Diagnostic value of methylated branched chain amino acid transaminase 1/IKAROS family zinc finger 1 for colorectal cancer

BACKGROUND The diagnostic value of combined methylated branched chain amino acid transaminase 1(BCAT1)/IKAROS family zinc finger 1(IKZF1)in plasma for colorectal cancer(CRC)has been explored since 2015.Recently,several related studies have published their results and showed its diagnostic efficacy.AIM To analyze the diagnostic value of methylated BCAT1/IKZF1 in plasma for screening and postoperative follow-up of CRC.METHODS The candidate studies were identified by searching the PubMed,Embase,Cochrane Library,CNKI,and Wanfang databases from May 31,2003 to June 1,2023.Sensitivity,specificity,and diagnostic accuracy were calculated by merging ratios or means.RESULTS Twelve eligible studies were included in the analysis,involving 6561 participants.The sensitivity of methylated BCAT1/IKZF1 in plasma for CRC diagnosis was 60%[95%confidence interval(CI)53-67]and specificity was 92%(95%CI:90-94).The positive and negative likelihood ratios were 8.0(95%CI:5.8-11.0)and 0.43(95%CI:0.36-0.52),respectively.Diagnostic odds ratio was 19(95%CI:11-30)and area under the curve was 0.88(95%CI:0.85-0.91).The sensitivity and specificity for CRC screening were 64%(95%CI:59-69)and 92%(95%CI:91-93),respectively.The sensitivity and specificity for recurrence detection during follow-up were 54%CONCLUSION The detection of methylated BCAT1/IKZF1 in plasma,as a non-invasive detection method of circulating tumor DNA,has potential CRC diagnosis,but the clinical application prospect needs to be further explored.

Pocket Modification of x-Amine Transaminase AtATA for Overcoming the Trade-Off Between Activity and Stability Toward 1-Acetonaphthone

Amine transaminases(ATAs)catalyze the asymmetric amination of prochiral ketones or aldehydes to their corresponding chiral amines.However,the trade-off between activity and stability in enzyme engineering represents a major obstacle to the practical application of ATAs.Overcoming this trade-off is important for developing robustly engineered enzymes and a universal approach for ATAs.Herein,we modified the binding pocket of co-ATA from Aspergillus terreus(AtATA)to identify the key amino acid residues controlling the activity and stability of AtATA toward 1-acetonaphthone.We discovered a structural switch comprising four key amino acid sites(R128,V149,L182,and L187),as well as the"best"mutant(AtATAD224K/V149A/L182 F/L187F;termed M4).Compared to the parent enzyme AtATAD224K(AtATAPa),M4 increased the catalytic efficiency(k_(cat)/K_(m)^(1-acetonaphthone),where kcatis the constant of catalytic activities and is 10.1 min^(-1),K_(m)^(1-acetonaphthoneis) Michaelis-Menten constant and is 1.7 mmol·L^(-1))and half-life(t1/2)by 59-fold to 5.9 L·min^(-1)·mmol-1and by 1.6-fold to 46.9 min,respectively.Moreover,using M4 as the biocatalyst,we converted a 20 mmol·L^(-1)aliquot of 1-acetonaphthone in a 50 mL scaled-up system to the desired product,(R)-(+)-1(1-naphthyl)ethylamine((R)-NEA),with 78%yield and high enantiomeric purity(R>99.5%)within 10 h.M4 also displayed significantly enhanced activity toward various 1-acetonaphthone analogs.The related structural properties derived by analyzing structure and sequence information of robust ATAs illustrated their enhanced activity and thermostability.Strengthening of intramolecular interactions and expansion of the angle between the substratebinding pocket and the pyridoxal 5’-phosphate(PLP)-binding pocket contributed to synchronous enhancement of ATA thermostability and activity.Moreover,this pocket engineering strategy successfully transferred enhanced activity and thermostability to three other ATAs,which exhibited 8%-22%sequence similarity with AtATA.This research has important implications for overcoming the trade-off between ATA activity and thermostability.

