Could a reduced hemoglobin, albumin, lymphocyte, and platelet (HALP) score predict autoimmune hepatitis and degree of liver fibrosis?

SUMMARY OBJECTIVE: Autoimmune hepatitis is a rare inflammatory disease of the liver that is characterized by elevated liver enzymes. The hemoglobin, albumin, lymphocyte, and platelet score, which is derived from hemoglobin, serum albumin, circulating lymphocyte count, and platelet count, is also associated with inflammatory conditions. The aim was to examine the hemoglobin, albumin, lymphocyte, and platelet score of patients with autoimmune hepatitis and to compare it to that of healthy individuals in this retrospective analysis. METHODS: Subjects diagnosed with autoimmune hepatitis were enrolled in the study, and healthy individuals were enrolled as controls. Moreover, autoimmune hepatitis subjects were grouped into mild or moderate/advanced fibrosis. Furthermore, aspartate to platelet ratio index, Fibrosis-4, and hemoglobin, albumin, lymphocyte, and platelet scores of the autoimmune hepatitis patients and controls were compared. In addition, the hemoglobin, albumin, lymphocyte, and platelet score of the autoimmune hepatitis patients with mild fibrosis is compared to that of those with moderate/advanced fibrosis. RESULTS: The mean hemoglobin, albumin, lymphocyte, and platelet score of the autoimmune hepatitis patients was 44.2±14.5 while this value was 76.8±15.5 in control subjects. The hemoglobin, albumin, lymphocyte, and platelet score was significantly reduced in autoimmune hepatitis patients than healthy controls (p<0.001). The hemoglobin, albumin, lymphocyte, and platelet score was significantly and negatively correlated with C-reactive protein, aspartate, alanine transaminase, gamma glutamyl transferase, aspartate to platelet ratio index, and Fibrosis-4 values. A hemoglobin, albumin, lymphocyte, and platelet score that was lower than 52.3 had 83% sensitivity and 73% specificity in predicting autoimmune hepatitis. The sensitivity and specificity of the hemoglobin, albumin, lymphocyte, and platelet score were higher than the Fibrosis-4 score in predicting moderate/advanced fibrosis in autoimmune hepatitis. CONCLUSION: We suggest that the hemoglobin, albumin, lymphocyte, and platelet score be used as an additional noninvasive diagnostic tool for autoimmune hepatitis and to predict moderate/advanced liver fibrosis in patients with autoimmune hepatitis.

Asociación de fibrosis hepática mediante elastografía por shear wave 2D y score APRI

Introducción: Las hepatopatías son un problema prevalente a nivel mundial. La biopsia hepática ha sido hasta la fecha el gold standard para valorar el grado de fibrosis, sin embargo, con el advenimiento de nuevos métodos no invasivos, costo-efectivos para el sistema sanitario, cada vez recurrimos menos a esta. En nuestro medio se introdujo recientemente la elastografía por onda cizallamiento con imagen biplanar, lo que implica una curva de aprendizaje por parte de los técnicos. Objetivo: Valorar la asociación de los grados de fibrosis hepática determinado por la elastografía por onda de cizallamiento con imagen biplanar (2D-SWE) y el score APRI en pacientes portadores de enfermedad hepática asistidos en el servicio de hepatología del Hospital Pasteur.Médica 2. Metodología: Se incluyeron los pacientes con enfermedad hepática de cualquier etiología, asistidos entre el 01/10/21 al 31/08/22, mayores de 15 años, de ambos sexos y que han sido valorados con elastografía por onda de cizallamiento con imagen biplanar (2D-SWE) y analítica sanguínea realizado por el equipo médico del servicio mencionado en los últimos 6 meses. Resultados: Se incluyeron 158 pacientes. Se encontró mayor prevalencia de enfermedad hepática en mujeres, con predominio de la etiología de enfermedad por hígado graso no alcohólico (EHGNA) e infección por virus de hepatitis C (VHC). Se evidenció asociación positiva entre la elastografía (2D-SWE) y el score APRI para el diagnóstico o exclusión de enfermedad hepática avanzada, sin diferencia estadísticamente significativa entre los dos médicos hepatólogos. Conclusiones: Existe asociación entre la elastografía por SWE y el score APRI para el diagnóstico de enfermedad hepática avanzada en la población general y por etiología.

Introduction: Liver diseases are a prevalent problem worldwide. To date, liver biopsy has been the gold standard for assessing the degree of fibrosis; however, with the advent of new non-invasive, cost-effective methods for the healthcare system, we are resorting to it less and less. Shear wave elastography with biplanar imaging was recently introduced in our setting, which implies a learning curve for technicians. Objective: To assess the association of the degrees of liver fibrosis determined by shear wave elastography with biplanar imaging (2D-SWE) and the APRI score in patients with liver disease treated in the hepatology service of the Pasteur Hospital. Methodology: Patients with liver disease of any etiology, attended between 01/10/21 and 08/31/22, over 15 years of age, of both sexes and who have been evaluated with shear wave elastography with biplanar image were included. (2D-SWE) and blood analysis performed by the medical team of the aforementioned service in the last 6 months. Results: 158 patients were included. A higher prevalence of liver disease was found in women, with a predominance of the etiology of nonalcoholic fatty liver disease (NAFLD) and hepatitis C virus (HCV) infection. A positive association was evident between elastography (2D-SWE) and the APRI score for the diagnosis or exclusion of advanced liver disease, with no statistically significant difference between the two hepatologists. Conclusions: There is an association between SWE elastography and the APRI score for the diagnosis of advanced liver disease in the general population and by etiology.

