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Objective:To investigate the prognostic value of the ratio of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) combined with activated partial thromboplastin time (APTT) in elderly patients with non-valvular atrial fibrillation (NVAF) treated with rivaroxaban.Methods:One hundred and twenty-two elderly patients with NVAF who were anticoagulated with rivaroxaban from June 2020 to June 2021 in the Third Central Hospital of Tianjin were enrolled and divided into four groups based on the median method. The patients in the Q1 group ( n = 32) have low AST/ALT/low APTT. The patients in the Q2 group ( n = 27) have low AST/ALT/high APTT. The patients in the Q3 group ( n = 29) have high AST/ALT/low APTT. The patients in the Q4 group ( n = 34) have high AST/ALT/high APTT. The efficacy endpoint events, and safety endpoint events were analyzed in the four groups, and univariate and multivariate Cox regression analyses were performed for the composite endpoint events. Results:The effectiveness endpoint events were mainly cardiovascular deaths, the number of which in the Q1 to Q4 groups was 0 (0), 1 (3.70%), 4 (13.79%), and 5 (14.71%), respectively. The safety endpoint events were mainly non-major bleeding events, the number of which in the Q1 to Q4 groups was 5 (15.62%), 2 (7.41%), 6 (20.69%), and 5 (14.71%), respectively. Compared to the Q1 group, the Q4 group had an increased risk of composite endpoint events after incorporating traditional risk factor correction ( HR: 3.851, 95% CI: 1.167 to 12.704). Conclusions:AST/ALT ratio combined with APTT can provide risk stratification for distant bleeding and cardiovascular adverse events in elderly NVAF patients treated with rivaroxaban anticoagulation and has some predictive value for their prognosis.
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Objective@#To determine incidence, predictors, and impact of liver injury among hospitalized COVID-19 patients@*Methods@#This is a retrospective cohort study of hospitalized COVID-19 patients at the University of the PhilippinesPhilippine General Hospital. Liver injury (LI) was defined as ALT elevation above institutional cut-off (>50 u/L) and was classified as mild (>1x to 3x ULN), moderate (>3x to 5x ULN), or severe (>5x ULN). Significant liver injury (SLI) was defined as moderate to severe LI. Univariate analysis of SLI predictors was performed. The impact of LI on clinical outcomes was determined and adjusted for known predictors -age, sex, and comorbidities.@*Results@#Of the 1,131 patients, 565 (50.04%) developed LI. SLI was associated with male sex, alcohol use, chronic liver disease, increasing COVID-19 severity, high bilirubin, AST, LDH, CRP, and low lymphocyte count and albumin. An increasing degree of LI correlated with ICU admission. Only severe LI was associated with the risk of invasive ventilation (OR: 3.54, p=0.01) and mortality (OR: 2.76, p=0.01). Severe LI, male sex, cardiovascular disease, and malignancy were associated with longer hospital stay among survivors.@*Conclusion@#The liver injury occurred commonly among COVID-19 patients and was associated with important clinicodemographic characteristics. Severe liver injury increases the risk of adverse outcomes among hospitalized patients.
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COVID-19ABSTRACT
@#Abstract: Objective To explore the threshold of ALT for initiating antiviral therapy in HBV infected patients, and to provide a basis for initiating antiviral therapy in chronic HBV-infected patients. Methods This retrospective cohort study recruited 707 consecutive treatment-naïve chronic hepatitis B (CHB) patients undergoing diagnostic liver biopsy in the department of infectious diseases of the Affiliated Hospital of Yan′an University from October 2013 to August 2018. Liver biopsy specimens were obtained under ultrasound guidance using Menghini 16G disposable needles. The METAVIR scoring system, which is commonly used internationally, was used to divide the patients into the group with mild liver tissue injury and the group with significant liver tissue injury, and the alanine aminotransferase (ALT) levels were measured separately. Receiver operating characteristic (ROC) curve and Mann-Whitney U test were used to evaluate the diagnostic value of ALT for significant liver tissue injury under different demographic characteristics. Results Of 707 patients, 292 (41.30%) had significant liver tissue injury confirmed by liver biopsy (METAVIR ≥A2 and/or F2). When the ULN of ALT was set to NICE criteria (30 U/L for males, 19 U/L for females), AASLD criteria (35 U/L for males, 25 U/L for females) and EASL or APASL criteria (40 U/L for males and females), CHB patients with <ULN accounted for 32.38%, 35.03% and 36.07% of significant liver tissue injury, respectively. And significant liver tissue injury in CHB patients with 1-2×ULN accounted for 41.99%, 41.85% and 50.30%, respectively. The optimal ALT critical values were 33 U/L for overall patients, 25 U/L for females, 45 U/L for males, 45 U/L for ≤30 years olds, 33 U/L for>30 years olds, 22 U/L for HBeAg negative and 31 U/L for HBeAg positive patients. Conclusions The threshold of ALT for initiating antiviral therapy in chronic HBV patients should be individualized, especially should be down-regulated for the females, olders and HBeAg-negative patients.
