Serum N-glycomic markers in combination with panels improves the diagnosis of chronic hepatitis B

Aim. The present study aimed to evaluate the changes in the serum N-glycome profiles in chronic hepatitis B (CHB) patients and to assess the role of N-glycome-derived markers in the noninvasive diagnosis of liver fibrosis.Materials and Methods. After liver biopsy for pathological grading and staging, 128 CHB patients underwent serum N-glycomic analysis using DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) and sensitive markers were screened.Results. Peaks 1, 2, 8 and 10 in the N-glycome profiles could, to some extents, distinguish liver fibrosis at different stages. In addition, the N-glycome-derived marker log(peak2/peak8) possessed the highest diagnostic accuracy. The areas under the receiver operating characteristic (AUROCs) curves of the log(peak2/peak8) were 0.675, 0.736 and 0.754 in the diagnosis of significant fibrosis, advanced fibrosis and early cirrhosis, respectively. In combination with some marker panels (SLFG, S index, Fibrometer, Hui, Forns, APRI and Hepascore), it showed the best diagnostic potency in distinguishing significant fibrosis (SLFG + log[peak2/peak8], AUROC = 0.813) from advanced fibrosis (SLFG + log[peak2/peak8], AUROC = 0.899) and a better diagnostic potency in the identification of early cirrhosis (S index + log[peak2/peak8], AUROC = 0.903, lower than Hui model [AUROC = 0.927]) in the validation cohort.Conclusions. N-glycomic changes are present in the serum of CHB patients with liver fibrosis, and N-glycan profiling is a noninvasive and effective tool to assess the liver fibrosis, especially in combination with serum marker panels.     

Comparison of non-invasive liver fibrosis biomarkers in HIV/HCV co-infected patients: the fibrovic study--ANRS HC02

BACKGROUND/AIMS: To compare non-invasive biological liver fibrosis scores, as alternatives to liver biopsy, in HIV/HCV co-infected patients. METHODS: Two hundred and seventy-two HIV/HCV patients, nai ve for HCV treatment, underwent liver biopsy [197 (72%) men, 39.9 years, fibrosis stage (Metavir) F1 (25%), F2 (40%), F3 (25%), F4 (10%), median CD4 486/mm(3) and median HIV viral load 3.5log. Fibrotest (FT), Hepascore (HS), Fibrometer (FM), SHASTA, APRI, Forns index, and Fib-4 were tested in order to differentiate patients with mild to moderate fibrosis (F2) and those with advanced fibrosis (F3). The AUROC and the rate of well-classified patients were compared to liver biopsy. RESULTS: FT, HS, and FM were able to stage liver fibrosis in all patients with AUROCs of 0.78, 0.84 and 0.89 for the diagnosis of F2, respectively. The correlation coefficient indexes were 0.37, 0.46 and 0.48, respectively. The rates of well-classified patients were 62%, 68% and 71%, respectively. Fib-4, APRI and the Forn's index were only able to stage 37-61% of patients and showed lower accuracies. Using a combination of FT, HS and FM did not significantly increase the performance of each test. CONCLUSIONS: In HIV/HCV co-infected patients, Fibrometer, Hepascore and Fibrotest outperformed other non-invasive liver fibrosis biomarkers for the prediction of significant liver fibrosis.     

Two or more synchronous combination of noninvasive tests to increase accuracy of liver fibrosis assessement in chronic hepatitis C; results from a cohort of 446 patients

Background

The prediction of fibrosis is an essential part of the assessment and management of patients with chronic liver disease. Non-invasive tests (NITs) have a number of advantages over the traditional standard of fibrosis assessment by liver biopsy, including safety, cost-effectiveness, and widespread accessibility.

Objectives

The aim of this study was to determine the accuracy of certain biomarkers and transient elastography (TE) alone or in combination to predict the stage of liver fibrosis in chronic hepatitis C (CHC). Also, we examined whether the combination of certain biomarkers and TE could increase the diagnostic accuracy of liver fibrosis assessment.

Patients and Method

A total of 446 patients who were previously diagnosed with CHC were included in the study. In the study group, 6 blood-based scores (APRI, Forns, Fib-4, Hepascore, FibroTest, and Fibrometer) were calculated, and TE was performed to validate the stage of fibrosis, compared with liver biopsy (LB) as the standard.