Introdução: As doenças hepáticas são um problema prevalente em todo o mundo. Até o momento, a biópsia hepática tem sido o padrão ouro para avaliar o grau de fibrose, porém, com o advento de novos métodos não invasivos e de baixo custo para o sistema de saúde, recorremos cada vez menos a ela. A elastografia por onda de cisalhamento com imagem biplanar foi introduzida recentemente em nosso meio, o que implica uma curva de aprendizado para os técnicos. Objetivo: Avaliar a associação dos graus de fibrose hepática determinados pela elastografia por ondas de cisalhamento com imagem biplanar (2D-SWE) e o escore APRI em pacientes com hepatopatia atendidos no serviço de hepatologia do Hospital Pasteur. Metodologia: Foram incluídos pacientes portadores de doença hepática de qualquer etiologia, atendidos entre 10/01/21 e 31/08/22, maiores de 15 anos, de ambos os sexos e que foram avaliados com elastografia por onda de cisalhamento com imagem biplanar. ( 2D-SWE) e análises sanguíneas realizadas pela equipa médica do referido serviço nos últimos 6 meses. Resultados: foram incluídos 158 pacientes. Foi encontrada maior prevalência de doença hepática em mulheres, com predomínio da etiologia da doença hepática gordurosa não alcoólica (DHGNA) e da infecção pelo vírus da hepatite C (HCV). Foi evidente uma associação positiva entre a elastografia (2D-SWE) e o escore APRI para o diagnóstico ou exclusão de doença hepática avançada, sem diferença estatisticamente significativa entre os dois hepatologistas. Conclusões: Existe associação entre a elastografia SWE e o escore APRI para o diagnóstico de doença hepática avançada na população geral e por etiologia.

Changes of APRI score in HBeAg-negative treatment-naive chronic hepatitis B patients receiving 3 year entecavir therapy / 中华实验和临床病毒学杂志

Objective@#We aimed to evaluate changes towards liver fibrosis during entecavir(ETV)treatment by non-invasive fibrosis markers in chronic hepatitis B (CHB) patients who need antiviral therapy.@*Methods@#Totally 303 HBeAg negative treatment-naive CHB patients were enrolled and liver biopsy was performed before starting antiviral therapy in this study. Totally 196 patients who need antiviral therapy were treated with ETV for at least 3 years. A clinical and virological evaluation was performed at baseline and again after 1, 2 and 3 years during ETV treatment. AST-to-platelet ratio index (APRI) was used to assess dynamic changes of liver fibrosis in HBeAg negative CHB patients after 1, 2, 3 years of ETV treatment.@*Results@#All enrolled patients experienced liver biopsy at baseline. According to Metavir fibrosis stages, F1, F2, F3 and F4 patients were 107, 125, 54 and 17, respectively. The APRI score enabled the correct identification of patients with severe fibrosis (METAVIR F3-F4). The APRI values significantly decreased in F2 and F3 patients after 1 year ETV therapy (P<0.01). But for F4 patients, APRI values decreased significantly at year 3 (P<0.05).@*Conclusions@#APRI values decreased significantly during ETV treatment in HBeAg-negative CHB patients indicating that these noninvasive fibrosis tests might be useful for monitoring improvement of liver fibrosis and assessing treatment efficacy during long-term ETV treatment.

Three noninvasive liver fibrosis evaluation methods in diagnosis of early cirrhosis for chronic HBV infected patients with mild abnormal liver function / 中华临床感染病杂志

Objective To compare FibroTouch, serum hepatic fibrosis index and aspartate aminotransferase-to-platelet ratio index (APRI) in diagnosis of liver fibrosis and early cirrhosis for patients with chronic HBV infection with mild abnormal liver function.Methods One hundred and seven chronic HBV infected patients with alanine transaminase (ALT)≤80 U／L who underwent liver biopsy in Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2014 to January 2017 were enrolled in the study.According to the liver biopsy pathology , the patients were divided into mild liver fibrosis group (S1, n＝26 ), significant fibrosis group ( S2-3, n ＝34 ) and early cirrhosis group ( S4, n ＝47 ).The differentiations of liver stiffness measurement (LSM), Laminin(LN), Collagen Type ⅢN-peptide(PⅢP N-P), Collagen Type IV(CⅣ), Hyaluronic acid ( HA) and APRI were compared among the three groups , and their correlations with fibrosis were analyzed with Spearman rank correlation analysis .Logistic regression analysis was performed to establish a multi-index model for predicting the degree of liver fibrosis , and the receiver operating characteristic (ROC) curves were drawn to compare and analyze the predictive value for different stages of liver fibrosis.Results The LSM in the significant fibrosis group was higher than that in the mild liver fibrosis group (Z＝-2.611, P＜0.01).The levels of PⅢP N-P,CIV,LN and HA in early cirrhosis group were higher than those in mild liver fibrosis group (Z＝-4.026,-4.205,-2.938 and-3.156, all P＜0.01).LSM and APRI in early liver cirrhosis group was higher than that in mild liver fibrosis group(Z＝-5.789 and -4.308, both P＜0.01) and significant liver fibrosis group (Z＝-3.460 and -3.498, both P＜0.01).PLT in early liver cirrhosis group was lower than that in mild liver fibrosis group and significant liver fibrosis group (Z＝-4.533 and -3.206, both P＜0.01).The correlation analysis showed that the values of LSM , CIV, PⅢP N-P and APRI were positively correlated with the stage of liver fibrosis (r＝0.606, 0.418, 0.396 and 0.470, respectively; all P＜0.01).There was no significant difference in the efficacy of each single index in predicting hepatic fibrosis S≥2 and S＝4 (all P＞0.05). The prediction of liver fibrosis models were established with Logistic regression analysis .The model 1 Logit (P)＝-3.810+0.385×LSM+0.052×CIV was used for predicting liver fibrosis S≥2; the area under the receiver operating characteristic curve ( AUC) was 0.839, with specificity of 96.0%, and the diagnostic efficacy was superior to PⅢP N-P, CⅣand APRI(Z＝2.579, 2.145 and 2.219, all P＜0.05), but there was no significant difference compared with LSM ( Z ＝1.001, P ＞0.05).The model 2 Logit ( P)＝-4.291+0.105×LSM+0.028×CIV+2.682×APRI was used for predicting liver fibrosis S ＝4; its AUC was 0.865 with sensitivity of 82.9%and specificity of 81.8%, and the diagnostic efficacy was superior to LSM, PⅢP N-P, CⅣand APRI (Z＝2.309, 2.485, 2.403 and 2.103, all P＜0.05).Conclusions For chronic HBV infected patients with mild abnormal liver function , FibroTouch can be selected as a noninvasive method to predict liver fibrosis S≥2.The diagnostic efficacy of the prediction model 2, based on the combination of LSM, CIV and APRI is superior to each single index , which can improve the prediction level of early cirrhosis.