Persistent hypertransaminasemia in asymptomatic children: A stepwise approach

We aimed to examine the major causes of isolated chronic hypertransaminasemia in asymptomatic children and develop a comprehensive diagnostic flow diagram. A MEDLINE search inclusive of publications throughout August 2012 was performed. We found only a small number of publications that had comprehensively investigated this topic. Consequently, it was difficult to construct a diagnostic flowchart similar to those already available for adults. In children, a "retesting panel" prescription, including gamma-glutamyl transpeptidase and creatine kinase in addition to aminotransferases, is considered a reasonable approach for proficiently confirming the persistence of the abnormality, ruling out cholestatic hepatopathies and myopathies, and guiding the subsequent diagnostic steps. If re-evaluation of physical and historical findings suggests specific etiologies, then these should be evaluated in the initial enzyme retesting panel. A simple multistep diagnostic algorithm incorporating a large number of possible pediatric scenarios, in addition to the few common to adults, is available. Accurately classifying a child with asymptomatic persistent hypertransaminas-emia may be a difficult task, but the results are critical for preventing the progression of an underlying, possibly occult, condition later in childhood or during transition. Given the high benefit/cost ratio of preventing hepatic deterioration, no effort should be spared in diagnosing and properly treating each case of persistent hypertransaminasemia in pediatric patients.

Aspartate transaminase to platelet ratio index in hepatitis C virus and Schistosomiasis coinfection

AIM: To assess the diagnostic accuracy,of aminotransferase-to-platelet ratio index(APRI) alone and with antischistosomal antibody(Ab) in patients with hepatitis C virus(HCV) and schistosomiasis coinfection. METHODS: This retrospective study included medical records of three hundred and eighty three Egyptianmen patients who had undergone percutaneous liver biopsy between January 2006 to April 2014 in tertiary care hospital in Qatar for diagnosis or monitoring purpose were selected. Data of patients > 18 years of age were included in the study. The values of HCV RNA titer and antischistosomal antibody titer were also taken into consideration. Patients were excluded from the study if they had any other concomitant chronic liver disease,including; history of previous antiviral or interferon therapy,immunosuppressive,therapy,chronic hepatitis B infection,human immunodeficiency virus co-infection,autoimmune hepatitis,decompensated liver disease,hepatocellular carcinoma,prior liver transplantation,and if no data about the liver biopsy present. RESULTS: Median age of patients was 46 years. About 7.1% had no fibrosis,whereas 30.4%,37.5%,20.4%,and 4.6% had fibrosis of stage Ⅰ,Ⅱ,Ⅲ,and Ⅳ respectively. In bivariate analysis,APRI score,levels of AST,platelet count and age of patient showed statistically significant association with liver fibrosis(P < 0.0001); whereas antischistosomal antibody titer(P = 0.52) and HCV RNA titer(P = 0.79) failed to show a significant association. The respective AUC values for no fibrosis,significant fibrosis,severe fibrosis and cirrhosis of APRI score were 63%,73.2%,81.1% and 88.9% respectively. This showed good sensitivity and specificity of APRI alone for grading of liver fibrosis. But the inclusion of anti-Schistosoma antibody did not improve the prediction of fibrosis stage. CONCLUSION: The study results suggest that noninvasive biochemical markers like APRI are sensitive and specific in diagnosing the degree of fibrosis and cirrhosis in patients with coinfection of HCV and schistosomiasis as compared to biopsy. The addition of antischistosomal Ab to APRI did not improve sensitivity for predicting the degree of cirrhosis.

Diagnosis of Infectious Mononucleosis by Combined Detection of Atypical Lymphocytes and Transaminase

In order to explore the value of combined detection of atypical lymphocytes （ATL） and transaminase （alanine aminotransferase, ALT＇ asparate aminotransferase, AST） in the diagnosis of infectious mononucleosis （IM）, The data of blood routine and liver function were collected from 54 IM patients, 34 acute hepatitis （AH） patients, 44 upper respiratory infection （URI） patients in Union Hospital during March 2002 to March 2005. Same data were also collected from 40 healthy children as normal control. These data were analyzed retrospectively. Both proportion of atypical lymphocytes and enzyme activity of transaminase were elevated simultaneously （ALT〉40 IU/L, AST〉45 IU/L） in 57.4% （31/54） IM patients. There was significant difference （P〈0.01） between IM group and the other groups. Combined detection of atypical lymphocytes and transaminase can be regarded as a diagnostic marker of infectious mononucleosis.

