Baseline Aspartate Aminotransferase Research Articles

Prognosis of Acute HEV Infection in Patients With Liver Cirrhosis: A Retrospective Study of 628 Chinese Patients.

Acute hepatitis E virus infection is a serious global health problem, which a significant cause of morbidity and mortality. The aim of the present study was to characterise the clinical features and therapeutic response of patients with acute HEV infection and identify risk factors for poor prognosis. In a retrospective study from 01 January 2014 to 01 Januray 2022, we collected baseline data from all patients eligible for acute hepatitis E virus (HEV) infection and followed up with all patients via interviews and medical records. We explored the clinical feature of Chinese patients with acute HEV infection. The follow-up data of patients were used to identify risk factors for poor prognosis. In total, 628 acute hepatitis E (AHE) patients fulfilled the inclusion criteria and did not meet the exclusion criteria. Among them, 452 were males and 176 were females (M:F = 2.57:1). The median age at diagnosis was 57.0 years (interquartile range: 46-64 years). The median baseline serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were elevated in this cohort (642.3 U/L, 216.2 U/L, 104.1 μmol/L, respectively). The median hospitalisation duration was 16 days. Compared with patients without other liver diseases, patients with liver cirrhosis show lower baseline ALT and AST level, poorer coagulation indices and higher MELD scores. According to multivariate analysis, liver cirrhosis, high MELD score, low albumin concentration was found to be independent predictors of poor prognosis in patients with AHE. Our study used a lager sample size to validate that some demographic and serological features were quite different between patients with/without CLDs. Liver cirrhosis was a significant independent predictor of poor prognosis in acute HEV hepatitis.

Assessment of liver and kidney function in patients with ankylosing spondylitis on long-term non-steroidal anti-inflammatory drug therapy.

This study aimed to analyze the status of liver [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] and kidney (serum creatine) function in ankylosing spondylitis (AS) patients assuming continuously non-steroidal anti-inflammatory drugs (NSAIDs) alone over a long period. Between 2013 and 2022, there were records of 385 AS patients. Of them, 56 were receiving only NSAIDs, and the files of these patients were retrospectively analyzed. Demographic and clinical characteristics were collected. Blood tests, including serum creatinine, AST, and ALT, were assessed at each visit. Of the 56 patients, 39 were male. The mean age was 45.30 years, and the follow-up period was 9.80 years. Of them, 44.6% used indomethacin, 26.8% naproxen, 17.9% diclofenac, 5.4% acemethazine, 3.6% meloxicam, and 1.8% celecoxib. The mean baseline serum creatinine was 0.71 mg/dL. The mean baseline serum AST and ALT were 19.6 u/L and 22.9 u/L, respectively. Baseline creatinine, AST, and ALT were not statistically significantly different between sexes. There was a statistically significant difference between mean creatinine concentrations at baseline and at year 3. One patient on naproxen discontinued treatment due to elevated creatinine. The creatinine level decreased during the patient's follow-up. Liver enzymes above 3 times the normal value were not seen in any patient. Based on real-world data, long-term use of NSAIDs has generally not led to acute liver and kidney injury or progressive impairment of hepatorenal function requiring discontinuation of treatment.

Homograft Aortic Root Replacement for Destructive Prosthetic Valve Endocarditis: Results in the Current Era.

Background: Destructive aortic prosthetic valve endocarditis portends a high morbidity and mortality, and requires complex high-risk surgery. Homograft root replacement is the most radical and biocompatible operation and, thus, the preferred option. Methods: A retrospective analysis was conducted on 61 consecutive patients who underwent a cardiac reoperation comprising homograft aortic root replacement since 2010. The probabilities of survival were calculated with the Kaplan-Meier method, whereas multivariable regression served to outline the predictors of adverse events. The endpoints were operative/late death, perioperative low cardiac output and renal failure, and reoperations. Results: The operative (cumulative hospital and 30-day) mortality was 13%. The baseline aspartate transaminase (AST) and associated mitral procedures were predictive of operative death (p = 0.048, OR [95% CIs] = 1.03 [1-1.06]) and perioperative low cardiac output, respectively (p = 0.04, OR [95% CIs] = 21.3 [2.7-168.9] for valve replacement). The latter occurred in 12 (20%) patients, despite a normal ejection fraction. Survival estimates (±SE) at 3 months, 6 months, 1 year, and 3 years after surgery were 86.3 ± 4.7%, 82.0 ± 4.9%, 75.2 ± 5.6, and 70.0 ± 6.3%, respectively. Survival was significantly lower in the case of AST ≥ 40 IU/L (p = 0.04) and aortic cross-clamp time ≥ 180 min (p = 0.01), but not when excluding operative survivors. Five patients required early (two out of the five, within 3 months) or late (three out of the five) reoperation. Conclusions: Homograft aortic root replacement for destructive prosthetic valve endocarditis can currently be performed with a near 90% operative survival and reasonable 3-year mortality and reoperation rate. AST might serve to additionally stratify the operative risk.

