从常规指标中建立肝纤维化非创伤性诊断模型

目的在慢性乙型肝炎病毒（HBV）感染患者中建立基于常规实验室指标的肝纤维化非创伤性诊断模型,为传统的肝穿刺活检提供简便的非创伤性替代手段。方法采用Logistic回归等方法分析386例慢性HBV感染患者的常规实验室指标与肝纤维化分期的关系,建立诊断模型。用受试者工作曲线（ROC）等方法验证和比较该模型与Forns指数、APRI指数、Hepascore及SLFG模型的诊断价值。结果各指标组合模型对肝纤维化分期的诊断价值优于单项常规实验室指标,其中SLFG模型、S指数和Hepascore均具有较好的表现。由γ-谷氨酰转肽酶（GGT）、血小板（PLT）和白蛋白（Alb）三个常规指标组成的S指数（S指数=1000×GGT/（PLT×Alb2））判断有无明显肝纤维化和有无早期肝硬化时的受试者工作曲线下面积（AUC）分别达到0.686和0.762。使用以下推荐界值,S指数〈0.1预测无明显肝纤维化的灵敏度为90.4%,S指数≥0.5预测存在明显肝纤维化的特异度为86.2%;S指数〈0.3预测无早期肝硬化的灵敏度为84.8%,S指数≥1.5预测存在早期肝硬化的特异度为97.7%。结论由常规实验室指标建立的简单组合S指数,能较准确而方便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。     

AAR和API评估慢性乙型病毒性肝炎肝纤维化临床价值的比较

目的比较谷草转氨酶-谷丙转氨酶的比值（AAR）和年龄-血小板指数（API）对慢性乙型病毒性肝炎肝纤维化的临床价值。方法172例慢性乙型病毒性肝炎患者均接受肝组织病理检查，并同时检测肝功能和血常规，用ROC曲线评价AAR和API诊断慢性乙型病毒性肝炎肝纤维化的能力。结果肝纤维化S0、S1、S2、S3和S4的AAR无显著差异（P〉0．05），肝纤维化分期与AAR的相关系数（rs）=0．107（P〉0．05），ROC曲线分析显示AAR诊断显著肝纤维化和肝硬化的AUC均〈0．7；肝纤维化S4的API高于S0、S1、S2和s3（P〈0．01），肝纤维化分期与API的rs=0．314（P〈0．01），ROC曲线分析显示API诊断显著肝纤维化的AUC〈0．7（P〉0．05），但诊断肝硬化的AUC达到0．773（P〈0．01），敏感度（SN）达到70．83％，特异度（sP）达到72．18％。结论AAR对于评估慢性乙型病毒性肝炎肝纤维化的临床价值不大；API与肝纤维化分期有一定的相关性，可以用于肝纤维化S4的诊断，但对肝纤维化s1、s2和s3的区分能力有限。     

