Higher Serum Alanine Aminotransferase Research Articles

Protective role of ginseng extract against oxidative stress, reproductive and some biochemical parameters alterations induced by doxorubicin in male rats

This study investigates the modulating effect of ginseng against testicular toxicity, oxidative stress and changes in some biochemical parameters induced by doxorubicin. Twenty male rats were divided into four groups. The 1st group received distilled water orally (control group), The 2nd group received doxorubicin (5 mg/kg b.wt. intrapertenoineal) once a week for eight weeks, The 3rd group received ginseng extract (200 mg/kg b.wt.) daily for eight weeks and the 4th group received doxorubicin with ginseng extract by the same doses as in the 2nd and the 3rd groups respectively. At the end of the 8th week, blood and semen samples were taken for biochemical and semen analysis, respectively. The doxorubicin treated group had significantly higher serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), Creatine kinase (CK) and lactate dehydrogenase (LDH) along with lower levels of total protein, albumin and globulin. In addition, a significant decrease in antioxidant enzymes (SOD, CAT, GSHPx), and glutathione (GSH) associated with higher level of malondialdehyde (MDA) were observed. At the same time, the group that took doxorubicin with ginseng did not differ from control group in terms of these parameters. Male fertility study showed changes in testosterone and semen analysis in both groups treated with doxorubicin, while the group that took doxorubicin with ginseng showed an improvement towards control levels of these parameters. Thus ginseng supplement can reduce the negative effects of doxorubicin- induce. Â

Frequency of metabolic syndrome among newly detected type 2 diabetic patients with non-alcoholic fatty liver disease and high serum alanine aminotransferase levels

Background: Non-alcoholic fatty liver disease (NAFLD) is emerging as one of the most common causes of chronic liver disease world-wide. It has strong association with obesity, type 2 diabetes mellitus (T2DM) and metabolic syndrome. We aimed to investigate the prevalence of metabolic syndrome in newly detected T2DM patients having NAFLD with high serum alanine aminotransferase (ALT) level.
 Methods: In this cross-sectional study, 110 newly detected T2DM patients with high serum ALT level were evaluated. To find out the etiology of high serum ALT level, abdominal ultrasonography was done to detect NAFLD cases along with other relevant investigations. All NAFLD cases then underwent further evaluation for the prevalence of metabolic syndrome.
 Results: Out of 110 study subjects, NAFLD was detected in 80 (72.7%) individuals. According to International Diabetic Federation (IDF) criteria, metabolic syndrome was detected in 56 (56/80, 70%) of NAFLD cases. Among the 56 patients with NAFLD, male were 24 (42.9%) and female were 32 (57.1%) and 14 (14/56, 25%) cases had all five components of metabolic syndrome. Metabolic syndrome was found in all female NAFLD subjects (32, 100%). Mean age of patients with metabolic syndrome was 43.11±10.77 years and mean body mass index (BMI) was 27.87±3.72 kg/m2. Hypertension was found in 37.5% cases. High BMI (e”25 kg/m2) was found in 87.5% cases. Mild, moderate and severe fatty liver were found in 28.6%, 46.4% and 25% cases respectively. Dyslipidemia was found in all (56, 100%) NAFLD subjects with metabolic syndrome. Metabolic syndrome had significant correlation with BMI (p 0.00), abdominal obesity (p 0.00) and serum triglyceride level (p 0.04).
 Conclusion: Over two-thirds of T2DM patients having NAFLD had metabolic syndrome in this study.
 Birdem Med J 2020; 10(1): 21-25

Occult hepatitis C virus infection among Egyptian hemodialysis patients and its potential effect on anemia management