Diagnostic accuracy of RPR, FIB-4, APRI and AAR in liver fibrosis patients with chronic hepatitis B / 中国实用内科杂志

OBJECTIVE: We intended to evaluate the diagnostic efficiency of red cell distribution width to platelet ratio(RPR),and compare it with other three markers of fibrosis-4(FIB-4), aspartate aminotransferase-to-platelet-ratio-index(APRI) and aspartateaminotransferase-to-alanine aminotransferase ratio(AAR) for judging liver fibrosis and fibrosis severity in patients with chronic hepatitis B(CHB). METHODS: who had not received antiviral treatment met the requirements of this cross-sectional study. Hematology,biochemistry, virology testing and liver biopsy were performed. Receiver-operating characteristic curves were constructed and the area under the ROC curve was calculated. RESULTS: The cut-off value for distinguishing F0-1, F2-3 and F4 was 0.079, 0.141 and 0.279,respectively(P<0.001) for RPR; 1.194, 3.703 and 4.383(P<0.001) for FIB-4; 0.384, 0.660 and 1.441, respectively(P<0.001) for APRI; and 0.915, 0.850 and 0.960(P=0.706) for AAR. The sensitivity was 76.09% for RPR, 78.26% for FIB-4, 97.83% for AAR and80.43% for APRI; specificity was 81.48% for RPR, 75.93% for FIB-4, 14.81% for AAR and 80.43% for APRI; the AUROC was 0.787 for RPR, 0.778 for FIB-4, 0.540 for AAR and 0.759 for APRI. The common cut-off value was 0.11, 1.94, 0.60 and 0.59 for RPR, FIB-4, AAR and APRI respectively. CONCLUSION: RPR, FIB-4 and APRI have good efficiency in appraising significant and severe fibrosis in patients with CHB, however RPR is superior to FIB-4 and FIB-4 is superior to APRI, therefore, RPR is a better index in evaluating liver cirrhosis.

Correlation between FibroScan, APRI Detecting the degree of esophageal and gastric varices of liver cirrhosis / 中华肝脏病杂志

Objective@#To investigate the predictive value of transient elastography (FibroScan), aspartate aminotransferase-to-platelet ratio index (APRI) in the detection of esophagogastric varices in patients with liver cirrhosis. @*Methods@#236 patients with liver cirrhosis who met the criteria were selected. All patients underwent gastroscopy. According to the degree of esophagogastric varices, patients were divided into four groups: none, mild, moderate, and severe. The patient's liver stiffness (LSM) and aspartate aminotransferase- to-platelet ratio index (APRI) were measured within 3 days of gastroscopy. One-way analysis of variance was used to compare multi-group data. The ROC curves of LSM, APRI, LSM+APRI in patients with liver cirrhosis with esophageal varices were plotted and their area under the ROC curve (AUC) were compared. @*Results@#The area under the ROC curve of LSM, APRI, LSM + APRI in patients with mild esophagogastric varices were 0.856, 0.900, and 0.906, respectively; moderate esophagogastric varices were 0.857, 0.924, and 0.923 respectively; and severe esophagogastric varices were 0.801, 0.903, and 0.901, respectively. @*Conclusion@#APRI and LSM+APRI have better predictive value for patients with cirrhosis who have esophagogastric varices.