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Objective:To analyze the clinical and pathological characteristics of chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) and not receiving antiviral therapy.Methods:This study retrospectively included CHB patients diagnosed by liver biopsy at the Third Hospital of Hebei Medical University from January 2008 to December 2022. According to the HBV DNA and HBeAg status of "immune tolerance period and immune control period", these patients were divided into three groups: chronic HBV carrier group, inactive HBsAg carrier group and indeterminate group including the patients that did not meet the inclusion criteria of the above two groups. Kruskal-Wallis H test was used for comparison of continuous data between multiple groups. Mann-Whitney U test was used for comparison of continuous data and ordered categorical data between two groups. Chi-square test or Fisher′s exact test was used for comparison of categorical data between two groups. Results:A total of 284 CHB patients with normal ALT were enrolled. There were 64, 88 and 132 cases in the chronic HBV carrier group, inactive HBsAg carrier group and indeterminate group, respectively. Histopathological analysis revealed that there were 182 (64.08%) cases with pathological inflammation grade (G) and/or fibrosis stage (S)≥2, 155 (54.58%) with S≥2 and 120 (42.25%) with G≥2. The proportion of patients with G and/or S≥2 in the indeterminate group [70.45% (93/132)] was higher than that in the chronic HBV carrier group [48.44% (31/64)] and inactive HBsAg carrier group [65.91% (58/88)] (both P<0.05). Patient′s age and the ratio of patients with S≥2 in the chronic HBV carrier group [33 years old, 39.06% (25/64)] were smaller than those in the inactive HBsAg carrier group [39 years old, 56.82% (50/88)] and the indeterminate group [39 years old, 60.61% (80/132)] (all P<0.05). Patients in the inactive HBsAg carrier group (19 U/L) had lower ALT levels than those in the chronic HBV carrier group (26 U/L) and the indeterminate group (23 U/L) (both P<0.05). The proportion of patients with cytoplasmic/cytoplasmic nuclear-type HBcAg was higher in patients with G and/or S≥2 than in patients with G and S<2 [73.08% (57/78) vs 32.08% (17/53), P<0.05], and the proportion of patients with cytoplasmic/cytoplasmic nuclear-type HBcAg increased gradually with age. The proportion of patients with cytoplasmic/cytoplasmic nuclear-type HBcAg was higher in patients with G and/or S≥2 than in patients with G and S<2 in the chronic HBV carrier status and indeterminate groups [93.33% (28/30) vs 43.33%(13/30), P<0.05; 59.46% (22/37) vs 12.50% (2/16); both P<0.05]. There was a statistically significant difference in the incidence of significant liver injury between patients≤ 30 years old and >30 years old [52.7% (39/74) vs 68.1% (143/210), P<0.05]. Conclusions:Significant liver injury occurred in 64.08% (182/284) of CHB patients with normal ALT not receiving antiviral therapy, which required the attention of clinicians. Among CHB patients with normal ALT, the expression site of HBcAg in hepatocytes was related to the occurrence of significant liver injury and could be expected to serve as an important indicator for predicting the patient′s status and the necessity of antiviral treatment. CHB patients with positive HBV DNA who were older than 30 years required antiviral treatment, and CHB patients≤30 years with normal ALT and significant hepatic tissue damage also required antiviral treatment.