GGT/Alb比值对慢性HBV感染者肝纤维化的无创诊断价值

目的评价GGT/Alb比值对慢性HBV感染者肝纤维化程度的无创诊断价值。方法回顾分析2018年1月—2020年3月安徽医科大学附属巢湖医院经肝穿刺活检的慢性HBV感染者资料。根据肝穿刺病理检查结果,将322例患者按照肝纤维化程度分为S0～1(183例)、S2(68例)、S3(35例)、S4(36例)。收集患者的血常规、病毒学、血生化等临床指标。正态分布的计量资料多组间比较采用单因素方差分析,非正态分布的计量资料多组间比较采用Kruskal-Wallis H秩和检验;计数资料采用χ~2检验。采用Spearman等级相关分析评估3种无创模型GGT/Alb比值、APRI评分和FIB-4指数与肝纤维化程度的相关性。绘制GGT/Alb比值的受试者工作特征曲线(ROC)评价其诊断价值。结果随着肝纤维化程度的加重,患者的Alb(F=7.351)、HBV DNA(χ~2=2.820)和PLT(F=6.182)逐渐降低,而年龄(χ~2=3.145)、GGT(χ~2=6.149)、GGT/Alb比值(χ~2=7.064)、APRI评分(χ~2=9.022)和FIB-4指数(χ~2=8.254)逐渐升高,差异有统计学意义(P值均0.05)。Spearman等级相关性分析得出,GGT/Alb比值与肝纤维化分期呈正相关(r=0.396,P 0.01),其相关系数高于APRI评分(r=0.327,P 0.01)和FIB-4指数(r=0.370,P 0.01)。ROC曲线结果显示,在显著肝纤维化、严重肝纤维化和肝硬化患者中,GGT/Alb比值的ROC曲线下面积(AUC)(分别为0.680、0.676、0.695)与APRI评分(AUC分别为0.692、0.698、0.728)和FIB-4指数(AUC分别为0.659、0.661、0.684)相当,差异均无统计学意义(P值均 0.05)。GGT/Alb比值分别以0.435、0.465和0.465为截断值,其用于诊断显著肝纤维化、严重肝纤维化和肝硬化患者的灵敏度分别为69.1%、66.2%和69.0%,特异度分别为65.4%、65.9%和67.0%。结论与APRI评分和FIB-4指数一样,GGT/Alb比值是一种简单、实用的肝纤维化无创诊断模型,可以对慢性HBV感染者肝纤维程度的诊断提供参考价值。     

血清学指标和瞬时弹性成像技术联合诊断慢性乙型肝炎纤维化和预测肝硬化食管静脉曲张程度的价值

目的分析对慢性乙型肝炎及肝硬化患者予以瞬间弹性成像技术、血清学指标、肝组织活检的临床诊断效果。方法选择2017年2月至2018年6月住院的142例慢性乙型肝炎感染患者,行血清学指标、胃镜、瞬时弹性成像与肝组织活检,对患者的血清学指标、肝炎肝纤维化程度等检查指标进行分析,并探讨各指标的临床应用价值。结果肝纤维化S2～S4期患者的AST、ALT、TBil、PLT、Glb、肝纤维化四项、APRI及FIB-4指数、LSM值与肝纤维化S0～S1期的患者相比,均存在明显差异(P0.05)。乙型肝炎肝硬化合并重度食管静脉曲张者LSM值明显高于未合并静脉曲张的肝硬化患者(P0.05)。ROC曲线下面积分析显示,LSM值、HA及FIB-4指数、APRI指数对肝纤维化的诊断效能最高,而APRI指数、LSM值对乙型肝炎肝硬化食管静脉曲张的预测效能最佳。经Logistic多元线性回归分析,HA、LSM值是乙型肝炎肝纤维化的影响因素,APRI、LSM值是乙型肝炎肝硬化食管静脉曲张的影响因素。结论血清学指标与瞬间弹性成像技术对诊断乙型肝炎肝纤维化程度,预测肝硬化食管静脉曲张程度有较高的应用价值。     

ARFI、Forns指数、FIB-4和APRI无创诊断慢性乙型病毒性肝炎肝纤维化的研究

目的声辐射力脉冲成像技术(ARFI)及血清学诊断模型(Forns指数、FIB-4、APRI)对慢性乙型病毒性肝炎肝纤维化评估的价值。方法 111例确诊为慢性乙型病毒性肝炎患者,根据肝组织活检病理分期结果分组:无明显肝纤维化组(S0、S1)40例,明显肝纤维化组(≥S2)48例、早期肝硬化组(S4)23例。每例患者同期进行ARFI、Forns指数、FIB-4、APRI的评估。比较无创诊断模型与肝脏病理的相关性,并根据受试者工作特征曲线(ROC)分析无创诊断模型对肝纤维化的诊断价值。结果ARFI、Forns指数、FIB-4、APRI 4种无创诊断方法与肝组织活检具有良好的一致性,其皮尔逊相关系数(Pearson correlation coefficient)分别为0.882、0.639、0.589、0.418。明显肝纤维化组(≥S2)及早期肝硬化组,ARFI的诊断价值均优于FIB-4(Z=2.882,P=0.004;Z=3.215,P=0.001)、APRI(Z=4.850,P0.001;Z=3.198,P=0.001)、Forns指数(Z=2.182,P=0.029;Z=2.798,P=0.005)。结论 ARFI对明显肝纤维化及早期肝硬化的诊断具有较高的价值,值得推广。     