BackgroundHepatitis C virus (HCV) infection is still a main health problem in hemodialysis (HD) patients. The prevalence of occult hepatitis C infection (OCI) in HD patients may be underestimated, and its possible influence on anemia management has not been studied. We aimed to determine the existence of OCI in Egyptian HD patients as well as its possible effect on anemia management.Patients and methodsThis cross-sectional multicenter study included 98 HCV-negative HD patients (negative for both anti-HCV antibody and HCV-RNA), 43 anti-HCV-positive HD patients, and 10 volunteer people matched for age and sex as a healthy control group. Serology test for anti-HCV antibody, reverse-transcription PCR for HCV-RNA (both serum and peripheral mononuclear cell (PMNC)), complete blood count (CBC), liver transaminases, serum iron, serum ferritin, and high-sensitivity C-reactive protein (hsCRP) were done. The average erythropoiesis-stimulating agent (ESA) doses were calculated over 6 months, and ESA resistance index was calculated. The frequency of packed red blood corpuscle (RBC) transfusion for each patient was recorded.ResultsOur HD patients had significant higher levels of serum ferritin (P=0.011), higher serum alanine aminotransferase and aspartate aminotransferase (P=0.002 and 0.006, respectively), higher hsCRP (P<0.0001), and significant lower level of hemoglobin (P<0.0001) compared with the healthy control group. The prevalence of OCI was 8.16% (8 of 98 patients). OCI patients had significant longer dialysis duration, higher transaminases, higher hsCRP, higher serum ferritin, and higher frequency of packed RBCs transfusion (P<0.0001), whereas mean hemoglobin levels and ESA resistance index showed insignificant differences compared with HCV-negative HD patients. Using logistic regression analysis, frequency of packed RBC transfusion and aspartate aminotransferase were the only independent predictors for OCI (P=0.012 and 0.049, respectively), and by multivariate analysis, no significant predictors were found to be associated with anemia in patients with OCI.ConclusionThe prevalence of OCI in our study was 8.16%. OCI had no effect on anemia managements.

High Concentration of Serum Aspartate Aminotransferase in Older Underweight People: Results of the Kanagawa Investigation of the Total Check-Up Data from the National Database-2 (KITCHEN-2).

Background: Aspartate aminotransferase (AST) is pivotal in amino acid metabolism. However, the serum activity of AST, which leaks from multiple organs, including liver and skeletal muscle, is unknown in older underweight people, who are at high risk of skeletal muscle mass loss. Therefore, we measured the serum activities of AST and alanine aminotransferase (ALT), a liver-specific transaminase, in a large, community-based cross-sectional study. Methods: Clinical parameters and lifestyles were characterized in 892,692 Japanese people with a wide range of body mass indexes (BMIs; 13–39.9 kg/m2), aged 40–74 years old, who were undergoing a medical checkup. A general linear model was used to calculate the estimated mean of serum AST (EM-AST) in each BMI category after adjustment for confounding factors, including past history of cardiovascular disease and waist circumference. Results: Severe underweight (BMI 13–14.9 kg/m2) was present in 910 subjects (0.1%). Raw serum AST showed a J-shaped relationship with BMI, which was blunted in older subjects (60–74 years), and similar, but less curved relationships were identified for raw serum ALT and gamma-glutamyl transferase. These J-shaped relationships in serum AST were not altered when subjects were classified by sex, past history of cardiovascular and cerebrovascular diseases, and habitual exercise. EM-AST showed a U-shaped relationship, with a minimum at BMI 21–22.9 kg/m2, regardless of age and waist circumference. Conclusions: High serum AST but normal serum ALT is highly prevalent in older underweight people and might reflect skeletal muscle pathology.

Presenting features and treatment outcomes of chronic lymphocytic leukaemia in a resource poor Southern Nigeria.

