Higher AST Research Articles

Helicobacter pylori cagA/vacAs1-m1 strain is associated with high risk of fibrosis in metabolic-dysfunction-associated steatotic liver disease

Introduction and ObjectivesRecent studies have suggested an association between H. pylori and metabolic dysfunction associated steatotic liver disease (MASLD). We aim to evaluate the association of H. pylori virulence genes with non-invasive markers of liver injury and fibrosis in MASLD subjects. Patients and MethodsA total of 362 dyspeptic patients who underwent gastroscopy were selected. Biochemical, clinical parameters, ultrasound, FIB-4 score, liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE), gastric biopsies, and H. pylori virulence genes (cagA, vacA) were evaluated. ResultsA cohort comprised of 61 % women and 39 % men with a median age of 52 (40–60) years. MASLD was observed in 42 %, and H. pylori-positive in 45 %. No differences were observed regarding H. pylori status at co-morbid metabolic conditions. In MASLD cohort, H. pylori-positive was associated with higher AST, ALT, FIB-4 and LSM. Indeed, carriers of cagA/vacA-s1/m1-positive allelic combination were associated with higher AST, ALT, FIB-4 and LSM but not cagA/vacA-s1/m1-negative. The OR for high-risk of significant/advanced- fibrosis by VCTE (≥8 kPa) with H. pylori-positive was 2.56 (95 % CI, 1.2–5.75) and for cagA/vacA-s1/-m1-positive allelic carriers was 4.01 (95 % CI, 1.38–11.56), but non-significant association in cagA/vacA-s1/-m1-negative. After adjusting for age, gender, diabetes, BMI and hypertension the OR for VCTE ≥8 kPa with H. pylori-positive was 2.43 (95 % CI, 1.88–12.44), and cagA/vacA-s1/m1-positive allelic carriers was 4.06 (95 % CI, 1.22–14.49). ConclusionsIn our cohort of functional dyspepsia (FD) patients with MASLD, H. pylori was associated with non-invasive markers of liver injury and fibrosis. Carriers of cagA/vacA-s1/m1-positive allelic combination showed an independent risk of significant/advanced fibrosis by VCTE.

Association of liver function markers and apolipoprotein E ε4 with pathogenesis and cognitive decline in Alzheimer's disease.

Alzheimer's disease (AD) is a complex neurodegenerative disorder influenced by various factors, including liver function, which may impact the clearance of amyloid-β (Aβ) in the brain. This study aimed to explore how the apolipoprotein E (APOE) ε4 allele affects the relationship of liver function markers with AD pathology and cognition. We analyzed data from two independent cohorts, including 732 participants from the Hallym University Medical Center and 483 from the Alzheimer's Disease Neuroimaging Initiative, each group consisting of individuals with and without the APOE ε4 allele. Cross-sectional analyses evaluated the associations of liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, total bilirubin, and albumin) with AD diagnosis, amyloid positron emission tomography (PET) burden, and cerebrospinal fluid biomarkers for AD (Aβ42, total tau, and phosphorylated tau181) at baseline. Longitudinally, we investigated the associations between these liver enzymes and changes in cognitive performance over the course of a year. Logistic and linear regression models were used to analyze these associations and mediation analyses were conducted to assess whether age and amyloid PET burden mediated these associations. Only in the APOE ε4 carrier group, a high AST to ALT ratio and low ALT levels were significantly associated with AD diagnosis, increased amyloid PET burden, and faster longitudinal decline in cognitive function in both cohorts. In particular, the AST to ALT ratio was associated with cerebrospinal fluid Aβ42 levels exclusively in the APOE ε4 carrier group in the Alzheimer's Disease Neuroimaging Initiative cohort but not with phosphorylated tau181 or total tau levels. Moreover, mediation analyses from both cohorts revealed that in the APOE ε4 carriers group, age did not mediate the associations between liver enzymes and AD diagnosis or amyloid PET burden. However, amyloid PET burden partially mediated the association between liver enzymes and AD diagnosis exclusively in the APOE ε4 carriers group. This study provides valuable insights into the significant association of the APOE ε4 allele with liver enzymes and their potential role in Aβ-related pathogenesis and cognition in AD. Further research is required to elucidate the underlying mechanisms and potential therapeutic implications of these findings.

Evaluation of alanine aminotransferase/aspartate aminotransferase ratio and high-density lipoprotein for predicting neonatal adverse outcomes associated with intrahepatic cholestasis of pregnancy.