Prevalence of advanced liver fibrosis and steatosis in type-2 diabetics with normal transaminases:A prospective cohort study

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and type-2 diabetes mellitus(T2DM)have an intricate bidirectional relationship.Individuals with T2DM,not only have a higher prevalence of non-alcoholic steatosis,but also carry a higher risk of progression to nonalcoholic steatohepatitis.Experts still differ in their recommendations of screening for NAFLD among patients with T2DM.AIM To study the prevalence of NAFLD and advanced fibrosis among our patient population with T2DM.METHODS During the study period(November 2018 to January 2020),59 adult patients with T2DM and 26 non-diabetic control group individuals were recruited prospectively.Patients with known significant liver disease and alcohol use were excluded.Demographic data and lab parameters were recorded.Liver elastography was performed in all patients.RESULTS In the study group comprised of patients with T2DM and normal alanine aminotransferase levels(mean 17.8±7 U/L),81%had hepatic steatosis as diagnosed by elastography.Advanced hepatic fibrosis(stage F3 or F4)was present in 12%of patients with T2DM as compared to none in the control group.Patients with T2DM also had higher number of individuals with grade 3 steatosis[45.8%vs 11.5%,(P<0.00001)and metabolic syndrome(84.7%vs 11.5%,P<0.00001)].CONCLUSION A significant number of patients with T2DM,despite having normal transaminase levels,have NAFLD,grade 3 steatosis and advanced hepatic fibrosis as measured by liver elastography.

Activity of transaminase enzyme and testosterone hormone in blood of Awassi rams during different season

Objective:To monitor the levels of aspartate transaminase (AST) and alanine transaminase (ALT) enzymes and testosterone hormone in months and seasons of Iraq.Methods: In this experiment, 20 (2.0-3.5 years old) Iraqi Awassi rams were used which were housed in semi opened shade. Blood samples (2-3 mL) were collected once a week for over period 12 mo. AST and ALT activities were measured by using colorimetric method, and testesterone analysis was performed with an automatic analyzer.Results: The activities of both AST and ALT enzymes were increased significantly (P<0.05) during summer, on monthly basis, June showed the significantly highest value (P<0.05). The present study revealed that testosterone in autumn and summer was recorded significantly highest (P<0.05) in comparison with other seasons and on monthly basis the significant (P<0.05) highest level of testosterone was found between September and August months.Conclusions: AST and ALT enzymes are the highest during summer, and on monthly basis they are the highest in June, while testosterone level is recorded highest in autumn season, and on monthly basis November shows the highest value.

Upregulation of miR-143-3p attenuates oxidative stress-mediated cell ferroptosis in cardiomyocytes with atrial fibrillation by degrading glutamic-oxaloacetic transaminase 1

Oxidative stress-mediated cell death in cardiomyocytes contributes to the development of atrial fibrillation.However,the detailed mechanisms are still unclear.In the present study,we established atrial fibrillation models in mice.The cardiomyocytes were isolated from atrial fibrillation mice and normal mice and were cultured in vitro,respectively.The results showed that cell proliferation and viability in cardiomyocytes with atrial fibrillation were significantly lower than the cells from the normal mice.Consistently,atrial fibrillation cardiomyocytes were prone to suffer from apoptotic cell death.Also,the oxidative stress and ferroptosis-associated signatures were significantly increased in atrial fibrillation cardiomyocytes compared to normal cardiomyocytes,and ferroptosis inhibitor and NAC rescued cell viability in atrial fibrillation cardiomyocytes during in vitro cell culture.In addition,low-expressed miR-143-3p was observed in atrial fibrillation cardiomyocytes compared to normal cardiomyocytes,and overexpression of miR-143-3p increased cell proliferation and inhibited cell death in atrial fibrillation cardiomyocytes.Furthermore,glutamic-oxaloacetic transaminase 1 could be negatively regulated by miR-143-3p in normal cardiomyocytes,and miR-143-3p overexpression inhibited cell ferroptosis in atrial fibrillation cardiomyocytes by sponging glutamic-oxaloacetic transaminase 1.Collectively,overexpression of miR-143-3p increased cell viability and promoted cell proliferation in cardiomyocytes with atrial fibrillation by inhibiting glutamic-oxaloacetic transaminase 1 mediated oxidative damages and cell ferroptosis.