Chronic lymphocytic leukaemia is a relatively common haematological malignancy affecting older adults, accounting for about 20% of haematological malignancies in Nigeria. Diagnosis of this disease depends on the demonstration of clonal lymphocytosis > 5 × 109/L with a characteristic immunophenotypic pattern amidst other clinical and laboratory features. To determine the predominant clinical and laboratory features of CLL at presentation and their relationship with patient survival. This study also aims at examining the relationship between treatment protocol and outcome. This is a retrospective study with 8 years data (2010-2018) collected from four different centers. Data was analyzed using SPSS 20.0. There were a total of 97 cases, with a male: female ratio of 1.1:1. The median age at presentation was 59 years. Approximately 55% of the patients presented at Binet stage C, with splenomegaly in 93.2% and 78% were anaemic. The mean white cell count was 137.9 ± 14.7 × 109/L, with a median absolute lymphocyte count of 86 × 109/L. The commonest treatment regimen was chlorambucil and prednisolone and males had a superior response. The number of chemotherapy cycles, serum alkaline phosphatase and aspartate transaminase correlated positively with duration of survival. Mortality rate over the five year period was 14.3%. CLL was found to present in younger patients when compared to previous studies with a median age of 57 years at diagnosis. Our study showed a slight female preponderance and better response to therapy in males. Majority of the patients presented in Binet stage C and were treated with chlorambucil-based drug combinations compared to more current treatment with Fludarabine-based combinations. A high serum alanine transaminase and alkaline phosphatase was found to positively correlate with survival amongst this patient population.

Thrombospondin-4 expression as a prognostic marker in hepatocellular carcinoma

Background and aimsThe extracellular calcium-binding protein family member thrombospondin-4 (THBS4) regulates cell migration, proliferation, attachment, adhesion, angiogenesis, neural development, tissue structure, organ development, pain signal transduction, and tumor growth. The aim of this study was to study THBS4 expression in hepatocellular carcinoma (HCC) and determine if it was a prognostic marker for this malignancy. MethodsWe used immunohistochemistry and tissue microarrays to evaluate THBS4 expression in 84 HCC and matched para-cancerous tissues. Then, we assessed relationships between THBS4 expression and clinicopathological parameters. ResultsTHBS4 expression was higher in HCCs than in matched para-cancerous tissues (P < 0.001). There was a significant correlation between high THBS4 levels and preoperative serum alanine aminotransferase (P < 0.04). In HCC patients, high THBS4 expression was associated with shorter overall and disease-free survival compared with low THBS4 expression. Additionally, subgroup analysis showed that high THBS4 levels were only associated with poor overall survival for alpha-fetoprotein >40 ng/mL (P = 0.028) and cirrhosis (P = 0.002). Multivariate analysis showed that high THBS4 expression was an independent prognostic factor for both overall and disease-free survival. ConclusionsOur data suggest that THBS4 may play a role in HCC development, and thus may be an independent prognostic marker and/or potential therapeutic target for HCC patients.

The SLC16A11 risk haplotype is associated with decreased insulin action, higher transaminases and large-size adipocytes.

Objective A haplotype at chromosome 17p13 that reduces expression and function of the solute carrier transporter SLC16A11 is associated with increased risk for type 2 diabetes in Mexicans. We aim to investigate the detailed metabolic profile of SLC16A11 risk haplotype carriers to identify potential physiological mechanisms explaining the increased type 2 diabetes risk. Design Cross-sectional study. Methods We evaluated carriers (n = 72) and non-carriers (n = 75) of the SLC16A11 risk haplotype, with or without type 2 diabetes. An independent sample of 1069 subjects was used to replicate biochemical findings. The evaluation included euglycemic-hyperinsulinemic clamp, frequently sampled intravenous glucose tolerance test (FSIVGTT), dual-energy X-ray absorptiometry (DXA), MRI and spectroscopy and subcutaneous abdominal adipose tissue biopsies. Results Fat-free mass (FFM)-adjusted M value was lower in carriers of the SLC16A11 risk haplotype after adjusting for age and type 2 diabetes status (β = -0.164, P = 0.04). Subjects with type 2 diabetes and the risk haplotype demonstrated an increase of 8.76 U/L in alanine aminotransferase (ALT) (P = 0.02) and of 7.34 U/L in gamma-glutamyltransferase (GGT) (P = 0.05) compared with non-carriers and after adjusting for gender, age and ancestry. Among women with the risk haplotype and normal BMI, the adipocyte size was higher (P < 0.001). Conclusions Individuals carrying the SLC16A11 risk haplotype exhibited decreased insulin action. Higher serum ALT and GGT levels were found in carriers with type 2 diabetes, and larger adipocytes in subcutaneous fat in the size distribution in carrier women with normal weight.