Results

Significant fibrosis (F ≥ 2) was predicted with an AUROC of 0.727, 0.680, 0.714, 0.778, 0.688, 0.797, and 0.751 for the APRI, Forns, Fib-4, FibroTest, Hepascore, and Fibrometer scores and TE (Fibroscan), respectively. Severe fibrosis (F ≥ 3) was predicted, with AUROCs ranging between 0.705 and 0.811 for Hepascore and Fibrometer, respectively. Of the biomarkers, Fibrometer had the highest AUROC value in predicting both significant and severe fibrosis. The combination of APRI or FIB-4 with Fibrometer increased the diagnostic accuracy for significant fibrosis (from 69.07 to 82.27 for APRI, P = 0.001 and from 57.74 to 81.33, P = 0.001 for Fib-4). Combining APRI or Fib-4 with TE also increased the diagnostic accuracy (from 69.07 to 80.70%, P = 0.001 for APRI and from 57.74 to 81.33%, P = 0.001 for Fib-4) for significant fibrosis. The association that included Fibrotest was also reliable for the improvement of diagnostic accuracy. These combinations were more accurate or the assessment of severe fibrosis.

Conclusions

The synchronous association between a simple, inexpensive score and a complex but expensive score or TE increases the diagnostic accuracy of non-invasive methods for the assessment of liver fibrosis stage.     

四种方法诊断慢性乙型肝炎合并轻度肝脂肪变患者肝纤维化比较

目的 比较血清学诊断模型APRI、FIB-4 和Forns指数及FibroScan检查评估合并轻度肝脂肪变的CHB患者肝纤维化的价值。方法 在309例经肝活检病理学检查确诊的CHB患者中,194例无肝脂肪变,115例合并轻度肝脂肪变,同期行FibroScan检查,得到肝硬度值（LSM）,收集实验室检查指标,根据公式计算出相应的APRI、FIB-4、Forns指数。以肝组织病理学表现为金标准,根据受试者工作曲线（ROC）评价4种方法诊断两组患者肝纤维化的效能。结果 两组患者LSM、APRI、FIB-4、Forns指数差异均无统计学意义（P均＞0.05）;在未合并肝脂肪变组,LSM、APRI、FIB-4、Forns指数诊断CHB患者明显肝纤维化（≥F2）的ROC曲线下面积（AUROC）分别为0.77、0.69、0.72、0.69（P均<0.05）,其相应的截断点分别为10.2、0.5、0.9、5.3;诊断肝硬化（≥F4）时,其AUROC分别为0.86、0.72、0.77、0.77（P均<0.05）,其相应的截断点分别为11.8、0.6、1.3、5.1;在合并肝脂肪变组,它们诊断CHB患者≥F2肝纤维化的AUROC分别为0.79、0.67、0.74、0.77（P均<0.05）,其相应的截断点分别为9.7、0.4、1.1、5.7;诊断≥F4的AUROC分别为0.88、0.71、0.75、0.78（P均<0.05）,其相应的截断点分别为11.8、1.1、1.5、5.4; APRI 和FIB-4不能诊断两组患者轻度肝纤维化（P＞0.05）;LSM诊断两组≥F2肝纤维化及≥F3或≥F4进展性肝纤维化或肝硬化的效能均优于APRI。结论 APRI评价合并轻度肝脂肪变的CHB患者肝纤维化效能较差,而LSM、FIB-4、Forns指数诊断效能较好,其中轻度肝脂肪变可能影响Forns指数诊断CHB患者肝纤维化效能。     

Simpler score of routine laboratory tests predicts liver fibrosis in patients with chronic hepatitis B

Background and Aim: In recent years, a great interest has been dedicated to the development of noninvasive predictive models to substitute liver biopsy for fibrosis assessment and follow‐up. Our aim was to provide a simpler model consisting of routine laboratory markers for predicting liver fibrosis in patients chronically infected with hepatitis B virus (HBV) in order to optimize their clinical management. Methods: Liver fibrosis was staged in 386 chronic HBV carriers who underwent liver biopsy and routine laboratory testing. Correlations between routine laboratory markers and fibrosis stage were statistically assessed. After logistic regression analysis, a novel predictive model was constructed. This S index was validated in an independent cohort of 146 chronic HBV carriers in comparison to the SLFG model, Fibrometer, Hepascore, Hui model, Forns score and APRI using receiver operating characteristic (ROC) curves. Results: The diagnostic values of each marker panels were better than single routine laboratory markers. The S index consisting of γ‐glutamyltransferase (GGT), platelets (PLT) and albumin (ALB) (S‐index: 1000 × GGT/(PLT × ALB²)) had a higher diagnostic accuracy in predicting degree of fibrosis than any other mathematical model tested. The areas under the ROC curves (AUROC) were 0.812 and 0.890 for predicting significant fibrosis and cirrhosis in the validation cohort, respectively. Conclusions: The S index, a simpler mathematical model consisting of routine laboratory markers predicts significant fibrosis and cirrhosis in patients with chronic HBV infection with a high degree of accuracy, potentially decreasing the need for liver biopsy.     

