Elevated Aminotransferase Levels Research Articles

Clinical analysis and follow-up results of 25 children with glycogen storage disease

Objective: To investigate the clinical characteristics, genetic characteristics and follow-up of hepatic glycogen accumulation in order to further improve the prognosis of children with hepatic glycogen accumulation. Methods: Clinical data of hospitalized children diagnosed with hepatic glycogen accumulation disease in the Department of gastroenterology, Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2010 to April 2023 were collected and retrospectively analyzed. The results of laboratory examination and gene sequencing were analyzed, and the patients with more than 3 cases (n) were grouped according to the genetic results: Group 1 was type Ⅰ (n=8), group 2 was type Ⅲ (n=5), and group 3 was type Ⅸ a (n=8). The growth, development and prognosis of the children were followed up, and the related clinical characteristics of pediatric hepatic glycogen accumulation were summarized. Results: A total of 25 children with hepatic accumulation of glycogen were included in the study, including 15 males and 10 females. The mean age of diagnosis was (29.1±13.5) months. There were 12 cases (48%) with varying degrees of hypoglycemia, and 2 cases (8%) with severe hypoglycemia. There were 19 cases with height retardation (76%), 4 cases with anemia (16%), 3 cases with proteinuria (12%), and 1 case with cholestasis (4%). The genetic results showed that there were 4 cases of type Ⅰ a (16%), 4 cases of type Ⅰ b (16%), 1 case of type Ⅱ (4%), 5 cases of type Ⅲ (20%), 2 cases of type Ⅳ (8%), 1 case of type Ⅵ (4%), and 8 cases of type Ⅸ (32%). By analyzing the three subgroups, there were statistically significant differences in uric acid and triglyceride (P<0.05), while there were no statistically significant differences in aminotransferase levels, fasting blood glucose, lactic acid, cholesterol and low density lipoprotein levels (P>0.05). The height-specific age Z scores of the three groups were compared, which were -2.86±1.62, -1.46±1.06 and -1.83±0.98, respectively. After at least 1 year of follow-up, the growth and development of groups 2 and 3 were significantly improved compared with group 1 (P<0.05), and the Z scores were -2.28±1.07, 0.20±1.54 and 0.10±1.44. After more than 1 year of follow-up, all the children with type IX had stopped using raw corn starch and had normal transaminase. 4 patients with type Ia were taking raw corn starch orally regularly. Aminotransferase, uric acid and lactic acid were normal, and hypoglycemia was detected among them.Among the 4 cases of type Ⅰb, 1 case had recurrent respiratory and intestinal infections, and 2 cases had Crohn's disease.4 cases of type Ⅲ had stopped using raw corn starch and adopted high protein and low carbohydrate diet. The aminotransferase was normal except for high creatine kinase. One case of type Ⅵ died of liver failure.2 cases were type Ⅳ, 1 died and 1 had a slightly elevated transaminase level. Conclusion: When it is found that the children have liver enlargement, elevated aminotransferase, fasting hypoglycemia, and backward growth and development, it is necessary to be vigilant about liver glycogen accumulation.Clinical manifestations, biochemical indicators combined with genetic examination are helpful for the diagnosis of hepatic glycogen accumulation. Meanwhile, nutritional management is targeted according to the metabolic characteristics of different subtypes, and attention is paid to growth and development.

Induction of Cyp2e1 contributes to asparaginase-induced hepatocyte sensitization to lipotoxicity

One of the leading therapies for acute lymphoblastic leukemia (ALL) is the chemotherapeutic agent PEGylated E. coli-derived-l-asparaginase (PEG-ASNase). Due to the high risk of dose-limiting liver injury, characterized by clinically elevated levels of hepatic transaminases, PEG-ASNase therapy is generally avoided in adult patients. Our preclinical investigations have indicated that PEG-ASNase-induced liver injury is associated with the release of free fatty acids (FFAs) from white adipose tissue (WAT), suggesting potential lipotoxic effects. However, it remains uncertain whether PEG-ASNase directly induces hepatotoxicity or sensitizes hepatocytes to FFA-induced toxicity. Our results show that PEG-ASNase treatment results in hepatocyte apoptosis and lipid peroxidation. Ex vivo and in vitro studies in mouse and human WAT suggest that PEG-ASNase induces the expression of adipose triglyceride lipase (ATGL), activates the lipase, and stimulates adipose tissue lipolysis, suggesting that the FFAs from WAT may contribute to the observed liver injury. Moreover, treatment with PEG-ASNase sensitizes hepatocytes to FFA-induced lipotoxicity. Mechanistically, our RNA-sequencing (RNA-seq) analyses reveal that PEG-ASNase-induced sensitization to lipotoxicity is accompanied by the induction of Cyp2e1. We demonstrated that this sensitization effect is attenuated by both pharmacological and genetic inhibition of Cyp2e1. Our findings suggest that PEG-ASNase therapy induces WAT lipolysis and sensitizes hepatocytes to hepatic lipotoxicity in a Cyp2e1-dependent manner.

