Clinical and pathological characteristics of chronic hepatitis B patients with normal alanine aminotransferase and not receiving antiviral therapy / 中华微生物学和免疫学杂志

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.

Sound touch elastography linear combined with ultrasound score for staging liver fibrosis in patients with chronic hepatitis B / 中华超声影像学杂志

Objective:To study the value of sound touch elastography (STE) linear combined with ultrasound score (US) in the diagnosis of chronic hepatitis B (CHB) liver fibrosis, and to investigate whether their combination can improve the diagnostic efficiency of subdividing the degree of CHB liver fibrosis. Furthermore, a comparison with STE linear combined with the serological model was performed to seek the optimal linear combination model.Methods:A total of 313 subjects were enrolled from September 2018 to December 2021 in Shenzhen Third People′s Hospital Affiliated to Guangdong Medical University, including 259 patients with CHB who had completed liver biopsy and 54 healthy volunteers. CHB patients were divided into liver fibrosis group (F1-F4 group) according to METAVIR classification standard, and healthy volunteers were used as the control group. All subjects underwent liver ultrasound examination, STE and blood biochemical indexes of liver function. The US was performed according to the liver ultrasound examination, and the liver stiffness measurement (LSM) was measured by STE, aspartate aminotransferase and platelet ratio index (APRI) was calculated by blood biochemical index. Fisher discriminant analysis was used to establish the linear combination (LC) diagnostic marker of US and LSM, and the linear combination (LC2) diagnostic marker of LSM and APRI, successively. Spearman rank correlation coefficient was used to analyze the correlations between US, LSM, APRI, LC2, LC and pathological results. The ROC curves of US, LSM, APRI, LC2 and LC for diagnosing CHB liver fibrosis were plotted, and the diagnostic efficiency of above diagnostic markers was evaluated according to the accuracy, sensitivity, specificity and area under the ROC curve (AUC).Results:The formula for the linear combination of US and LSM was LC=0.986 0×US+ 0.166 7×LSM, and LC was highly positively correlated with pathological findings ( rs=0.851, P<0.001), higher than US, LSM, LC2 and APRI ( rs=0.825, 0.775, 0.802, 0.586, all P<0.001). LC showed the best diagnostic efficiency. The AUCs for diagnosing ≥F1, ≥F2, ≥F3 liver fibrosis and =F4 cirrhosis were 0.945, 0.911, 0.954, 0.955, respectively, which superior to the AUCs of US (0.913, 0.879, 0.934 and 0.916, respectively), the AUCs of LSM (0.860, 0.871, 0.934 and 0.952, respectively) and the AUCs of LC2(0.899, 0.883, 0.941, 0.946, respectively). Compared with US, the AUC of LC diagnosis of ≥F1, ≥F2, ≥F3 liver fibrosis and =F4 cirrhosis increased by 3.2%, 3.2%, 2.0% and 3.9%, respectively, with all significant differences ( P<0.05). Compared with LSM, the AUC of LC increased by 8.5%, 4.0%, 2.0% and 0.3%, respectively, with significant difference ( P<0.05) except for stage =F4 cirrhosis.Compared with LC2, the AUC of LC increased by 4.6%, 2.8%, 1.3% and 0.9%, respectively, and there were significant differences in the diagnosis of ≥F1 and ≥F2 liver fibrosis ( P<0.05). Moreover, the overall efficiency of LC2 was not significantly improved than LSM, the difference was not significant ( P>0.05). Conclusions:US, LSM, LC2 and LC can be used to diagnose the degree of CHB liver fibrosis, but LC is better than US or LSM and LC2 alone, especially in the subdivision of mild liver fibrosis, which is a promising new diagnostic marker to subdivide the degree of CHB liver fibrosis.

Retrospective investigation on the normal range of serum alanine aminotransferase levels in healthy adults in Ningbo area / 中华传染病杂志

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.

Prognostic value of AST/ALT ratio combined with APTT regimen in NVAF patients receiving rivaroxaban anticoagulant therapy / 国际生物医学工程杂志

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.

Effect of hepatic artery reconstruction techniques on prognosis of liver transplantation / 器官移植

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.