慢性乙型肝炎病毒感染患者肝纤维化非创伤性诊断模型的应用评价

目的在慢性乙型肝炎病毒（HBV）感染患者中评价肝纤维化非创伤性诊断模型的诊断价值,为其在临床诊疗上的应用提供参考。方法对131例慢性HBV感染患者进行肝活检的病理学分级、分期,并检测血清指标以计算S指数、SI,FG模型、Hepascore、Forns指数和APRI指数等诊断模型。用受试者工作曲线（ROC）等方法验证和比较各模型的诊断价值。结果各指标组合模型对肝纤维化程度都具有一定诊断价值。其中由γ-谷氨酰转肽酶（GGT）、血小板（PI。T）和白蛋白（Alb）三个常规指标组成的s指数在验证组中表现最佳[S指数：1000×GGT／（PLT×Alb^2）]。其判断有无明显肝纤维化、有无重度肝纤维化和有无早期肝硬化时的ROC曲线下面积（AUC）分别达0．797、0．880和0．881。以S指数〈0．1预测无明显肝纤维化,S指数≥0．5预测存在明显肝纤维化,验证组中40．5％病例可被正确预测。以S指数〈0．3预测无早期肝硬化,S指数≥1．5预测存在早期肝硬化,验证组中68．7％病例可被正确预测。结论肝纤维化非创伤性诊断模型能较好地区分存在明显肝纤维化或早期肝硬化的慢性HBV感染患者,其中以S指数最为简便有效,它的应用可以减少一部分慢性HBV感染患者肝活检的需要。     

Validation and comparison of simple noninvasive indexes for predicting liver fibrosis in HIV-HCV-coinfected patients: ANRS CO3 Aquitaine cohort

BACKGROUND:  Although an increasing number of noninvasive fibrosis markers are available in HCV-monoinfected patients, data on the performance of these tests in HIV-HCV-coinfected patients are lacking.
OBJECTIVE:  To assess the diagnostic performance for predicting hepatic fibrosis stage of four simple and inexpensive noninvasive indexes (FIB-4, APRI, Forns, and platelet count) in HIV-HCV-coinfected patients.
METHODS:  Two hundred consecutive HIV-HCV-coinfected patients from the ANRS-CO3 Aquitaine cohort who underwent liver biopsy were studied. Fibrosis stage was assessed according to Metavir scoring system by a single pathologist unaware of the data of the patients. Diagnostic performances were assessed by measuring the areas under the receiver operating characteristic curves (AUROC) and the percentage of patients correctly identified (PCI).
RESULTS:  For predicting significant fibrosis (F ≥ 2), APRI, Forns index, and FIB-4 had AUROCS of 0.77, 0.75, and 0.79, with 39%, 25%, and 70% of PCI, respectively. For predicting severe fibrosis (F ≥ 3), FIB-4 had AUROC of 0.77 with 56% of PCI. For predicting cirrhosis (F4), FIB-4, APRI, and platelet count had AUROCs of 0.80, 0.79, and 0.78, with 59%, 60%, and 76% of PCI, respectively. Overall, diagnostic performances of the different indexes did not differ significantly for both significant fibrosis and cirrhosis.
CONCLUSION:  The use of these noninvasive indexes could save liver biopsies in up to 56–76% of cases for the prediction of severe fibrosis-cirrhosis. However, given the high percentage of misclassified cases for significant fibrosis, such indexes do not appear currently suitable for use in clinical practice in HIV-HCV-coinfected patients.     