Podwyższenie wartości markerów stresu oksydacyjnego u pacjentów z niealkoholową stłuszczeniową chorobą wątroby z wysokim stężeniem aminotransferazy alaninowej w surowicy

Podwyższenie wartości markerów stresu oksydacyjnego u pacjentów z niealkoholową stłuszczeniową chorobą wątroby z wysokim stężeniem aminotransferazy alaninowej w surowicy

Joint associations of serum uric acid and ALT with NAFLD in elderly men and women: a Chinese cross-sectional study

BackgroundEpidemiological evidence suggests sex difference in serum uric acid (SUA) and alanine aminotransferase (ALT) might be a potential explanation for the gender difference in prevalence of non-alcoholic fatty liver disease (NAFLD). However, few epidemiology data in China have tested this hypothesis.MethodsWe conducted a cross-sectional study to assess the joint associations between SUA and serum ALT with NAFLD among elderly Chinese men and women.ResultsAmong 7569 participants with a mean age of 59.8 years (± 13.4 years), 56.6% of women and 43.4% of men were diagnosed as NAFLD, respectively. A positive association between SUA and NAFLD prevalence was observed in both men and women. NAFLD prevalence was 2.74 times (95% CI 2.00–3.76) higher for men and 4.60 times (95% CI 3.39–6.24) higher for women with the highest quintiles of SUA levels compared to those with the lowest levels. SUA levels were significantly associated with prevalence of mild- and severe-steatosis (P < 0.01). In addition, the ORs of NAFLD among participants with high SUA levels and high serum ALT was 10.75 (95% CI 3.56–32.46) for men and 7.96 (95% CI 2.83–22.39) for women, compared with those with low SUA levels and low serum ALT.ConclusionsSUA levels were positively associated with NAFLD prevalence, and the association was slightly stronger in women than in men. A significant joint association of SUA and serum ALT with NAFLD prevalence was observed in all participants, which was slightly stronger in men than in women.

Association Between High Levels of Hepatitis B Core Antibody and Seroclearance of Hepatitis B e Antigen in Individuals With Chronic Hepatitis B Virus Infection

For chronic hepatitis B patients, hepatitis B e antigen (HBeAg) seroclearance signals a transition from an immunologically active phase to an inactive carrier state with a reduction in hepatitis B virus (HBV) DNA levels and a reduced risk of hepatocellular carcinoma (HCC).1 Predictors of HBeAg seroclearance include lower HBV DNA levels, viral genotype, the precore mutation, and higher serum alanine aminotransferase (ALT) levels.2.

Clinical disparity of elevated serum alanine aminotransferase (ALT) levels among the working population of Taipei, Taiwan