To determine the association between lipid metabolism and intrahepatic cholestasis of pregnancy (ICP), and explore the value of maternal alanine aminotransferase/aspartate aminotransferase (ALT/AST) and high-density lipoprotein (HDL) in predicting adverse neonatal outcomes in women with ICP. A total of 147 pregnant women with ICP admitted to The Fourth Hospital of Shijiazhuang and 120 normal pregnant women in the same period were selected in this study. The Mann-Whitney U test and Chi-square tests were used to compare the differences in clinical data. Multivariate logistic regression was used to analyze the relationship between ALT/AST and the occurrence of adverse pregnancy outcomes in patients with ICP. The combined predictive value of ALT/AST and HDL was determined by receiver operating characteristic (ROC) curve analysis. Among 147 women with ICP, 122 women had total bile acid (TBA) levels of 10-39.9 µmol/L, and 25 had TBA ≥ 40 µmol/L. There was significantly lower gestational age in patients with severe ICP than in those with mild and control groups (all p<0.05), and the weight of newborns in the maternal ICP group was significantly lower than in the control group (p<0.05). Increasing TBA levels was associated with higher AST, ALT, ALT/AST, and lower HDL level (all p<0.05). Meanwhile, higher levels of ALT/AST was positively associated with neonatal hyperbilirubinemia [adjusted odds ratio (AOR) = 4.019, 95% CI [1.757-9.194, p=0.001] and cardiac injury [AOR = 3.500, 95% CI [1.535-7.987], p=0.003]. HDL was a significant protective factor for neonatal hyperbilirubinemia and cardiac injury [AOR = 0.315, 95% CI [0.126-0.788], p=0.014; AOR = 0.134 (0.039-0.461), p=0.001]. The area under the ROC curve (AUC) for prediction of neonatal hyperbilirubinemia by ALT/AST combined with HDL was 0.668 [95% CI [56.3-77.3%], p = 0.002], and the sensitivity and specificity were 47.1% and 84.0%, respectively. To predict neonatal cardiac injury, the AUC value was 0.668 [95% CI [56.4-77.1%], p = 0.002], with sensitivity and specificity were 41.2% and 87.1%, respectively. The levels of higher ALT/AST and lower HDL were significantly associated with the risk of ICP-related adverse neonatal outcomes. Moreover, ALT/AST combined with HDL has moderate clinical value in predicting the adverse outcomes of neonatal hyperbilirubinemia and cardiac injury.

Medium-short chain fatty acids cannot spare the essential fatty acids of low marine diets in golden pompano (Trachinotus ovatus)

Based on the essential fatty acids (EFA) precision nutrition, a blend oil (BO) of fish oil and terrestrial oils was developed, and applied successfully to the low marine diets of golden pompano (Trachinotus ovatus). To evaluate whether medium- and short-chain fatty acids (MCFA and SCFA), efficient energy supplements for animals, can spare the dietary EFA, four iso-proteic (48%) and iso-lipidic (11%) low fishmeal (FM) diets (D1-D4, contained 6% FM) were formulated and fed T. ovatus juveniles (initial weight ∼8.50 g) for 9 weeks in sea cages. Control diets (D1) contained 8% BO, while the BO of diets D2-D4 were replaced 50% with coconut oil, coconut oil + sodium butyrate, and coconut oil + n-3 LC-PUFA enriched oil, respectively. The results showed that compared to the D1 group, the growth performance of D2 and D3 were significantly lower, while a comparable growth was detected in the D4 group. The muscle and hepatic n-3 PUFA levels in the D2 and D3 groups were significantly low, and these fatty acid contents were modified in the D4 group. Meanwhile, the muscle textural firmness of the D2-D4 groups was decreased. Regarding the health index of fish, compared to the D1 group, high serum triglyceride (TG) contents and low HDL/LDL ratio were detected in the D2-D4 groups, and high ACP, AST, and ALT activities were observed in these groups. Meanwhile, high HSI and low hepatic enzymatic activities of CAT and ALT were measured in the D2-D3 groups. Additionally, the mRNA levels of hepatic fatty acid synthesis-related genes (fas, acc, and pparγ) were significantly increased in D2-D4 groups, and the expression levels of lipid catabolism genes (cpt-1 and lpl) showed an upward trend. Moreover, the D2 group exhibited the lowest intestinal wall thickness, the mRNA levels of intestine anti-inflammatory cytokines (il-10) were up-regulated in the D2-D4 groups, and the highest mRNA levels of pro-inflammatory cytokines (il-8) were detected in the D2 group. In conclusion, the EFA deficiency leads to a decline in the growth and muscle quality of T. ovatus fed low marine diets, which cannot be mitigated by the addition of medium-short chain fatty acids. The results indicated that MCFA and SCFA cannot spare the EFA of low marine diets in T. ovatus.

Incidence, risk factors, and outcomes of acute liver injury in hospitalized adults with acute kidney injury: a large multicenter study.