白细胞介素-34、血小板、谷氨酰转肽酶及白蛋白和球蛋白的比值联合诊断模型评估慢性乙型肝炎肝纤维化的价值

目的探究白细胞介素-34(IL-34)、血小板(PLT)、谷氨酰转肽酶(GGT)以及白蛋白和球蛋白的比值(A/G)在慢性乙型肝炎患者中的水平及其诊断严重纤维化和早期肝硬化的价值。方法选择2015年8月至2018年2月在无锡市第五人民医院就诊的214例患者作为研究对象,均行肝脏穿刺术确定其肝纤维化程度。采用酶联免疫吸附法检测IL-34水平,采用血细胞分析仪检测血液中PLT水平,采用全自动生物化学分析仪检测GGT水平,采用琼脂糖电泳法检测蛋白电泳,并计算A/G。探究IL-34、PLT、GGT和A/G与肝纤维化程度的相关性,以及诊断严重纤维化和早期肝硬化的效能。结果慢性乙型肝炎患者血清IL-34、GGT水平随肝纤维化程度加重而升高,血清PLT水平和A/G随肝纤维化程度加重而降低。由IL-34、PLT、GGT和A/G构成的肝纤维化程度诊断模型(模型A)对严重肝纤维化和早期肝硬化均有较高的诊断效能。模型A诊断严重肝纤维化的效能高于IL-34、PLT、GGT、A/G、FIB-4和S指数。模型A诊断早期肝硬化的效能高于IL-34、PLT、GGT、A/G和FIB-4。结论由IL-34、PLT、GGT和A/G构成的肝纤维化程度诊断模型能够较为准确地评估肝纤维化程度,重复性较高,便于临床动态监测肝纤维化程度。     

GGT/PLT比值对广东地区慢性乙型肝炎患者肝纤维化分期的预测价值

目的探讨GGT/PLT比值(GPR)预测广东地区慢性乙型肝炎患者肝纤维化分期的价值。方法收集2010年1月-2016年12月于广州市第八人民医院行肝活组织检查诊断为慢性乙型肝炎的患者501例,其中HBe Ag阳性335例,HBe Ag阴性166例。分析比较GPR、GGT、AST/PLT指数(APRI)及FIB-4对肝纤维化分期(F1~F4)的预测价值。Spearman相关系数分析诊断模型指标与肝纤维化分期的相关性,采用受试者工作特征(ROC)曲线下面积评估各模型对肝纤维化分期的预测价值。结果肝活组织病理检查作为金标准,F1~F4期患者分别为141、183、139、38例。Spearman相关分析显示,HBe Ag阳性和HBe Ag阴性患者GGT、GPR、APRI和FIB-4均与肝纤维化分期呈正相关(r值分别为0.459、0.526、0.320、0.470、0.272、0.366、0.288、0.388,P值均0.001),PLT与肝纤维化分期呈负相关(r值分别为-0.333、-0.349,P值均0.001)。ROC曲线分析结果显示,GPR对于HBe Ag阳性慢性乙型肝炎患者明显肝纤维化(≥F2)、进展期肝纤维化(≥F3)及早期肝硬化(F4)的预测价值优于GGT和APRI(P值均0.05),而与FIB-4的预测价值相近(P值均0.05);GPR对于HBe Ag阴性慢性乙型肝炎患者明显肝纤维化(≥F2)的预测价值优于GGT和APRI(P值均0.05),对进展期肝纤维化(≥F3)的预测价值优于GGT(P0.05),而对早期肝硬化(F4)的预测价值与GGT、APRI、FIB-4相近(P值均0.05)。结论 GPR可以作为广东地区慢性乙型肝炎患者肝纤维化分期的无创生化预测指标,尤其是对于HBe Ag阳性患者,其预测价值与FIB-4相近,亦不亚于APRI。     