The Impact of SARS-CoV-2 on Liver Diseases and Potential Phytochemical Treatments

Abstract The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has brought about numerous challenges. One of these challenges is the impact of SARS-CoV-2 on the liver. Although this virus primarily affects the lungs, it can induce elevated transaminase levels and the development of scar tissue in the liver, exacerbating preexisting liver conditions. Individuals with preexisting conditions, such as non-alcoholic fatty liver disease (NAFLD), alcohol-induced liver disease (ALD), and hepatocellular carcinoma (HCC), face an increased risk of mortality from COVID-19. However, drugs currently used to treat COVID-19 have undesirable side effects that make them unsuitable for patients with pre-existing liver conditions. In this review, we explore the potential of phytochemicals, such as apigenin, berberine, curcumin, epigallocatechin-3-gallate, quercetin, resveratrol and silymarin, for treatment of the liver conditions NAFLD, ALD and HCC. We also discuss significant associations between phytochemicals and COVID-19 by depicting their molecular interactions. Based on the discussed overlapping functions, it is important to assess the therapeutic efficacy of phytochemicals that possess hepatoprotective properties as potential alternative COVID-19 treatments.

Disparities in steatosis prevalence in the United States by Race or Ethnicity according to the 2023 criteria

IntroductionThe 2023 nomenclature defined criteria for steatotic liver disease (SLD), including metabolic dysfunction-associated SLD (MASLD), alcohol-associated liver disease (ALD), and the overlapping MASLD/ALD (MetALD). We aimed to assess racial and ethnic disparities in the SLD prevalence among United States (US) adults based on this new nomenclature.MethodsWe undertook a cross-sectional study employing the 2017–2018 National Health and Nutrition Examination Survey (NHANES) database. We identified SLD according to a controlled attenuation parameter ≥288 dB/m, liver stiffness ≥7.2 kPa, or elevated aminotransferase levels. Alcohol use thresholds were established according to the updated SLD definition. We estimated prevalences using the complex design of the NHANES survey. Multivariable logistic regressions with complex design weights were employed.ResultsA total of 5532 individuals are included. The mean age is 45.4 years, and 50.9% are women. The adjusted estimated prevalence of MASLD is 42.4% (95% CI: 41.1–43.8%), MetALD 1.7% (95% CI: 1.3–2.0%), and ALD 0.6% (95% CI: 0.3–0.8%). Hispanics exhibit a higher prevalence of SLD, but there are no significant differences in advanced fibrosis prevalence due to SLD among racial/ethnic groups. In MASLD, men, individuals aged 40–64 and ≥65 years, Hispanics, those with health insurance, higher BMI, diabetes, hypertension, hypertriglyceridemia, and low high-density lipoprotein (HDL) cholesterol or use of lipid-lowering agents are independently associated with a higher risk, while Blacks have the lowest risk. In MetALD, men and higher BMI are independently associated with a higher risk of MetALD in adjusted multivariable analysis. In ALD, the adjusted multivariable analysis shows that only health insurance is independently associated with a lower ALD risk.ConclusionsMASLD prevalence is high in the US, especially in men, older individuals, and Hispanics. MetALD and ALD prevalence was substantial but could be underestimated.

5-Fluorouracil combined with CalliSphere drug-eluting beads or conventional transarterial chemoembolization for unresectable hepatocellular carcinoma: a propensity score weighting analysis