Predictive value of preoperative liver function for perioperative massive blood transfusion in patients undergoing ascending aorta surgery / 中国输血杂志

【Objective】 To explore the predictive value of preoperative liver function for massive blood transfusion (MBT) in patients undergoing ascending aorta surgery. 【Methods】 Data from 238 patients undergoing ascending aorta surgery in the Department of Cardiovascular Surgery at The Affiliated Lihuili Hospital of Ningbo University were collected. Preoperative liver function tests were performed for all patients. Based on the perioperative transfusion volumes of red blood cell suspension, patients were divided into the MBT group, non-MBT group, and no blood transfusion (NBT) group. Clinical data during the perioperative period were compared among different groups. Receiver operating characteristic curve (ROC curve) analysis was used to assess the predictive value of liver function indicators for MBT and determine cut-off values. 【Results】 Compared with the non-MBT group and NBT group, the MBT group showed statistically significant differences in preoperative levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), direct bilirubin (DBIL), and serum albumin (SA) (P28.50 U/L, ALT >40.00 U/L, SA ≤34.55 g/L, and DBIL >4.25 μmol/L, there was a significant increase in the transfusion volume of various blood components and the incidence of MBT. 【Conclusion】 Preoperative liver function indicators (AST, ALT, SA, DBIL) have a moderate predictive value for MBT in patients undergoing ascending aorta surgery.

Value of the combined use of aminotransferase-to-platelet ratio index and total bile acid for predicting parenteral nutrition-associated cholestasis in preterm infants with gestational age <34 weeks / 中国当代儿科杂志

OBJECTIVES@#To explore the value of the combined use of aspartate aminotransferase-to-platelet ratio index (APRI) and total bile acid (TBA) for predicting parenteral nutrition-associated cholestasis (PNAC) in preterm infants with gestational age <34 weeks.@*METHODS@#A retrospective analysis was performed on medical data of 270 preterm infants born at <34 weeks of gestation who received parenteral nutrition (PN) during hospitalization in the First Affiliated Hospital of Wannan Medical College from January 2019 to September 2022, including 128 infants with PNAC and 142 infants without PNAC. The medical data between the two groups were compared, and predictive factors for the development of PNAC were explored through multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was used to evaluate the value of APRI alone, TBA alone, and the combination of both for predicting PNAC.@*RESULTS@#TBA levels in the PNAC group after 1, 2, and 3 weeks of PN were higher than those in the non-PNAC group (P<0.05). APRI in the PNAC group after 2 and 3 weeks of PN was higher than that in the non-PNAC group (P<0.05). Multivariate logistic regression analysis showed that elevated APRI and TBA after 2 weeks of PN were predictive factors for PNAC in preterm infants (P<0.05). ROC curve analysis showed that the sensitivity, specificity, and area under the curve (AUC) for predicting PNAC by combining APRI and TBA after 2 weeks of PN were 0.703, 0.803, and 0.806, respectively. The AUC for predicting PNAC by combining APRI and TBA was higher than that of APRI or TBA alone (P<0.05).@*CONCLUSIONS@#After 2 weeks of PN, the value of combining APRI and TBA for predicting PNAC is high in preterm infants with gestational age <34 weeks.

Predictors and outcomes of hospitalized COVID-19 patients with liver injury

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.

Exploration on ALT threshold for initiating antiviral therapy in chronic HBV-infected patients based on results of 707 liver puncture cases / 中国热带医学

@#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.

Relationship between liver function tests & cardiovascular risk factors in stage 3-5 pre-dialysis chronic kidney disease

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.

Changes in liver function test levels in HIV patients undergoing highly active antiretroviral therapy (HAART). Longitudinal study in Lima, Peru / Cambios en los valores de las pruebas de función hepática en pacientes con VIH en terapia antirretroviral de gran actividad (TARGA). Estudio longitudinal en Lima, Perú

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.

Factores asociados a esteatosis hepática no alcohólica en pacientes del área rural del cantón Chambo / Factors Associated with Nonalcoholic Hepatic Steatosis in Patients from the Rural Area of Chambo town

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.

Expressions and roles of key enzymes in serine synthesis pathway in NaAsO2-treated HaCaT cells / 环境与职业医学