慢性乙型肝炎肝纤维化无创性诊断模型的建立

目的建立由临床及血清指标组成的综合诊断模型，以无创性的评估慢性乙型肝炎肝纤维化。方法慢性乙型肝炎患者270例，随机分成模型组（195例）和验证组（75例），均行肝活组织检查及病理分期，并按纤维化程度设定不同判别终点（≥S2，≥S3，S4），同时检测、记录26项临床和实验室常用指标，包括年龄、性别、血常规、生化、凝血酶原时间、病毒载量及血清纤维化四项标志物等参数。在模型组，对指标依次行单因素分析和多因素Logistic回归分析，筛选出与研究终点相关的独立预测因子，在此基础上构建诊断肝纤维化的指数模型，最后在独立的验证组中检验模型的诊断效率。结果在模型组，建立了一个由年龄、血小板计数、γ-谷氨酰转肽酶和透明质酸四项指标构成的判别肝纤维化程度的指数模型（FibroIndex）。受试者工作特征曲线（ROC）分析显示，FibroIndex判别≥s3的ROC曲线下面积（AUC）为0．889，以积分3．0为界值，诊断的敏感性90．2％，特异性76．1％，准确性82．0％，且其积分与肝纤维化分期呈良好的正向线性相关（r=0．731，p〈0．01）I该指数判别≥s2和s4的界值分别为2．2、5．4，诊断的AUC分别为0．873．0．872，敏感性、特异性分别为79％、82％和83％、75％。将FibroIndex以同样标准应用于验证组，其与模型组AUC比较差异无统计学意义，两组的诊断效率总体上相近。结论运用无创诊断模型评价慢性肝炎肝纤维化严重程度具有敏感、准确和可重复性，并有望在一定程度上替代肝活组织检查来监测慢性乙型肝炎肝纤维化的动态变化。     

凝血酶原时间与肝促凝血活酶试验在慢性乙型病毒性肝炎纤维化分期的诊断价值

判断凝血酶原时间（PT）与肝促凝血活酶试验（HPT）诊断慢性乙型病毒性肝炎患者肝纤维化分期的作用.选取72名经肝活检病理证实的慢性乙型病毒性肝炎患者,检测不同肝纤维化分期血浆PT及HPT（分别以秒、活动度、率及国际标准化比率计）,并通过ROC曲线分析两者诊断肝纤维化、早期肝硬化的价值.慢性乙型病毒性肝炎患者S0-S3期PT组间无差异,只有S4期明显升高或降低,且与S0、S1、S2、S3期比较有显著性差异（P＜0.01）.而HPTS0-S2组间无显著性差异外,其它两两比较均有显著性差异（P＜0.01）.通过ROC曲线分析,PTs及HPTs诊断S4的阈值为14.05秒、19.75秒时,敏感度及特异度分别为0.889、0.814;0.889、0.907.PTA及HPTA的诊断阈值为85.5%、70.5%时,诊断S4期的敏感度及特异度分别为0.889、0.814;0.889、0.907.因此,HPT、PT在肝纤维化分期的诊断中有一定的作用,且前者优于后者.     

