Higher Serum Alanine Aminotransferase Levels Research Articles

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

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

Prevalence, characteristics, and risk factors of non-alcoholic fatty liver disease in North East of Iran: a population-based study

BackgroundNonalcoholic fatty liver disease (NAFLD) is a common dietary disorder caused by fatty changes in the liver parenchyma and hepatocytes without alcohol consumption. The present study aimed to investigate the prevalence, characteristics, and risk factors of NAFLD in the Mashhad Persian Cohort Study population.MethodThe present population-based cross-sectional study included all PERSIAN Organizational Cohort study in Mashhad University of Medical Sciences (POCM), Mashhad, Iran by census sampling method. Eligible participants were divided into two groups due to their NAFLD condition (NAFLD positive or NAFLD negative). All enrolled participants were evaluated based on their clinical aspects, anthropometric measures, laboratory tests, and ultrasound features. Statistical analysis was conducted using SPSS software version 16 (SPSS Inc., Chicago, USA –version 16). A P-value less than 0.05 was considered as the significance level.ResultsA total of 1198 individuals were included in the study, of which 638 (53.3%) were male and the rest were female. The mean age of the participants was 46.89 ± 8.98 years. A total of 246 patients (20.53%) were NAFLD positive, of which 122 (49.59%) were in grade 1, 112 (45.52%) were in grade 2, and 12 (4.87%) were in grade 3. The prevalence of fatty liver was significantly higher in males than in females (p < 0.001). There were significant differences between NAFLD positive and NAFLD negative participants in terms of having a history of hypertension (P = 0.044), body mass index (P < 0.001), body fat percentage (P = 0.001), waist circumference (P < 0.001), liver craniocaudal length (P = 0.012), fasting blood sugar (FBS) (P = 0.047), aspartate aminotransferase (AST) (P = 0.007), and alanine aminotransferase (ALT) (P = 0.001). Further analysis revealed a strong significant association between BMI, previous history of hypertension, higher levels of serum ALT, and NAFLD (P < 0.05).ConclusionIt can be concluded that ultrasound findings accompanied by laboratory AST and ALT level enzymes could be a cost-benefit approach for NAFLD early diagnosis. The craniocaudal size of the liver could be a beneficent marker for estimating the severity of the disease; however, more studies are recommended to evaluate this variable for future practice against the issue.

Higher serum alanine aminotransferase levels and the incidence of hypertension: The Kailuan cohort study

ObjectiveThe association between serum alanine aminotransferase (ALT) concentrations and the incidence of hypertension remains unclear. To explore the association between serum ALT levels and the risk of incident hypertension based on the Kailuan cohort study. MethodsPeople who had participated in health check-ups in 2006–2007 without hypertension, cardiovascular, or liver diseases were enrolled and received follow-ups every two years until December 2017. Hypertension was defined as systolic blood pressure/diastolic blood pressure ≥140/90 mmHg or using anti-hypertensive medication. A multivariable-adjusted Cox regression model was used to estimate the hazard ratio (HR) and its corresponding 95 % confidence intervals (95 % CIs). ResultsDuring 10.5 years of follow-up, 24,023 (50.7 %) participants were diagnosed with hypertension. The HR of incident hypertension was 1.02 (95 % CI=1.01–1.03) for each 10 U/L increment of ALT concentrations. Participants with elevated ALT levels (>40 U/L) had an increased incidence of hypertension by 7 % (HR =1.07; 95 % CI=1.01–1.13). Besides, the HR was 1.10 (95 % CI=1.06–1.15), 1.13 (95 % CI=1.08–1.18), and 1.22 (95 % CI=1.16–1.30) (P for trend <0.001) in (10–20], (20–30], and (30–40] groups, compared with ≤10 U/L group. In addition, participants whose ALT levels decreased to the normal range at the first follow-up had a 23 % lower incidence of hypertension than those with elevated ALT levels at baseline and the first follow-up. ConclusionPeople with higher serum ALT levels may have an increased risk of incident hypertension and thus may benefit from heightened surveillance for hypertension and lifestyle interventions to reduce the risk of hypertension.

Quantitative PCR-based high-sensitivity detection of HBV-DNA levels reflects liver function deterioration in patients with hepatitis B virus-related cirrhosis.