Non-invasive fibrosis markers for assessment of liver fibrosis in chronic hepatitis delta

Assessment of liver fibrosis by non-invasive means is clinically important. Studies in chronic hepatitis delta (CHD) are scarce. We evaluated the performance of eight serum fibrosis markers [fibrosis-4 score (FIB-4), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), age-platelet index (API), AST-to platelet-ratio-index (APRI), Goteborg University Cirrhosis Index (GUCI), Lok index, cirrhosis discriminant score (CDS) and Hui score] in CHD and chronic hepatitis B (CHB). Liver stiffness was assessed by transient elastography (TE) in CHD. The ability of fibrosis markers to detect significant fibrosis and cirrhosis were evaluated in 202 CHB and 108 CHD patients using published and new cut-offs through receiver operating characteristics (ROC) analysis. The latter was also applied to obtain cut-offs for TE. APRI, Fib-4, API and Hui score were assessed for significant fibrosis, and APRI, GUCI, Lok index, CDS and AAR for cirrhosis determination. Fibrosis markers displayed weak performance in CHB for significant fibrosis with area under ROC (AUROC) curves between 0.62 and 0.71. They did slightly better for CHD. TE displayed an AUROC of 0.92 and performed better than serum fibrosis markers (p < 0.05 for fibrosis markers). For cirrhosis determination, CDS and Lok Index displayed an AUROC of 088 and 0.89 in CHB and GUCI, Lok index and APRI displayed AUROCs around 0.90 in CHD. TE displayed the best AUROC (0.95). Hence TE is superior to serum fibrosis markers for diagnosing significant liver fibrosis and cirrhosis. GUCI, Lok index and APRI displayed a reasonable performance in CHD, which needs further confirmation.     

A novel noninvasive index for the prediction of moderate to severe fibrosis in chronic hepatitis B patients

BackgroundsThe evaluation of liver fibrosis stages is essential for the clinical management of chronic hepatitis B (CHB).AimsTo develop and validate a novel noninvasive index for moderate to severe fibrosis (≥S2) in CHB patients.MethodsA total of 401 CHB patients who underwent liver biopsy were divided into the training (n = 300) and validation (n = 101) cohort. Histological severity was scored using a modified Scheuer system. Clinical and laboratory assessments were collected.ResultsIn the training cohort, PACG, a novel index combining the quantitative hepatitis B core antibody (qAnti-HBc), platelet count (PLT), and albumin globulin ratio (A/G), presented better diagnostic performance (AUROC = 0.814) than that of APRI (0.735, p = 0.007) and FIB-4 (0.749, p = 0.014). In the validation cohort, the AUROC of the PACG, APRI, FIB-4 and Fibroscan were 0.834, 0.806, 0.791 and 0.810, respectively. More importantly, a higher and lower cutoff of PACG for predicting ≥S2 fibrosis or not had a >90% sensitivity and specificity, with a diagnostic accuracy of 85.9%.ConclusionPACG is a promising noninvasive alternative to liver biopsy in CHB patients for the evaluation of moderate to severe fibrosis.     

肝脏剪切波弹性成像对慢性乙型肝炎患者肝纤维化的评估价值

目的 探讨应用剪切波弹性成像(SWE)诊断慢性乙型肝炎(CHB)患者肝纤维化的效能.方法 2017年1月～2020年1月我院收治的CHB患者76例,使用超声检测肝脏杨氏模量值,同时行肝活检病理学检查.计算谷草转氨酶/血小板比率指数(APRI)和肝纤维化-4因子指数(FIB-4).采用多因素Logistic回归分析影响肝...     

Validation of Non-invasive Fibrosis Scores for Predicting Advanced Fibrosis in Metabolic-associated Fatty Liver Disease

Background and AimsMetabolic-associated fatty liver disease (MAFLD) is a newly proposed terminology from 2020; yet, the applicability of conventional noninvasive fibrosis models is still unknown for it. We aimed to evaluate the performance of conventional noninvasive fibrosis scores in MAFLD.MethodsThe NHANES 2017-2018 datasets were used to compare the performances of different noninvasive fibrosis scores in MAFLD, including the aspartate aminotransferase (AST) to platelet ratio index (APRI), body mass index (BMI)-AST/alanine aminotransferase (ALT) ratio and diabetes score (BARD), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS). Moreover, Asian patients with biopsy-proven MAFLD were enrolled to further validate the findings.ResultsA total of 2,622 participants in the National Health and Nutrition Examination Survey (NHANES) cohort and 293 patients with MAFLD in the Asian cohort were included. Patients in the Asian cohort had a lower BMI and higher liver enzymes (p<0.001). The area under the receiver operating characteristic curve (AUROC) of NFS was the largest in the NHANES cohort and Asian cohorts (0.679 and 0.699, respectively). The AUROC of NFS was followed by APRI, FIB-4, and BARD in the NHANES cohort (0.616, 0.601, and 0.589, respectively). In the Asian cohort, the AUROC of APRI, FIB-4, and BARD for predicting advanced fibrosis were 0.625, 0.683, and 0.615, respectively. The performance of FIB-4 was better in the Asian cohort than that in the NHANES cohort.ConclusionsNFS is better for predicting advanced fibrosis in MAFLD. FIB-4 can be an alternative choice for MAFLD with high liver enzymes when NFS is unavailable. Novel efficient noninvasive fibrosis scoring systems are highly required for patients with MAFLD.     