Population pharmacokinetic modeling of oral brepocitinib in healthy volunteers and patients with immuno-inflammatory diseases.

The objective of this population pharmacokinetic (PK) analysis was to characterize the concentration-time profile of brepocitinib plasma concentration after single- and multiple-oral administration in healthy volunteers (HVs) and patients with immuno-inflammatory diseases. Blood samples from phase I HV and phase II clinical studies of patients with alopecia areata, psoriasis, psoriatic arthritis, ulcerative colitis (UC), vitiligo, and hidradenitis suppurativa were analyzed using a nonlinear mixed-effects modeling approach. Effects of patients' characteristics on brepocitinib exposure were investigated. Overall, 8552 brepocitinib plasma concentrations from 775 individuals were included in the analysis. The PKs of brepocitinib were adequately described by a two-compartment model with first-order absorption and a lag time for tablet formulation, dose-dependent bioavailability, and Box-Cox transformed interindividual variabilities on apparent clearance (CL/F) and apparent central volume of distribution (Vc/F). For a typical 70-kg non-Asian female patient with baseline aspartate aminotransferase of 22 unit/liter, CL/F and Vc/F estimates were 17.5 L/h and 88.5 L, respectively. Asians had a higher exposure (independent of body weight), caused by a 10% lower CL/F when compared to other individuals. Independent of baseline body weight, the male population showed 13% higher Vc/F compared to the female population. Patients with UC were predicted to have 46% slower absorption rate compared to other individuals. The PKs of brepocitinib were well-characterized by a two-compartment model with first-order absorption and dose-dependent bioavailability. Several covariates, such as race and sex, were identified to have statistically significant, but not clinically meaningful, effects on the estimated PK parameters.

Effect of the Xanthine Oxidase Inhibitor Febuxostat on the Cardio-Ankle Vascular Index in Asymptomatic Patients with Hyperuricemia and Liver Dysfunction: A Sub-Analysis of the PRIZE Study.

The effect of uric acid (UA)-lowering therapy with xanthine oxidoreductase (XOR) inhibitors on the development of cardiovascular disease requires further investigation. This study aimed to evaluate the long-term effects of febuxostat on arterial stiffness, focusing on liver function. The PRIZE study involved random assignment of patients with asymptomatic hyperuricemia to receive either add-on febuxostat treatment (febuxostat group) or non-pharmacological treatment (control group). Of the 514 participants, 23 and 14 patients in the febuxostat and control groups, respectively, underwent assessment of arterial stiffness using the cardio-ankle vascular index (CAVI). The participants in each group were further grouped on the basis of their baseline alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels (above or below the media value or 30 U/L). The primary endpoint was the change in the CAVI from baseline to 12 and 24 months. Overall, no significant differences were found between the control and febuxostat groups in the least-squares mean estimates of changes in CAVI at 24 months (mean between-group difference, -0.41 [95% CI, -1.05 to 0.23]; p=0.204). However, there were significant differences in participants with higher baseline ALT or AST levels above 30 U/L at 24 months (mean between-group difference, -1.12 [95% CI, -2.23 to -0.01]; p=0.048 for ALT ≥ 30 U/L and -1.08 [95% CI, -2.13 to -0.03]; p=0.044 for AST ≥ 30 U/L). Two-year treatment with febuxostat demonstrated a beneficial effect on CAVI in patients with hyperuricemia and liver dysfunction.