To investigate the clinical implication of quantitative polymerase chain reaction (PCR)-based high-sensitivity detection of hepatitis B virus (HBV)-DNA levels in patients with HBV-related liver cirrhosis (LC). From January 2020 to December 2022, 100 fasting serum samples were collected and retrospectively analyzed from patients with treated HBV-related LC attending the Suzhou Hospital of Integrated Traditional Chinese and Western Medicine and Suzhou Guangci Cancer Hospital. Patients were divided into a negative group (HBV-DNA < 20 IU/mL) and a positive group (HBV-DNA ≥ 20 IU/mL) according to their high-sensitivity HBV-DNA test results. The clinical characteristics and serological indicators of the two groups were compared, mainly including gender, age, liver function [total protein (TP), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL)], lipids [total cholesterol (TC) and triglycerides (TG)], platelets (PLT), five serum liver fibrosis markers [cholyglycine (CG), hyaluronic acid (HA), laminin (LN), precollagen type III (PCIII), and type IV collagen (IV-C)], serum gastrointestinal tumor markers [α-fetoprotein (AFP) and carcinoembryonic antigen (CEA)], and hepatitis B surface antigen (HBsAg). The differences between the two groups in terms of liver function Child-Pugh grades and the incidence of hepatocellular carcinoma (HCC) were also compared. There were 39 patients in the positive group, including 29 males and 10 females, and 61 patients in the negative group, including 38 males and 23 females, with no statistically significant differences in gender and age distribution between the two groups (P > 0.05). The levels of serological indicators (TP, ALB, AST, GGT, ALP, TBIL, DBIL, IBIL, TC, TG, PLT, CG, HA, LN, PCIII, IV-C, AFP, CEA, and HBsAg) in both groups showed no significant differences (P > 0.05), but the ALT level in the positive group was higher than that in the negative group (P < 0.0001). The positive group had worse Child-Pugh grades and higher HCC incidence compared to the negative group (P < 0.0001, P = 0.028). Patients with HBV-related LC and HBV-DNA ≥ 20 IU/mL have higher serum ALT levels, worse liver function Child-Pugh grades, and higher HCC incidence than those with HBV-DNA < 20 IU/mL. High-sensitivity HBV-DNA quantification can reflect the deterioration of liver function in patients with HBV-related LC to some extent.

The prevalence and impact of small intestine bacterial overgrowth in biliary atresia patients.

Acute cholangitis is an ominous complication in biliary atresia (BA) patients. We investigated the prevalence of small intestine bacterial overgrowth (SIBO) in BA patients and its role in predicting acute cholangitis. There are 69 BA patients with native liver recruited into this study prospectively. They received hydrogen and methane-based breath testing (HMBT) to detect SIBO after recruitment and were followed prospectively in our institute. There are 16 (23.19%) subjects detected to have SIBO by HMBT. BA subjects with SIBO were noted to have higher serum alanine aminotransferase levels than others without SIBO (P = 0.03). The risk of acute cholangitis is significantly higher in BA patients with SIBO than in others without SIBO (62.50% vs. 15.09%, P < 0.001). The logistic regression analysis demonstrated that BA subjects with SIBO have a higher risk of acute cholangitis than others without SIBO (odds ratio = 9.38, P = 0.001). Cox's proportional hazard analysis further confirmed the phenomena in survival analysis (hazard ratio = 6.43, P < 0.001). The prevalence of SIBO in BA patients is 23.19% in this study. The presence of SIBO is associated with the occurrence of acute cholangitis in BA patients. What is the key message of your article? Acute cholangitis is common in BA, and is associated with SIBO after hepatoportoenterostomy in this study. What does it add to the existing literature? This study demonstrated that SIBO is common in BA after hepatoportoenterostomy, and is predictive of acute cholangitis and elevated serum ALT levels in BA. What is the impact? This prospective cohort study provides data regarding the significance of SIBO on the risk of acute cholangitis in BA patients.

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

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

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

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

From the Editor’s Desk...

From the Editor’s Desk...