Acute kidney injury (AKI) and acute liver injury (ALI) were associated with poor outcomes during hospitalization, respectively. However, the clinical outcome of AKI combined with ALI (AKI-ALI) remains unknown. The current study aimed to describe AKI-ALI's incidences, risk factors, and outcomes. The study population included patients aged 18-99years with enough serum creatinine and liver testing hospitalized at 19 medical centers throughout China between 2000 and 2021. AKI was defined by Kidney Disease Improving Global Outcomes and ALI was defined by the change of liver enzymes based on Asia Pacific Association of Study of Liver consensus guidelines. Cox proportional hazard model was used to identify risk factors for AKI-ALI, and a time-dependent Cox proportional hazard regression model was used to estimate the association between AKI-ALI and in-hospital mortality. Among the 18,461 patients with AKI, 1689 (9.1%) combined with ALI. Male patients or those who have used nonsteroidal anti-inflammatory drugs or vasopressors, and who have heart failure or shock, with higher AST or GGT values, were associated with an increased risk of AKI-ALI. Compared with AKI-nonALI, patients with AKI-ALI were at higher risk of in-hospitalized mortality (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.54, 2.00). In addition, a stronger association between AKI-ALI and in-hospital mortality was found in those with lower AKI grades (p for interaction = 0.037). ALI was not uncommon among patients with AKI, especially in patients who used vasopressors and had shock. This study highlights the association between AKI-ALI and a significantly increased risk of mortality. It suggests that dynamic monitoring of liver function is essential, particularly in patients with AST and GGT exceeding the normal upper limit, to improve the in-hospital prognosis of AKI patients.

Association Between Insulin Resistance Indices and Liver Function Parameters Among Women With Polycystic Ovary Syndrome.

This study aimed to investigate whether polycystic ovary syndrome (PCOS) status changes the association between insulin resistance (IR) indices and liver function parameters among women. This is a cross-sectional, population-based study. We selected 1101 subjects aged ≥20 years from participants of Tehran Lipid and Glucose Study (TLGS). All of them had known the status of PCOS, and all variables were related to the IR indices and liver function parameters. The main outcome measures were TG/HDL-C and triglyceride-glucose (TyG) and liver function parameters (hepatic steatosis index [HSI], alanine transaminase [ALT] and aspartate transaminase [AST]). In the present study, there was no significant difference between the PCOS and the non-PCOS regarding the presence of liver function abnormalities. A model adjusted by age and BMI showed that the upper tertile of TyG index was positively associated with high AST (OR = 3.04 [95% CI: 1.20-7.68], p < 0.05), high ALT (4.76 [3.07-7.36], p < 0.05) and high HSI (8.44 [1.82-39.17], p < 0.05). Although the history of diabetes had a positive impact on elevated AST (1.66 [1.15, 2.40], p < 0.05), the third tertile of TG/HDL-C was associated with increased odds of elevated ALT (3.35 [2.21-5.06]) and HSI (6.55 [1.17-36.46]), whereas the second tertile of TG/HDL-C (OR = 2.65, CI 95%: 1.74-4.03) was also positively associated with elevated ALT. PCOS had no significant association with elevated liver function tests. The highest tertile of TyG index and the TG/HDL-C ratio as a surrogate of IR might play a role in detecting abnormalities of liver function parameters among women. However, PCOS status cannot change the association between IR and liver dysfunction.

A Validation Study of Non-invasive Scoring Systems for Assessing Severity of Hepatic Fibrosis in a Cohort of South Indian Patients With Non-alcoholic Fatty Liver Disease

IntroductionLiver biopsy is the gold standard for diagnosing and staging NAFLD. But liver biopsy has its limitations. Non-invasive tests (NITs) eliminate many of the drawbacks of liver biopsy. We did a retrospective observational study to validate the non-alcoholic fatty liver disease Fibrosis Score (NFS score) and Fibrosis Score 4 (FIB-4 index) against the gold standard liver biopsy in a cohort of south Indian patients with NAFLD. Material and MethodsA retrospective observational analytical study of patients who had a liver biopsy with a diagnosis of NAFLD and had all the data for aetiology assessment and NIT calculation within 4 weeks of biopsy were included in the study. On liver biopsy NAFLD was scored as per NIH’s NASH committee (NASH CRN) grading system. NAFLD Fibrosis Score (NFS) and FIB-4 index were calculated and scores more than 0.676 and 2.67 respectively was taken as the cut-off to predict advanced fibrosis. The sensitivity, specificity, positive predictive value, negative predictive value and area under the ROC curve for NFS score and FIB-4 score to diagnose advanced fibrosis were calculated. ResultsA total of 147 patients were included in the study. Of these 56 (38.1%) patients had advanced fibrosis (Stage 3, 4). Patients with advanced fibrosis were more likely to be older and have DM. Patients with advanced fibrosis had lower platelet count, higher AST, lower albumin and higher AST/ALT ratio. The NFS of > 0.676 had a sensitivity of 68% and specificity of 100% and FIB-4 index of >2.67 had a sensitivity of 67% and specificity of 95.6 % in diagnosing advanced fibrosis in our study. ConclusionThe non-invasive scoring systems NAFLD Fibrosis Score (NFS) and FIB-4 index, can be used as a bedside tool for diagnosing Liver fibrosis in NAFLD allowing liver biopsy to be used in a more targeted manner for patients diagnosed with advanced fibrosis on NITs.