Changes of liver fat content and transaminases in obese children after 12-mo nutritional intervention

AIM:To assess a relationship between longitudinal changes in liver fat content and biochemical parameters in obese children after 1-year nutritional intervention.METHODS:Forty-six obese children, 21 males and 25females, aged 6-14 years, underwent metabolic measurements, liver ultrasonography(US) and chemicalshift magnetic resonance imaging(MRI) examinations at baseline and after 1-year nutritional intervention. A child was defined obese if her/his body mass index(BMI)was above the age- and sex-adjusted BMI Cole's curve passing through the cut-off of 30 kg/m2 at 18 years.BMI Z scores were calculated and adjusted for age and gender by using the Cole's LMS-method and Italian reference data. Biochemistry included serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST). Abdominal US and chemical-shift MRI were performed according to a randomized sequence.The same radiologist performed US by a GE Logiq 9(General Electric Healthcare Medical Systems, Milwaukee, WI, United States) using a 3.5-MHz convex array transducer. Liver echogenicity was evaluated independently on videotape by 3 radiologists unaware of the child and MRI outcomes, and a consensus was established. Another experienced radiologist, unaware of the child and US data, performed the abdominal chemicalshift MRI with a 1-t system NT-Intera(Philips Medical Systems, Best, The Netherlands) and a phased-array coil. Liver fat fraction(FF) on MRI was judged elevated when greater than 9%. A FF>18% was considered expressing more severe cases of fatty liver according to Fishbein. A nutritional-behavioral intervention was recommended to promote a normocaloric balanced diet and active lifestyle based on the Italian guidelines for treatment of childhood obesity.RESULTS:Compared to baseline, at the end of intervention children showed lower intakes of energy(mean± SD:2549±1238 Kcal vs 1770±622 Kcal, P<0.0001), total fat(90±47 g vs 52± 23g, P<0.0001),carbohydrates(356±174g vs 241±111 g, P=0.001),and protein(99±48g vs 75±23g, P=0.006) intakes. Prevalence of FF≥9% declined from 34.8%to 8.7%(P<0.01), with a mean reduction of 7.8%(95%CI:5.0-10.6). At baseline, FF was associated with liver biochemical parameters(maximum P<0.001). At the end of the intervention association was found with AST(P=0.017). Change of FF was associated with change in AST(P =0.027) and ALT(P=0.024). Rate of increased liver echogenicity declined from 45.6% to21.7%(P<0.0001). Liver echogenicity was associated with ALT at baseline only(P<0.001). An age-and sexadjusted multiple regression analysis showed that FF change was independently associated with change in serum AST(adjusted regression coefficient 0.348, P=0.048).CONCLUSION:The results suggest that in obese children longitudinal changes in liver fat content based on MRI may be associated with change in serum transaminases suggesting novelty in monitoring nonalcoholic fatty liver disease.

Prognostic performance of an index based on lactic dehydrogenase and transaminases for patients with liver steatosis and COVID-19

BACKGROUND Metabolic associated fatty liver disease(MAFLD)is associated with complications and mortality in patients with coronavirus disease 2019(COVID-19).However,there are no prognostic scores aimed to evaluate the risk of severe disease specifically in patients with MAFLD,despite its high prevalence.Lactate dehydrogenase,aspartate aminotransferase and alanine aminotransferase have been used as markers of liver damage.Therefore,we propose an index based on lactate dehydrogenase,aspartate aminotransferase and alanine aminotransferase for the prediction of complications and mortality in patients with MAFLD and COVID-19.AIM To evaluate the prognostic performance of an index based on lactate dehydrogenase and transaminases(aspartate aminotransferase/alanine aminotransferase)in patients with COVID-19 and MAFLD[liver fibrosis and nutrition(LNF)-COVID-19 index].METHODS In this retrospective cohort study,two cohorts from two different tertiary centers were included.The first was the derivation cohort to obtain the score cutoffs,and the second was the validation cohort.We included hospitalized patients with severe COVID-19 and MAFLD.Liver steatosis was evaluated by computed tomography scan.Area under the receiver operating characteristic(ROC)curve analysis and survival analysis were used.RESULTS In the derivation cohort,44.6%had MAFLD;ROC curve analysis yielded a LFN-COVID-19 index>1.67 as the best cutoff,with a sensitivity of 78%,specificity of 63%,negative predictive value of 91%and an area under the ROC curve of 0.77.In the multivariate analysis,the LFN-COVID-19 index>1.67 was independently associated with the development of acute kidney injury(odds ratio:1.8,95%confidence interval:1.3-2.5,P<0.001),orotracheal intubation(odds ratio:1.9,95%confidence interval:1.4-2.4,P<0.001),and death(odds ratio:2.86,95%confidence interval:1.6-4.5,P<0.001)in both cohorts.CONCLUSION LFN-COVID-19 index has a good performance to predict prognosis in patients with MAFLD and COVID-19,which could be useful for the MAFLD population.