慢性乙型肝炎肝纤维化非创伤性诊断评分表模型的建立

目的 从慢性乙型肝炎患者的临床、生物化学及影像学等临床常用的非创伤性指标中,构建诊断肝纤维化的评分表模型。方法 374例临床诊断为慢性乙型肝炎患者,行肝组织活检术,常规检查血常规、生物化学、病毒载量、血清透明质酸（HA）、超声检查肝脏及脾脏厚径、年龄等,根据各临床指标在肝组织病理分期的相对比值,制定各变量的分值,构建诊断肝纤维化的评分表模型,用受试者工作特征曲线（ROC曲线）评价评分表模型的诊断预测能力。结果 建模组314例慢性乙型肝炎患者中,由血小板计数、白蛋白/球蛋白（A/G）、脾厚、透明质酸（HA）、年龄5项指标构成判断肝纤维化的评分表模型（SZFibroS模型）。ROC曲线分析显示,SZFibroS ≥ 5.4,诊断≥ S2的敏感性为78.2%,特异性为67.7%,受试者工作特征曲线下面积（AUC）为0.8153。60例验证组验证该模型的准确度为76.7%。结论 运用该非创伤性评分表模型评价慢性乙型肝炎的肝纤维化程度,简单易记、可重复性好,具有较高的敏感性及准确性,可在一定程度上替代肝组织活检来监测慢性乙型肝炎肝纤维化的动态变化。     

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.     

A novel noninvasive algorithm for the assessment of liver fibrosis in patients with chronic hepatitis B virus infection

Several noninvasive blood biomarkers have been established for the assessment of liver fibrosis in patients with chronic hepatitis B virus (HBV) infection, but their clinical performance remains inconclusive. Here, we compared the diagnostic performance of these biomarkers and developed a novel algorithm for assessing liver fibrosis. Six hundred and sixteen chronically HBV‐infected and treatment‐naïve patients who underwent liver biopsy were enrolled and randomly divided into training (N=410) and internal validation cohorts (N=206). One hundred and fifty‐nine patients from another centre were recruited as an external validation cohort. Receiver operating characteristic (ROC) curves were used to analyse the performance of the gamma‐glutamyltransferase‐to‐platelet ratio (GPR), red cell volume distribution width‐to‐platelet ratio (RPR), FIB‐4 index, aspartate aminotransferase‐to‐platelet ratio index (APRI) and HBV DNA level against liver histology, and a novel algorithm was developed using the recursive partitioning and regression tree (RPART) method. In the training cohort, the area under the ROC curve of FIB‐4 was significantly higher than that of APRI (P=.038) but was comparable to those of GPR, RPR and HBV DNA; however, the performance of the biomarkers was similar among the validation cohort. The established RPR‐HBV DNA algorithm performed better in the training cohort than any individual blood biomarker, and the corresponding sensitivity, specificity, positive predictive value and negative predictive value were 63%, 90%, 72% and 80%, respectively. In the internal and external validation cohorts, the performance of the algorithm in assessing liver fibrosis was also superior to that of other biomarkers. These results suggest that the established RPR‐HBV DNA algorithm might improve the diagnostic accuracy of liver fibrosis in treatment‐naïve patients with chronic HBV infection, although additional studies are warranted to confirm these findings.     

Serum N-glycan markers for diagnosing liver fibrosis induced by hepatitis B virus