Twenty Years’ Experience of Midgut Malrotation and Volvulus in a Tertiary Center in Northern Taiwan: A Retrospective Study

BackgroundEarly diagnosis and surgical intervention for midgut malrotation with bowel obstruction are crucial. We aimed to identify risk factors for adverse outcomes in infants with midgut malrotation and to develop a prediction model. MethodsWe reviewed the operation records of infants surgically diagnosed with midgut malrotation at Chang Gung Children’s Medical Center between January 2000 and December 2020. Patients were classified into the poor-outcome group (PO) if they underwent bowel resection or experienced mortality; all others were categorized as the favorable-outcome group (FO). Data on demographics, initial presentations, laboratory results, radiographic or sonographic findings, maternal conditions, and outcomes were collected and analyzed. Fisher’s exact test, the independent sample t-test, and the Mann-Whitney test were utilized for comparative analysis when suitable. ResultsThe study included 103 infants. Eleven were in the PO group, and 92 were in the FO group. Initial presentations such as respiratory distress, poor activity, and shock status were notably more prevalent in the PO group. The INR, hemoglobin, HCO3, base excess, and aspartate transaminase values showed significant variation between the two groups. Multivariate analysis identified that lower hemoglobin (OR 0.677, p = 0.043) and higher AST (OR 1.036, p = 0.044) were independent predictors of adverse outcomes. An AST/Hb ratio of < 3.78 demonstrated a high negative predictive value (98.6%) for an adverse outcome in midgut malrotation. ConclusionsPrompt diagnosis and surgical treatment of midgut malrotation are vital to prevent bowel resection or mortality. The independent predicting factors for poor outcomes include low hemoglobin and elevated AST levels.

Clinical Management practice and Therapeutic Outcomes of Chronic Liver Disease patients in the Conflicted area of North Ethiopia

Background: In the 21st century, low- and middle income, war prone and drought-prone areas in developing nations have seen a fast rise in the prevalence of chronic liver disease (CLD). An estimated 240 million people worldwide are infected with HIV, and 780,000 deaths are attributed to it each year, according to the World Health Organization (WHO). Objective: We want to assess the efficacy of in-hospital care for CLD patients by verifying and evaluating current management practices. Method: A retrospective descriptive study of patients with chronic liver disease who were followed up on at Debre Berhan Hospital between July 2018 and January 2021 was conducted. Results: Out of a total of 209 patients tested, 127 (or 60.74%) were males aged 41.44±12.89 of years. Ascites complications were presented in over 44% of cases. Using the laboratory data, 65 patients (31.10%) and 71 patients (33.97%) were found to have abnormally high AST and ALT values on LFTs testing. AUROC analysis was carried out with a 95% CI for Child-Pugh of 0.61 (0.53-0.75, P=0.14), MELD 0.75 (0.63-0.72, P=0.26), and ALBI 0.53 (0.31-0.54, P=0.29). Conclusion: Based on the predictive data, 87 (41.63%) patients were successfully treated and released, whereas 57(27.27%) were recommended for further care, and 47 died due to co-morbid conditions. Although, the study period coincides with the COVID-19 pandemic, more analysis of the obtained data is necessary.

The biochemical effect correlated with pulmonary dysfunction and complications in obese patients

Objective: Obesity, an epidemic metabolic disorder, is associated with various biochemical, inflammatory, oxidative and immunological pathways. We aimed to investigate the biochemical effect correlated with pulmonary dysfunction and complications in overweight and obese patients. Material and Methods: We aimed to evaluate retrospectively the effect of biochemical parameters on pulmonary dysfunction and complications in 79 overweight and obese patients. The correlative effect of biochemical values, including CRP, and spirometric measurements, such as forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1), on pulmonary dysfunction and complications in 79 overweight and obese patients seen in the outpatient clinic were evaluated. Body mass index (BMI), FEV1 and FVC, and total biochemistry values, including creatinine, AST, ALT and CRP values were correlated among each other. Results: Low FVC levels, leukocytosis, high AST and ALT levels, and comorbidities of obesity are significantly associated with high BMI values by univariate analysis in these patients. Higher AST levels are significantly correlated with higher leucocyte counts, and both AST and ALT levels are significantly correlated with platelet counts. Conclusion: We investigated the effect of biochemical parameters on pulmonary dysfunction and complications in obese patients. Obesity can be helpful to categorize high-risk patients with low FVC levels in the context of respiratory diseases and high AST and ALT levels for other comorbidities as steatohepatitis, diabetes mellitus and coronary artery disease. This study sheds light on future research on obese patients for prognosis of these diseases, because of their biochemical profile correlation with pulmonary dysfunction and complications.