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Objective:To reevaluate the upper limit of normal (ULN) of serum alanine aminotransferase (ALT) by retrospectively analyzing the ALT levels in healthy people in Ningbo area.Methods:A total of 56 140 people who underwent health examination and detection of liver biochemical indexes in the Affiliated Hospital of Medical School of Ningbo University and Yinzhou Huamao Hospital of Ningbo from 2018 to 2020 were enrolled. After excluding relevant factors that may lead to liver injury, 11 411 people were included to compare the difference of serum ALT levels among different genders and age groups (20 to 29 years, 30 to 39 years, 40 to 49 years and 50 to 59 years) to determine the ALT ULN in different gender groups. Statistical methods were performed using two independent samples t test and analysis of variance. Results:The serum ALT of males was (19.20±7.90) U/L, which was higher than that of females ((13.75±6.17) U/L), with statistical significance ( t=41.16, P<0.001). The serum ALT ULN in males and in females were 35 U/L and 26 U/L, respectively. The serum ALT levels of 20 to 29, 30 to 39, 40 to 49 and 50 to 59 years old groups were (15.48±7.61) U/L, (16.21±7.40) U/L, (17.36±7.52) U/L and (18.77±7.57) U/L, respectively.The difference was statistically significant ( F=71.51, P<0.001). Serum ALT level in 50 to 59 years old group was higher than that in 20 to 29 years old group, and the difference was statistically significant ( t=13.11, P<0.01). In males, the ALT ULN of 20 to 29 years old was the lowest of 34.43 U/L, and highest of 35.29 U/L in 40 to 49 years old. In females, the ALT ULN in the 20 to 29 years old group was the lowest of 23.01 U/L, and the ALT ULN in the 50 to 59 years old group was the highest of 30.79 U/L. ALT ULN increased with age in females. The serum ALT of males was higher than that of females in all age groups ( t=29.55, 26.91, 13.43 and 4.62, respectively, all P<0.05). Conclusions:The serum ALT level is significantly correlated to gender and age. The serum ALT ULNs of healthy adult are 35 U/L in males and 26 U/L in females in Ningbo area.
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Objective To evaluate the effect of different techniques of hepatic artery reconstruction on postoperative hepatic artery complications and clinical prognosis in liver transplantation. Methods Clinical data of 140 liver transplant recipients were retrospectively analyzed. All recipients were divided into the conventional hepatic artery reconstruction group (n=123) and special hepatic artery reconstruction group (n=17) according to hepatic artery reconstruction methods. Intraoperative and postoperative clinical indexes, the incidence of postoperative hepatic artery complications and survival rate were compared between two groups. Results The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at postoperative 1 d, total bilirubin (TB) at postoperative 7 d and prothrombin time international normalized ratio (PT-INR) at postoperative 30 d in special hepatic artery reconstruction group were higher than those in conventional hepatic artery reconstruction group, and the differences were statistically significant (all P < 0.05). There were no significant differences in the operation time, anhepatic phase, intraoperative blood loss, intraoperative transfusion volume of red blood cells, cold or warm ischemia time, the length of intensive care unit (ICU) stay, the length of hospital stay and postoperative blood flow of liver allograft between two groups (all P > 0.05). In the conventional hepatic artery reconstruction group, 5 recipients developed hepatic artery complications, whereas no hepatic artery complications occurred in the special hepatic artery reconstruction group, with no significant difference between two groups (P > 0.05). In the special hepatic artery reconstruction group, the 1-, 3- and 5-year cumulative survival rates were equally 82.4%, compared with 85.0%, 78.9% and 75.6% in the conventional hepatic artery reconstruction group, respectively. There was no significant difference between two groups (all P > 0.05). Conclusions When hepatic artery variations and (or) lesions are detected in donors and recipients, use of special hepatic artery reconstruction may effectively restore the hepatic arterial blood flow of liver allograft after liver transplantation, and will not affect the incidence of hepatic artery complications and survival rate of the recipients following liver transplantation.