Purpose: To explore sex variations in the prevalence and factors of high serum alanine aminotransferase (ALT) level among the working population in Taipei, Taiwan.Methods: This study included 8,351 healthy adults (5,247 men and 3,104 women) who admitted to a teaching hospital voluntarily for a physical examination in 2009. The definitions of occupations include computer and mathematical occupations, architecture and engineering occupations, community and social service occupations, sales and related occupations, office and administrative support occupations, and production occupations. The age distribution of $\leq$ 29 yrs, 30-39 yrs, 40-49 yrs, and $\geq$ 50 yrs were 22.5\%, 36.8\%, 23.5\%, and 17.2\%, respectively. Fasting blood samples were drawn using venipuncture and participants were interviewed with a structured questionnaire.Results: The overall prevalence of high serum ALT level ($\geq $ 40 U/L) was 17.1\%. After stratified the data according to age into four age groups ($\leq$ 29yrs, 30-39 yrs, 40-49 yrs, and $\geq$ 50 yrs) , the men participants revealed a higher prevalence of high serum ALT levels for all age groups than the women participants. Bases on multiple logistic regression models, for the men, the significant factors were associated with high serum ALT level and included age (OR = 0.96, 95\% CI: 0.95-097), BMI [no matter whether overweight (OR = 2.45, 95\% CI: 1.99-3.02) or obese (OR = 4.02, 95\% CI: 3.22-5.03)], hypercholesterolemia (yes vs. no, OR = 1.25, 95\% CI: 1.05-1.48), hypertriglyceridemia (OR = 1.25, 95\% CI: 1.04-1.50), high FPG levels (OR = 1.48, 95\% CI: 1.05-2.09), high AST levels (OR = 26.71, 95\% CI: 19.00-37.54), hyperuricemia (OR = 1.48, 95\% CI: 1.25-1.76), high ALP levels (OR = 1.20, 95\% CI: 1.00-1.45), and high glutamic acid transaminase levels (OR = 4.31, 95\% CI: 3.61-5.14). For the women subjects, the statistically significant factors that were associated with high serum ALT level included BMI [no matter whether overweight (OR = 3.53, 95\% CI: 1.87-6.67) or obese (OR = 4.32, 95\% CI: 2.26-8.23)], high AST levels (yes vs. no, OR = 38.49, 95\% CI: 21.45-49.28), high BUN levels (yes vs. no, OR = 1.66, 95\% CI: 1.03-2.29), and high glutamic acid transaminase levels (yes vs. no, OR = 9.87, 95\% CI: 5.79-16.83).Conclusion: In conclusion, the clinical problem of elevated serum ALT level is important in the working population. Many subjects are asymptomatic and the diagnosis of high serum ALT level should be considered with sex, age, hyperuricemia, high AST levels, high ALP levels, high glutamic acid transaminase levels, and metabolic risk factors in mind.

Effect of probiotic supplementation on liver function and lipid status in rats.

High gut microflora quality plays a crucial role in cardiovascular protection and undisturbed liver function. Currently, the most effective methods to ameliorate gut microbiota influence on the host&rsquo;s cardiovascular health state are investigated. Next to low low-density lipoprotein (LDL) and low non-high-density lipoprotein (non-HDL) serum levels, triglycerides (TG) seem to be a new goal of cardioprotective treatment and prevention. Moreover, it has been documented that high serum alanine transaminase (ALT) is a reliable marker of cardiovascular risk. Probiotics are a well proven factor decreasing blood LDL and total cholesterol (TCH) concentrations. However, the effect of probiotics on serum TG and ALT levels remains underinvestigated. The aim of the study was to compare the effect of 6-week-long supplementation with&nbsp;&nbsp;&nbsp;&nbsp; a multispecies probiotic mixture in two doses on body mass, liver function and lipid profile in the rat model. Thirty &lsquo;Wistar&rsquo; rats were randomly divided into the control group &ndash; KK, a group receiving a probiotic in a daily dose of 2.5&times;109 CFU (PA) and a group receiving a probiotic in a daily dose of 1&times;1010 CFU (PB) for 6 weeks. After 6 weeks body mass, liver mass, serum concentrations of TCH, LDL, high-density lipoprotein (HDL), TG, ALT and aspartate transaminase (AST) were determined. Neither at baseline nor at the end of the experiment were there any differences in the body mass&nbsp; of rats between all three groups. At the completion of the study the liver mass of the rats was significantly lower in the PA and PB vs. KK group. In group PB a significantly lower serum concentration of TG and ALT compared to the KK group was registered at the end of the trial. Six-week-long supplementation with multispecies probiotic mixture exerts a favorable and dose-dependent effect on liver function and lipid profile in the rat model and may also have a favorable influ- ence on cardiovascular impairments. Thus, the inclusion of probiotics supplementation in cardiovascular risk management should be considered.

Host and viral factors associated with serum hepatitis B virus RNA levels among patients in need for treatment.

