatopathies. The observed changes in metabolic parameters could provide invaluable insight into the pathophysiology, diagnosis, and prognosis of hepatopathies.

Hesperidin ameliorates cisplatin induced hepatotoxicity and attenuates oxidative damage, cell apoptosis, and inflammation in rats

Cisplatin is one of the most widely used chemotherapeutic anti-cancer drugs that is associated with multiple systemic toxicities limiting its use. The present study aimed to evaluate the hepato-protective effect of hesperidin against cisplatin-induced toxicity. Thirty-two adult male albino rats were equally split into four groups, the first group served as control received normal saline, the second group (CIS) received a single intraperitoneal dose of cisplatin (7.5 mg/kg bw) on the 22nd day of the experiment, the third group (HES) treated once daily with hesperidin (200 mg/kg bw, orally) for 21 days, and the last group (HES + CIS) pretreated once daily with hesperidin followed by a single intraperitoneal dose of cisplatin. Twenty-four hours later, samples were collected for further investigations. CIS-intoxication resulted in a significant decrease in the erythrogram along with thrombocytopenia leukopenia, and lymphopenia. Furthermore, CIS administration significantly elevated serum activity of liver enzymes, total, and indirect bilirubin as well serum glucose, total cholesterol, and triglycerides levels, meanwhile serum total protein, and globulin levels were significantly reduced. The hepatic MDA was markedly elevated with a concomitant decline in the hepatic antioxidant enzymes and severe alterations in the hepatic tissue architecture in CIS-intoxicated rats. Additionally, CIS-induced overexpression of hepatic Bax, caspase-3, and TNF-α, with no effect on hepatic expression of IL-10. Interestingly, HES pretreatment improved the CIS-induced hemato-biochemical, molecular and histopathological alterations. In conclusion, hesperidin hepato-protective effects against CIS might be mediated by its antioxidant, anti-inflammatory, and anti-apoptotic properties.

Serum haptoglobin concentration and liver enzyme activity as indicators of systemic inflammatory response syndrome and survival of sick calves.

BackgroundIncreased concentration of haptoglobin (Hp) in serum is associated with survival of critically ill humans and horses. High serum activity of liver‐derived enzyme is associated with sepsis in children and foals.Hypothesis/ObjectivesInvestigate whether admission serum Hp and glutamic dehydrogenase (GLDH) are associated with systemic inflammatory response syndrome (SIRS) and survival of sick calves.AnimalsOne hundred two calves.MethodsRetrospective cross‐sectional study. Electronic medical records from all calves <30 days of age admitted to a teaching hospital for 8 years were reviewed. The signalment, clinicopathological findings, the presence of SIRS, final diagnosis, hospitalization time and outcome were recorded. A Cox proportional hazard ratio (HzR) were calculated to assess the association between clinicopathological variables and survival to discharge.ResultsSerum Hp concentrations were similar between SIRS (0.29 g/L; range, 0.05‐3.6) and non‐SIRS calves (0.22 g/L; range, 0‐4.2; P = .62). GLDH activity was similar between SIRS (12 U/L; range, 1‐1025) and non‐SIRS calves (9 U/L; range, 2‐137; P = .2). Absent suckle reflex (HzR: 6.44, 95% CI: 1.44‐28.86), heart rate (HR) < 100 beats per minute (bpm; HzR: 12.2; 95% CI: 2.54‐58.62), HR > 140 bpm (HzR: 3.59, 95% CI: 1.05‐12.33), neutrophil count <1.7 × 109/L (HzR: 7.36; 95% CI: 2.03‐26.66) and increased gamma‐glutamyl transferase activity (every 50‐unit, HzR: 1.12; 95% CI: 1.03‐1.21) were predictive of nonsurvival.Conclusions and Clinical ImportanceThe use of Hp and GLDH for prediction of survival in sick calves cannot be recommended at this time.