The gamma‐glutamyl transpeptidase‐to‐albumin ratio predicts significant fibrosis and cirrhosis in chronic hepatitis B patients

Background/Aim Simple, inexpensive and clinically available noninvasive liver fibrosis tests are highly needed. We aimed to develop a novel noninvasive index for predicting significant fibrosis and cirrhosis in chronic hepatitis B (CHB) patients. Methods Using liver histology as gold standard, we developed a novel index to predict significant fibrosis and cirrhosis in CHB patients and then compared the diagnostic accuracy of the novel index, aspartate transaminase‐to‐platelet ratio index (APRI), and fibrosis index based on four factors (FIB‐4) in a training set (606 patients) and a validation set (216 patients) from the same patient catchment area. Results Of 606 CHB patients in the training set, 33.2% had significant fibrosis and 11.4% had cirrhosis. In multivariable analysis, gamma‐glutamyl transpeptidase (GGT) (OR=1.032, p<0.001) and albumin (OR=0.953, p=0.048) were independent predictors of significant fibrosis. Consequently, a GGT‐to‐albumin ratio (GAR) was developed. In the training set, the area under the receiver operating characteristic curve (AUROC) of GAR was significantly higher than that of APRI and FIB‐4 to predict ≥F2 (0.82, 0.70, and 0.68, respectively), ≥F3 (0.86, 0.76, and 0.75, respectively), and F4 (0.88, 0.75, and 0.73, respectively), respectively. In the validation set, the AUROC of GAR was also better than APRI and FIB‐4 for predicting ≥F2 (0.81, 0.63 and 0.61, respectively), ≥F3 (0.88, 0.78, and 0.76, respectively) and F4 (0.92, 0.85, and 0.78, respectively), respectively. Conclusions GAR is a more accurate noninvasive index than APRI and FIB‐4 to stage significant fibrosis and cirrhosis in CHB patients and represents a novel noninvasive alternative to liver biopsy.     

FibroScan分别与GPR、APRI、NFS、FIB-4联合应用对慢性乙型肝炎合并非酒精性脂肪性肝病进展期肝纤维化的诊断价值比较

目的评价FibroScan、GPR、APRI、NFS、FIB-4单独应用及FibroScan分别与GPR、APRI、NFS、FIB-4联合应用对慢性乙型肝炎(CHB)合并非酒精性脂肪性肝病(NAFLD)患者进展期肝纤维化的诊断价值。方法选取2014年11月-2018年8月在四川省人民医院行肝穿刺病理检查并确诊为CHB合并NAFLD的患者92例。根据肝穿刺病理SAF分级诊断标准,分为轻中度肝纤维化(F1+F2)组(n=69)和进展期肝纤维化(F3)组(n=23)。同时应用FibroScan测得肝脏硬度值,根据临床指标分别计算GPR、APRI、NFS、FIB-4。计量资料两组间比较采用Mann-Whitney U检验;相关性分析采用Spearman秩相关;多因素二元logistic回归构建联合预测因子(向前逐步回归法),绘制受试者工作特征曲线(ROC曲线),计算ROC曲线下面积(AUC),并采用Delong方法进行比较,评价各种无创诊断方法单独及联合应用对CHB合并NAFLD进展期肝纤维化的诊断价值。结果轻中度肝纤维化组的FibroScan、GPR、APRI、NFS及FIB-4水平明显低于进展期肝纤维化组(Z值分别为-4.910、-3.425、-3.837、-3.873、-3.990,P值均<0.05)。相关性分析结果显示,FibroScan、GPR、APRI、NFS、FIB-4与肝纤维化病理分期均呈正相关(r值分别为0.518、0.361、0.405、0.407、0.418,P值均<0.001)。FibroScan、GPR、APRI、NFS及FIB-4单独应用对诊断进展期肝纤维化均有一定价值(AUC分别为0.844、0.740、0.770、0.771、0.779,P值均<0.001),但FibroScan诊断价值并不优于GPR、APRI、NFS、FIB-4(P值均>0.05)。将FibroScan分别与GPR、APRI、NFS、FIB-4联合,诊断进展期肝纤维化的AUC均较单独应用时明显提高(Z值分别为1.977、2.076、2.361、2.206,P值均<0.05);将FibroScan与GPR+APRI+NFS+FIB-4同时联合诊断进展期肝纤维化的AUC及95%可信区间为0.896(0.813~0.950)。结论FibroScan、GPR、APRI、NFS及FIB-4诊断进展期肝纤维化均有一定的临床价值,FibroScan分别与GPR、APRI、NFS、FIB-4联合诊断进展期肝纤维化的效能优于单项血清学模型,其中FibroScan联合NFS或FIB-4的临床价值可能最佳。     