Diagnostic value of two liver imaging techniques combined with serological models for hepatitis B virus-related liver fibrosis / 中华传染病杂志

Objective@#To compare the diagnostic efficacy of transient elastography (TE) FibroScan and acoustic radiation force impulse imaging (ARFI) combined with serological models including aspartate aminotransferase-to-platelet ratio (APRI) and fibrosis-4 (FIB-4) in hepatitis B virus-related fibrosis.@*Methods@#Sixty-seven patients with chronic HBV infection from October 2014 to May 2017 in Department of Infectious Diseases, Putuo Hospital were enrolled. Both FibroScan and ARFI were conducted in all patients together with serological tests. According to the golden standard of pathology results, the diagnosis values of FibroScan, ARFI combined with APRI or FIB-4 were compared as noninvasive assessment for liver fibrosis. Data with homogeneity of variance were tested by t test, and data with heterogeneity of variance were tested by Mann-Whitney U test.@*Results@#Based on the pathology results, the receiver operating characteristic (ROC) areas under the curve (AUC) of APRI, FIB-4, FibroScan and ARFI in diagnosis of hepatic fibrosis ≥S2 were 0.752, 0.612, 0.885, and 0.850, respectively. The AUC of ROC curve in diagnosis of hepatic fibrosis ≥S3 were 0.746, 0.733, 0.851, and 0.863, respectively. The AUC of ROC curve in diagnosis of hepatic fibrosis ≥S4 were 0.782, 0.705, 0.962 and 0.981, respectively. Combined liver imaging technique and serological tests, such as APRI with FibroScan, APRI with ARFI, FIB-4 with FibroScan or FIB-4 with ARFI, the AUC of ROC curve in the 4 groups in diagnosis of hepatic fibrosis ≥S2 were 0.887, 0.861, 0.893, and 0.853, respectively; in the diagnosis of hepatic fibrosis ≥S3 were 0.873, 0.871, 0.900, and 0.875, respectively; and in diagnosis of hepatic fibrosis ≥S4 were 0.952, 0.981, 0.969, and 0.981, respectively. FibroScan and ARFI were positively correlated with liver inflammation (r=0.467, P=0.000; r=0.371, P=0.002) and jaundice (r=0.424, P=0.000; r=0.0.312, P=0.01), while negatively correlated with platelet (r=-0.331, P=0.006; r=-0.312, P=0.01). The AUC of ROC curve of FibroScan, ARFI and their combination with serological model were significantly increased compared with the single serological model (all P<0.05).@*Conclusions@#Serological models such as APRI and FIB-4 as well as liver imaging techniques such as FibroScan and ARFI are all valuable in assessment of hepatic fibrosis, while FibroScan and ARFI have better diagnostic value. ARFI is convenient to application for its integration with the ordinary ultrasound system. The sensitivity and specificity for diagnosis of hepatic fibrosis could be improved by combining serological model with FibroScan or ARFI. Combination of APRI and ARFI show the highest accuracy in diagnosis of hepatic fibrosis. Combination of serological models and transient elastic liver imaging is recommended for assessment and follow-up of HBV-related fibrosis.

Value of aspartate aminotransferase-to-platelet ratio index in judging the indication for antiviral therapy in patients with chronic HBV infection and alanine aminotransferase less than two times of upper limit of normal / 临床肝胆病杂志

Objective To investigate the value of aspartate aminotransferase-to-platelet ratio index (APRI) in judging the indication for antiviral therapy [liver inflammation grade (G) ≥2 or fibrosis stage (S) ≥2] in patients with chronic HBV infection and alanine aminotransferase (ALT) ＜ 2 × upper limit of normal (ULN).Methods A retrospective analysis was performed for the clinical data of 207 patients with chronic HBV infection and ALT ＜ 2 × ULN who were admitted to Nanyang Central Hospital from January 2015 to June 2017,and according to liver inflammation grade and fibrosis stage,these patients were divided into G ＜ 2 + S ＜ 2 group with 87 patients and G ≥2 or S ≥2 group with 120 patients.The results of liver biopsy and laboratory examination were recorded,and APRI was calculated.The Spearman correlation analysis was performed to investigate the correlation of APRI with liver inflammation grade and fibrosis stage.The area under the receiver operating characteristic curve (AUC) was used to investigate the value of ALT,aspartate aminotransferase (AST),platelet count (PLT),and APRI in judging the indication for antiviral therapy in patients with ALT ＜ 2 × ULN.The t-test or the Wilcoxon rank-sum test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups.Results APRI was positively correlated with liver inflammation grade and fibrosis stage (r =0.661 and 0.597,P ＜0.001).Among ALT,AST,PLT,and APRI,APRI had the highest value in judging the indication for antiviral therapy,with AUCs of 0.913 in the G≥2 or S≥2 group,0.882 in the G≥2 group,and 0.881 in the S≥2 group.APRI had an AUC of 0.913 (95％ confidence interval:0.871-0.954) in predicting the indication in the G ≥ 2 or S ≥2 group at the optimal cut-off value of 0.5324;when APRI was ≥0.5324,the patients had marked liver histological changes,i.e.,G≥2 or S≥2,which met the indication for antiviral therapy.APRI had a sensitivity of 87.50％,a specificity of 89.66％,a positive predictive value of 92.11％,and a negative predictive value of 83.87％.Conclusion For patients with chronic HBV infection and ALT ＜ 2 × ULN,APRI has a good value in evaluating liver pathological changes and judging the timing of antiviral therapy and can reduce the frequency of invasive assessment of histological changes via liver biopsy.