Hepatitis B virus (HBV) RNA in serum is a novel biomarker for intrahepatic HBV replication and treatment response. For its proper use, it is essential to identify factors influencing serum HBV RNA level. Using a rapid amplification of complimentary DNA (cDNA) ends (RACE) PCR technique (lower limit of detection [LLD], 800 copies/mL [c/mL]), serum HBV RNA levels were measured in samples of 488 untreated individuals with chronic HBV infection who were eligible to treatment according to currently used recommendations. We explored the association of serum levels of HBV RNA with patient‐ and virus‐associated factors. HBV genotype distribution was 21/10/20/46/3% for A/B/C/D/other. Mean HBV RNA serum level was 5.9 (1.6) log10 c/mL (hepatitis B e antigen [HBeAg]‐positive chronic hepatitis B [CHB], 6.5 [1.2] log c/mL; HBeAg‐negative CHB, 4.1 [1.2] log c/mL; P < 0.001). By multivariable linear regression, factors associated with lower HBV RNA level were HBeAg negativity (β = –0.69; P < 0.001), HBV genotypes A (β = –0.13; P = 0.002), B (β = –0.07; P = 0.049), and C (β = –0.61; P < 0.001) in comparison to D, and presence of HBV basal core promoter mutation either alone (β = –0.14; P = 0.001) or in combination with precore mutation (β = –0.22; P < 0.001). Higher serum alanine aminotransferase (ALT) was associated with higher HBV RNA (β = 0.23; P < 0.001). HBV RNA correlated strongly with HBV DNA (HBeAg‐pos, r = 0.72; P < 0.001; HBeAg‐neg, r = 0.78; P < 0.001) and moderately with quantitative hepatitis B surface antigen (qHBsAg; HBeAg‐pos, r = 0.54; P < 0.001; HBeAg‐neg, r = 0.19; P = 0.04) and quantitative hepatitis B surface antigen (qHBeAg; r = 0.41; P < 0.001). Conclusion: In this multiethnic cohort of 488 untreated individuals with CHB, factors associated with serum HBV RNA level were HBeAg status, serum ALT, HBV genotype, and presence of basal core promotor mutations. For the future use of serum HBV RNA as a clinical marker, it seems mandatory to take these factors into consideration. (Hepatology 2018).

The analysis of clinical characteristics and disease activity in ankylosing spondylitis patients with hyperuircemia

Objective: to investigate the clinical characteristics and disease activity in ankylosing spondylitis (AS) patients with hyperuricemia. Method: Laboratory tests, magnetic resonance imaging, disease activity and functional index of AS patients from Fudan University Zhongshan Hospital were collected. T test, square test were applied to investigate the difference between AS patients with hyperuricemia and AS patients with normal serum uric acid in clinical characteristics and disease activity in AS patients. Result: Among all the AS patients, 23.4% (22/94) patients accompanied with hyperuricemia. AS patients accompanied with hyperuricemia showed significant younger age (28.9±7.9 vs 35.8±11.1, P=0.002); higher serum alanine aminotransferase (33.6±23.6 vs 19.8±12.4, P=0.014), aspartate aminotransferase (23.8±8.7 vs 18.6±9.6, P=0.025) and creatinine (78.4±12.5 vs 69.8±13.3, P=0.009), lower Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (11.2±8.8 vs 17.9±12.0, P=0.027) and Bath Ankylosing Spondylitis Functional Index (BASFI) (0.7±0.9 vs 1.8±2.2, P=0.002) compared with AS patients whose serum uric acid level is normal. Conclusion: AS Patients with younger age, impaired hepatic and renal funtion and lower scores in BASDAI and BASFI tend to accompany with hyperuricemia.

Effects of short-term anti-inflammatory glucocorticoid treatment on clinicopathologic, echocardiographic, and hemodynamic variables in systemically healthy dogs.