Value of gamma-glutamyltranspeptidase-to-platelet ratio in diagnosis of hepatic fibrosis in patients with chronic hepatitis B

AIM To investigate the value of the gamma-glutamyltraspeptidase(GGT)-to-platelet(PLT) ratio(GPR) in the diagnosis of hepatic fibrosis in patients with chronic hepatitis B(CHB). METHODS We included 390 untreated CHB patients in this study. The GPR, aspartate aminotransferase(AST)-to-PLT ratio index(APRI), and fibrosis-4(FIB-4) of all patients were analysed to determine if these parameter were correlated with age, gender, medical history, liver function [total bilirubin(TBil), alanine aminotransferase(ALT), and AST], GGT, PLT count, or hepatic fibrosis stage. The GPR, APRI, and FIB-4, as well as the combination of the GPR and APRI or the GPR and FIB-4 were assessed in different cirrhosis stages using receiver operating characteristic(ROC) curve analysis to evaluate their value in diagnosing hepatic fibrosis in CHB patients. RESULTS The GPR, APRI, and FIB-4 were not correlated withCHB patients' age, gender, or disease duration(P 0.05), but all of these parameters were positively correlated with serum ALT, AST, GGT, and PLT count(P 0.01). Additionally, the GPR, APRI, and FIB-4 were positively correlated with hepatic fibrosis(P 0.01); the areas under the ROC curve for the GPR in F1, F2, F3, and F4 stages were 0.723, 0.741, 0.826, and 0.833, respectively, which were significantly higher than the respective values for the FIB-4 and APRI(F1: 0.581, 0.612; F2: 0.706, 0.711; F3: 0.73, 0.751; and F4: 0.799, 0.778). The respective diagnostic cut-off points for each stage were 0.402, 0.448, 0.548, and 0.833, respectively. The diagnostic sensitivity and specificity were, respectively, 88.8% and 87.5% in F1, 72.7% and 89.7% in F2, 81.3% and 98.6% in F3, and 80% and 97.4% in F4 when the GPR and APRI were connected in parallel; 86.6% and 90.2%, 78.4% and 96%, 78.6% and 97.4%, and 73.2% and 97.9%, respectively, when the GPR and APRI were connected in series; 80.2% and 89%, 65% and 89%, 70.3% and 98.5%, and 78.8% and 96.8%, respectively, when the GPR and FIB-4 were connected in parallel; and 83.6% and 87.9%, 76.8% and 96.6%, 72.7% and 98%, and 74.4% and 97.7%, respectively, when the GPR and FIB-4 were connected in series.CONCLUSION The GPR, as a serum diagnostic index of liver fibrosis, is more accurate, sensitive, and easy to use than the FIB-4 and APRI, and the GPR can significantly improve the sensitivity and specificity of hepatic fibrosis diagnosis in CHB when combined with the FIB-4 or APRI.     