Application of APRI score and FIB-4 index in prognostic evaluation of patients with chronic liver failure / 中华临床感染病杂志

Objective To assess the prognostic value of APRI score and FIB-4 index for patients with chronic liver failure.Methods Clinical data of 426 patients with chronic liver failure admitted in the First Affiliated Hospital of Xinjiang Medical University from March 2005 to September 2014 were retrospectively analyzed.The MELD score,APRI score and FIB-4 index were calculated.Patients were divided into survival group and fatal group according to survival situation within 3 month after admission.Logistic regression was used to analyze the differences in all the indexes between the survival group and fatal group.Receiver operating characteristic (ROC) curve was used to assess the value of the above indexes in predicting the 3-month survival.Results Among 426 patients 244 died within three months after admission.Univariate analysis and multivariate Logistic regression showed that MELD score and FIB-4 index were statistically significant between the survival and fatal groups (Z =-4.783 and-4.104,x2 =26.31 and 11.34,both P ＜ 0.01).The area under the ROC curve of MELD score,APRI score and FIB-4 index was 0.635,0.511 and 0.616 for predicting 3-month survival,respectively.Compared with the APRI score,MELD score and FIB4 index were statistically different (x2 =13.669 and 6.341,P ＜ 0.05 or P ＜ 0.01).When MELD score ＞ 28,FIB-4 index ＞ 11.27,the patient has a high fatality rate and poor prognosis within three months.Conclusion FIB-4 index can be used to evaluate the short-term prognosis of patients with chronic liver failure,and the higher score of FIB-4 index predicts the worse prognosis.

Value of FIB-4 and APRI index in evaluating the severity of liver fibrosis among patients with chronic hepatitis B / 国际检验医学杂志

Objective To explore the value of FIB-4 and APRI index on evaluating the severity of liver fibrosis among patients with chronic hepatitis B(CHB).Methods A total of 218 CHB were enrolled in the study.Based on the staging of liver fibrosis,the patients were divided into 2 groups as S0-S2 group(n=120) and S3-S4 group(n=98).Differences in clinical data,laboratory indexes,FIB-4 and APRI index were compared between two groups.The correlation between FIB-4 index,APRI index and liver fibrosis were analyzed by Spearman correlation test.Receiver operator curve(ROC) test was used to determine the evaluating value of FIB-4 index and APRI index for the severity of liver fibrosis.Results To evaluate the staging≥S2 of liver fibrosis,the value of FIB-4 index was better than APRI index(Z=1.998,P=0.046).And to evaluate the staging≥S3 and S4 of liver fibrosis,the value of FIB-4 index for evaluating the staging≥S3(Z=1.177,P=0.239) or S4(Z=0.267,P=0.789) was the same as APRI index.Conclusion FIB-4 index and APRI index are both effective on evaluating the severity of liver fibrosis among patients with CHB,but the value of FIB-4 index is better than APRI index for evaluating early liver fibrosis.

Diagnostic Value of APRI Combined With FIB-4 for Significant Liver Fibrosis in Patients With Chronic Hepatitis B / 胃肠病学

Background:The diagnostic accuracy of APRI and FIB-4 for liver fibrosis in patients with chronic hepatitis B is nothigh,especially for significant liver fibrosis (F≥2). Noninvasive diagnosis for liver fibrosis has become a research hotspot;and the diagnostic value of APRI combined with FIB-4 is not clear. Aims:To investigate the diagnostic value ofAPRI combined with FIB-4 for significant liver fibrosis in patients with chronic hepatitis B. Methods:A total of 171patients with chronic hepatitis B from January 2011 to October 2016 at General Hospital of Xinjiang Military Region wereenrolled. Liver biochemical indices,routine blood test and liver biopsy pathology were performed. APRI and FIB-4 werecalculated,ROC curve was drawn,and cutoff value of APRI and FIB-4 for diagnosing significant liver fibrosis wasdetermined,and mode of APRI combined with FIB-4 for diagnosing significant liver fibrosis was established. Results:Withthe increase in degree of liver fibrosis,APRI and FIB-4 were gradually increased (P < 0. 05). Area under ROC curve(AUC)for APRI and FIB-4 were 0. 812 and 0. 770,respectively. The sensitivity of FIB-4 for diagnosing significant liverfibrosis was higher than that of APRI. Sensitivity,specificity,negative predictive value,positive predictive value,andaccuracy of APRI combined with FIB-4 for diagnosing significant liver fibrosis were superior to APRI or FIB-4 used alone;and the specificity,accuracy of mode 2 were superior to mode 1. Conclusions:APRI combined with FIB-4 can increasethe accuracy for diagnosing significant liver fibrosis.

Expression, purification and detection of activities of AprA and its inhibitor AprI from Pseudomonas aeruginosa / 军事医学

Objective To clone and express the alkaline protease AprA , one important virulence factor secreted by Pseudomonas aeruginosa(PAE)in Escherichia coli, to clone and express the inhibitor of AprA (AprI) and its substrate flagellin , and to detect the function of AprA and the inhibitory function of AprI .Methods The genes encoding AprA ,AprI and flagellin gene were amplified respectively by PCR using PAE PAO 1 genome DNA as the template .The expression vec-tors (pET-28a-AprA, pET-28a-AprI and pET-28a-Flagellin) were constructed and transformed into E.coli BL21(DE3) respectively.The recombinant AprA protein was expressed by IPTG induction and purified via denaturing and renaturation. The recombinant AprI and flagellin were expressed and purified by Ni 2+affinity chromatography .The cleavage activities of AprA on flagellin were detected by SDS-PAGE.Results Recombinant AprA , AprI and flagellin protein were expressed and purified .It was demonstrated that AprA cleaved flagellin , which was blocked by AprI .Conclusion Recombinant AprA could cleave its substrates as an alkaline protease , and its inhibitor AprI inhibits the activities of AprA .This study will contribute to further investigations on the role of AprA in the pathogenesis of PAE .