Stability of Aspartate Transaminase in Blood Specimens Subjected to Various Storage Temperatures and Times Prior to Centrifugation

Aspartate Transaminase (AST) is an enzyme used to diagnose medical problems and found in erythrocytes other than in the heart, liver, skeletal muscles, kidney, and brain. Prolonged serum-clot contact time and the fluctuation in storage temperature are possible reasons for the changes in chemical constituents in serum. The objective of this experimental study was to determine the effect of the storage time (three and six hours) before centrifugation and the storage temperature (4℃ and 28℃) on the stability of AST in blood. Methods: The study sample consisted of fifty-three healthy adult volunteers. Five milliliters of blood samples were collected from each subject and then aliquoted into five Eppendorf tubes. One of the aliquots was centrifuged within 30 minutes of collection, and the AST assay was done to obtain the control (baseline) value. Two of the remaining aliquots were stored at 4℃ while the other two aliquots were stored at room temperature for three hours and six hours, respectively prior to centrifugation. The difference between the baseline AST values and paired values of samples at different times of storage and temperatures was analyzed using the non-parametric Wilcoxon signed-rank test. Results: Significant differences were found in AST level compared to the baseline value when samples were stored at room temperature for three hours (p=0.027) and six hours at room temperature (p=0.011). Conclusions: AST in blood was unstable for at least three hours at room temperature (28℃). At 4℃, AST was stable for up to six hours, and blood samples can be stored at 4℃ for up to six hours for analysis of AST.

One-Year Survival for Developing Acute Kidney Injury in Adult Patients with AMI Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation.

The incidence of cardiogenic shock cases treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support has been on the rise. Acute kidney injury (AKI) is a significant complication of cardiogenic shock and a frequent serious complication in patients requiring ECMO-supported therapy. AKI is strongly associated with unfavorable patient prognosis. However, there is a paucity of data on the influence of AKI on the prognosis of patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS) who are receiving ECMO support, particularly with regard to long-term outcomes. This retrospective observational study included 103 patients in the People's Hospital of Guangxi Zhuang Autonomous Region from January 2017 and June 2022. AKI was defined according to Kidney Disease Improving Global Outcome (KDIGO) criteria. Cox regression and logistic regression were used to identify risk factors. In this study, the incidence of AKI was 63.11%, with AKI stage 1, 2, and 3 accounting for 21.36%, 12.62%, and 29.13%, respectively. Patients with severe AKI had significantly higher in-hospital mortality (43.33% vs 27.40%, P < 0.001), 30-day mortality (60.00% vs 31.51%, P = 0.001), and 1-year mortality (63.67% vs 34.25%, P<0.001) than those without severe AKI. Furthermore, severe AKI significantly increased the risk of one-year mortality (HR 10.816, CI 3.118-37.512, P<0.001). Baseline serum creatinine, baseline platelet, and active cardiopulmonary resuscitation were independent predictors of one-year mortality. In addition, baseline white blood cell count, baseline aspartate aminotransferase, baseline alanine aminotransferase (ALT), baseline serum creatinine, preoperative lactate, and postoperative mean arterial pressure were independent risk factors of severe AKI during hospitalization. In patients with AMI-CS receiving ECMO support, AKI is highly prevalent. Development of severe AKI significantly increased the risk of one-year mortality.

A novel nomogram for predicting HBeAg seroclearance in HBeAg-positive chronic hepatitis B patients treated with nucleos(t)ide analogues

Introduction and ObjectivesSeroclearance of hepatitis B e antigen (HBeAg) is an important treatment goal for patients with chronic hepatitis B (CHB). This study developed a nomogram for predicting HBeAg seroclearance in CHB patients treated with nucleos(t)ide analogues (NAs). Patients and MethodsFive hundred and sixty-nine CHB patients treated with NAs from two institutions between July 2016 to November 2021 were retrospectively included. One institution served as the training set (n = 374) and the other as the external validation set (n = 195). A predictive nomogram was established based on cox regression analysis. ResultsThe overall HBeAg seroclearance rates were 27.3 and 21.5 % after the median follow-up of 100.2 weeks and 65.1 weeks in the training set and validation set, respectively. In the training set, baseline aspartate aminotransferase, gamma-glutamyl transpeptidase, HBeAg, and hepatitis B core antibody levels were independently associated with HBeAg seroclearance and were used to establish the HBEAg SeroClearance (ESC)-nomogram. The calibration curve revealed that the ESC-nomogram had a good agreement with actual observation. The ESC-nomogram showed relatively high accuracy for predicting 48 weeks, 96 weeks, and 144 weeks of HBeAg seroclearance in the training set (AUCs: 0.782, 0.734 and 0.671) and validation set (AUCs: 0.699, 0.718 and 0.689). The patients with high ESC-nomogram scores (≥ 79.51) had significantly higher cumulative incidence of HBeAg seroclearance and seroconversion than patients with low scores (< 79.51) in both sets (P < 0.01). ConclusionsThe novel ESC-nomogram showed good performance for predicting antiviral efficacy in HBeAg-positive CHB patients with NAs treatment.

