Although a range of blood traits have been reported to be associated with influenza A(H1N1)pdm09 (H1N1pdm09) disease severity, their underlying causal relationships and biological mechanisms have remained unclear. This study aimed to investigate the causal relationship between blood traits and H1N1pdm09 using a two-sample Mendelian randomization analysis. Based on the data from our in-house genome-wide association study (GWAS) on H1N1pdm09 disease severity (Ncase [severe] = 70, Ncontrol [mild] = 95) and GWAS summaries of 44 blood traits from Biobank Japan (N = 12 303-143 658), we identified the potential causal effect of blood traits on severe H1N1pdm09. The inverse variance weighted method analysis revealed significant causal effects of lower aspartate aminotransferase (AST, β = -3.212, p = 0.019), low-density-lipoprotein cholesterol (LDL-C, β = -1.372, p = 0.045), and basophil counts (Baso, β = -1.638, p = 0.047) on severe H1N1pdm09 disease. Additionally, polygenic risk score analysis further confirmed genetic overlap between these blood traits and severe H1N1pdm09 disease. This study provided evidence linking the lower level of AST, LDL-C, and lower count of Baso with severe H1N1pdm09 disease, potentially identifying new therapeutic targets for patients with severe influenza.

This study aimed to examine the association of liver enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl-transferase (GGT), with type 2 diabetes (T2D) risk, particularly their dose-response relationship.
This cross-sectional study enrolled participants aged >20 years old who underwent physical examination at our local hospital from November 2022 to May 2023. A generalized additive model (GAM) was fit to assess the dose-response relationship between liver enzymes and T2D risk. Furthermore, data from the UK Biobank (n=217,533) and National Health and Nutrition Examination Survey (NHANES 2011-2018; n= 15,528) were analyzed to evaluate whether the dose-response relationship between liver enzymes and T2D differed by population differences.
A total of 14,100 participants were included (1,155 individuals with T2D and 12,945 individuals without diabetes) in the analysis. GAM revealed a non-linear relationship between liver enzymes and T2D risk (P non-linear < 0.001). Specifically, T2D risk increased with increasing ALT and GGT levels (range, <50 IU/L) and then plateaued when ALT and GGT levels were >50 IU/L. Elevated AST within a certain range (range, <35 IU/L) decreased the risk of T2D, whereas mildly elevated AST (>35 IU/L) became a risk factor for T2D. The UK Biobank and NHANES data analysis also showed a similar non-linear pattern between liver enzymes and T2D incidence.
Liver enzymes were non-linearly associated with T2D risk in different populations, including China, the UK, and the US. Elevated ALT and GGT levels, within a certain range, could increase T2D risk. More attention should be given to liver enzyme levels for early lifestyle intervention and early T2D prevention. Further studies are necessary to explore the mechanism of the non-linear association between liver enzymes and T2D risk.

UNASSIGNED: Predicting severe preeclampsia with need for intensive care is challenging. To better predict high-risk pregnancies to prevent adverse outcomes such as eclampsia is still an unmet need worldwide. In this study we aimed to develop a prediction model for severe outcomes using routine biomarkers and clinical characteristics.
UNASSIGNED: We used machine learning models based on data from an intensive care cohort with severe preeclampsia (n=41) and a cohort of preeclampsia controls (n=40) with the objective to find patterns for severe disease not detectable with traditional logistic regression models.
UNASSIGNED: The best model was generated by including the laboratory parameters aspartate aminotransferase (ASAT), uric acid and body mass index (BMI) with a cross-validation accuracy of 0.88 and an area under the curve (AUC) of 0.91. Our model was internally validated on a test-set where the accuracy was lower, 0.82, with an AUC of 0.85.
UNASSIGNED: The clinical routine blood parameters ASAT and uric acid as well as BMI, were the parameters most indicative of severe disease. Aspartate aminotransferase reflects liver involvement, uric acid might be involved in several steps of the pathophysiologic process of preeclampsia, and obesity is a well-known risk factor for development of both severe and non-severe preeclampsia likely involving inflammatory pathways..[Figure: see text].

Introduction Isotretinoin is a bioactive retinoic acid variant that is taken orally to treat moderate to severe acne vulgaris. One of the adverse effects of isotretinoin is elevated liver enzymes. This study estimated the prevalence of liver enzyme changes during isotretinoin use among dermatology clinic patients in Al-Ahsa, Kingdom of Saudi Arabia. Methods This study was a retrospective analysis that reviewed the medical data of 97 patients with acne at the King Faisal University Polyclinic who were taking systemic isotretinoin. It determined the baseline, second, and last readings of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Among the 97 patients, 67 (69.1%) were female and 30 (30.9%) were male. Results Of the patients, 41 (50.6%) weighed 51-70 kg, and 45 (46.4%) were 21-23 years old. The age of acne onset was 20 years or younger. Most patients had a starting isotretinoin dose of 10-20 mg and an ending dose of 30-40 mg over six months. Ninety (92.8%) patients had not used isotretinoin in the past. Before treatment, AST was elevated in three (3.1%) patients, and ALT was elevated in two (2.1%) patients. In the last readings, AST was elevated in eight (8.2%) patients, and ALT was elevated in four (4.1%) patients. Conclusion The result of this study indicates that the incidence of high levels of AST and ALT with oral isotretinoin was low. So frequent laboratory monitoring is not recommended since the elevation was not associated with any morbidity and carries financial and emotional burdens. An exception is patients with higher body weight, males, and those whose acne started at age 16-19, in whom frequent monitoring may be considered for AST more than ALT.