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Background & objectives: Cardiovascular disease (CVD) remains the leading cause of mortality among patients with chronic kidney disease (CKD). Liver function tests (LFTs) have emerged as markers of CVD risk in some population-based studies. Hence, in the present study the relation between LFTs and biochemical cardiovascular risk factors (CRFs) were evaluated in CKD patients. Methods: A total of 246 patients with stage 3-5 pre-dialysis CKD were enrolled. Demographics, LFTs [alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT)] and biochemical CRFs were recorded retrospectively. Glomerular filtration rate (GFR) was calculated using CKD-EPI equation. Results: ALT was positively correlated with GFR, albumin, triglyceride and 25-hydroxyvitamin D and negatively correlated with CRP and intact parathyroid hormone (iPTH); AST was positively correlated with GFR, albumin, high-density lipoprotein cholesterol (HDL-C) and 25-hydroxyvitamin D and negatively correlated with CRP and iPTH; GGT was positively correlated with GFR, CRP and triglyceride and negatively correlated with HDL-C. In diabetic patients, ALT correlated positively with GFR; AST correlated positively with GFR and HDL-C, but correlated negatively with iPTH. In the correlation analysis between GFR and CRF, GFR was positively correlated with albumin, triglyceride and 25-hydroxyvitamin D and negatively correlated with CRP, iPTH and albuminuria in both total study population and diabetic group. A partial correlation analysis revealed no correlation between LFTs and CRFs after being controlled for GFR. Interpretation & conclusions: The results of the present study suggest that the relationship between LFTs and biochemical CRFs seems to be a function of impaired GFR.
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Abstract Introduction: Estimating and monitoring changes in liver function tests is necessary to prevent the occurrence of chronic liver disease in HIV patients undergoing highly active antiretroviral therapy (HAART). Objective: To determine the variation liver profile test levels in HIV patients undergoing HAART. Materials and methods: Retrospective longitudinal study conducted in 100 HIV patients treated at the Hospital Nacional Hipólito Unanue, Lima, Peru, between 2015 and 2017. Patients in all stages of clinical infection under HAART and with liver function panel results for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and total protein (TP) were included. Three follow-up liver function tests (every 3 months) were performed while undergoing HAART and participants were categorized as having normal or elevated levels for all liver markers. Differences between the samples analyzed were determined using the paired-samples T test, with a 95% confidence interval and a significance level of p<0.05. Results: Participants' mean age was 33±9.56 years and 67% were male. Mean serum AST, ALT and ALP values decreased between the first and the third measurement (p=0.021, p=0.076 and p=0.002, respectively). No significant differences in GGT and TP levels were observed between the three measurements, nor between patients with normal and elevated AST, ALT, ALP and TP values, but significant differences were observed for GGT (p=0.010). Conclusions: Variations in liver marker levels were observed in all participants, with a decreasing trend in AST, ALT and ALP between the early and late stages of HAART, implying that this therapy could play a role in liver tissue damage.
Resumen Introducción. Para prevenir el desarrollo de enfermedad hepática crónica en pacientes con VIH, durante la terapia antirretroviral de gran actividad (TARGA) se deben estimar y monitorear cambios en el perfil hepático. Objetivo. Determinar la variación de las concentraciones del perfil hepático en pacientes con VIH durante la TARGA. Materiales y métodos. Estudio retrospectivo longitudinal realizado en 100 pacientes con VIH atendidos en el Hospital Nacional Hipólito Unanue, Lima, Perú, entre 2015 y 2017. Se incluyeron pacientes en todos los estadios de infección clínica que estuvieran recibiendo TARGA y en los que se contara con resultados del perfil hepático para alanina aminotransferasa (ALT), aspartato aminotransferasa (AST), fosfatasa alcalina (FA), gammaglutamiltranspeptidasa (GGT) y proteínas totales (PT). Se realizaron tres análisis de control de la función hepática durante la TARGA (1 cada 3 meses) y los participantes se agruparon en niveles normales y elevados para todos los marcadores hepáticos. Las diferencias entre las muestras analizadas fueron determinadas mediante la prueba t-Student para muestras relacionadas, con un intervalo de confianza de 95% y un nivel de significancia de p<0.05. Resultados. La edad promedio fue de 33±9.56 años y el 67% fueron varones. Los valores séricos promedio de AST, ALT y FA disminuyeron entre la primera y la tercera medición (p=0.021, p=0.076 y p=0.002, respectivamente). No se observaron diferencias significativas en los niveles de GGT y PT entre las tres mediciones, ni entre los pacientes con valores normales y elevados para AST, ALT, FA y PT, pero sí para GGT (p=0.010). Conclusiones. Se observaron variaciones en los niveles de los marcadores hepáticos de todos los participantes, con una tendencia a la reducción en AST, ALT y FA entre las etapas iniciales y finales de la terapia, lo que implica que la TARGA podría ejercer un rol en el daño tisular hepático.