Nonalcoholic Fatty Liver Disease Incidence and Remission and Their Predictors During 7 Years of Follow-up Among Finns.

The incidence and remission of nonalcoholic fatty liver disease (NAFLD) are sparsely studied outside Asia. This prospective study aimed to investigate NAFLD incidence and remission, and their predictors among a general Finnish population. The applied cohort included 1260 repeatedly studied middle-aged participants with data on liver ultrasound and no excessive alcohol intake. Hepatic steatosis was assessed by liver ultrasound with a 7.2-year study interval. Comprehensive data on health parameters and lifestyle factors were available. At baseline, 1079 participants did not have NAFLD, and during the study period 198 of them developed NAFLD. Of the 181 participants with NAFLD at baseline, 40 achieved NAFLD remission. Taking multicollinearity into account, key predictors for incident NAFLD were baseline age (odds ratio 1.07; 95% CI, 1.02-1.13; P = .009), waist circumference (WC) (2.77, 1.91-4.01 per 1 SD; P < .001), and triglycerides (2.31, 1.53-3.51 per 1 SD; P < .001) and alanine aminotransferase (ALAT) (1.90, 1.20-3.00 per 1 SD; P = .006) concentrations as well as body mass index (BMI) change (4.12, 3.02-5.63 per 1 SD; P < .001). Predictors of NAFLD remission were baseline aspartate aminotransferase (ASAT) concentration (0.23, 0.08-0.67 per 1 SD; P = .007) and WC change (0.38, 0.25-0.59 per 1 SD; P < .001). During follow-up, NAFLD developed for every fifth participant without NAFLD at baseline, and one-fifth of those with NAFLD at baseline had achieved NAFLD remission. NAFLD became more prevalent during the follow-up period. From a clinical perspective, key factors predicting NAFLD incidence and remission were BMI and WC change independent of their baseline level.

Prediction of response to sofosbuvir-based therapy using serum interleukin-12 and single nucleotide polymorphism of the interleukin 28B gene as predictive factors in HCV positive genotype-4 patients.

Some hepatitis-C virus patients have resistance to direct-acting-antivirals (DAAs). Genetic polymorphisms have been associated with drug resistance. This study aimed to evaluate the role of interleukin (IL)-28B gene polymorphism and IL-12 levels as predictors for a response to sofosbuvir/ribavirin (SOF/RBV) with (triple-therapy) or without (dual-therapy) Peg-alpha-interferon. 92 hepatitis C virus (HCV)/RNA (+)-patients treated with dual (n = 72) or triple (n = 20) therapy. IL28B genetic polymorphism and IL-12 level assessments. 30.4% of the patients were IL28B C/C genotype, 56.5% C/T-genotype, and 13% T/T-genotype. Mean baseline IL-12 levels were 27.5 ± 3.0 pg/mL. Rapid viral response was achieved in 86/92 patients. All patients achieved end-of-treatment virologic response. The 12- and 24-week sustained virologic responses (SVR) were achieved in 76 patients (82.6%), that is, a relapse was found in 16 patients (17.4%). 8 and 12-weeks after antiviral therapy, IL-12 levels decreased significantly, and became comparable to those of the control-group. That drop in IL-12 levels was similar across the dual- and triple-therapy patients. Finally, logistic regression analysis showed that the increase in baseline aspartate aminotransferase (AST) and T/T genotyping had an independent effect on increasing the probability a SVR failing in both dual- and triple-therapy groups (P = .0007 and P = .02, respectively). Single-nucleotide polymorphism (SNP) in IL-28B and IL-12 levels play roles as predictors in DAAs resistance.

Baseline aspartate aminotransferase activity is closely related to COVID-19 mortality: A bidirectional cohort study

Baseline aspartate aminotransferase activity is closely related to COVID-19 mortality: A bidirectional cohort study

Population Pharmacokinetics and Exposure-Response Analysis of Tremelimumab 300mg Single Dose Combined with Durvalumab 1500mg Q4W (STRIDE) in Patients with Unresectable Hepatocellular Carcinoma.