OBJECTIVE To investigate mechanisms by which anti-inflammatory doses of orally administered intermediate-acting glucocorticoids (prednisone) could predispose dogs to progression of heart disease or congestive heart failure. ANIMALS 11 client-owned dogs with allergic dermatitis and 11 matched healthy control dogs. PROCEDURES Clinicopathologic, echocardiographic, and hemodynamic variables were measured. Dogs with allergic dermatitis then received prednisone (1 mg/kg, PO) once daily for 14 consecutive days beginning on day 0 (baseline), followed by a tapering and washout period; control dogs received no treatment. Measurements were repeated on days 7, 14, and 35. Linear mixed modeling was used to compare changes in variables across measurement points and between dog groups. RESULTS Prednisone administration caused no significant changes in serum sodium or potassium concentration, blood glucose concentration, or target echocardiographic variables. The change from baseline in systolic arterial blood pressure at day 7 was significantly greater in prednisone-treated dogs than in control dogs. Expected changes in hematologic and serum biochemical values with prednisone administration (neutrophilia, eosinopenia, isosthenuria, and high serum alkaline phosphatase and alanine aminotransferase activities) also occurred in the prednisone-treated dogs. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that anti-inflammatory doses of orally administered glucocorticoids have the potential to adversely impact cardiac function in dogs by causing an increase in blood pressure and thus increased cardiac afterload.

Memory Regulatory T cells Increase Only In Inflammatory Phase of Chronic Hepatitis B Infection and Related to Galectin-9/Tim-3 interaction

CD4+Foxp3+ regulatory T cells (Tregs) are the main immune suppressors with subpopulation of inflamed-tissue related memory Tregs (mTregs) and non-related resting Treg (rTregs). Previously, Treg was proposed to be the cause of chronicity of hepatitis B virus (HBV) infection but with controversies. We then investigated the role of mTregs in distinct immune phases of chronic HBV infection, especially the non-inflammatory versus inflammatory phases. It was found mTregs but not rTregs increased only in the inflammatory phase and correlated with serum alanine aminotransferase (ALT) level. These mTregs accumulated in the inflamed liver, expressed significantly higher Tim-3, CCR4, CCR5 and fewer CCR7, and possessed potent suppressive function. These mTregs mainly originated from natural Tregs because of high Helios expression. Hierarchical clustering analysis showed higher frequency of mTreg was concordant with higher serum ALT and galectin-9 levels. Furthermore, galectin-9 could expand mTregs through galectin-9/Tim-3 interaction. In conclusion, increased mTregs are found only in inflammatory phase of chronic HBV infection. Galectin-9, associated with liver inflammation, contributes to the expansion of mTregs through galectin-9/Tim-3 interaction. Therefore, this expansion of mTregs only reflects as an immune regulatory mechanism to limit the on-going liver damages rather than the cause of chronicity of HBV infection.

Hepatitis B virus (HBV) X gene mutations and their association with liver disease progression in HBV-infected patients.

Hepatitis B virus (HBV) is one of the most widespread human pathogens causing chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). This study investigated the clinical impact of single and combinational mutations in HBx gene on the pathogenesis of HCC during progressive stages of liver disease. The patients were categorized into inactive HBV carriers, active carriers, cirrhosis and HCC groups based on disease severity. Male sex, age > 50 years, and high serum alanine aminotransferase level were associated with risk of progressive liver disease. I127T, V131I, and F132Y/I/R mutations showed a significant increasing trend associated with the disease progression to HCC. H94Y and K130M mutations were also significantly associated with severe liver disease. One double mutation (K130M+V131I) and two triple mutations (I127T+K130M+V131L and K130M+V131I+F132Y) were observed, with significant rising prevalence through progressive clinical phases of liver disease to HCC. Several single and combinational mutations in HBx correlating with severity and progressive clinical phases of HBV infection were identified. The mutational combinations may have a synergistic effect in accelerating the progression to HCC. These specific patterns of HBx mutations can be useful in predicting the clinical outcome of HBV-infected patients and may serve as early markers of high risk of developing HCC.