Purpose Most of the research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019 [COVID-19]) has mainly focused on the lungs as a key organ involved in the disease, while very little data is available regarding the involvement of other organs including the liver and kidneys, which are also reported to be severely affected by the disease. The objective of this study was to analyze the effect of COVID-19 disease on liver and kidney functions and to determine their association with the severity and mortality of the disease. This was a retrospective cross-sectional analysis of medical records. Methods A total of 100 confirmed COVID-19 adult patients from Madinah, Saudi Arabia hospitalized between April 28 and June 30, 2020, were included and categorized into asymptomatic, mild to moderate, and severely ill patients. We analyzed the clinical status of liver and renal functioning in all three groups. Results Most patients (51%) were diagnosed with mild to moderate disease, 27% of patients were severely ill and 22% of patients were asymptomatic. The liver and renal functional analysis showed that the severity of the COVID-19 patients was significantly associated with renal impairments exhibiting higher levels of creatinine and urea (P<0.05) with high levels of liver enzymes as indicators for liver damage. Conclusion We concluded from the present study that severely ill COVID-19 patients were more prone to have abnormal liver and renal functions. The present findings, however, demand further study of the association between liver and kidney impairments with COVID-19 infection for better clinical management.

The long-term laboratory aspects of the effects of coronavirus disease 2019 (COVID-19) on liver function are still not well understood. Therefore, this study aimed to evaluate the hepatic clinical laboratory profile of patients with up to 20 months of long-term COVID-19. A total of 243 patients of both sexes aged 18 years or older admitted during the acute phase of COVID-19 were included in this study. Liver function analysis was performed. Changes were identified in the mean levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), and ferritin. A ferritin level of >300 U/L was observed in the group that presented more changes in liver function markers (ALT, AST, and GGT). Age ≥ 60 years, male sex, AST level > 25 U/L, and GGT level ≥ 50 or 32 U/L were associated with an ALT level > 29 U/L. A correlation was found between ALT and AST, LDH, GGT, and ferritin. Our findings suggest that ALT and AST levels may be elevated in patients with long-term COVID-19, especially in those hospitalised during the acute phase. In addition, an ALT level > 29 U/L was associated with changes in the levels of other markers of liver injury, such as LDH, GGT, and ferritin.

Accumulating evidence has revealed that the aspartate aminotransferase to alanine aminotransferase (AST/ALT) ratio is a promising novel biomarker for insulin resistance (IR) and metabolic diseases. However, research on the association between the AST/ALT ratio and the incidence of diabetes progressing from prediabetes remains lacking. Herein, this study aimed to evaluate the relationship between the baseline AST/ALT ratio and risks of diabetes in patients with prediabetes.
This was a retrospective cohort study involving a total of 82,683 participants across 32 regions and 11 cities in China from 2010 to 2016. Data was obtained based on the DATADRYAD database from the health check screening program. Participants were stratified according to the interquartile range of the AST/ALT ratio (groups Q1 to Q4). The Cox proportional hazard model and smooth curve fitting were used to explore the relationship between the baseline AST/ALT ratio and the risk of diabetes in prediabetic patients. In addition, subgroup analysis was used to further validate the stability of the results.
The mean age of the selected participants was 49.9 ± 14.0 years, with 66.8% of them being male. During the follow-up period 1,273 participants (11.3%) developed diabetes progressing from prediabetes during the follow-up period. Participants who developed diabetes were older and were more likely to be male. The fully-adjusted Cox proportional hazard model revealed that the AST/ALT ratio was negatively associated with the risk of diabetes in prediabetic patients (HR = 0.40, 95% CI: 0.33 to 0.48, P < 0.001). Higher AST/ALT ratio groups (Q4) also presented with a lower risk of progressing into diabetes (HR = 0.35, 95% CI: 0.29 to 0.43, P < 0.001, respectively) compared with the lowest quintile group (Q1). Through subgroup analysis and interaction tests, it was found that the association stably existed in all subgroup variables, and there were a stronger interactive effects in people with age < 45 years, and TG ≤ 1.7 mmol/L in the association between AST/ALT ratio and diabetes incidences in patients with prediabetes (P for interaction < 0.05).
According to our study, a higher AST/ALT ratio is associated with a lower risk of progressing into diabetes from prediabetes. Regular monitoring of AST/ALT ratio dynamics and corresponding interventions can help prevent or slow prediabetes progression for diabetes.