A novel single-dose regimen of 300mg tremelimumab in combination with durvalumab (STRIDE) has demonstrated a favorable benefit-risk profile in the phase1/2 Study22 trial (in patients with unresectable hepatocellular carcinoma, uHCC) and in the phase3 HIMALAYA study. The current analysis evaluated the population pharmacokinetics (PopPK) of tremelimumab and durvalumab, and the exposure-response (ER) relationship for efficacy and safety of STRIDE in patients with uHCC. Previous PopPK models for tremelimumab and durvalumab were updated using data from previous studies in various cancers combined with data from Study22 and HIMALAYA. Typical population mean parameters and associated inter- and intra-individual variability were assessed, as was the influence of covariates. Individual exposure metrics were derived from the individual empirical Bayes estimates as drivers for ER analysis related to efficacy and safety from HIMALAYA. The observed pharmacokinetics of tremelimumab in uHCC were well described by a 2-compartment model with both linear and time-dependent clearance. All identified covariates changed tremelimumab PK parameters by <25%, and thus had minimal clinical relevance; similar results were obtained from durvalumab PopPK analysis. None of tremelimumab or durvalumab exposure metrics were significantly associated with overall survival (OS), progression-free survival (PFS), or adverse events. Baseline aspartate aminotransferase and neutrophil-to-lymphocyte ratio (NLR) were associated with OS (P<.001) by the Cox proportional hazards model. No covariate was identified as a significant factor for PFS. No dose adjustment for tremelimumab or durvalumab is needed based on PopPK covariate analyses or ER analyses. Our findings support the novel STRIDE dosing regimen in patients with uHCC.

The delayed clearance of Talaromyces marneffei in blood culture may be associated with higher MIC of voriconazole after antifungal therapy among AIDS patients with talaromycosis.

This study aimed to investigate the influencing factors of delayed clearance of Talaromyces marneffei (T. marneffei) in blood culture of patients with acquired immune deficiency syndrome (AIDS) complicated with talaromycosis after antifungal therapy. The patients with AIDS complicated with talaromycosis were retrospectively enrolled, and divided into two groups according to the blood T. marneffei culture results in two weeks after antifungal therapy. The baseline clinical data were collected and the antifungal susceptibility of T. marneffei was tested. A total of 190 patients with AIDS and talaromycosis were enrolled, of whom 101 cases remained positive for T. marneffei (Pos-group) while the other 89 cases were negative in blood culture (Neg-group) after two weeks' antifungal treatment. The Pos-group had a higher baseline Aspartate aminotransferase (AST, 78.5 vs. 105 U/L; P = 0.073) and lower CD4+ T cells level (11 vs. 7 cells/μl; P = 0.061). The percentage of isolates with higher MICs of voriconazole (VOR) and fluconazole (FLU) in the Pos-group were significantly higher than those in the Neg-group (χ2 = 12.623, P < 0.001 and χ2 = 9.356, P = 0.002, respectively). By multivariate logistic regression, the MIC value for VOR was identified as the prognostic variable that may influence the clearance of T. marneffei in blood culture after antifungal therapy among AIDS patients with talaromycosis. The delayed negative conversion of blood T. marneffei-culture may be associated with some factors especially higher MIC of VOR, indicating the possibility of drug resistance of T. marneffei.

Impact of etiology of hepatocellular carcinoma on treatment outcomes in a real-world database.