Glutathione Reductase, Liver Transaminases and Atypical Lymphocytes Count as Early Predictive Biomarkers in Diagnosis of Thrombocytopenia in Dengue Viral Infection

Objective: The aim of the study is to identify whether Atypical Lymphocyte (AL), liver transaminases, and Glutathione Reductase (GR) can be used as potential biomarkers in the assessment of severity and thrombocytopenia in dengue. Methods: A cross-sectional analytical study was carried out on diagnosed dengue patients admitted to Nawaloka Hospital, Sri Lanka. Blood samples were taken from patients (n = 50) on the day of admission, 3rd and 5th day from admission for analysis of GR, aspartate transaminase, alanine transaminase, platelets, white blood cells, and Atypical Lymphocytes (AL). Results: GR level of all three measured stages had a higher area under the curve (>88%), high sensitivity and specificity compared to liver transaminases. A significant regression model represents on admission GR and AL levels as predictive variables to platelet levels in day 03 from admission (Day 3 Platelet level = 127155.3 - 383 * GR - 0.431 * AL). Conclusion: Liver transaminases, GR, and AL% can be considered as a profile of predictive biomarkers in early diagnosis of severity of dengue infection. The degree of thrombocytopenia can be predicted using on admission GR and AL% level in acute dengue viral infection.

Investigation of minerals, testosterone, and transaminases in the semen and serum of fertile and infertile men belongs to different age groups

The present study was aimed to assess the potential of infertility to induce the adverse effects with reference to testosterone, Triiodothyronine (T3), Thyroxine (T4), Alanine Aminotransferase (ALT), Aspartate Amino-transferase (AST), zinc, copper and iron. All the samples were divided into four groups according to age and disorder (Group 1, 10 infertile men of 25-40 years;Group 2, 10 fertile men of 25-40 years;Group 3, 10 infertile men of 41- 60 years and Group 4, 10 fertile men of 41-60 years). Semen and blood samples were analyzed by atomic absorption spectrophotometry to determine minerals while, Testosterone, T3 and T4 were determined by enzyme immunoassay kits. ALT and AST were determined using standard kit assay method. The levels of testosterone and T3 and AST in the fertile semen of 41-60 years age group were increased significantly (P ≤ 0.001) as compared to that of fertile semen of 25-40 years age group. While, the level of T4 in the fertile semen of 41-60 years age group was decreased significantly (P ≤ 0.001) as compared to that of fertile semen of 25-40 years age group. In case of fertile serum, only the level of testosterone was significantly decreased (P ≤ 0.05) in the 41-60 years age group as compared to 25-40 years age group. The levels of testosterone and Cu in the infertile serum of 41-60 years age group were decreased significantly (P ≤ 0.001). While, the levels of T3, T4, ALT and Fe in the infertile serum of 41-60 years age group were increased significantly (P ≤ 0.05) as compared to that of infertile serum of 25-40 years age group.