Transient elastography and APRI score: looking at false positives and false negatives. Diagnostic performance and association to fibrosis staging in chronic hepatitis C

Although long regarded as the gold standard for liver fibrosis staging in chronic hepatitis C (CHC), liver biopsy (LB) implies both the risk of an invasive procedure and significant variability. The aim of this study was to evaluate the diagnostic performance for transient elastography (TE) and aspartate aminotransferase to platelet index (APRI) used alone and in combination compared to liver biopsy and to analyze false positive/negative results. Patients with CHC, and no previous clinical diagnosis of cirrhosis were enrolled to undergo liver biopsy, TE and APRI. A total of 182 adult patients with a median age of 55 years and median body mass index of 26.71 kg/m2 were analyzed. On LB, 56% of patients had significant levels of fibrosis (METAVIR F≥2) and 28% had advanced fibrosis (F3/F4). The strongest performance for both tests was observed for exclusion of advanced fibrosis with good negative predictive values (89 and 86%, respectively). Low necroinflammatory activity on LB was associated with false negative TE. False positives were associated with NASH and smaller LB fragments. Correlation between APRI and Fibroscan for F≥2 was 100% and 84% for F≥3 and remained high in both false negative and false positive instances, correctly identifying F<2 in 71% of cases and F<3 in 78% (and potentially foregoing up to 84% of LB). We concluded that low individual performance indicators could be attributable to limitations of LB. Poorer differentiation of lower levels of fibrosis is a known issue for LB and remains so for noninvasive tests. Good predictability is possible, however, for advanced fibrosis.

The diagnostic value of RTE and APRI for evaluating the degree of liver fibrosis who with chronic liver disease at early stage / 重庆医学

Objective To investigate the diagnostic value of the real-time tissue elastography (RTE)and AST/PLT ratio in-dex (APRI)for the assessment of the early stage liver fibrosis in chronic liver disease patients.Methods Totally 90 patients with chronic liver disease were enrolled in the present study.The RTE score and the area percentage of the blue color (AREA,one of the elastic characteristics),the AST and PLT were recorded.Compared the results among different stages of liver fibrosis reported by biopsy considered as the gold standard for the assessment of liver fibrosis.The accuracy of the diagnosis of liver fibrosis by RTE scores,AREA and APRI were compared.Results RTE scores,AREA and APRI increased with the stage of liver fibrosis. Taking ≥S1 as the diagnosis standard of the early stage liver fibrosis,the area under the curve of ROC for RTE scores,AREA and APRI were 0.88,0.92,0.76 (P <0.05).Conclusion RTE is a new and promising sonography-based noninvasive method for the assessment of hepatic fibrosis in patients with chronic liver disease.Combined RTE with APRI have great clinical significance in di-agnosing the early stage liver fibrosis in chronic liver disease patients.

Can Combinations of Non-Invasive Parameters Replace Liver Biopsy in the Diagnosis of Hepatic Fibrosis in Egyptian Patients with Chronic Hepatitis C.

Aims: Liver biopsy has always been represented as the standard reference for assessment of hepatic fibrosis although it has several limitations. This study aimed at evaluating the accuracy of noninvasive methods for diagnosis of hepatic fibrosis in adult Egyptian patients with chronic hepatitis C virus (HCV) infection. Study Design: Cross sectional study. Place and Duration of Study: This study was conducted in Al-Ahrar General Hospital (local treatment centre for Hepatitis C virus), Sharkia Governorate, Egypt and the Tropical Medicine Department, Zagazig University Hospitals, Sharkia Governorate, Egypt in the period from April 2011 to March 2012. Methodology: Fifty chronic HCV patients were selected out of 255 chronic HCV patients awaiting assessment for combined pegylated interferon/ribavirin therapy according to the modified guidelines of the National Committee for Control and Prevention of viral Hepatitis C in Egypt. Diagnosis of HCV was confirmed by detection of anti-HCV antibody and positivity for HCV RNA for more than 6 months. All patients were assessed by liver biopsy and noninvasive methods namely aspartate transaminase/platelet ratio (APRI), abdominal ultrasonography measuring caudate/right lobe ratio and liver stiffness measurement. Results: The accuracy in diagnosis of liver fibrosis using different methods in comparison to liver biopsy was 60%, 84%, 88%, 90%, 92% and 84% for APRI, ultrasonography, Fibroscan, combined Fibroscan/APRI, Fibroscan/ultrasonography and APRI/ultrasonography respectively. The sensitivity was 62.5%, 87.5%, 87.5%, 90.6%, 93.8 and 87.5 for APRI, ultrasonography, Fibroscan, combined Fibroscan/APRI, Fibroscan/ultrasonography and APRI/ultrasonography respectively. The specificity was 55.6%, 77.8%, 88.9%, 88.9%, 88.9 and 77.8 for APRI, ultrasonography, Fibroscan, combined Fibroscan/APRI, Fibroscan/ultrasonography and APRI/ultrasonography respectively. Conclusion: Fibroscan appeared superior to APRI score and abdominal ultrasonography in diagnosis of liver fibrosis. Combined Fibroscan /ultrasonography performed better than other combinations for the prediction of significant hepatic fibrosis.