This study aimed to assess the effectiveness and safety of 5-Fluorouracil (5-Fu) combined with conventional transarterial chemoembolization (cTACE) compared to 5-Fu combined with drug-eluting bead transarterial chemoembolization (DEB-TACE) using CalliSpheres for the treatment of unresectable hepatocellular carcinoma (HCC) using propensity score weighting methods. This retrospective analysis included 131 patients with HCC treated with 5-Fu combined with cTACE (5-Fu-cTACE group, n = 65) or DEB-TACE (5-Fu-DEB-TACE group, n = 66) at the Affiliated Hospital of North Sichuan Medical College from January 2019 to December 2022. Based on the baseline data and laboratory indicators, propensity score weighting was used to reduce confounding bias. Modified response evaluation criteria in solid tumors (mRECIST) were used to evaluate clinical efficacy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the disease control rate (DCR), objective response rate (ORR) and adverse events (AEs). PFS was assessed using Kaplan‒Meier analysis and Cox proportional hazards models. The ORRs at 1 month (M1) after treatment in the 5-Fu-DEB-TACE group and 5-Fu-cTACE group were 90.9% and 76.9%, respectively (P = 0.029), while at this time, the DCRs were 93.9% in the 5-Fu-DEB-TACE group and 90.8% in the 5-Fu-cTACE group (P = 0.494). At 3 months (M3) after treatment, the 5-Fu-DEB-TACE group had a higher ORR (84.8% vs. 56.9%, P < 0.001) and DCR (84.8% vs. 72.3%, P = 0.08). The ORR at 6 months (M6) was also higher in the 5-Fu-DEB-TACE group than in the 5-Fu-cTACE group (72.7% vs. 50.8%, P = 0.01). The median PFS after treatment with 5-Fu-DEB-TACE was longer than that after treatment with 5-Fu-cTACE (11 months vs. 6 months) (P = 0.004). Cox proportional hazards regression analysis indicated that 5-Fu-DEB-TACE (HR = 0.590, P = 0.044), Model for End-Stage Liver Disease (MELD) intermediate risk (HR = 2.470, P = 0.010), BCLC stage B (HR = 2.303, P = 0.036), BCLC stage C (HR = 3.354, P = 0.002) and ascitic fluid (HR = 2.004, P = 0.046) were independent predictors of PFS. No treatment-related deaths occurred in this study. The 5-Fu-DEB-TACE group had a greater incidence of abdominal pain (72.7% vs. 47.7%, P = 0.003). However, the incidence of postoperative elevated transaminase levels was higher in the 5-Fu-cTACE group (83.1% vs. 66.6%, P = 0.031). Subgroups analysis showed patients receiving 5-Fu-DEB-TACE have better PFS compared to those receiving 5-Fu-cTACE in the BCLC stage A group (P = 0.0093), BCLC stage B group (P = 0.0096), multifocal group (P = 0.0056), Child-Pugh stage A group (P<0.001), non- extrahepatic metastasis group (P = 0.022), non-vascular invasion group (P = 0.0093), and the group with a largest tumor diameter ≥ 5 cm (P = 0.0048). At M1, M3, and M6, patients with preserved liver function and in some cases of low tumor burden had higher Objective Response Rate (ORR) and Disease Control Rate (DCR) (P < 0.05). Compared with 5-Fu-cTACE, 5-Fu-DEB-TACE has superior therapeutic efficacy, prolongs PFS, and reduces hepatotoxicity. However, it is associated with an increased incidence of postoperative abdominal pain.

Outbreak investigation of food poisoning attributed to Omphalotus japonicus using polymerase chain reaction‐based sequencing

AbstractObjectiveThis study aims to report and analyse an outbreak of Omphalotus japonicus poisoning following mushroom ingestion in Taiwan, and to employ PCR methods for accurate identification of the toxic mushrooms involved.MethodsA descriptive observational study was conducted involving a family of four who ingested the mushrooms in the mountainous rural area of Yilan County, Taiwan. Data were collected through interviews with the affected individuals and a review of their medical records. Due to the destruction of the mushroom samples, Polymerase Chain Reaction (PCR) methods were utilized for identification. Genomic DNA was extracted from the raw fruiting bodies, and specific primers targeting the internal transcribed spacer region of the nuclear ribosomal DNA were designed for PCR detection.ResultsThree family members (mother, daughter, and son) experienced gastrointestinal symptoms, including nausea, vomiting, abdominal cramps, and diarrhea, approximately 30 min after consuming the mushrooms. Upon admission to the emergency room, they were hydrated and monitored, with laboratory results showing slightly elevated alanine transaminase levels. The affected individuals recovered within 12 h and were discharged in good condition on day 2. PCR analysis of the mushroom sample confirmed the identification of Omphalotus japonicus, known to produce Illudin S and Illudin M, which cause acute gastrointestinal symptoms. This case represents the first documentation of using PCR‐based sequencing to diagnose Omphalotus japonicus poisoning in the English literature.

Secondary Dengue Infection Elicits Earlier Elevations in IL-6 and IL-10 Levels.

This study investigates the kinetics of interleukine-6 (IL-6) and interleukine-10 (IL-10) levels in dengue virus (DENV) infections during the febrile stage. Viremic patients were categorized into two phases based on anti-DENV IgM presence. Among 259 patients, 71% were in Phase I and 29% in Phase II. Secondary infections, accounting for 38.2% of cases, exhibited earlier elevations of IL-6 and IL-10 than primary infections, suggesting that pre-existing immune memory primes faster cytokine release. Thrombocytopenia and elevated aspartate transaminase (AST) levels were associated with Phase II, secondary infections, and hospitalization. Elevated IL-6 and IL-10 levels correlated with low platelet counts, linking them to clinical manifestations. The key finding is that IL-6 and IL-10 levels rise earlier in secondary infections compared to primary infections, whereas elevated cytokine levels typically occur later in the febrile phase. This study highlights the importance of cytokine dynamics in DENV infections, particularly during the early stages. The observation of cytokine concentration changes, especially in viremic samples, provides insights into the progression of dengue disease. Further research with broader cytokine panels is warranted to validate and expand these findings.