This study was intended to evaluate whether the safety and efficacy of dual antiplatelet treatment in patients with minor ischemic stroke (MIS) or transient ischemic attack (TIA) could be modified by the aminotransferase level. Also, we sought to assess the interaction between aminotransferase level and CYP2C19 loss-of-function status on the efficacy of dual antiplatelet therapy.
This study is a post hoc analysis of the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) study, a double-blinded randomized control trial. We included 5,133 patients with a complete workup of baseline alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. The primary outcome is stroke or TIA recurrence within 90 days. Cox proportional hazard models were used in the evaluation of the efficacy of antiplatelet treatment in patients with different aminotransferase levels and subgroups categorized by the aminotransferase level × CYP2C19 loss-of-function status.
The median age of all the included patients was 62 years; 66.3% of the patients were male. More recurrent stroke or TIA occurred in patients with elevated ALT and AST levels within 90 days compared to patients with normal ALT and AST levels (14.5 vs. 11.2%, p = 0.029). Dual antiplatelet treatment with aspirin and clopidogrel reduced recurrence compared with aspirin alone in patients with both normal (adjusted hazard ratio [HR], 95% confidence interval [CI]: 0.72 [0.60-0.86], p < 0.001) and elevated (adjusted HR [95% CI]: 0. 57 [0. 35-0. 92], p = 0. 020) ALT and AST levels (p = 0.64 for interaction). No significant difference in treatment efficacy on 90-day all-cause death or bleeding events was found.
Dual antiplatelet treatment was safe for minor stroke or high-risk TIA patients with mildly elevated aminotransferase. Mild elevation of ALT or AST did not undermine the protective efficacy of the dual antiplatelet regimen in reducing recurrent stroke or TIA within 90 days after MIS or TIA. The interaction between the CYP2C19 loss-of-function allele carrier status and aminotransferase level on the efficacy of dual antiplatelet treatment was not observed.

UNASSIGNED: Initial reports indicate a high incidence of abnormal aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in patients with COVID-19 and possible association with acute kidney injury (AKI). We aimed to investigate clinical features of elevated transaminases on admission, its association with AKI, and outcomes in patients with COVID-19.
UNASSIGNED: A retrospective analysis of the registered data of hospitalized patients with laboratory-confirmed COVID-19 and assessment of the AST and ALT was performed. Multinomial logistic regression was used to determine factors associated with community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI).
UNASSIGNED: The subjects comprised 828 patients (mean age = 65.0±16.0 years; 51.4% male). Hypertension was present in 70.3% of patients, diabetes mellitus in 26.0%, and chronic kidney disease in 8.5%. In-hospital mortality was 21.0%. At admission, only 41.5% of patients had hypertransaminasemia. Patients with elevated transaminases at admission were younger, had higher levels of inflammatory markers and D-dimer, and poorer outcomes. The AKI incidence in the study population was 27.1%. Patients with hypertransaminasemia were more likely to develop AKI (33.5% vs. 23.3%, p = 0.003). Patients with predominantly elevated AST (compared to elevated ALT) were more likely to have adverse outcomes. Multinomial logistic regression found that hypertension, chronic kidney disease, elevated AST, and hematuria were associated with CA-AKI. Meanwhile, age > 65 years, hypertension, malignancy, elevated AST, and hematuria were predictors of HA-AKI.
UNASSIGNED: Elevated transaminases on admission were associated with AKI and poor outcomes. Patients with elevated AST were more likely to have adverse outcomes. Elevated AST on admission was associated with CA-AKI and was a predictor of HA-AKI.

UNASSIGNED: The main aim of the present study is to investigate the independent association objectively measured level of physical activity (PA) and serum concentration of liver aminotransferases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) among seemingly healthy individuals.
UNASSIGNED: The current secondary study was conducted in the framework of Khuzestan Comprehensive Health Study, a large population-based multicentric cross-sectional study, conducted between 2016 and 2019 on 18,966 individuals living in Khuzestan province, southwestern Iran. International PA Questionnaire was used for evaluating PA levels, and participants were divided into three groups: low, moderate, and high PA, and ALT and AST were compared between these groups.
UNASSIGNED: The mean ± standard deviation age of participants was 38.65 ± 11.40 years. The majority of participants were female (71%). The mean concentration of ALT in total sample was 18.22 ± 13.06 (male: 23.65 ± 16.26 and female: 15.57 ± 10.06), while the mean concentration of ALT in total sample was 19.61 ± 8.40 (male: 22.44 ± 10.03 and female: 18.23 ± 7.08). A statistically significant inverse correlation was found between AST (r = -0.08, P = 0.02) and ALT (r = -0.038, P < 0.001) with total PA score. The mean concentration of ALT was 19.96 ± 13.63 in people with low PA, 17.62 ± 12.31 with moderate PA, and 18.12 ± 13.47 with high PA (P < 0.001). The mean concentration of AST in total sample was 20.37 ± 8.85 in people with low PA, 19.21 ± 8.83 with moderate PA, and 19.75 ± 8.85 with high PA (P < 0.001). The difference between people in different levels of PA in terms of mean concentration of AST was remained significant (P = 0.003); however, the difference for ALT was not remained significant after adjusting potential confounders.
UNASSIGNED: The current study based on large sample showed that PA had a statistically negative association with the concentration of liver aminotransferases in the seemingly healthy individuals; however, the observed associations were weak. People in the lowest levels of PA had the highest levels of ALT and AST.