Clinical significance of low transaminase levels in children with inflammatory bowel disease

Background Low alanine aminotransaminase (LALT) levels may be seen in patients with inflammatory bowel disease (IBD),but there has been no study about the frequency and its clinical significance.We aimed to analyze the frequency of LALT,and its clinical significance in children with IBD.Methods The study included the 89 patients with IBD without hepatobiliary involvement.LALT was defined as ALT levels < 5 U/L.Demographic and clinical findings and outcome of the patients with and without LALT were compared.Results LALT was found 47.1% of the patients.At initial examination,it was more common in female patients (92.3 vs.41.3%,P < 0.001) and patients with CD (57.7 vs.30.2%,P=0.01).75% of the patients with penetrating Crohn's disease (CD) had LALT (P=0.002).Hemoglobin (10.4±2.1 vs.11.7± 1.9 g/dL,P=0.01),folic acid (5.2±3.3 vs.8.6±5.9 ng/mL,P =0.02) and serum albumin levels (3.6 ± 0.8 vs.4.7 ± 5 g/dL,P =0.002) were significantly low in patients with LALT.LALT was associted with the disease relapse within 2 weeks in 12 of the 16 patients with LALT whereas it was seen in 16 of the 73 patients without LALT during the follow-up (75 vs.21.9%,P < 0.001).Additionally,steroid dependency was more common in patients with LALT during the follow-up (62.5 vs.12.3%,P<0.001).Conclusions LALT is common in children with IBD especially in CD and associated with low hemoglobin,albumin and folic acid levels.It may be a marker of relapse and steroid dependency.

Growth rate,body composition, digestive enzymes and transaminase activities,and plasma ammonia concentration of different weight Jian carp(Cyprinus carpio var. Jian)

The present study investigated the effect of body weight on body composition, digestive and absorptive capacity, transaminase activities in hepatopancreas and muscle, and plasma ammonia concentration of Jian carp(Cyprinus carpio var.Jian). A total of 750 Jian carps(18.0 ± 0.2 g) were randomly distributed into five groups with three replicates and fed the same diet for 56 days. Tissue and plasma samples were collected on days 14, 28,42, and 56. The results were used to develop a mathematical model for specific growth rate, body moisture and fat content, aspartate transaminase activity and alanine aminotransferase activity in hepatopancreas and muscle, plasma ammonia concentration, and trypsin, chymotrypsin, lipase, and amylase activities in hepatopancreas and intestine, activities of creatine kinase, Na^+/K^+-ATPase, alkaline phosphatase, and γ-glutamyl transpeptidase in intestine in Jian carp. There were linear relationships between natural logarithms of above indexes and body weight. The body moisture and fat content, digestive and absorptive enzymes activities, and transaminase activities showed negative allometry against body weight of Jian carp which were partial reasons to explain fish growth rate decreasing.

Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B:A real-world study

BACKGROUND The efficacy and safety profile of tenofovir amibufenamide(TMF)in chronic hepatitis B(CHB)patients is not well-established.AIM To compare the efficacy and safety of TMF and tenofovir alafenamide(TAF)over a 48-wk period in patients with CHB.METHODS A total of 215 subjects meeting the inclusion criteria were enrolled and divided into two groups:TMF group(n=106)and the TAF group(n=109).The study included a comparison of virological response(VR):Undetectable hepatitis B virus DNA levels,alanine transaminase(ALT)normalization rates,renal function parameters,and blood lipid profiles.RESULTS At 24 and 48 wk,VR rates for the TMF group were 53.57%and 78.57%,respectively,compared with 48.31%and 78.65%for the TAF group(P>0.05).The VR rates were also similar in both groups among patients with low-level viremia,both hepatitis B e antigen(HBeAg)-positive and HBeAg-negative subgroups.The TMF cohort showed ALT normalization and renal safety profiles similar to the TAF group.There was a notable increase in total cholesterol levels in the TAF group(P=0.045),which was not observed in the TMF group(P>0.05).In patients with liver cirrhosis,both groups exhibited comparable VR and ALT normalization rates and renal safety profiles.However,the fibrosis 4 score at 48 wk showed a significant reduction in the TAF group as compared to the TMF group within the liver cirrhosis subgroup.CONCLUSION Our study found TMF is as effective as TAF in treating CHB and has a comparable safety profile.However,TAF may be associated with worsening lipid profiles.