Characteristics of autoimmune hepatitis in a sample of Egyptian children

BackgroundAutoimmune hepatitis is a rare liver disease that can be presented aggressively in children. Early treatment can control the hyper immune state and save the liver. The aim of the workTo assess clinical manifestations, biochemical features, and response to immunosuppressive drugs in children with AIH. Methods25 children with AIH, based on the International Scoring Criteria of Autoimmune Hepatitis (IAIHG score system), recruited from Pediatric Hepatology clinic, Benha University Hospitals have been analyzed for their clinical, biochemical features, histological profile and their response to treatment. Results25 children were 15 female (60%) and 10 male (40%) their ages ranged from 3 to 15 years old. The main clinical presentation were jaundice (68.0%), abdominal pain (48.0%), acute hepatic-like illness was the first presentation in (32.0%), hepatomegaly (80.0%), splenomegaly (40.0%) lower limb edema (12.0%), and ascites (12.0%). All patients at first presentations had high serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum immunoglobulin G (IgG). According to the autoantibody profile, all children were classified as AIH type 1 as no patient was seropositive for anti-liver kidney microsome antibody (anti-LKM). Prednisone with or without azathioprine was started and complete remission noticed in 13 (52.0%) while 12 (48.0%) had relapses. ConclusionAIH type 1 was the main type of autoimmune hepatitis in children referred to Benha University Hospitals. Females more affected than boys. The combination of prednisone and azathioprine are effective in abating the inflammatory process in most of the cases. Early diagnosis and treatment of AIH had apparently good outcome in children.

Treatment of mandibular osteomyelitis in two red-necked wallabies (Macropus rufogriseus) by means of intensive long-term parenteral drug administration and serial computed tomographic monitoring

CASE DESCRIPTION 2 female red-necked wallabies (Macropus rufogriseus) were evaluated because of sudden-onset mandibular swelling, ptyalism, and hyporexia. CLINICAL FINDINGS Physical examination revealed a mandibular swelling with a fluctuant center in both wallabies. Hematologic analysis revealed leukocytosis with a mature neutrophilia and monocytosis in one wallaby (case 1) and a slight neutrophilia, hyperglobulinemia, and high serum alanine aminotransferase activity in the other (case 2). Cytologic examination of the swelling revealed a uniform population of gram-negative rods in case 1 and neutrophilic inflammation in case 2. Radiography revealed a soft tissue mandibular swelling with osteolucency around mandibular incisor roots in both wallabies. Computed tomography revealed changes consistent with chronic active mandibular osteomyelitis and reactive bone formation, but also sequestra formation not appreciable via radiography. TREATMENT AND OUTCOME Long-term antimicrobial treatment was initiated with clindamycin (17 to 21 mg/kg [7.7 to 9.5 mg/lb], IV, q 12 h for 40 to 55 days) and high-dose benzathine penicillin G (80,000 U/kg [36,364 U/lb], SC, q 12 h for 150 days). Serial CT was performed to evaluate response to treatment and resolution of disease. A CT scan 18 months after the initial evaluation revealed complete resolution of osteomyelitis and sequestra. CLINICAL RELEVANCE Advanced imaging and long-term treatment and management were integral to the successful outcome for these wallabies, given that the osseous changes visible on CT images were not visible on standard radiographs, guiding therapeutic decision-making. This report provides new therapeutic and diagnostic monitoring information to assist clinicians with similar cases.

Antioxidant protection by β-selenoamines against thioacetamide-induced oxidative stress and hepatotoxicity in mice.

Thioacetamide (TAA) is a hepatotoxin that rapidly triggers the necrotic process and oxidative stress in the liver. Nevertheless, organic selenium compounds, such as β-selenoamines, can be used as pharmacological agents to diminish the oxidative damage. Thus, the aim of this study was to investigate the protective effect of the antioxidant β-selenoamines on TAA-induced oxidative stress in mice. Here, we observed that a single intraperitoneal injection of TAA (200mg/kg) dramatically elevated some parameters of oxidative stress, such as lipid peroxidation and reactive oxygen species (ROS) production, as well as depleted cellular antioxidant defenses. In addition, TAA-induced edema and morphological changes in the liver, which correlate with high serum aspartate and alanine aminotransferase enzyme activities, and a decrease in cell viability. Conversely, a significant reduction in liver lipid peroxidation, ROS production, and edema was observed in animals that received an intraperitoneal injection of β-selenoamines (15.6mg/kg) 1h after TAA administration.