Prognostic value of elevated transaminase levels as predictors of adverse outcomes in patients with acute myocardial infarction

Aim. To assess the prevalence of elevated serum liver transaminases (LTs), including alanine aminotransferase (ALT) and aspartate aminotransferase (ALT), and their impact on in-hospital and long-term mortality in patients with acute myocardial infarction (AMI).Materials and methods. The prospective observational study included 416 consecutive AMI patients (median age 65 years, 40.9% female, 46.9% with ST elevation) without prior liver diseases, who underwent coronary angiography within 24 hours after hospitalization. AST and ALT levels were measured upon admission. LTs were considered as abnormal when their levels exceeded the local upper limit of normal. Clinical endpoints were all-cause in-hospital and 18-month mortality. Associations between clinical endpoints and various risk factors, including LT levels, were assessed by the multivariate logistic regression analysis.Results. Elevated LT levels were seen in 28.6% of AMI patients: an isolated increase in ALT was noted in 17.8% of patients, while an isolated increase in AST was registered in 25% of cases. In-hospital and 18-month mortality was 5.8 and 11.3%, respectively. Abnormal LT levels were associated with the presence of ST elevation (odds ratio (OR) 1.873, 95% confidence interval (CI) 1.218–2.881, p = 0.004), lower systolic and diastolic blood pressure (OR 0.993, 95% CI 0.986–1.0, p = 0.04 and 0.979, 95% CI 0.964–0.994, p = 0.007, respectively), higher Killip class (OR 1.510, 95% CI 1.142–1.999, p = 0.004), and higher creatinine level (OR 1.010, 95% CI 1.003–1.016, p = 0.004). In the multivariate analysis, elevated LT levels were independently associated with in-hospital and 18-month mortality (OR 3.607, 95% CI 1.199–10.848, p = 0.022 and 2.182, 95% CI 1.011–4.708, p = 0.047, respectively).Conclusion. Elevated LT levels were present in about a third of patients with AMI. They were associated with specific clinical, biological, and prognostic features, including in-hospital and long-term mortality in AMI patients.

Serum liver enzymes and risk of stroke: Systematic review with meta-analyses and Mendelian randomization studies.

Previous observational studies have identified correlations between liver enzyme levels and stroke risk. However, the strength and consistency of these associations vary. To comprehensively evaluate the relationship between liver enzymes and stroke risk, we conducted meta-analyses complemented by Mendelian randomization (MR) analyses. Following the PRISMA guidelines, we performed meta-analyses of prospective studies and conducted subgroup analyses stratified by sex and stroke subtype. Subsequently, adhering to the STROBE-MR guidelines, we performed two-sample bidirectional univariable MR (UVMR) and multivariable MR (MVMR) analyses using the largest genome-wide association studies summary data. Finally, the single-nucleotide polymorphisms associated with liver enzymes on sex differences underwent gene annotation, gene set enrichment, and tissue enrichment analyses. In the meta-analyses of 17 prospective studies, we found the relative risks for serum γ-glutamyl transferase (GGT) and alkaline phosphatase (ALP) were 1.23 (95% CI: 1.16-1.31) and 1.3 (95% CI: 1.19-1.43), respectively. Subgroup analyses revealed sex and stroke subtype differences in liver enzyme-related stroke risk. Bidirectional UVMR analyses confirmed that elevated GGT, alanine aminotransferase, and aspartate aminotransferase levels were associated with increased stroke occurrence. The primary results from the MVMR analyses revealed that higher ALP levels significantly increased the risk of stroke and ischemic stroke. Gene set and tissue enrichment analyses supported genetic differences in liver enzymes across sexes. Our study provides evidence linking liver enzyme levels to stroke risk, suggesting liver enzymes as potential biomarkers for early identification of high-risk individuals. Personalized, sex-specific interventions targeting liver enzymes could offer new strategies for stroke prevention.

Expected 8-Week Prenatal vs 12-Week Perinatal Tenofovir Alafenamide Prophylaxis to Prevent Mother-to-Child Transmission of Hepatitis B Virus: A Multicenter, Prospective, Open-Label, Randomized Controlled Trial.

The course of maternal antiviral prophylaxis to prevent mother-to-child transmission of hepatitis B virus (HBV-MTCT) varies greatly, and it has not been demonstrated in a randomized controlled study. In this multicenter, open-label, randomized controlled trial, eligible pregnant women with HBV DNA of 5.3-9.0 log 10 IU/mL who received tenofovir alafenamide fumarate (TAF) from the first day of 33 gestational weeks to delivery (expected 8 week) or to 4 weeks postpartum (expected 12 week) were randomly enrolled at a 1:1 ratio and followed until 6 months postpartum. All infants received standard immunoprophylaxis (hepatitis B immunoglobulin and vaccine). The primary end point was the safety of mothers and infants. The secondary end point was the HBV-MTCT rate of infants at the age of 7 months. Among 119 and 120 intention-to-treat pregnant women, 115 and 116 women were followed until delivery, and 110 and 112 per-protocol mother-infant dyads in 2 groups completed the study. Overall, TAF was well tolerated, no one discontinued the therapy due to adverse events (0/239, 0%, 95% confidence interval [CI] 0%-1.6%), and no infant had congenital defects or malformations at delivery (0/231, 0%, 95% CI 0%-1.6%). The infants' physical development at birth (n = 231) and at 7 months (n = 222) was normal. Furthermore, 97.0% (224/231, 95% CI 93.9%-98.5%) of women achieved HBV DNA <5.3 log 10 IU/mL at delivery. The intention-to-treat and per-protocol infants' HBV-MTCT rates were 7.1% (17/239, 95% CI 4.5%-11.1%) and 0% (0/222, 95% CI 0%-1.7%) at the age of 7 months. Comparatively, 15.1% (18/119, 95% CI 9.8%-22.7%) vs 18.3% (22/120, 95% CI 12.4%-26.2%) of women in the 2 groups had mildly elevated alanine aminotransferase levels at 3 months and 6 months postpartum, respectively ( P = 0.507); notably, no one experienced alanine aminotransferase flare (0% [0/119, 95% CI 0%-3.1%] vs 0% [0/120, 0%-3.1%]). Maternal TAF prophylaxis to prevent HBV-MTCT is generally safe and effective, and expected 8-week prenatal duration is feasible. ClinicalTrials.gov , NCT04850950.