Assessment of the Relationship Between Liver Enzymes and Cardiovascular Disease: A Study in Bangladeshi Adults.

Elevated liver enzyme levels are suggested to be associated with an increased risk of cardiovascular disease (CVD). However, few studies have explored the relationship between liver enzymes and myocardial infarction (MI). This study aimed to evaluate the potential association of elevated liver enzymes with MI within a population group in Bangladesh. In this cross-sectional study, 348 participants were enrolled, 189 with MI in the CVD group and 159 in the control group. Serum levels of liver enzymes (AST, ALT and GGT) and other biochemical parameters were measured using standard methods. Multivariate logistic regression models were applied to determine the associations between elevated liver enzymes and CVD. In the CVD group, 51.6%, 30.9% and 67.7% of individuals had elevated serum AST, ALT and GGT levels, respectively. On the contrary, the control group had 17.0%, 15.1% and 35.2% of individuals with high serum AST, ALT and GGT levels, respectively. Overall, 71.8% of the subjects in the CVD group and 44.7% of the subjects in the control group had at least one or more elevated liver enzymes (p < 0.001). The mean level of all three liver enzymes was significantly higher in the CVD group than in the control group (p < 0.001). In both the CVD and control groups, males had higher levels of liver enzymes than females. In the regression models, the serum levels of AST, ALT and GGT showed a positive and independent association with the prevalence of CVD (p < 0.001). However, GGT showed the strongest association among the three enzymes. This study shows a high prevalence of liver enzyme abnormalities in individuals with CVD. Serum levels of AST, ALT and GGT were independently associated with the prevalence of CVD. This suggests that measuring liver enzyme levels could be a useful marker in predicting CVD at an early stage.

Links between gut microbiome, metabolome, clinical variables and non-alcoholic fatty liver disease severity in bariatric patients.

Bacterial species and microbial pathways along with metabolites and clinical parameters may interact to contribute to non-alcoholic fatty liver disease (NAFLD) and disease severity. We used integrated machine learning models and a cross-validation approach to assess this interaction in bariatric patients. 113 patients undergoing bariatric surgery had clinical and biochemical parameters, blood and stool metabolite measurements as well as faecal shotgun metagenome sequencing to profile the intestinal microbiome. Liver histology was classified as normal liver obese (NLO; n = 30), simple steatosis (SS; n = 41) or non-alcoholic steatohepatitis (NASH; n = 42); fibrosis was graded F0 to F4. We found that those with NASH versus NLO had an increase in potentially harmful E. coli, a reduction of potentially beneficial Alistipes putredinis and an increase in ALT and AST. There was higher serum glucose, faecal 3-(3-hydroxyphenyl)-3-hydroxypropionic acid and faecal cholic acid and lower serum glycerophospholipids. In NAFLD, those with severe fibrosis (F3-F4) versus F0 had lower abundance of anti-inflammatory species (Eubacterium ventriosum, Alistipes finegoldii and Bacteroides dorei) and higher AST, serum glucose, faecal acylcarnitines, serum isoleucine and homocysteine as well as lower serum glycerophospholipids. Pathways involved with amino acid biosynthesis and degradation were significantly more represented in those with NASH compared to NLO, with severe fibrosis having an overall stronger significant association with Superpathway of menaquinol-10 biosynthesis and Peptidoglycan biosynthesis IV. In bariatric patients, NASH and severe fibrosis were associated with specific bacterial species, metabolic pathways and metabolites that may contribute to NAFLD pathogenesis and disease severity.

Phase Ib trial of erdafitinib (E) combined with enfortumab vedotin (EV) following platinum and PD-1/L1 inhibitors for metastatic urothelial carcinoma (mUC) with FGFR2/3 genetic alterations (GAs).