508 Background: Hepatocellular carcinoma (HCC) is a common and deadly form of liver cancer. Systemic therapy with combination atezolizumab and bevacizumab (A/B) is the new treatment standard; yet fewer than 30% experience treatment response. The etiology of HCC (viral, alcohol, or NASH) and its impact on treatment response is unknown. Thus, we sought to determine the impact of etiology on survival outcomes of patients treated with A/B. Methods: This study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. Patients with HCC receiving first-line A/B after January 1, 2020 were eligible for inclusion. We used a validated algorithm to adjudicate cohort by likely etiology (viral, alcohol and NASH). The primary outcome was median real-world overall survival (OS), defined from initial receipt of A/B until death or censored at last receipt of A/B by etiology. The secondary outcome was real-world time to treatment discontinuation (TTD -a validated surrogate that approximates progression-free survival) defined as time from initial receipt of A/B to progression, death, or treatment discontinuation for more than 120 days or censored at last clinical contact by etiology. The Kaplan-Meier method, Cox proportional hazards model and the log-rank test was used to test for differences between etiologies. Results: In total, 429 eligible HCC patients were included (n=216, 50.3% Viral; n=68, 15.8% Alcohol; n=145, 33.8%, NASH). In the total cohort, median OS was 9.4 months (95% CI 7.1-10.9) and median TTD was 5.7 months (5.0-7.0); by etiology, OS medians were 10.1 (7.2-14.0), 9.8 (6.1-13.9), 7.5 (5.3-11.0) months, and TTD medians were 6.1 (5.0-8.0), 5.8 (3.7-7.8), and 5.5 (2.6-7.0) months, for Viral-HCC, Alcohol-HCC, and NASH-HCC respectively. No significant difference in the hazard of death or TTD by etiology were observed in the unadjusted or adjusted Cox regression analyses (see table). The multivariate model included age, ECOG performance status, receipt of prior locoregional therapy, albumin-bilirubin (ALBI) grade, and baseline aspartate aminotransferase. Conclusions: In this large cohort study of US patients with HCC, we did not identify a significant association between etiology and survival or time to treatment discontinuation outcomes, although outcomes were numerically worse in patients with NASH. Although the underlying microenvironment and oncogenesis may differ by etiology, further research is needed to identify those most likely to benefit from A/B. [Table: see text]

Low Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) Ratio Associated with Increased Cardiovascular Disease and its Risk Factors in Healthy Japanese Population

This study aimed to evaluate the association between aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio and cardiovascular disease, and risk factors in a healthy Japanese population. A retrospective cohort study was conducted at St. Luke's International Hospital, Tokyo, Japan, between 2005 and 2018. We included all participants who visited the hospital for voluntary health checkups. Our primary outcome was the development of cardiovascular disease, and the secondary outcomes were cardiovascular risk factors. We grouped the participants into quartiles (Qs) according to their baseline AST/ ALT ratios and examined the outcomes of patients in each group. 87,740 participants were included in this study. The mean age of the participants was 44.9 years [standard deviation (SD): 12.1], and 43,191 (49.2%) were men. The mean AST and ALT levels were 21.7 IU/L (SD 10.0) and 22.4 IU/L (SD 16.5), respectively, resulting in a mean AST/ALT ratio of 1.1 (0.4). During the median follow-up of 1,829 days (interquartile range 756-3,470), 1,493 (1.7%) participants developed cardiovascular disease, 831 (1%) experienced ischemic heart disease, and 723 (0.8%) experienced strokes. Those in the Q1 AST/ALT ratio group had significantly higher hazard ratios compared to those in the Q3 AST/ ALT ratio group [adjusted hazard ratio (HR)=1.32, 95% confidence interval (CI): 1.12-1.56 for cardiovascular disease; HR=1.36, 95%CI: 1.09-1.68 for ischemic heart disease; HR=1.28, 95%CI: 1.00-1.65 for stroke]. However, those belonging to the Q4 or Q5 AST/ALT ratio groups was not statistically different for primary outcomes compared to the Q3 AST/ALT ratio group. In contrast, the adjusted HRs for all secondary outcomes decreased in a dose-dependent manner as the AST/ALT ratio increased. A Q1 AST/ALT ratio was associated with an increased risk of cardiovascular disease compared to the Q3 AST/ALT ratio in the Japanese population, which is in contrast with the Western population. In our study, Q4 or Q5 AST/ALT ratios were not associated with cardiovascular disease compared to the Q3 AST/ ALT ratio. As for cardiovascular risk factors, the risk decreased as the AST/ALT ratio increased.

Association Between Serum Aminotransferases and Risk of New-Onset Cardiometabolic Disease in a Healthy Chinese Population: A Cohort Study.