COVID-19-induced transaminitis and hyperbilirubinemia:Presentation and outcomes

The risk of liver injury in patients with coronavirus disease 2019(COVID-19)infection is quite evident.Furthermore,liver function test abnormalities are still detected in COVID-19 patients despite the development of antivirals and the availability of several types of vaccines.This editorial describes liver involvement during COVID-19 infection in patients with or without preexisting liver injury,such as chronic liver disease,to elucidate COVID-19-induced liver function abnormalities and their severity,pathophysiology,clinical manifestations,and clinical and laboratory outcomes.We also discuss the effect of vaccination against COVID-19 to better understand host factors,such as age,gender,and race,on the incidence and severity of liver dysfunction at initial presentation and during the illness.Finally,we summarize the results of relevant meta-analyses published to date and highlight the importance of adequate liver function monitoring in the current climate of the overwhelming COVID-19 pandemic.

COVID-19 and the liver:Are footprints still there?

The coronavirus disease 2019(COVID-19)hit the entire world as a global pandemic and soon became the most important concern for all patients with chronic diseases.An early trend in higher mortality in patients with acute respiratory distress attracted all researchers to closely monitor patients for the involvement of other systems.It soon became apparent that patients with chronic liver diseases are at increased risk of mortality given their cirrhosis-associated immune dysfunction.Additionally,liver function abnormalities were noted in patients with severe COVID-19.Profound cytokine storm,direct viral infection,drugs and reactivation of viral infections were causes of deranged liver functions.Here,we discuss the relation between COVID-19 and chronic liver disease,specifically cirrhosis,hepatitis B,hepatitis C,and non-alcoholic fatty liver disease(NAFLD),as well as the liver manifestations of COVID-19.The metabolic syndrome,obesity,diabetes mellitus and NAFLD were found to worsen outcome in different studies reported worldwide.Decompensated cirrhosis should be considered a risk factor for death and severe COVID-19.Recently,COVID-19 related cholangiopathy has also been reported with changes of secondary sclerosing cholangitis.The long-term persistence of viral antigens in gut epithelia raises concern regarding the future risk of autoimmune liver diseases.

Effects of Purified Indian Cattle Tick Rhipicephalus microplus Saliva Toxins on Various Enzymes in Blood Serum, Liver and Muscles of Albino Mice

In the present investigation, in vivo effects of purified ticks’ saliva toxin were evaluated on the level of certain important cellular metabolic enzymes i.e. acid phosphatase (ACP), alkaline phosphatase (ALP), glutamate pyruvate transaminase, glutamate oxaloacetate transaminase and lactic dehydrogenase. For this purpose, sub-lethal doses, 40% and 80% of 24 h LD50 purified saliva toxins of Rhipicephalus microplus (Canestrini, 1888) were injected subcutaneously in the albino mice. In treated mice saliva toxins targeted membrane-bound enzymes i.e. serum acid phosphatase and alkaline phosphatase, its level was increased from 118.30% to 163.63% at the 6th hr in comparison to the control. Besides this, the levels of serum glutamate pyruvate transaminase (GPT) and glutamate oxaloacetate transaminase (GOT) and lactic dehydrogenase (LDH) also increased up to 161.11% (at 6th hr), 148.27 (at 8th hr) and 125.45% (at 6th hr) respectively in comparison to control. An increase in the level of LDH showed insufficient oxygen supply, massive disintegration of cells and leakage of the enzyme into the circulation. It clearly indicated the toxic effects of saliva toxins on the membrane of blood cells, hepatocytes and myocardial muscle cell functions in albino mice. On the other hand activity of acetyl cholinesterase was reduced by 65.51% at the 6th hr of the saliva toxin injection in comparison to the control. This inhibition of acetyl cholinesterase activity caused the accumulation of acetylcholine molecules at the synaptic junctions and led to prolonged activation of acetylcholine receptors. It caused permanent stimulation of nerves and muscle cells that may result in muscular paralysis and finally death of the animal.