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La hepatopatía crónica más prevalente en el mundo es la esteatosis hepática no alcohólica. Así, se realizó una investigación con el objetivo de determinar los factores asociados a esa patología en pacientes atendidos en el Centro de salud tipo B Chambo, Ecuador, durante 2020. Se realizó un estudio con enfoque cuantitativo, de tipo no experimental, correlacional y retrospectivo. Las historias clínicas seleccionadas aportaron los datos de las variables de interés. La media de la edad de los involucrados fue de 54,43 ± 8,10 años. El 60,38% tenía hipertensión arterial, el 52,83% diabetes mellitus, el 62,26% sobrepeso u obesidad y el 49,06% dislipidemia, determi-nando que estas comorbilidades tuvieron una relación significativa con la enfermedad objeto de estudio, la que resultó más incidente en edades mayores de 50 años. Las personas sedentarias o con bajos niveles de actividad física mostraron de ALT y AST.
The most prevalent chronic liver disease in the world is nonalcoholic fatty liver disease. Thus, research aimed to determine the factors associated with this pathology in patients treated at the Type B Chambo Health Center, Ecuador, during 2020. A study was carried out with a quantitati-ve, non-experimental, correlational, and retrospective approach. The selected medical records provided the information for the variables of interest. The mean age of the population was 54.43 ± 8.10 years of age. 60.38% had arterial hypertension, 52.83% diabetes mellitus, 62.26% overweight or obesity and 49.06% dyslipidemia. It was determined that these comorbidities had a significant relationship with the disease under study, which was more incident in ages older than 50. Sedentary people or those ones with low levels of physical activity showed ALT and AST.
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Humans , Male , Female , Middle Aged , Comorbidity , Abiotic Factors , Liver Diseases , Exercise , Cholesterol , OverweightABSTRACT
Objective: To investigate hypertriglyceridemia and hepatomegaly caused by Schisandrae Sphenantherae Fructus (FSS) and Schisandra chinensis Fructus (FSC) oils in mice. Methods: Mice were orally administered a single dose of Schisandrae Fructus oils. Serum and hepatic triglyceride (TG), triglyceride transfer protein (TTP), apolipoprotein B48 (Apo B48), very-low-density lipoprotein (VLDL), hepatocyte growth factor (HGF), alanine aminotransfease (ALT) and liver index were measured at 6-120 h post-dosing. Results: FSS and FSC oil caused time and dose-dependent increases in serum and hepatic TG levels, with maximum increases in the liver (by 297% and 340%) at 12 h post-dosing and serum (244% and 439%) at 24-h post-dosing, respectively. Schisandrae Fructus oil treatments also elevated the levels of serum TTP by 51% and 63%, Apo B48 by 152% and 425%, and VLDL by 67% and 38% in mice, respectively. FSS and FSC oil treatments also increased liver mass by 53% and 55% and HGF by 106% and 174%, but lowered serum ALT activity by 38% and 22%, respectively. Fenofibrate pre/ co-treatment attenuated the FSS and FSC oil-induced elevation in serum TG levels by 41% and 49% at 48 h post-dosing, respectively, but increased hepatic TG contents (by 38% and 33%, respectively) at 12 h post-dosing. Conclusions: Our findings provide evidence to support the establishment of a novel mouse model of hypertriglyceridemia by oral administration of FSS oil (mainly increasing endogenous TG) and FSC oil (mainly elevating exogenous TG).
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Objective:To investigate the effect of alanine aminotransferase(ALT) level in early pregnancy and its interaction with maternal body mass index(BMI) on neonatal birth weight.Methods:Data of full-term singleton delivery mother-infant pairs from 2014 to 2016 in Wenzhou were collected. The exposure(ALT>40 U/L) and non-exposure(ALT≤40 U/L) groups were matched using 1∶4 propensity score matching. Logistic regression analysis was used to analyze the relationship between increased ALT level in the first trimester and abnormal birth weight as well as the effect of its interaction with BMI on abnormal birth weight.Results:Multivariate analysis showed that the risks of macrosomia and large for gestational age(LGA) in pregnant women with ALT>40 U/L were 1.584(95% CI 1.323-1.896) and 1.292(95% CI 1.142-1.461) compared with those with ALT≤40 U/L. ALT in the first trimester displayed an additive interaction with BMI on the risk of macrosomia [the relative excess risk due to interaction( RERI)=2.032, 95% CI 0.307-3.757, the attributable proportion due to interaction( API)=0.448, 95% CI 0.221-0.684, the synergy index( S)=2.348, 95% CI 1.274-4.324]. In addition, there was no interaction between ALT and BMI on the risk of LGA, and nor did the association of ALT in the first trimester with low birth weight or small for gestational age exist. Conclusion:ALT>40 U/L in the first trimester increases the risk of high birth weight, especially in overweight or obese pregnant women in the first trimester. Therefore, it is suggested to strengthen the monitoring of ALT level in obese pregnant women during the first trimester.