Investigation of Biochemical and Inflammatory Markers in COVID-19 Patients Hospitalized in the Intensive Care Unit: An Observational Study in Northern Iran

Background: Since the first documentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there has been a notable emphasis on it in a brief period, especially as the mortality rate and confirmed cases steadily rise. The rapid and accurate laboratory identification of an ongoing COVID-19 infection is essential for efficient pandemic control. For diagnostic purposes, various testing methods have been developed to detect the severity of COVID-19. These diagnostic methods play a crucial role in identifying and managing the spread of the virus within communities worldwide. Methods: This cross-sectional observational study was conducted from February to June 2020, spanning four months. Patient clinical records and laboratory biomarkers data were collected. Results: In this study, 263 patients were involved, with an average age of 59.38 ± 15.26 years, and 51.3% of them (135 patients) were male. The typical hospital stay was 9.25 ± 6.9 days. The patients were divided into three groups: Those who survived (49.4%), those receiving treatment (4.9%), and those who did not survive (45.6%), with all treated patients surviving. An important connection was observed between serum lactate dehydrogenase (LDH), creatine phosphokinase (CPK), urea, leukocytosis, lymphopenia, high polymorphonuclear neutrophil (PMN) counts, and poor patient outcomes (P-value &lt; 0.05). Elevated aspartate transaminase (AST) levels also showed a close relationship with adverse outcomes (P-value = 0.05). Furthermore, most patients with hyponatremia, high fasting blood glucose, and elevated serum creatinine levels did not survive, despite lacking statistical significance. Conclusions: Serum biomarkers serve as prognostic indicators for the severity of COVID-19 patients. Leveraging these markers aids in promptly diagnosing patients at high mortality risk and facilitates more effective treatments in the disease's initial phases. These biomarkers can help healthcare providers identify patients at higher risk of complications and guide the implementation of targeted interventions to improve patient outcomes.

Epidemiology and clinical characteristics of acute viral gastroenteritis in 350 paediatric patients hospitalised between 2019 and 2022 in the Military Institute of Medicine – National Research Institute in Warsaw, Poland: a single-centre retrospective analysis

Introduction and objective: Acute gastroenteritis, a common childhood illness worldwide, manifests with symptoms including fever, abdominal pain, vomiting, and diarrhoea. It is highly contagious, with transmission occurring through contaminated water, food, or poor hygiene. Globally, 1.7 billion cases of diarrhoeal diseases are diagnosed annually, causing approximately 525,000 deaths among children under the age of five. Dehydration caused by diarrhoea is a primary cause of hospitalisation, particularly in developing countries. Aim: Analysis of the aetiology, frequency, and seasonal distribution of viral pathogens responsible for acute gastroenteritis in children hospitalised between 2019 and 2022 at the Military Institute of Medicine – National Research Institute in Warsaw, Poland. Materials and methods: Medical records of patients aged 0 to 18 diagnosed with rotavirus, norovirus, and adenovirus-induced acute gastroenteritis were analysed. The pathogens had been identified with reliable immunochromatographic tests. Exclusion criteria encompassed bacterial infections, dietary errors, and inflammatory conditions. Data examined included age, gender, aetiology of gastroenteritis, seasonality, duration of hospitalisation, and clinical symptoms (diarrhoea, vomiting, fever, abdominal pain, and dehydration). Laboratory results such as white blood cell count, C-reactive protein, electrolyte levels, and organ function markers were also evaluated. Results: Data from 350 children hospitalised between 2019 and 2022 were analysed. The highest number of hospitalisations occurred in 2019 and 2022, with fewer cases in 2020–2021, likely reflecting the impact of the COVID-19 pandemic. Most patients were between 6 and 12 months old. Rotavirus infection commonly presented with fever, vomiting, diarrhoea, and dehydration. Adenovirus and mixed infections were associated with slightly higher C-reactive protein levels, while rotavirus infections showed mildly elevated aspartate aminotransferase levels. Haematocrit, blood urea nitrogen, creatinine, and electrolyte levels were similar across all cases. Conclusions: Our analysis showed that rotavirus was the most frequent cause of acute viral diarrhoea in children, followed by norovirus and adenovirus, with mixed infections being the least common. The peak incidence occurred in autumn and winter, except in 2021, reflecting changes in the dynamics of infections related to the coronavirus pandemic. Biochemical findings were not sufficiently characteristic to infer the aetiology of the disease.