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

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

Osr1 regulates hepatic inflammation and cell survival in the progression of non-alcoholic fatty liver disease

Odd-skipped related 1 (Osr1) is a novel tumor suppressor gene in several cancer cell lines. Non-alcoholic steatohepatitis (NASH) is considered as a high-risk factor for hepatocellular carcinoma (HCC). This study is aimed to investigate the novel role of Osr1 in promoting the progression of hepatic steatosis to NASH. Following 12 weeks of diethylnitrosamine (DEN) and high-fat diet (HFD), wildtype (WT) and Osr1 heterozygous (Osr1+/−) male mice were examined for liver injuries. Osr1+/− mice displayed worsen liver injury with higher serum alanine aminotransferase levels than the WT mice. The Osr1+/− mice also revealed early signs of collagen deposition with increased hepatic Tgfb and Fn1 expression. There was overactivation of both JNK and NF-κB signaling in the Osr1+/− liver, along with accumulation of F4/80+ cells and enhanced hepatic expression of Il-1b and Il-6. Moreover, the Osr1+/− liver displayed hyperphosphorylation of AKT/mTOR signaling, associated with overexpression of Bcl-2. In addition, Osr1+/− and WT mice displayed differences in the DNA methylome of the liver cells. Specifically, Osr1-responsible CpG islands of Ccl3 and Pcgf2, genes for inflammation and macrophage infiltration, were further identified. Taken together, Osr1 plays an important role in regulating cell inflammation and survival through multiple signaling pathways and DNA methylation modification for NAFLD progression.

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

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

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

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

Evaluation of the mechanism of cordyceps polysaccharide action on rat acute liver failure.

IntroductionThis study aimed to investigate the mechanism of action of cordyceps polysaccharide on rat acute liver failure (ALF).Material and methodsSixty rats were randomly divided into five groups: a normal group, a model group without cordyceps polysaccharide and groups with cordyceps polysaccharide in three different doses (5, 10 and 20 mg/ml). Serum alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL) contents were measured for assessing liver function. Hematoxylin and eosin (HE) staining was used for observing liver pathology. Apoptosis was detected through the method of terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining. Protein expression levels of caspase-1, interleukin-18 (IL-18), IL-10, vascular endothelial growth factor (VEGF), and stromal cell-derived factor-1α (SDF-1α) in liver tissue were detected by Western blot. Proliferating cell nuclear antigen (PCNA) and signal regulatory protein-α1 (SIRPα1) contents were measured by PCR.ResultsThe rat ALF model was established with D-galactosamine induced by lipopolysaccharide (LPS). After modelling, tissue HE staining showed typical manifestation of acute liver injury that emerged in the rat ALF model. The liver failure group showed higher levels of serum ALT and AST, as well as hepatocyte apoptosis, than the groups treated with cordyceps polysaccharide. Cordyceps polysaccharide can effectively suppress the protein expression of caspase-1, IL-18, and IL-10, while simultaneously increasing the protein expression of VEGF and SDF-1α, as well as the mRNA expression of PCNA and SIRPα1.ConclusionsCordyceps polysaccharide can alleviate the immune response and inflammatory injury in ALF by regulating the balance of pro-inflammatory and anti-inflammatory factors and reducing the apoptosis.

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.&#x0D; 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.&#x0D; 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).&#x0D; Conclusion: Over two-thirds of T2DM patients having NAFLD had metabolic syndrome in this study.&#x0D; Birdem Med J 2020; 10(1): 21-25

Downregulating Serine Hydroxymethyltransferase 2 Deteriorates Hepatic Ischemia-Reperfusion Injury through ROS/JNK/P53 Signaling in Mice

Background Serine hydroxymethyltransferase 2 (SHMT2) activity ensures that cells have a survival advantage in ischemic conditions and regulates redox homeostasis. In this study, we aimed to investigate the role of SHMT2 after hepatic ischemia-reperfusion (IR), which involves hypoxia, ischemic conditions, and cell apoptosis. Methods A 70% IR model was established in C57BL/6J mice with or without SHMT2 knockdown. H&E staining, liver weight/body weight, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels and cell apoptosis were tested to analyze liver damage and function. Then, the related cellular signals were probed. Results The level of SHMT2 protein was significantly increased at 24 h and 48 h after IR (p < 0.001). Mice in the shSHMT2 group showed more necrotic areas and histological damage at 24 h (p < 0.01) after IR and higher levels of serum ALT and AST (p < 0.05) compared with those of mice in the scramble group. After IR for 24 h, the expression of TUNEL in the shSHMT2 group was significantly higher than that in the scramble group, as shown by histological analysis (p < 0.01). Mechanistically, the JNK/P53 signaling pathway was activated by IR, and knockdown of SHMT2 exacerbated hepatocyte apoptosis. Conclusions Knockdown of SHMT2 worsens IR injury through the ROS/JNK/P53 signaling pathway. Our discovery expands the understanding of both molecular and metabolic mechanisms involved in IR. SHMT2 is a possible therapeutic target to improve the prognosis of liver transplantation (LT) and subtotal hepatectomy.