超声弹性成像结合血清学指标诊断慢性乙型肝炎患者肝纤维化价值评价

目的 探讨应用超声弹性成像结合血清学指标诊断慢性乙型肝炎(CHB)患者肝纤维化的价值。方法 2015年1月～2018年6月我院诊治的CHB患者358例,接受肝穿刺和超声检查,记录肝组织剪切波速度(SWV),使用化学发光免疫分析仪测定血清透明质酸(HA)、Ⅳ型胶原(ⅣⅣ-Col)和Ⅲ型前胶原(PⅢNP),计算天冬氨酸氨基转移酶/血小板比值(APRI)和基于四因子指数(FIB-4),应用多因素Logistic回归分析影响肝纤维化发生的独立危险因素,应用受试者工作特征(ROC)曲线下面积(AUC)评估各项指标诊断肝纤维化的准确性。 结果 经肝组织病理学检查,发现F0期42例,F1期96例,F2期86例,F3期72例和F4期62例;220例≥F2期患者肝组织SWV为(3.12±0.65)m/s,显著大于138例≤F1期患者【(1.72±0.51)m/s,P<0.05】;≥F2期患者血清HA水平为(128.1±14.7)μg/L,显著高于≤F1期患者【(75.4±10.1)μg/L,P<0.05】,AST/ALT比值为(0.96±0.41),显著大于≤F1期患者【(0.80±0.27),P<0.05】,血清Ⅳ-Col水平为(36.7±14.3)μg/L,显著高于≤F1期患者【(24.9±9.2)μg/L,P<0.05】,APRI评分为(0.83±0.52)分,显著大于≤F1期患者【(0.61±0.49)分,P<0.05】,FIB-4指数为(1.70±0.98),显著大于≤F1期患者【(1.23±0.67),P<0.05】;多因素Logistic回归分析结果表明,SWV、AST/ALT比值、HA、Ⅳ-Col、APRI和FIB-4为影响肝纤维化发生的危险因素(P<0.05),SWV诊断肝纤维化的正确率为86.9%,血清HA为84.2%,APRI和FIB-4分别为82.5%和81.8%。结论 应用SWV联合血清学指标可提高CHB患者肝纤维化诊断的准确性,值得进一步研究。     

Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis

The aspartate aminotransferase-to-platelet ratio index (APRI), a tool with limited expense and widespread availability, is a promising noninvasive alternative to liver biopsy for detecting hepatic fibrosis. The objective of this study was to update the 2007 meta-analysis to systematically assess the accuracy of APRI in predicting significant fibrosis, severe fibrosis, and cirrhosis stage in hepatitis C virus (HCV) monoinfected and HCV / human immunodeficiency virus (HIV) coinfected individuals. Studies comparing APRI versus biopsy in HCV patients were identified via a thorough literature search. Areas under summary receiver operating characteristic curves (AUROC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to examine the APRI accuracy for the diagnosis of significant fibrosis, severe fibrosis, and cirrhosis. Heterogeneity was explored using meta-regression. Twenty-one additional studies were eligible for the update and, in total, 40 studies were included in this review (n = 8,739). The summary AUROC of the APRI for the diagnosis of significant fibrosis, severe fibrosis, and cirrhosis were 0.77, 0.80, and 0.83, respectively. For significant fibrosis, an APRI threshold of 0.7 was 77% sensitive and 72% specific. For severe fibrosis, a threshold of 1.0 was 61% sensitive and 64% specific. For cirrhosis, a threshold of 1.0 was 76% sensitive and 72% specific. Moreover, we found that the APRI was less accurate for the identification of significant fibrosis, severe fibrosis, and cirrhosis in HIV/HCV coinfected patients. CONCLUSION: Our large meta-analysis suggests that APRI can identify hepatitis C-related fibrosis with a moderate degree of accuracy. Application of this index may decrease the need for staging liver biopsy specimens among chronic hepatitis C patients.     

The validity of serum markers for fibrosis staging in chronic hepatitis B and C

Assessment of liver fibrosis is critical for successful individualized disease management in persons with chronic hepatitis B (CHB) or chronic hepatitis C (CHC). We expanded and validated serum marker indices to provide accurate, reproducible and easily applied methods of fibrosis assessment. Liver biopsy results from over 284 CHB and 2304 CHC patients in the Chronic Hepatitis Cohort Study (‘CHeCS') were mapped to a F0–F4 equivalent scale. APRI and FIB‐4 scores within a 6‐month window of biopsy were mapped to the same scale. A novel algorithm was applied to derive and validate optimal cut‐offs for differentiating fibrosis levels. For the prediction of advanced fibrosis and cirrhosis, the FIB‐4 score outperformed the other serum marker indices in the CHC cohort and was similar to APRI in the CHB cohort. The area under the receiver operating characteristic curves (AUROC) for FIB‐4 in differentiating F3–F4 from F0–F2 was 0.86 (95% CI: 0.80–0.92) for CHB and 0.83 (95% CI: 0.81–0.85) for CHC. The suggested cut‐offs based on FIB‐4 model produced high positive predictive values [CHB: 90.0% for F0–F2, 100.0% for cirrhosis (F4); CHC: 89.7% for F0–F2; 82.9% for cirrhosis (F4)]. In this large observational cohort, FIB‐4 predicted the upper and lower end of liver fibrosis stage (cirrhosis and F0–F2, respectively) with a high degree of accuracy in both CHB and CHC patients.     