Background The key enzymes of serine synthesis pathway (SSP) play an important role in tumor growth, proliferation, and invasion, but their roles in arsenic carcinogenesis are unclear. Objective To observe the effects of NaAsO2 treatment on the expressions of key enzymes [such as phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH)] of SSP and on the ability to proliferate and migrate in human immortalized skin keratinocytes (HaCaT) and NaAsO2-induced malignantly transformed HaCaT (T-HaCaT), and to explore the roles of SSP key enzymes in arsenic carcinogenesis. Methods (1) The T-HaCaT cells constructed earlier by our research team were divided into a passage control (0 μmol·L−1 NaAsO2) group, a T-HaCaT (0.5 μmol·L−1 NaAsO2) group, a NCT503 (PHGDH inhibitor, 25 μmol·L−1) group, and a NCT503 (25 μmol·L−1) + T-HaCaT (0.5 μmol·L−1 NaAsO2) group. Western blotting was used to detect the protein expression levels of SSP key enzymes in the passage control group and the T-HaCaT group. CCK8 assay and cell scratch test were used to detect the proliferation and migration rates of cells in each group respectively. (2) Well-grown logarithmic-phase HaCaT cells were treated with 0, 0.625, 1.25, and 2.5 μmol·L−1 NaAsO2 for 0, 24, 48, and 72 h to detect cell proliferation rate and protein expression levels of SSP key enzymes. In the subsequent experiment, HaCaT cells were pretreated with 25 μmol·L−1 NCT503 for 6 h, and then treated with 2.5 μmol·L−1 NaAsO2 for 72 h continuously. The experimental groups included a control (0 μmol·L−1 NaAsO2) group, an exposure (2.5 μmol·L−1 NaAsO2) group, a pretreatment (25 μmol·L−1 NCT503) group, and a pretreatment (25 μmol·L−1 NCT503) + exposure (2.5 μmol·L−1 NaAsO2) group, to detect the proliferation rate of cells in each group. Results The protein expression level of PHGDH in the T-HaCaT group were 1.60 times higher than that in the passage control group (P<0.05), and its proliferation rate (177.51%±14.69%) and migration rate (53.85%±0.94%) were also higher than the passage control group’s (100.00%±0.00% and 24.30%±2.26%) (both Ps<0.05), respectively. After the NCT503 intervention, the proliferation rate (144.97%±8.08%) and migration rate (35.80%±0.99%) of cells in the NCT503 + T-HaCaT group were lower than those in the T-HaCaT group (both P<0.05). The proliferation rate of HaCaT cells after NaAsO2 exposure for 72 h increased with the increase of exposure concentration (r=0.862, P<0.05), and consistently, the protein levels of SSP key enzymes in HaCaT cells in each exposure group were higher than those in the control group (all P<0.05). The proliferation rate of HaCaT cells treated with 2.5 μmol·L−1 NaAsO2 increased with the extension of exposure time (r=0.775, P<0.05), which was consistent with the changes of PHGDH levels in cells. After the NCT503 intervention, the proliferation rate of the pretreatment + exposure group was significantly lower than that of the exposure group (P<0.05). Conclusion The key enzymes of SSP may play an important role in the proliferation of T-HaCaT cells induced by NaAsO2.

A case report of macro-AST with isolated elevated aspartate aminotransferase in a child / 中华检验医学杂志

We need to consider the macro-AST when the elevated AST activity cannot be explained. A 3-year-old child was found to have an increase in serum AST activity, but no obvious abnormality be found ofter examination. The PEG precipitation assay showed that the activity was 98.7%, which was diagnosed as macro-AST.

A noninvasive model to predict liver fibrosis in chronic hepatitis B patients with ALT less than upper limit of normal level / 中华临床感染病杂志

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.

Liver histopathological changes in chronic HBV infection patients with alanine aminotransferase at different upper limits of normal value / 中华临床感染病杂志

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.

The value of Fib4 and APRI in predicting liver failure after hepatectomy in patients with hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To evaluate the value of preoperative aspartate aminotransferaseto platelet ratio index (APRI) and fibrosis index 4 (Fib4) in predicting posthepatectomy liver failure (PHLF) of primary hepatocellular carcinoma.Methods:The data of 587 patients with hepatocellular carcinoma admitted to the First Affiliated Hospital of Xinjiang Medical University from January 2014 to January 2020 were retrospectively collected and analyzed, including 412 males and 175 females, aged (56.8±11.2) years. Univariate and multivariate logistic regression were used to analyze the influencing factors of PHLF. The ability of Child-Pugh score, model for end-stage liver diseas (MELD) score, APRI and Fib4 to predict PHLF was evaluated through the receiver operating characteristic (ROC) curve of subjects.Results:Among 587 patients, 186 (31.7%) had liver failure after hepatectomy. In multivariate logistic regression analysis, APRI ( OR=2.660, 95% CI: 1.314-5.384, P=0.007) and Fib4 ( OR=1.322, 95% CI: 1.157-1.511, P<0.001) were risk factors for PHLF in patients with hepatocellular carcinoma. The higher the number, the greater the risk of PHLF. The predicted area under the ROC curve of PHLF in patients with hepatocellular carcinoma was Fib4(0.719)>APRI(0.686)>MELD score(0.618)>Child-Pugh score(0.565). Conclusion:APRI and Fib4 were risk factors of PHLF in patients with hepatocellular carcinoma. They predict the occurrence of PHLF better than Child-Pugh score and MELD score.

Effect of alanine aminotransferase in early pregnancy on neonatal birth weight / 中华内分泌代谢杂志

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.