Effect of Purified Paper Wasp Ropalidia marginata Venom Toxin Enzyme Activity in Blood Serum, Liver, and Gastrocnemius Muscle of Albino Mice

In the present, investigation effects of sub-lethal dose of purified paper wasp Ropalidia marginata venom toxins were evaluated on important metabolic enzymes i.e. ALP ACP, GPT, GOT, LDH, and AchE enzyme activity in serum, liver, and gastrocnemius muscles of albino mice. Alkaline phosphatase was found to be increased up to 119.9% at the 6th hr of the toxin injection in comparison to control. This elevation may be due to cytolysis. Maximum increase i.e., 153.33% level of glutamate pyruvate transaminase (GPT) was found at 6 hrs of 40% of 24-h LD50 treatment while it was found to be 151.1% at 6 hrs of 24 hr 80% of LD50, venom injection. A significant elevation was observed in LDH activity in serum, liver, and muscles, while the activity of AchE was decreased in serum, liver, and gastrocnemius muscles of albino mice after injecting the sub-lethal dose of Ropalidia marginata venom. This increase in the activity of LDH produces liver damage, massive disintegration and necrosis of hepatic cells. This elevation in LDH level led to a significant increase in the glucose catabolism and elevated oxidative stress in muscle and liver cells. It also displays insufficient oxygen supply and consequently leads to cell death. In experimental animals, venom toxin treatment decreased AchE level, and animals showed muscular paralysis. When mice were treated with 40% and 80% of 24-h LD50 of purified venom caused a significant (p < 0.05) elevation in the level of ACP, GOT, GPT, and LDH while the reduction in ALP and AChE level. Present study will be useful in the development of prototypes for study of pharmacological and therapeutic effects of various venom toxins. For this purpose structure activity relationship of enzyme and venom toxin, its due interaction to various metabolic enzymes and receptors must be explored.

HBV genotype characterization and distribution in patients with HBV-related liver diseases in Zhejiang Province, P. R. China: possible association of co-infection with disease prevalence and severity

BACKGROUND: There are 8 well-documented genotypes of hepatitis B virus (HBV) at this time point. Genotyping can be accomplished based on a partial sequence of hepatitis B virus (HBV) genome such as the pre-S or S gene. Several methods have been developed and used for HBV genotyping including direct sequencing, restriction fragment length polymorphism, line probe assay and enzyme-linked immunoassay. Recently, a novel, rapid and cost-effective genotyping method based on PCR amplification assay using type-specific primers that can identify all six major genotypes has been developed. This study was undertaken to characterise HBV genotypes and investigate the association between the prevalence of different genotypes and the severity of HBV-induced liver diseases. METHODS: Serum samples from carriers of HBV and patients with HBV-related liver diseases from Zhejiang Province were screened for viral serological markers using commercially available radioimmunoassay (RIA) and enzyme linked immunosorbent assay (ELISA) kits. Serum HBV DNA load was determined by real-time detection PCR. A type-specific primer based the nested-PCR method was employed in the HBV genotyping. The genotype results obtained were confirmed by direct sequencing of nested PCR amplicons of the pre-S region. Ten samples of each genotype (B and C) were sequenced. RESULTS: The survey on a cohort of 125 HBV carriers in and around Hangzhou City, Zhejiang Province showed the existence of HBV genotypes A (0.8%), B (48%), C (40.8%), D (0.8%), mixed B and C (9.6%) and an absence of E and F genotypes. Distribution of HBV genotypes in patients with liver diseases revealed a statistically insignificant higher prevalence of genotype B in mild chronic hepatitis (CH). Among the three genotypes B, C and mixed B/C infections 11 (73.3%), 3 (20%) and 1 (6.7%), (P< 0.05), respectively in subjects with moderate CH, genotype B was significantly predominant. The infection patterns for genotypes B, C and B/C mixed in (i) liver cirrhosis (LC) 4 (23.5%), 10 (58.8%) and3 (17.7%) and (ii) hepatocellular carcinoma (HCC) 2 (28.6%), 5(71.4%) and 0 (0.0%) respectively revealed a marked association of C genotype with liver disease; however, the association was statistically insignificant (P >0.05). Differences in positive rate of HBeAg for the three genotypes B, 16(30.8%), C, 27(51.9%), and mixed B/C, 9(17.3%) were significant (P < 0. 05 ) , with genotype C showing predominance. CONCLUSIONS : These findings show an interesting distribution of HBV A-D genotypes in Zhejiang Province. Furthermore, our results indicate a novel and markedly high prevalence of mixed B/C genotype infections in subjects with severe CH and LC, and a possible association of mixed B/C infections with the severity of liver diseases in this region of China's Mainland.