Évaluation non invasive de la fibrose hépatique au cours des co-infections VIH et VHC et/ou VHB

Liver fibrosis must be evaluated during the diagnosis and follow-up of patients with chronic hepatitis. This evaluation is usually based on the histological analysis of liver biopsies, but in recent years, noninvasive methods have been developed to assess liver fibrosis, including various blood tests and FibroScan®. Blood tests use a combination of biological markers and are effective to diagnose liver fibrosis. APRI and FibroTest® have both demonstrated accuracy in HIV/HCV coinfected patients similar to that in monoinfected HCV patients. FibroMètre®, FibroTest® and Hepascore have similar AUROC measurements, which are higher than those produced by APRI in HIV/HCV coinfected and HBV patients. Measuring liver stiffness (FibroScan®) is an accurate method for the diagnosis of cirrhosis. It is simple to perform but costly.     

Acoustic Radiation Force Impulse Elastography with APRI and FIB-4 to Identify Significant Liver Fibrosis in Chronic Hepatitis B Patients

Introduction and aim. In chronic hepatitis B (CHB) patients with equivocal indication for antiviral therapy, therapeutic decision currently depends on histopathology of the liver. We aimed to evaluate if acoustic radiation force impulse (ARFI) in conjunction with aspartate transaminase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) score could replace liver biopsy to indicate treatment for CHB.Material and methods. We prospectively enrolled 101 clinically non-cirrhotic patients whose serum alanine aminotransferase was mildly elevated (1-2 folds above the upper normal limit) despite a high viral load (HBV DNA > 2,000 IU/mL). All participants underwent liver biopsy, and measurement of ARFI, APRI and FIB-4. The ability of the markers to distinguish fibrosis ≥ METAVIR F2 was evaluated.Results. According to histopathology, liver fibrosis was METAVIR F0 in 2 (2.0%), F1 in 43 (42.6%), F2 in 34 (33.7%), F3 in 16 (15.8%), and F4 in 6 (5.9%) patients, and was correlated with ARFI (p = 0.0001), APRI (p = 0.012), and FIB-4 (p = 0.004). The six patients with cirrhosis were included for analysis, and received antiviral therapy. The C statistics of ARFI, APRI, and FIB-4 for fibrosis ≥ F2 were 0.70 (95% confidence interval [CI], 0.59-0.80), 0.62 (95% CI, 0.51-0.73), and 0.64 (0.53-0.75), respectively. The cut-off values for 95% sensitivity and 95% specificity to identify significant fibrosis were 0.97 m/sec and 1.36 m/sec for ARFI, 0.36 and 1.0 for APRI, 0.63 and 2.22 for FIB-4, respectively. Using a combination of these 3 indices, 44 patients (43.6%) could be spared a liver biopsy procedure.Conclusions. A combination of ARFI, APRI, and FIB-4 may spare some CHB patients with equivocal indication for antiviral treatment a liver biopsy.     

Comparison of noninvasive models of fibrosis in chronic hepatitis B

Background and goals

Liver fibrosis influences treatment and surveillance strategies in chronic hepatitis B (CHB). This multicenter study aimed to examine the accuracy of serum fibrosis models in CHB patients including those with low alanine aminotransferase (ALT) levels and serially in those undergoing treatment.

Method

We examined noninvasive fibrosis models [Hepascore, Fibrotest, APRI, hepatitis e antigen (HBeAg)-positive and -negative models] in 179 CHB patients who underwent liver biopsy and fibrosis assessment by METAVIR and image morphometry. Serial Hepascore measurements were assessed in 40 subjects for up to 8.7?years.

Results

Hepascore was more accurate than Fibrotest [area under the curve (AUC) 0.83 vs. 0.72, P?=?0.05] and HBeAg-positive model (AUC 0.83 vs. 72, P?=?0.03) for significant fibrosis but was not significantly different to APRI or HBeAg-negative scores. Fibrosis area assessed by morphometry was correlated with Hepascore (r?=?0.603, P?<?0.001), Fibrotest (r?=?0.392, P?=?0.03), and HBeAg-positive (r?=?0.492, P?=?0.001) scores only. Among 73 patients with an ALT <60?IU/L, noninvasive models were useful to predict fibrosis (PPV 80?C90%) or exclude significant fibrosis (NPV 79?C100%). Hepascore increased significantly among patients monitored without treatment and reduced among patients undergoing therapy (0.05/year?±?0.03 vs. ?0.04/year?±?0.02, P?=?0.007).

Conclusions

Serum fibrosis models are predictive of fibrosis in CHB and assist in identifying subjects with low?Cnormal ALT levels for treatment.