The efficacy of aspartate aminotransferase-to-platelet ratio index for assessing hepatic fibrosis in childhood nonalcoholic steatohepatitis for medical practice / 소아과

PURPOSE: Childhood obesity is associated with nonalcoholic fatty liver disease (NAFLD), and it has become one of the most common causes of childhood chronic liver diseases which significant as a cause of liver related mortality and morbidity in children in the United States. The development of simpler and easier clinical indices for medical practice is needed to identify advanced hepatic fibrosis in childhood NAFLD instead of invasive method like liver biopsy. FibroScan and aspartate aminotransferase (AST)-to-platelet ratio index (APRI) have been proposed as a simple and noninvasive predictor to evaluate hepatic fibrosis in several liver diseases. APRI could be a good alternative to detect pathologic change in childhood NAFLD. The purpose of this study is to validate the efficacy of APRI for assessing hepatic fibrosis in childhood NAFLD based on FibroScan. METHODS: This study included 23 children with NAFLD who underwent FibroScan. Clinical, laboratory and radiological evaluation including APRI was performed. To confirm the result of this study, 6 patients received liver biopsy. RESULTS: Factors associated with hepatic fibrosis (stiffness measurement >5.9 kPa Fibroscan) were triglyceride, AST, alanine aminotransferase, platelet count, APRI and collagen IV. In multivariate analysis, APRI were correlated with hepatic fibrosis (>5.9 kPa). In receiver operating characteristics curve, APRI of meaningful fibrosis (cutoff value, 0.4669; area under the receiver operating characteristics, 0.875) presented sensitivity of 94%, specificity of 66%, positive predictive value of 94%, and negative predictive value of 64%. CONCLUSION: APRI might be a noninvasive, simple, and readily available method for medical practice to predict hepatic fibrosis of childhood NAFLD.

Four noninvasive score systems for diagnosis of liver fibrosis in patients with chronic hepatitis B / 中华临床感染病杂志

Objective To assess the value of S index and FIB-4 for diagnosis of liver fibrosis in patients with chronic hepatitis B (CHB) by comparing with traditional indexes APRI and Forns.Methods A total of 361 patients with confirmed CHB from the First Hospital of Nanjing Medical University and Huashan Hospital Affiliated to Fudan University during January 2006 and December 2011 were enrolled in the study.The clinical,laboratory and pathological data of patients were collected.Four noninvasive score systems APRI,Forns,S index and FIB-4 were computed.With liver biopsy as the gold standard,the area under the ROC curve (AUROC) was used to assess the value of above 4 score systems in diagnosis of liver fibrosis,and Z test was performed to evaluate the effectiveness of above systems.Results The areas under ROC curve (AUCs) of APRI,Forns,S index and FIB-4 for significant fibrosis (≥S2) were (0.737 ±0.027),(0.716 ± 0.028),(0.745 ± 0.026) and (0.781 ± 0.025),respectively.When the cut off value of FIB-4 was set at 1.62,the sensitivity,specificity,positive predictive value (PPV) and negative predictive value (NPV) for diagnosis of significant fibrosis were 59.3％,85.8％,89.4％ and 51.2％,respectively,which were better than Forn index (Z =3.28,P =0.001).While for S4 (cirrhosis) the AUCs of APRI,Foms,S index and FIB-4 were (0.687 ± 0.035),(0.792 ± 0.028),(0.863 ± 0.024) and (0.832 ± 0.025),respectively.When the cut off value of S index was set at 1.06,the sensitivity,specificity,PPV and NPV for diagnosis of cirrhosis were 77.9％,85.5％,59.4％ and 93.5％,respectively,which were better than APRI and Forns (Z =6.74 and 3.21,P ＜ 0.01).Conclusions APRI,Forns,S index and FIB-4 are simple and accurate methods for assessing liver fibrosis.FIB-4 and S index are better than APRI and Forns in diagnosis of significant fibrosis and cirrhosis,which may replace liver biopsy in certain extend.

Can aspartate aminotransferase to platelet ratio index replace liver biopsy in chronic hepatitis C.

Background and aim: We aimed to evaluate the accuracy of readily available laboratory tests (ALT, AST, platelet count, AST to platelet ratio index: APRI) in predicting liver fibrosis in chronic hepatitis C, in comparison to the predictive accuracy obtained by liver biopsy. Methods: One hundred and thirteen patients suffering from chronic hepatitis C (CHC) were included in this study. They included 76 children enrolled from the Pediatric Hepatology Unit and 37 adults enrolled from the Hepatology Unit of Tropical Medicine Department, Cairo University, Egypt. Fibrosis results obtained from liver biopsy were assigned a score from 0 to 4 score as per Metavir scoring. Results of serum ALT and AST levels were expressed as ratio of the upper limit of normal (ULN). Results: Of the pediatric patients, 28 (36.8%) showed no evidence of fibrosis on liver biopsy, 26 (34.2%) showed grade 1 fibrosis, and 22 (29%) had grade 2 fibrosis. Among the adult patients, 12 (32.4%) had grade 2 fibrosis and 25 patients (67.6%) had grades 3 to 4 fibrosis. There was a lack of correlation between the degree of fibrosis and AST levels, AST/ALT ratio, platelet count and APRI. The AUROC curve for predicting significant fibrosis was 0.5 for AST levels, 0.37 for AST/ALT ratio and 0.49 for APRI, in pediatric patients (p >0.05). In adult patients the AUROC curve for predicting significant fibrosis was 0.59 for AST levels, 0.76 for AST/ALT ratio and 0.63 for APRI (p >0.05). Conclusion: Liver biopsy remains the gold standard to assess the extent of hepatic fibrosis in patients with CHC.