Clinical observation of Rougan Huaxian granule combined with nucleoside antiviral drugs in treatment of patients with decompensated cirrhosis of hepatitis B / 中国综合临床

Objective:To explore the effects of Rougan Huaxian Granules combined with nucleoside antiviral drugs on liver and kidney function, portal hemodynamics, vascular activity, antiviral indexes and aspartate transaminase-platelet ratio index in patients with hepatitis B decompensated cirrhosis.Methods:A case-control study was conducted on 150 patients with hepatitis B decompensated cirrhosis who were hospitalized in Tangshan Infectious Disease Institute and Affiliated Hospital of North China University of Science and Technology from June 2017 to December 2019 were enrolled. The patients were divided into control group and observation group by computer random random number method, with 75 cases in each group. The control group was given routine liver protection and antiviral treatment; the observation group was given Rougan Huaxian granules on the basis of the control group treatment. Observe the changes of liver and kidney function, portal vein system hemodynamics, vascular activity, antiviral index and aspartate transaminase-platelet ratio index in the two groups. Independent sample T test was used to compare the measurement data between the two groups, paired T test was used for comparison between the same groups before and after treatment, and χ2 test was used for counting data. Results:There were no significant differences in gender, age, course of cirrhosis, Child grade of liver function and baseline data of indexes before treatment between 2 groups (ALL P>0.05). After treatment, alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen, creatinine,diameter of portal vein (Dpv), diameter of splenic vein (Dsv), endothelin-1, nitric oxide, glucagon (GLA), APRI,were all lower than before treatment. Comparison between groups, observation group ALT (51.60±15.97) U/L, AST (62.65±26.28) U/L, urea nitrogen (10.25±1.65) mmol/L, creatinine (78.54±14.09) μmol/L, Dpv (10.20±1.10) mm, Dsv (8.08±0.68) mm, endothelin-1 (31.93±6.35) ng/L, nitric oxide (41.38±8.06) μg/L, GLA (69.54±12.14) mg/L, APRI (3.14±1.35), were significantly lower than those of control group ((97.49±30.87) U/L, (96.03±25.63) U/L, (17.49±2.55) mmol/L, (116.43±22.77) μmol/L, (13.42±1.26) mm, (10.44±0.83) mm, (44.34+11.88) ng/L, (63.47±15.50) μg/L, (107.11+25.29) mg/L, (5.91±1.93)), the differences were statistically significant ( t values were respectively 11.43, 7.87, 20.64, 12.26, 16.62, 18.99, 7.98, 10.96, 11.60, 10.23, all P<0.05). After treatment, albumin, portal vein velocity (Vpv), and velocity of splenic vein blood flow (Vsv) were all higher in the two groups than before treatment. However, there was no significant difference in Vsv of the control group before and after treatment ( t=0.51, P=0.613). Comparison between groups, albumin (39.42±7.35) g/L, Vpv ((25.72±4.06) cm/s), Vsv ((24.22±6.15) cm/s) in the observation group were significantly higher than those in the control group (34.66±7.95) g/L, (19.38±3.46) cm/s, (19.54±5.88) cm/s ( t values were 3.81, 10.28, 4.76, all P<0.05). After treatment, the total effective rate (96.00%(72/75) vs. 86.67%(65/75), χ2=4.13, P=0.042), HBV DNA negative conversion rate (76.00%(57/75) vs. 58.67%(44/75), χ2=5.12, P=0.024), HBeAg negative conversion rate (50.67%(38/75) vs. 30.67%(23/75), χ2=6.22, P=0.013) and serum HBeAg/HBeAb conversion (28.00%(21/75) vs. 13.33%(10/75), χ2=4.92, P=0.027) in observation group were higher than those in control group, and the differences were statistically significant ( P<0.05). HBsAg negative rate (8.00%(6/75) vs. 5.33%(4/75), χ2=0.43, P=0.513) was higher than that of control group, but the difference was not statistically significant ( P>0.05). Conclusion:Rougan Huaxian Granules combined with nucleoside antiviral drugs has significant effect on patients with decompensated liver cirrhosis of hepatitis B, improve liver and kidney function, liver fibrosis and hemodynamics of the portal vein system, increase vascular activity function, and reduce hepatitis B virus (HBV) DNA load, HBV replication, aspartate transaminase-platelet ratio index, APRI, Toll-like receptor (TLR-4) and transforming growth factor β1 (TGF-β1) levels and improves the body′s immune status.

Celastrol induces ferroptosis in activated HSCs to ameliorate hepatic fibrosis via targeting peroxiredoxins and HO-1

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.