625 Background: Erdafitinib (E) is a treatment option in mUCpatients with somatic FGFR2/3 GAs after progression on platinum-based chemotherapy (PBC). Enfortumab Vedotin (EV) is approved as a single agent to treat mUC patients following prior PBC and PD1/L1 inhibitors or as second-line therapy for cisplatin-ineligible patients. Retrospective studies suggest that the activity of EV is not compromised by FGFR2/3 GAs. E and EV have different mechanisms of activity, and toxicities are mostly non-overlapping. Hence, there is rationale to evaluate the feasibility of combination E + EV, to overcome the difficulties of resistance and sequencing agents in mUC patients with FGFR2/3 GAs. Methods: This is an ongoing, single arm, multicenter, dose-escalation and expansion study of combination E + EV evaluating the safety, tolerability, pharmacokinetics (PK), and antitumor activity in patients with mUC harboring somatic FGFR2/3 GAs who have progressed after PBC and/or PD1/L1 inhibitor therapies. Dose escalation phase aims to identify the maximum tolerable dose and recommended phase 2 dose of EV at dose levels of 1 mg/kg and 1.25 mg/kg in combination with E at 8 mg/day as shown in the table. Preliminary safety, PK, and efficacy data for Dose Level (DL) 1 and 2 are presented in this abstract. Results: As of data cutoff, based on 3+3 design, total 8 patients are enrolled and finished dose limiting toxicity (DLT) period (1st cycle). Six patients were enrolled in DL1 with 1 DLT (skin rash) and 2 patients in DL2. The most common treatment-related adverse events (TRAE) included hyperphosphatemia (88%), mucositis (88%), hypercalcemia (75%), high AST (75%), hand foot syndrome (75%), peripheral neuropathy (75%), alopecia (63%), diarrhea (63%), hypoalbuminemia (63%) and hypomagnesemia (63%). Grade 3 TRAE included hand foot syndrome (50%), anemia (17%), rash (17%), anorexia (17%) and paronychia (17%). One patient developed grade 4 Stevens-Johnson syndrome related to EV which subsequently improved. PK data are available for all 6 subjects in DL1. The average steady-state Cmin of E and monomethyl auristatin E (MMAE) was 1430 ± 639 ng/mL and 1.4 ± 0.9 ng/mL, respectively, and the average Cmax of MMAE was 3.9 ± 0.9 ng/mL at DL1. All 8 patients are evaluable for response, and best response is partial response in all. Detailed safety and additional efficacy data will be presented. Conclusions: Combination E + EV is feasible and preliminarily exhibits antitumor activity. Dose escalation is ongoing to identify the MTD or recommended dose for expansion of the trial. Clinical trial information: NCT04963153 . [Table: see text]

Systemic inflammatory response syndrome in patients with severe fever with thrombocytopenia syndrome: prevalence, characteristics, and impact on prognosis

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is an emerging zoonosis with a high fatality rate in China. Previous studies have reported that dysregulated inflammatory response is associated with disease pathogenesis and mortality in patients with SFTS. This investigation aimed to evaluate the prevalence and characteristics of systemic inflammatory response syndrome (SIRS), and its impact on prognosis.MethodsData on demographic characteristics, comorbid conditions, clinical manifestations, laboratory parameters, and survival time of patients with SFTS were collected. Patients were divided into the non-SIRS and SIRS groups according to the presence of SIRS, then their clinical data were compared.ResultsA total of 290 patients diagnosed with SFTS were retrospectively enrolled, including 126(43.4%) patients with SIRS. Patients in the non-survivor group had more prevalence of SIRS than patients in the survivor group (P < 0.001), and SIRS (adjusted OR 2.885, 95% CI 1.226–6.786; P = 0.005) was shown as an independent risk factor for prognosis of patients with SFTS. Compared with patients without SIRS, patients with SIRS had lower WBC and neutrophils counts, and fibrinogen levels, but higher AST, LDH, amylase, lipase, CK, CK-MB, troponin I, APTT, thrombin time, D-dimer, CRP, IL-6, SAA levels, and viral load. The cumulative survival rate of patients with SIRS was significantly lower than that of patients without SIRS. Patients with SIRS also showed a higher incidence of bacterial or fungal infections than patients without SIRS.ConclusionsSIRS is highly frequent in patients with SFTS, and it is associated with high mortality.

Non-Invasive Prediction Scores for Hepatitis B Virus- and Hepatitis D Virus-Infected Patients-A Cohort from the North-Eastern Part of Romania.

Approximately 62-72 million people are infected worldwide with HDV. Patients with chronic hepatitis D (CHD) have a higher risk of developing cirrhosis or hepatocellular carcinoma (HCC) and an increased mortality rate compared to those with chronic hepatitis B (CHB). The stage of liver fibrosis or the risk of developing HCC can also be estimated by non-invasive scores, which are cost effective, easier to apply, and reproducible. In this study, we aimed to evaluate the predictive value of four non-invasive scores (FIB-4, APRI, AST/ALT ratio, and aMAP) in assessing severe fibrosis/cirrhosis and the presence of HCC in patients with HBV/HDV superinfection, as compared with HBV mono-infection. Our 8-year retrospective analysis revealed that HDV-infected patients had a 2-3 times higher risk of developing cirrhosis and HCC than HBV-mono-infected subjects. High AST and ALT baseline levels qualified as independent predictors for cirrhosis development in both groups. The following fibrosis scores, FIB-4, APRI score, and AAR, were significantly increased when cirrhosis was present at baseline and showed a good prediction for developing cirrhosis in the CHD group. The aMAP score, a risk predictor for HCC, showed significantly higher values in patients with HCC in both groups. Nonetheless, non-invasive scores should always be considered for monitoring patients with CHB and CHD, but only when associated with other diagnosis methods.