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Objective To evaluate the effect of coagulation function changes on the incidence of acute kidney injury (AKI) after liver transplantation. Methods Clinical data of 245 liver transplant recipients who met the inclusion and exclusion criteria were retrospectively analyzed. According to the incidence of AKI after liver transplantation, all recipients were divided into the AKI group (n=99) and non-AKI group (n=146). The incidence of AKI after liver transplantation was summarized. Perioperative parameters of the recipients were collected. The risk factors of AKI after liver transplantation were assessed by univariate and multivariate analysis. Results Among 245 recipients undergoing liver transplantation, 99 cases developed AKI after operation with an incidence rate of 40.4%. Preoperative serum creatinine levels of the recipients and the in-hospital fatality were relatively high in the AKI group (all P < 0.05). Compared with the recipients in the non-AKI group, those in the AKI group presented with significantly higher liver function parameters within postoperative 24 h, significantly decreased levels of stage Ⅱ coagulation parameters including coagulation factorsⅤ, Ⅶ, Ⅸ, Ⅹ, Ⅻ and protein S, protein C and antithrombin Ⅲ, evidently elevated prothrombin time international normalized ratio (PT-INR), remarkably increased stage Ⅲ coagulation parameters including D-dimer and fibrin degradation product (FDP) levels and considerably decreased fibrinogen (FIB) level (all P < 0.05). Thrombelastogram showed that the R value was increased, the α angle was decreased and the coagulation time was prolonged in the AKI group (all P < 0.05). Logistic regression analysis demonstrated that the increased R value of postoperative thrombelastogram [odd ratio (OR) 1.116, 95% confidence interval (CI) 1.018-1.223, P=0.019], and decreased levels of antithrombin Ⅲ (OR 0.974, 95%CI 0.955-0.993, P=0.007) were the independent risk factors of incidence of AKI after liver transplantation. Conclusions The incidence of AKI after liver transplantation is high, which is associated with the coagulation function changes of the recipients. Decreased coagulation factor activity (increased R value) and declined antithrombin Ⅲ level are the independent risk factors of AKI in liver transplantat recipients.
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【Objective】 To explore the optimized strategy of alanine aminotransferase(ALT) screening before blood donation, in order to reduce the waste of blood resources. 【Methods】 The blood donation scrapping of one blood center in Chongqing from January to April 2020 was analyzed retrospectively. The correlation between ALT test results by dry chemistry method and rate method in 500 blood donors, with ALT level close to the limit, was analyzed, and the abnormal rates of retest were stratified by initial results of ALT dry chemical method. 【Results】 Among blood donors enrolled in this study, the rate of ALT abnormality(0.89%, 43/4 846)was significantly higher than that of HBV (0.25%, 12/4 846), HCV (0.43%, 21/4 846) and HIV (0.19%, 9/4 846)(P<0.05). For the samples with pre-donation ALT close to the limit (40 U/L≤ALT≤50 U/L), a weak correlation between the results of dry chemistry method and rate method was observed, with correlation coefficient at 0.33 (P<0.05). The abnormal rates in retest were significantly higher in 45 U/L≤ ALT ≤50 U/L (10.7%, 22/206) group than that in the ALT < 45U/L group(P<0.05). 【Conclusion】 The ALT limit before blood donation should be set to 45 U/L. For blood donors with ALT within the range of (45~50) U / L, blood donation should be deferred until they passed retests by rate method.