Clinical and genetic profile of Chinese children with Danon disease: A single-center retrospective cohort study

BackgroundDanon disease (DD) is a rare X-linked dominant lysosomal storage disorder. Studies on DD pediatric patients are limited due to the small number of cases and challenges in early detection. MethodsWe retrospectively analyzed clinical and genetic data of 29 pediatric patients who visited our hospital for treatment or genetic counseling of DD from July 2014 to December 2023. ResultsThe mean age at diagnosis was 7.2±5.9 years for males (n=21) and 9.4±5.0 years for females (n=8). Asymptomatic elevated liver aminotransferase and/or creatine kinase (CK) levels were initial manifestations detected in 10 (48%) male patients and absent in female patients. Hypertrophic cardiomyopathy (HCM) was observed in 20 (95%) male and 7 (88%) female patients, while dilated cardiomyopathy (DCM) was not detected. Ventricular preexcitation (VP) was observed initially in 10 (36%) patients and in 15 (54%) at latest evaluation. Patients with VP had higher left ventricular posterior wall thickness in diastole z-scores than those without VP (5.6±2.2 vs. 3.5±2.1, p=0.029). During a median 2.7-years follow-up, two males received heart transplants. One boy and one girl died of heart failure and sudden cardiac arrest, respectively. Twenty-three pathogenic LAMP2 variants were identified, including seven novel variants. ConclusionsA retrospective review of 29 DD cases suggests an underrecognized asymptomatic period in male DD patients, characterized by elevations in serum CK and transaminases. HCM appears to be the only cardiac manifestation in pediatric female patients, unlike a high incidence of DCM in adult female patients. The incidence of VP may increase with disease progression.

Non-alcoholic fatty liver disease (NAFLD): A comparative study of clinico-socio-demographic characteristics among two diverse Indian population

Objectives. The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing not only in India but also globally. The aim of this observational study was to determine the clinico-pathological findings of NAFLD patients in two different geographic populations in India. Material and methods. This hospital-based cross-sectional study involved 140 consecutive patients with NAFLD from four centers, primarily diagnosed by ultrasound in Uttar Pradesh (Varanasi) and Odisha (Khordha). Clinical and sociodemographic data were collected from each patient of both the states and were compared. Outcomes. The study findings revealed that most of NAFLD patients were males (71.4%), aged around 39.6±10.86 years, with BMI indicating overweight (27.68 ± 4.25 Kg/m2). Patients from Uttar Pradesh (UP) had non-significantly higher rates of elevated transaminase levels [SGOT/SGPT- 40.2 (41.53)/47.35(60.93) IU/L], compared to those from Odisha [SGOT/SGPT-26(23.15)/29(45.40) IU/L]. Too cases of Odisha had non-significantly higher mean triglyceride levels compared to patients of UP. There was a significant difference in family type in-between the 2 regions (p=0.000), with Odisha having more number of nuclear families compared to UP. Cases from Odisha had non-significantly higher per capita monthly income (41.891 ± 43.23 INR) compared to UP (34.276 ± 27.66 INR). Statistically significant dietary preferences, were noticed in-between the 2 states with majority from Odisha favoring non-vegetarian diets (90.6%) compared to Uttar Pradesh (75.06%). Conclusions. Patients from Odisha had higher per capita monthly income, history of higher non-vegetarian diet consumption, higher hypertriglyceridemia and lesser transaminases compared to cases from Uttar Pradesh.

A Comparison of Kawasaki Disease during the SARS-CoV-2 Pandemic with Multisystem Inflammatory Syndrome in Children.

The purpose of this study was to compare and contrast Kawasaki disease (KD) with multisystem inflammatory syndrome in children (MIS-C) during the SARS-CoV-2 pandemic. A retrospective analysis of the medical records of patients diagnosed with KD and MIS-C at a single institution from July 2020 to November 2021 was performed. The study included 39 MIS-C patients (84.6% male) with a median age of 138 months and 17 KD patients (58.8% male) with a median age of 36 months. The MIS-C patients were older (p < 0.001) and had prolonged hospitalizations (p = 0.023), elevated neutrophil counts (p < 0.001), C-reactive protein (p < 0.001), procalcitonin (p < 0.001), interleukin-6 (p < 0.014), ferritin (p < 0.001), fibrinogen (p < 0.001), troponin I (p = 0.001), NT-proBNP (p < 0.001), and D-dimer levels (p < 0.001). There were more cases of hypotension (p = 0.024), decreased left ventricular function (p = 0.023), and a greater need for corticosteroids (p < 0.001), enoxaparin (p = 0.045), and therapeutic plasma exchange (p < 0.001). Kawasaki disease patients had a greater incidence of rash (p < 0.001), changes in oral mucosa (p < 0.001), conjunctival injection (p < 0.001), extremity changes (p < 0.001), and cervical lymphadenopathy (p < 0.001). They had a longer duration of fever (p < 0.001), elevated white blood cell count (p < 0.001), platelet count (p < 0.001), and alanine aminotransferase level (p < 0.001). The two groups were similar regarding the hemoglobin levels, erythrocyte sedimentation rates, albumin levels, and the frequency of coronary aneurysm, myocarditis, pericarditis, invasive mechanical ventilatory support, and intravenous immunoglobulin treatment. Advanced patient age, a greater presence of gastrointestinal and cardiac findings associated with hypotension, increased NT-proBNP levels, decreased left ventricular function, the use of various treatment modalities, and longer hospital stays suggest MIS-C, whereas prolonged fever and classical clinical features of KD favor KD.