Reduced valence state of iridium supported on antimony doped tin oxide as a highly active and robust oxygen evolution reaction electrocatalyst for proton exchange membrane-based electrolysis

We use facile microwaves (MWs)-assisted polyol method to synthesize metallic Ir-nanoparticles (Ir-NPs) supported on antimony-doped tin oxide (ATO). Parameters such as Ir loading, reaction temperature and reaction time were optimized to achieve high electrocatalytic performance of oxygen evolution reaction (OER) activity and durability under the corrosive OER environment of acidic electrolyzers. Electrocatalysts with varying Ir loading between 10 and 40 wt% were synthesized at two different temperatures (140 °C and 160 °C) to compare morphology, Ir valence state, OER activity and stability. This analysis has revealed efficient electrocatalyst synthesis with a narrow size distribution and homogeneous dispersion over the support surface. An electron rich state of Ir, contributing to the electrocatalyst activity and stability, was achieved at the synthesis temperature of 160 °C. Among the as-synthesized electrocatalysts, one, named Ir/ATO.AT-40-160, has demonstrated high activity (449 ± 2.7 A gIr−1) and high AST stability (75.1% retained current), reaching respectively 1.5 and 2 times those of a state-of-the-art commercial electrocatalyst. The high catalytic activity and excellent stability can both be attributed to the depressed overoxidation of the active Ir due to the low valence state, appropriate composition, and highly dispersed Ir NPs over the support surface.

Epidemiology and Prevalence of HBsAg in the Student Population of the Higher Institute of Technology of Mamou, Republic of Guinea

Introduction: Due to its frequency, complications and socio-economic consequences, hepatitis B constitutes an international public health problem comparable to that posed by other communicable diseases such as HIV, tuberculosis and malaria. Sub-Saharan Africa, with a prevalence rate between 8 and 18%, is a highly endemic region.&#x0D; Objective: To help protect the health of students through awareness and screening for the hepatitis B virus.&#x0D; Methods: This is a prospective and descriptive longitudinal study which lasted one month, from February 15 to March 15, 2023.&#x0D; Results: Among the 200 students screened for the hepatitis B virus, men were more represented (80.50%) than women (19.50%), with a m/f sex ratio of 4.12 in favor of men. The 17-25 age group was the largest (77%), followed by the 26-33 age group (19.5%), the 34-41 age group (3%) and the 42+ age group (0.5%). 32% of students say they have good knowledge of the hepatitis B virus, compared to 68% who say they have little knowledge. The majority reported television as a source (75.5%), followed by radio (16%), school (4%), newspapers (2.5%) and social media (2%). The vast majority identified sexual transmission (89%), followed by blood (9.5%) and saliva (1.5%). In terms of risky practices, the majority of students identify prostitution (82.5%), followed by tattooing (9%), piercing (5%) and acupuncture (3.5%). Concerning knowledge of the hepatitis B vaccine, the majority of students (67.5%) say they do not know the vaccine against the hepatitis B virus, compared to 32.5% who say they know the vaccine. The HBV prevalence test showed 11% carriage compared to 89% negative tests. Transaminase tests on positive cases gave 63.63% normal ALT versus 36.36% elevated ALT; 72.72% normal AST versus 27.27% high AST. Carriage was higher in men (86.36%) than in women (13.63%). Single students were the most represented with 95.45%, compared to 4.55% for married students. Students from the Technical Laboratory and Mechanical Design and Manufacturing Departments were the most represented with 27.27% each. They were followed by those of the Biomedical Equipment Technology and Computer Engineering Departments with 18.18% each. Finally, the Energy Department was the least represented in this series with 9.09%.&#x0D; Conclusion: This study showed that the hepatitis B virus is present at the Mamou Higher Institute of Technology. It is therefore important to introduce it into secondary school programs to improve knowledge of the hepatitis B virus in Guinea.

AST and ALT APRI Scores and Dysglycemia in Saudi Arabia: A Retrospective Population Study.