PurposeThis study aimed to investigate the association between serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and incident metabolic disease in a cohort of community-based older Chinese people.Patients and MethodsFive thousand healthy Gaohang residents who attended community health checks at the Shanghai East Hospital in 2013 were recruited. Biological, biochemical, and lifestyle variables were collected. The cohort was followed for new-onset metabolic disease in 2014 and 2017, with a final study population of 3,123 (63%) after follow-up. The study outcome included type-2 diabetes mellitus and metabolic syndrome.ResultsBaseline AST and ALT were associated with incident type-2 diabetes mellitus (HR 1.019, 95% CI 1.006–1.032, p = 0.003 and HR 1.016, 95% CI 1.008–1.025, p < 0.001 respectively). These associations persisted after adjusting for traditional risk factors including age, sex, income, waist circumference, systolic blood pressure, diastolic blood pressure, HbA1c, triglyceride, cholesterol, HDL and eGFR. Baseline AST and ALT were associated with incident metabolic syndrome in the crude analysis (HR 0.980, 95% CI 0.965–0.996, p = 0.012 and HR 0.992, 95% CI 0.988–0.997, p = 0.001, respectively). However, the association between AST and ALT with metabolic syndrome was non-significant after adjusting for biochemical parameters such as the lipid profile.ConclusionThis study demonstrated that serum AST and ALT are associated with new-onset type-2 diabetes mellitus, independent of traditional risk factors, in a cohort of older Chinese people. These findings may contribute to disease risk stratification and management in type-2 diabetes.

Efficacy and safety of direct-acting antiviral therapies and baseline predictors for treatment outcomes in hepatitis C patients: A multicenter, real-world study in Guangdong, China.

The data on direct-acting antivirals (DAAs) in chronic hepatitis C (CHC) patients in southern China with multiple genotypes circulating are limited. This study aims to evaluate the efficacy and safety of DAA regimens among CHC patients in Guangdong, China. A total of 220 patients receiving a variety of DAA were enrolled. The primary outcome was sustained virologic response (SVR) at 12 weeks. Resistance associated substitutions (RASs) were evaluated by deep sequencing. The overall SVR rate was 96.4%, and was 97.7% for genotype 1, 100% for genotype 2, 91.9% for genotype 3, 95.7% for genotype 6, and 100% for untyped. The overall incidence of adverse events (AEs) was 8.2% (18/220) and all the AEs were mild. Nonstructural proteins 5A RAS, 30K/31M, and Y93H were most prevalent at baseline and the end of treatment in non-SVR patients, respectively. Logistics regression showed that elevated alanine aminotransferase(ALT) and aspartate aminotransferase(AST) at baseline were specifically associated with non-SVR in patients with genotype 3 and 6 infections (p = 0.029 and p = 0.017) but not genotype 1 infection (p = 0.746 and p = 0.971), and baseline AST was the best predictor for SVR in genotypes 3 and 6 patients (area under curve = 0.890).Our studies demonstrated all DAA regimens achieved ideal SVR and were well tolerated. NS5A RAS were prevalent in non-SVR patients. Elevated ALT and AST as baseline predictors for non-SVR in genotypes 3 and 6 infections warrant further research in a larger cohort.

Long-term surveillance of liver histological changes in chronic hepatitis C patients completing pegylated interferon-α plus ribavirin therapy: an observational cohort study.

Background:For chronic hepatitis C (CHC) patients completing pegylated interferon (PegIFN)-α/ribavirin therapy, long-term liver histological changes remain largely unexplored.Methods:This observational cohort study included 85 CHC patients completing PegIFN-α/ribavirin therapy with liver biopsies performed at baseline and the end of surveillance (EOS). Median years between paired biopsies were 6.75 (interquartile range: 5.63–7.54).Results:In patients with baseline METAVIR fibrosis stages (F) <4 (able to undergo fibrosis progression; n = 77), cases achieving sustained virological response (SVR) (n = 52) had a significantly lower rate of fibrosis progression than non-SVR cases (n = 25) (3.8% versus 24.0%, p = 0.012). Among the entire cohort (n = 85), the rate of activity response [METAVIR activity grades (A) decreasing or maintaining at A0] in SVR cases (n = 59) was significantly higher than that in non-SVR cases (n = 26) (94.9% versus 65.4%, p = 0.001). For SVR cases among the entire cohort, independent predictors of fibrosis clearance included baseline F <2 [odds ratio (OR) = 7.877, p = 0.042] and aspartate transaminase (AST) levels declining by >70% at EOS compared with baseline (OR = 9.013, p = 0.038). For non-SVR cases among the entire cohort, baseline AST levels >80 U/l and glucose levels ⩽ 105 mg/dl independently predicted significant fibrosis (F2/F3/F4) at EOS (OR = 12.558, p = 0.049) and activity response (OR = 17.741, p = 0.047), respectively.Conclusions:Among CHC patients completing PegIFN-α/ribavirin therapy, SVR lowers the risk of liver histological progression but does not guarantee fibrosis clearance. For SVR cases, those with baseline F ⩾ 2 or without significantly declined follow-up AST levels should be specifically monitored. As for non-SVR cases, those with a higher baseline AST or glucose level should preferentially receive retreatment.