Comparison of Clinical Symptoms and Cardiac Lesions in Children with Typical and Atypical Kawasaki Disease.

The present study was performed to evaluate the clinical symptoms and cardiovascular complications in patients with typical and atypical Kawasaki disease (KD). This retrospective study was conducted on the medical records of 176 patients with KD for three years. The study population was divided into two groups of typical and atypical based on the KD clinical criteria. The two groups were compared in terms of demographic data, clinical symptoms, cardiac lesions, and laboratory markers. Based on the diagnostic criteria, 105 (60%) and 71 (40%) patients were diagnosed with typical and atypical KD, respectively. The mean age of the typical patients (38.16 months) was higher than that of the atypical group (24.03 months) at the time of diagnosis (p < 0.05). The results revealed no significant difference between the two groups regarding the seasonal distribution of KD onset (p = 0.422). However, the most common season for the diagnosis of the disease was spring, followed by winter. There was no significant difference between the two groups in terms of fever duration (p = 0.39). Furthermore, vomiting was more common in the atypical patients than in the typical group (p = 0.017). In terms of the cardiac lesions, ectasia (p = 0.005) and lack of tapering of the distal coronary vessels (p = 0.015) were more frequently detected in the atypical group than in the typical group. Considering the laboratory findings, thrombocytosis (p = 0.010) and anemia (p = 0.048) were more common in the atypical group, compared to those in the typical group. On the other hand, the typical group had a higher serum alanine aminotransferase level (adjusted for age) (p = 0.012) and Hyponatremia (serum sodium concentration ≤130 mmol/L) (p = 0.034). Based on the findings of the current study, the fever duration from onset to diagnosis was slightly more in atypical KD patients than in the typical group, but not statistically significant, possibly due to more timely diagnosis of atypical KD. There was no difference in coronary aneurysm between the two groups at the time of diagnosis. The atypical group had a higher frequency of coronary ectasia and lack of tapering, indicating cardiac involvement. Consequently, these conditions should be given more attention in the atypical patients. Furthermore, the higher frequency of anemia and thrombocytosis in the atypical patients can be useful for diagnosis of this kind of KD.

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

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.

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.

γδ T cells are indispensable for interleukin-23-mediated protection against Concanavalin A-induced hepatitis in hepatitis B virus transgenic mice.

Hepatitis B virus surface antigen (HBsAg) carriers are highly susceptible to liver injury triggered by environmental biochemical stimulation. Previously, we have reported an inverse correlation between γδ T cells and liver damage in patients with hepatitis B virus (HBV). However, whether γδ T cells play a role in regulating the hypersensitivity of HBsAg carriers to biochemical stimulation-induced hepatitis is unknown. In this study, using HBV transgenic (HBs-Tg) and HBs-Tg T-cell receptor-δ-deficient (TCR-δ-/- ) mice, we found that mice genetically deficient in γδ T cells exhibited more severe liver damage upon Concanavalin A (Con A) treatment, as indicated by substantially higher serum alanine aminotransferase levels, further elevated interferon-γ (IFN-γ) levels and more extensive necrosis. γδ T-cell deficiency resulted in elevated IFN-γ in CD4+ T cells but not in natural killer or natural killer T cells. The depletion of CD4+ T cells and neutralization of IFN-γ reduced liver damage in HBs-Tg and HBs-Tg-TCR-δ-/- mice to a similar extent. Further investigation revealed that HBs-Tg mice showed an enhanced interleukin-17 (IL-17) signature. The administration of exogenous IL-23 enhanced IL-17A production from Vγ4 γδ T cells and ameliorated liver damage in HBs-Tg mice, but not in HBs-Tg-TCR-δ-/- mice. In summary, our results demonstrated that γδ T cells played a protective role in restraining Con A-induced hepatitis by inhibiting IFN-γ production from CD4+ T cells and are indispensable for IL-23-mediated protection against Con A-induced hepatitis in HBs-Tg mice. These results provided a potential therapeutic approach for treating the hypersensitivity of HBV carriers to biochemical stimulation-induced liver damage.