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Objective:To establish a noninvasive prediction model for liver fibrosis in chronic hepatitis B (CHB) virus infection patients with alanine aminotransferase (ALT) less than upper limit of normal level.Methods:A total of 183 CHB patients with ALT <40 U/L admitted in the First Affiliated of Wenzhou Medical University from January 2014 to September 2017 were enrolled. There were 149 cases of non-marked liver fibrosis (F0-F2) and 34 cases of marked liver fibrosis (F3-F6) according to the Ishak scoring system. The clinical data, liver stiffness measurement (LSM), liver ultrasound imaging, serum biochemical features and hepatitis B virus related indexes of patients were retrospectively analyzed. The independent predictors of liver fibrosis were screened and a prediction model was constructed based on the results of multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was applied to evaluate the established model and other indicators in predicting liver fibrosis.Results:Multivariate logistic regression analysis showed that LSM ( OR=1.327, 95% CI 1.149-1.531), liver ultrasound scores ( OR=6.610, 95% CI 2.704-16.156) were independent predictors of liver fibrosis. The area under ROC curve(AUC)of the established model (LU) in predicting liver fibrosis was 0.873(95% CI 0.799-0.947), which was significantly greater than that of the ultrasound score, LSM, FIB-4, APRI and GPR (AUC=0.790, 0.804, 0.654, 0.673 and 0.770; Z=3.394, 1.982, 2.077, 3.168 and 2.165, all P<0.05 or <0.01). With the cut-off value of -1.787, the sensitivity and specificity of LU model were 85.3% and 77.2%, respectively. Conclusion:The established model (LU) can effectively predict the liver fibrosis in CHB patients with ALT less than upper limit of normal.
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Objective:To investigate the pathological characteristics in chronic HBV infection patients with different upper limits of alanine aminotransferase (ALT) normal values and the influencing factors of liver tissue injury.Methods:The clinical data of 667 chronic HBV infection patients with ALT<40 U/L and HBV DNA loads >30 IU/mL who received liver biopsy in Zhenhai District Hospital of Traditional Chinese Medicine and Hwa Mei Hospital from January 2014 to December 2020 were retrospectively analyzed. The enrolled patients were divided into ALTⅠ group (<30 U/L for males, <19 U/L for females), ALTⅡ group (≥30 U/L and <35 U/L for males, ≥19 U/L and <25 U/L for females) and ALT Ⅲ group (≥35 U/L and <40 U/L for males, ≥25 U/L and <40 U/L for females). According to the degree of liver inflammation (G) and fibrosis stage (S), the enrolled patients were divided into non-significant damage group (G<2 and S<2) and significant damage group (≥G2 or/and ≥S2). Ridit analysis was used to compare the G/S composition ratio among three ALT groups, Logistic regression was used to analyze the risk factors of liver injury, the receiver operating characteristic curve (ROC) and the area under the curve (AUC) were used to analyze the optimal diagnostic threshold of ALT.Results:There were significant differences in the composition ratio of G and S among the three ALT groups( χ2=13.926 and 14.702, both P<0.001). The constituent ratios of significant liver pathological damage in the three groups of ALT levels were 26.05% (99/380), 32.03% (41/128) and 46.54% (74/159), respectively( χ2=21.596, P<0.001). Multivariate logistic regression analysis showed that high white/globulin ratio and PLT counts( OR=0.246 and 0.986, both P<0.001)were the protective factors for liver tissue injury; while negative HBcAg staining and elevated ALT and GGT levels ( OR=3.797, 1.053 and 1.013, P<0.001 or <0.05) were the risk factors of liver injury. ROC curve demonstrated the ALT threshold of liver tissue damage in male and female patients were 25.6 U/L and 25.5 U/L. Conclusions:In chronic HBV infection patients with normal ALT, with the increase of ALT level, the degree of liver tissue pathological damage may become more severe. The study demonstrates that it is necessary to lower the ALT threshold for protecting patients from liver tissue pathological damage.
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Ferroptosis is a form of regulated cell death, characterized by excessive membrane lipid peroxidation in an iron- and ROS-dependent manner. Celastrol, a natural bioactive triterpenoid extracted from Tripterygium wilfordii, shows effective anti-fibrotic and anti-inflammatory activities in multiple hepatic diseases. However, the exact molecular mechanisms of action and the direct protein targets of celastrol in the treatment of liver fibrosis remain largely elusive. Here, we discover that celastrol exerts anti-fibrotic effects via promoting the production of reactive oxygen species (ROS) and inducing ferroptosis in activated hepatic stellate cells (HSCs). By using activity-based protein profiling (ABPP) in combination with bio-orthogonal click chemistry reaction and cellular thermal shift assay (CETSA), we show that celastrol directly binds to peroxiredoxins (PRDXs), including PRDX1, PRDX2, PRDX4 and PRDX6, through the active cysteine sites, and inhibits their anti-oxidant activities. Celastrol also targets to heme oxygenase 1 (HO-1) and upregulates its expression in activated-HSCs. Knockdown of PRDX1, PRDX2, PRDX4, PRDX6 or HO-1 in HSCs, to varying extent, elevated cellular ROS levels and induced ferroptosis. Taken together, our findings reveal the direct protein targets and molecular mechanisms via which celastrol ameliorates hepatic fibrosis, thus supporting the further development of celastrol as a promising therapeutic agent for liver fibrosis.