Prevalence of abnormal liver biochemistry and its impact on COVID-19 patients' outcomes: a single-center Greek study.

BackgroundAbnormalities in aminotransferases are frequently observed in hospitalized COVID-19 patients, but their clinical impact is poorly characterized.MethodsA total of 1046 patients hospitalized to the non-intensive care unit ward with documented COVID-19 were included retrospectively. Demographic, clinical and laboratory characteristics on admission and during hospital stay, including the presence of liver injury (LI), defined as aspartate aminotransferase (AST) >200 IU/L, were recorded.ResultsOn admission, 363 (34.7%) and 269 (25.7%) patients had abnormal AST and ALT values (i.e., >40 IU/L), respectively, while during hospitalization 53 (5%) patients fulfilled the criteria for LI. In multivariate logistic regression analysis, AST (odds ratio [OR] 1.023, 95% confidence interval [CI] 1.016-1.029; P<0.001), and ferritin (OR 1.01, 95%CI 1.001-1.02; P<0.001) were the baseline factors independently associated with the development of LI during hospital stay. One hundred twenty-three (11.7%) patients died during hospitalization. The independent variables associated with mortality were: age (hazard ratio [HR] 1.043, 95%CI 1.029-1.056; P<0.001), ferritin (HR 1.1, 95%CI 1.05-1.2; P<0.001), platelets (HR 0.996, 95%CI 0.994-0.999; P=0.003), and administration of remdesivir (HR 0.50, 95%CI 0.30-0.85; P=0.009). The patients with abnormal baseline AST (i.e., >40 IU/L), compared to those with normal AST values, had worse outcomes (log rank test: 8.8, P=0.003).ConclusionsElevated aminotransferases are commonly seen in COVID-19 patients. They possibly reflect disease severity and may be associated with in-hospital mortality.

Analysis of Clinical Characteristics and Chronic Factors of Drug-induced Liver Injury in Chronic Hepatitis B Infection: A Retrospective Study

Background: This study investigated clinical characteristics and chronic factors of drug-induced liver injury (DILI) among patients with chronic hepatitis B virus (HBV) infection. Methods: DILI patients were enrolled and divided into a DILI group and an HBV+DILI group. Laboratory indicators were recorded and analyzed. Multivariate logistic regression and the receiver operating characteristic (ROC) curve were used to determine risk factors and the predictive value for chronic DILI. Results: Of all the 114 patients, 87 were in the DILI group and 27 were in the HBV+DILI group. Baseline total bilirubin (TBIL), direct bilirubin (DBIL), and incidence of chronicity were significantly higher in the HBV+DILI group than in the DILI group (P = 0.017, P = 0.037, P = 0.045, respectively). However, platelet (PLT) and prothrombin activity (PTA) were significantly lower in the HBV+DILI group than in the DILI group (P = 0.022, P = 0.013, respectively). HBV infection, baseline aspartate aminotransferase (AST) &gt; 200 U/L, and TBIL &gt; 34.2 μmol/L were predictors of chronic DILI (OR = 4.481 [95% CI, 1.298 - 15.470], P = 0.018; OR = 8.478 [95% CI, 2.079 - 34.566], P = 0.003; OR = 7.358 [95% CI, 2.215 - 24.446], P = 0.001). The area under ROC curve (AUC) of joint diagnosis for chronic DILI was 0.814 (95% CI, 0.704 - 0.925, P &lt; 0.001), which was significantly higher than that of single parameter prediction. Also, the sensitivity, specificity, positive predictive value, and negative predictive value of joint diagnosis were 81.0%, 73.1%, 40.5%, and 94.4%, respectively. Conclusions: HBV infection aggravated liver injury. HBV infection, baseline AST &gt; 200 U/L, and TBIL &gt; 34.2 μmol/L were predictors of chronic DILI, and their joint diagnosis could be used to predict chronic DILI effectively.