Secundaire hemofagocytaire lymfohistiocytose bij diffuus grootcellig B-lymfoom: een casus

Secondary hemophagocytic lymphohistiocytosis in diffuse large-cell B lymphoma: a case-report Secondary hemophagocytic lymphohistiocytosis (sHLH) is a rare, life-threatening and often misunderstood condition characterized by uncontrolled immune activation. Patients typically present with a pentad of symptoms including fever, hepatosplenomegaly, cytopenias affecting at least 2 of 3 cell lines, and elevated transaminase and ferritin levels. Familial hemophagocytic lymphohistiocytosis (FHL), the primary form, mainly occurs in pediatric age. The underlying pathogenesis is associated with genetic defects affecting cellular immunity (CD8+ T-lymphocytes and natural killer cells). The secondary forms (sHLH) mainly occur in adulthood and are linked to underlying processes such as autoimmune diseases, malignancies or infections. Recent revisions of the diagnostic criteria, including the H-score, offer valuable guidance for clinical decision-making. Early detection is crucial, followed by a prompt initiation of immunosuppressive therapies, such as corticosteroids, methotrexate, etoposide or eventually a hematopoietic stem cell transplantation (HSCT). This case-report illustrates a 79-year-old woman with sHLH secondary to an underlying B-cell lymphoma, underscoring the significance of recognition, diagnosis and treatment.

Taurine can play a positive role in growth, liver health and resistance to Aeromonas hydrophila of yellow catfish Pelteobagrus fulvidraco exposed to ammonia stress for a long time

Ammonia is an important environmental pollutant that is toxic to most aquatic animals, and nutrient manipulation is an effective regulatory pathway. To assess the influence of taurine supplementation on growth, liver detoxification and anti-bacterial infection of yellow catfish subjected to ammonia exposure for a long time, three experiment diets with different taurine levels (0.50, 1.00, and 2.00 %) were formulated and fed to fish (7.28 ± 0.05) g under three ammonia levels (0.00, 25.00 and 50.00 mg/L total ammonia nitrogen) for 56 days. The results showed that hepatic glycogen and whole-body protein contents were reduced, suggesting that energy deficiency caused by ammonia poisoning plays an important role in growth inhibition; elevated serum alanine aminotransferase and aspartate aminotransferase levels suggest liver injury, which may be caused by oxidative stress (decreased activities of superoxide dismutase and catalase, and expressions of SOD and CAT) and inflammation (increased contents of tumor necrosis factor α, interleukin 1 and interleukin 8, and expressions of TNF α, IL 1 and IL8), analysis of tissue sections further confirmed this finding. Furthermore, after injection with Aeromonas hydrophila, cumulative mortality increased proportionally with the rise in ammonia levels, the observed decrease in serum complements C3, C4, immunoglobulin M, and antibody titer contents emerged as a crucial factor contributing to the decreased disease resistance. The exogenous taurine was found to alleviate the negative impact of the above-mentioned ammonia poisoning. This study provides valuable insights into the mechanism of ammonia-induced aquatic toxicology in fish.

Dose compliance of estramustine phosphate in neoadjuvant chemohormonal therapy combined with degarelix acetate predicts the biochemical recurrence in patients with very high-risk prostate cancer who underwent robot-assisted radical prostatectomy.

The objective of this study is to evaluate the safety and efficacy of neoadjuvant degarelix acetate and low-dose estramustine phosphate for high-/very high-risk prostate cancer. Overall, 187 patients diagnosed with National Comprehensive Cancer Network high-/very high-risk cTanyN0M0 localized prostate cancer who consented to undergo robot-assisted radical prostatectomy after receiving neoadjuvant chemohormonal therapy for 6 months were prospectively enrolled between December 2017 and March 2023. Adverse events, perioperative and histopathological outcomes, and biochemical recurrence-free survival rates were examined. Survival analysis compared the estramustine phosphate completion and reduction groups. Thirty-six patients discontinued neoadjuvant therapy in <5 months owing to adverse events (n = 34) or other reasons (n = 2). Eleven were excluded for being in the postoperative castration range. Of the 140 patients who underwent surgery, 124 continued with two tablets of estramustine phosphate and 16 with one tablet. Overall, 82 patients were very high-risk. Histopathological outcomes were significantly worse in the very high-risk group than those in the high-risk group. Very high-risk status and estramustine phosphate reduction were significant factors in biochemical recurrence in multivariate analysis. The biochemical recurrence-free survival rate in very high-risk patients was significantly lower in the estramustine phosphate dose reduction group than in the completion group but not significant in high-risk patients. Major adverse events were anemia (n = 174), elevated transaminase levels (n = 68), and deep vein thrombosis (n = 24). Severe adverse events included acute coronary syndrome (n = 4) and pulmonary embolism (n = 3). Dose compliance with estramustine phosphate predicted biochemical recurrence in patients with very high-risk prostate cancer undergoing robot-assisted radical prostatectomy with neoadjuvant chemohormonal therapy.