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Cancer remains one of the leading causes of death globally and metastasis always leads to treatment failure. Here, we develop a versatile hydrogel loading photothermal agents, chemotherapeutics, and immune-adjuvants to eradicate orthotopic tumors and inhibit metastasis by combinational therapy. Hydrogel networks were synthesized via the thiol-Michael addition of polydopamine (PDA) with thiolated hyaluronic acid. PDA acted as a cross-linking agent and endowed the hydrogel with excellent photothermal property. Meanwhile, a chemotherapeutic agent, doxorubicin (DOX), was loaded in the hydrogel via π‒π stacking with PDA and an immune-adjuvant, CpG-ODN, was loaded via electrostatic interaction. The release of DOX from the hydrogel was initially slow but accelerated due to near infrared light irradiation. The hydrogels showed remarkably synergistic effect against 4T1 cancer cells and stimulated plenty of cytokines secreting from RAW264.7 cells. Moreover, the hydrogels eradicated orthotopic murine breast cancer xenografts and strongly inhibited metastasis after intratumoral injection and light irradiation. The high anticancer efficiency of this chemo-photothermal immunotherapy resulted from the strong synergistic effect of the versatile hydrogels, including the evoked host immune response. The combinational strategy of chemo-photothermal immunotherapy is promising for highly effective treatment of breast cancer.
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Although several artificial nanotherapeutics have been approved for practical treatment of metastatic breast cancer, their inefficient therapeutic outcomes, serious adverse effects, and high cost of mass production remain crucial challenges. Herein, we developed an alternative strategy to specifically trigger apoptosis of breast tumors and inhibit their lung metastasis by using natural nanovehicles from tea flowers (TFENs). These nanovehicles had desirable particle sizes (131 nm), exosome-like morphology, and negative zeta potentials. Furthermore, TFENs were found to contain large amounts of polyphenols, flavonoids, functional proteins, and lipids. Cell experiments revealed that TFENs showed strong cytotoxicities against cancer cells due to the stimulation of reactive oxygen species (ROS) amplification. The increased intracellular ROS amounts could not only trigger mitochondrial damage, but also arrest cell cycle, resulting in the in vitro anti-proliferation, anti-migration, and anti-invasion activities against breast cancer cells. Further mice investigations demonstrated that TFENs after intravenous (i.v.) injection or oral administration could accumulate in breast tumors and lung metastatic sites, inhibit the growth and metastasis of breast cancer, and modulate gut microbiota. This study brings new insights to the green production of natural exosome-like nanoplatform for the inhibition of breast cancer and its lung metastasis via i.v. and oral routes.
ABSTRACT
The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.
ABSTRACT
Background: The aim of the research was to study the biochemical profile of the male patients diagnosed with alcohol dependence syndrome and its correlation with the severity of dependence. Methodology: A descriptive study comprising of 60 patients admitted in the psychiatry de-addiction clinic at HSK hospital from 1st July 2017 to 31st December 2017 was done after taking institutional ethical committee clearance. A semi-structured proforma was used to determine the socio-demographic details like education, occupation, socio-economic status etc. the severity of dependence was determined using Severity of Alcohol Dependence Questionnaire (SADQ) scale and basic biochemical tests were performed. Descriptive analysis using an appropriate statistical test was done. Results: The mean age at presentation was 37.9 years. Out of 60 patients, 21 (35%) had mild dependence, 24 (40%) had moderate dependence and 15 (25%) had severe dependence. Hepatic enzymes AST and ALT were raised in 76.67% and 66.67% patients respectively. AST to ALT ratio was above 2 in 11.67% patients. There was a significant correlation between total SADQ scores and Alanine Transaminase (? = 0.281, P = 0.03, n = 60). Conclusion: The biochemical tests were deranged in most of the patients with alcohol dependence. Certain markers can be developed based on their significant association with the dependence levels, thus, helping in early diagnosis and prevention of alcohol dependence syndrome