Uso do score APRI na avaliação de doença hepática, após início de terapia antirretroviral, em pacientes portadores do HIV co-infectados com HCV versus monoinfectados por HIV / Evaluation of APRI score in liver disease following the introduction of antiretroviral therapy in HIV and HCV coinfected versus HIV monoinfected patients

INTRODUÇÃO: O impacto da terapia antirretroviral altamente ativa na progressão da fibrose hepática em pacientes co-infectados com HIV e hepatite C não está totalmente esclarecido. Marcadores não-invasivos de fibrose hepática podem ser considerados promissores no estadiamento e na monitorização da sua evolução. MÉTODOS: Um total de 24 pacientes, divididos em dois grupos: 12 monoinfectados por HIV e 12 co-infectados com HIV e HCV foram acompanhados de julho de 2008 a agosto de 2009, desde o início de HAART, a cada três meses, com avaliação de dados clínicos, epidemiológicos e laboratoriais, assim como o cálculo do índice da relação aspartato aminotransferase sobre plaquetas. O objetivo deste estudo foi comparar a progressão de APRI, marcador não-invasivo de fibrose hepática, entre populações portadoras do vírus do HIV e co-infectados com HIV e HCV. RESULTADOS: Os grupos estudados não mostraram diferenças quando avaliados idade, sexo, medida de CD4 e carga viral para HIV em todas visitas, tipo de HAART e APRI antes do início de HAART. O grupo de pacientes co-infectados com HIV e HCV apresentava APRI significativamente maior que o grupo de monoinfectados por HIV no terceiro (0,57 + 0,31 x 0,27 + 0,05, p = 0,02) e sexto mês (0,93 + 0,79 x 0,28 + 0,11, p = 0,04). CONCLUSÕES: Neste estudo, HAART foi associado com aumento de APRI no terceiro e sexto mês de seguimento nos pacientes co-infectados, sugerindo que nestes pode estar ocorrendo hepatotoxicidade cumulativa e síndrome inflamatória da reconstituição imune após início dos antirretrovirais.

INTRODUCTION: The impact of highly active antiretroviral therapy (HAART) on hepatic fibrosis progression in HIV and hepatitis C virus coinfected patients is not completely understood. Noninvasive hepatic fibrosis markers show great promise in determining liver fibrosis staging and monitoring disease progression. METHODS: Twenty-four patients divided equally into two groups: 12 HIV-monoinfected and 12 with HIV/HCV coinfected patients, were followed from July 2008 to August 2009, after initiating HAART, with clinical, epidemiological and laboratorial assessments every 3 months and calculation of the aspartate aminotransferase to platelet ratio index (APRI). This study aimed to compare the progression of APRI, a noninvasive hepatic fibrosis marker, among populations with HIV and HIV/HCV coinfection. RESULTS: No differences were observed between the groups regarding age, sex, measurement of CD4 and HIV viral load in all consultations, type of HAART and APRI before initiating HAART. Coinfected patients showed a significantly higher APRI than the monoinfected group in month 3 (0.57 ± 0.31 x 0.27 ± 0.105, p = 0.02) and 6 (0.93 ± 0.79 x 0.28 ± 0.11, p = 0.04). CONCLUSIONS: In the present study, HAART was associated with APRI increases over six months follow-up in HIV/HCV coinfected patients, suggesting that these may be experiencing cumulative hepatotoxicity and immune reconstitution inflammatory syndrome after initiating antiretroviral drugs.

Epidemiology of hepatitis C virus infection & liver disease among injection drug users (IDUs) in Chennai, India.

Background & Objectives: We characterized HCV antibody prevalence, viral persistence, genotype and liver disease prevalence among IDUs in Chennai, India as the study of the association of HIV with each of these states is important and there are no data available. Methods: Between 2005-2006, 1158 IDUs were recruited and followed semi-annually. All were tested for HCV antibodies at baseline; a random sample of 400 antibody positives (200 HIV-positive and 200 HIV-negative) were tested for HCV RNA; 13 of these were sequenced. Assessment of asparate amino transferase (AST)-to-platelet ratio index (APRI) was done on 557 IDUs. Prevalence ratios of each outcome were examined. Results: Median age was 35 yr; 99 per cent were male. HCV antibody prevalence was 55 per cent and was associated with older age, being unmarried, longer injection history, tattoo and injecting at a dealer’s place. Of the 400 HCV antibody positive IDUs, 281 (70.3%) had persistent infection which was less common among hepatitis B-infected persons but not associated with HIV. Of the 13 samples sequenced, 11 (85%) were HCV genotype 3a. Fibrosis prevalence according to APRI was: HIV/HCV-uninfected, 4 per cent; HIV mono-infected, 3 per cent; HCV mono-infected, 11 per cent; HIV/HCV co-infected, 12 per cent (P<0.001). In addition to being associated with HCV and HIV/HCV, fibrosis prevalence was higher among those drinking alcohol frequently; daily marijuana use was protective. Interpretation & Conclusions: Our findings show that IDUs in Chennai have high HCV prevalence and associated disease burden. The burden will increase as access to antiretroviral therapy improves particularly given the high prevalence of HIV, HCV and alcohol use.