Shwachman-Diamond syndrome: A case report.

Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive genetic disease, the diagnosis is a big challenge for clinician, as the clinical manifestations of the disease are diverse. Here, we report a girl who diagnosed with SDS with the symptoms of recurrent fever, elevated transaminase levels, and granulocytosis. The aspects of diagnosis and treatment were discussed and a literature review was conducted. A 15-month-old girl admitted to our hospital because of recurrent fever, granulocytopenia, and elevated transaminase levels. The compound heterozygous variant of Shwachman-Bodian-Diamond syndrome c.258 + 2T > C:p.84Cfs3 and c.96C > G:p.Y32* were detected after sequencing the blood samples from the patient and her parents. Finally, she was diagnosed with SDS and she was treated with compound glycyrrhizin, granulocyte-colony stimulating factor, and antibiotic in the case of co-infection. During the follow-up, her liver function showed the level of transaminases decreased and she rarely had infection after the age of 15 months although neutropenia is still present. Patients with SDS lacks typical clinical symptoms, which presents a huge challenge for clinicians. Genetic testing techniques is playing an important role in the diagnosis of diseases. This patient without typical clinical manifestations such as exocrine pancreatic insufficiency and skeletal abnormality, we report this case aimed to strengthen the understanding of the disease.

Congenital bile acid synthetic disorder type 3 caused by CYP7B1 gene variation in 2 cases and literature review

Objective: To summarize the clinical features and genetic characteristics of Congenital bile acid synthetic disorder type 3 (BASD3) disorder caused by CYP7B1 gene variation. Methods: This was a case series study. Clinical data and genetic results of 2 cases of congenital bile acid synthetic disorder type 3 caused by CYP7B1 gene variations in the Department of Infectious Diseases, Children's Hospital of Fudan University at Xiamen and Department of Pediatrics, Women and Children's Hospital, School of Medicine, Xiamen University from January 2021 to December 2023 were retrospectively collected and analyzed. Literature up to December 2023 was searched from electronic databases of China National Knowledge Infrastructure (CNKI), Wanfang Data and PubMed with the combined keywords of " Congenital bile acid synthetic disorder type 3""Oxysterol 7-alpha-hydroxylase""Oxysterol 7α-Hydroxylase Deficiency""BASD3" and "CYP7B1 liver" both in Chinese and English. The main clinical features and genetic characteristics of BASD3 disorder caused by CYP7B1 gene variations were summarized. Results: Two BASD3 patients, 1 male and 1 female, were admitted at the ages of 3 months and 18 days, and 2 months and 7 days, respectively. Both patients presented with neonatal cholestasis and hepatomegaly. Biochemical evidence indicated direct hyper-bilirubinemia with elevated aminotransferase levels, while gamma-glutamyltransferase (GGT) and total bile acid levels were normal or nearly normal. Patient 1 was a compound heterozygotes of the CYP7B1 gene variants c.525-526insCAAGTTGG(p.Asp176GInfs*15) and c.334C>T(p.Arg112Ter). Patient 1 jaundice resolved and liver function tests normalized after oral administration of chenodeoxycholic acid (CDCA). Patient 2 was homozygous for variant c.334C>T(p.Arg112Ter) in CYP7B1 gene. Patient 2 was in liver failure status already and not reactive to oral CDCA administration. Patient 2 received living-related liver transplantation for enhanced abdominal CT revealed a liver tumor likely vascular origin. Literature review revealed no cases of BASD3 reported in Chinese literature, including 2 patients in this study, while 12 patients (9 males and 3 females) were reported in 9 English literatures. All of the 12 manifested jaundice and hepatosplenomegaly in infancy, with cirrhosis, liver failure, kidney enlargement, hypoglycemia, and spontaneous bleeding in some cases, polycystic kidney disease was demonstrated in 5 cases of them. The c.334C>T (p.Arg112Ter) of the CYP7B1 gene was homozygous in 4 cases and compound heterozygous in 2 cases. Among the 12 children, 6 cases received CDCA treatment, while 6 cases not. Four survived with their native liver in the 6 cases who received CDCA therapy, while none in the 6 cases not received CDCA therapy. Conclusions: BASD3 is a rare hereditary cholestatic disorder. Markedly elevated levels of conjugated bilirubin and aminotransferases, with normal or nearly normal GGT and total bile acid levels can serve as diagnostic clue. c.334C>T is the most common pathogenic variant of the CYP7B1 gene. Timely administration of CDCA may save the liver.