Hyperglycemia is a common symptom of numerous conditions, most notably diabetes mellitus and Cushing's syndrome, and the liver plays a pivotal role in the regulation of glucose metabolism. The AST-platelet ratio index (AST APRI score) and ALT-platelet ratio index (ALT APRI score) are novel parameters whose association with circulating glucose levels remains poorly studied. Laboratory data of 14,177 subjects were retrospectively analyzed for the association between AST and ALT APRI scores and fasting blood glucose (FBG) using the Mann-Whitney U and Kruskal-Wallis tests, Spearman's rank correlation coefficient, prevalence and odds ratio (OR) and ROC curve analysis. AST and ALT APRI scores showed progressive increases with FBG, and the mean FBG was significantly higher in subjects with high AST (104.9 ± 0.33 to 120.8 ± 3.27, p < 0.0001) and ALT (104.7 ± 0.34 to 111.6 ± 1.30, p < 0.0001) APRI scores. However, the AST APRI score but not the ALT APRI score was affected by age and gender. Notably, both elevated AST and ALT APRI scores were more prevalent in hyperglycemic subjects irrespective of gender and were associated with FBG, albeit through mediator variables. Increased AST (OR = 2.55, 95% CI: 1.46-2.06, p < 0.0001) and ALT (OR = 1.73, 95% CI: 1.46-2.06, p < 0.0001) APRI scores carried a significantly higher risk for hyperglycemia. Importantly, the ALT APRI score was superior to that of the AST APRI score in distinguishing hyperglycemic subjects. The AST and ALT APRI scores are inexpensive, novel markers of FBG and may serve as supportive evidence in the diagnosis and management of hyperglycemic conditions.

Dietary Zinc Status in Offspring of Pregnant Rats Fed on a Zinc-Deficient Diet Is Associated with Serum Albumin, Ast, and Alt Levels

Objective: This study was carried out to investigate whether dietary zinc status is associated with serum albumin, AST and ALT levels in male offspring of mother rats fed a zinc deficient diet. Methods: The study was carried out on male offspring (Groups 1, 2, 3) born to rats fed a zinc deficient diet and on male offspring (Group 4) born to mothers fed a standard diet. Group 1: Zinc deficient, Group 2; standard rat chow, Group 3: Zinc supplemented diet. Animals of group 4 were used as control group. After the completion of the experimental stages of the study, albumin, AST, ALT, free and total bilirubin levels in serum samples taken from animals were determined by spectrophotometric method. Results: Dietary zinc deficiency (group 1) significantly decreased serum albumin values (p&lt;0.004). Animals in both the zinc deficient (Group 1) group and the Group 2 animals born to mothers fed a zinc deficient diet and fed standard rat chow had the highest AST and ALT levels (p&lt;0.001). Conclusion: The present study is the first to show that dietary zinc status can directly affect liver function in rats born to zinc deficient mothers by causing changes in serum albumin, AST and ALT levels.

1582-P: Association of Low eGFR with Novel Liver Fibrosis Biomarker Mac-2 Binding Protein Glycosylation Isomer in Type 2 Diabetes Patients

Objective: Advanced liver fibrosis, which leads to liver cirrhosis and cancer, has been one of the major causes of death in type 2 diabetes (T2D). Efficient screening system is needed to detect liver fibrosis early and prevent its progression. A novel serum fibrosis biomarker Mac-2 binding protein glycan isomer (M2BPGi) has high sensitivity plus specificity, and can be used in combination with FIB-4 screening index (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]/platelet ratio). This study aimed to investigate the predictive factors for the early detection of liver fibrosis using a combination of these two approaches. Methods: This cross-sectional study consisted of T2D patients, with negative results for hepatitis viruses and no history of heavy drinking. FIB-4 high patients were divided into two groups based on M2BPGi (high, M2BPGi &amp;gt; 1.00; normal level, M2BPGi &amp;lt; 1.00. The levels of clinical biomarkers were measured among two groups and predictive factors were calculated for M2BPGi high patients. Results: From July to December 2021, a total of 311 FIB-4 high T2D patients (male/female, 202/109; age, 71.1 + 9.8; Body Mass Index, 24.5 + 3.9; HbA1c 7.4 + 3.3 %) were enrolled in this study. The M2BPGi high group (44,3%, n=138) showed a significantly longer duration of diabetes, high alkaline phosphatase (ALP), AST, ALT, and low eGFR than M2BPGi normal group (55.7%, n=173). In multiple logistic regression analysis, eGFR &amp;lt; 60 mL/min/1.73m2 was independently identified as a predictive factor for M2BPGi high (Odds Ratio [OR] 2.61, 95% C.I. 1.55-4.39 P &amp;lt; 0.01) as well as AST &amp;gt; 30 IU/ml (OR, 3.37) and ALP &amp;gt; 113 IU/ml (OR, 1.88). Conclusions: low eGFR is associated with liver fibrosis in type 2 diabetes patients, and requires more careful attention to liver related disease. Disclosure E.Suzuki: None. Y.Shinya: None. B.Kanari: None. M.Kambara: None. H.Takahashi: None.