BACKGROUND Hepatitis B virus (HBV) infection is the primary cause of hepatitis with chronic HBV infection,which may develop into liver fibrosis,cirrhosis and hepatocellular carcinoma.Detection of early-stage fibrosis related to HBV infection is of great clinical significance to block the progression of liver lesion.Direct liver biopsy is regarded as the gold standard to detect and assess fibrosis;however,this method is invasive and prone to clinical sampling error.In order to address these issues,we attempted to find more convenient and effective serum markers for detecting HBV-induced early-stage liver fibrosis.AIM To investigate serum N-glycan profiling related to HBV-induced liver fibrosis and verify multiparameter diagnostic models related to serum N-glycan changes.METHODS N-glycan profiles from the sera of 432 HBV-infected patients with liver fibrosis were analyzed.Significant changed N-glycan levels (peaks)(P 0.05) in differentfibrosis stages were selected in the modeling group,and multiparameter diagnostic models were established based on changed N-glycan levels by logistic regression analysis.The receiver operating characteristic (ROC) curve analysis was performed to evaluate diagnostic efficacy of N-glycans models.These models were then compared with the aspartate aminotransferase to platelet ratio index (APRI),fibrosis index based on the four factors (FIB-4),glutamyltranspeptidase platelet albumin index (S index),GlycoCirrho-test,and GlycoFibro-test.Furthermore,we combined multiparameter diagnostic models with alanine aminotransferase (ALT) and platelet (PLT) tests and compared their diagnostic power.In addition,the diagnostic accuracy of N-glycan models was also verified in the validation group of patients.RESULTS Multiparameter diagnostic models constructed based on N-glycan peak 1,3,4and 8 could distinguish between different stages of liver fibrosis.The area under ROC curves (AUROCs) of Model A and Model B were 0.890 and 0.752,respectively differentiating fibrosis F0-F1 from F2-F4,and F0-F2 from F3-F4,and surpassing other serum panels.However,AUROC (0.747) in Model C used for the diagnosis of F4 from F0-F3 was lower than AUROC (0.795) in FIB-4.In combination with ALT and PLT,the multiparameter models showed better diagnostic power (AUROC=0.912,0.829,0.885,respectively) when compared with other models.In the validation group,the AUROCs of the three combined models (0.929,0.858,and 0.867,respectively) were still satisfactory.We also applied the combined models to distinguish adjacent fibrosis stages of 432patients (F0-F1/F2/F3/F4),and the AUROCs were 0.917,0.720 and 0.785.CONCLUSION Multiparameter models based on serum N-glycans are effective supplementary markers to distinguish between adjacent fibrosis stages of patients caused by HBV,especially in combination with ALT and PLT.     

代谢综合征与慢性乙型病毒性肝炎及非酒精性脂肪性肝病患者肝纤维化程度的相关性研究

目的 比较慢性乙型病毒性肝炎患者和非酒精性脂肪性肝病患者代谢综合征患病率,以及代谢综合征对慢性乙型病毒性肝炎患者和非酒精性脂肪性肝病患者肝纤维化进展的影响.方法 对2008年1月至2009年6月在我院就诊的136例慢性乙型病毒性肝炎患者和110例非酒精性脂肪性肝病患者进行回顾性分析,调查其代谢综合征的患病率,测定肝功能及病毒学指标,进行肝脏病理学检查.采用t检验和X~2检验进行统计学分析.结果 代谢综合征总的患病率为28.5%,非酒精性脂肪性肝病患者代谢综合征患病率显著高于慢性乙型病毒性肝炎患者(分别为49.1%和11.8%).肝纤维化分期为S_(0～1)、S_(2～4)的慢性乙型病毒性肝炎患者代谢综合征的患病率分别为3.1%和19.7%(P＜0.01),代谢综合征、体重指数、天门冬氨酸转氨酶、γ-谷氨酰转肽酶及炎症程度均与其肝纤维化程度相关.在非酒精性脂肪性肝病患者中,非酒精性脂肪性肝炎患者代谢综合征患者率高于非酒精性脂肪肝(分别为55.4%和40.0%);纤维化分期为S_(0～1)、S_(2～4)的患者代谢综合征的患病率分别为36.2%和70.7%(P＜0.01);代谢综合征、丙氨酸转氨酶、天门冬氨酸转氨酶、γ-谷氨酰转肽酶及明显炎症均与其肝纤维化严重程度相关.结论 非酒精性脂肪性肝病患者代谢综合征的患病率高于慢性乙型病毒性肝炎患者,这两类患者代谢综合征与肝纤维化程度相关.     

ALT低于2倍正常值上限的慢性HBV感染者肝脏病理结果的预测因素分析

目的探索在ALT2倍正常值上限(2×ULN)的慢性HBV感染人群中,一般临床指标对肝脏病理结果的预测作用。方法收集2009年1月至2013年6月新乡医学院第一附属医院收治的122例ALT2×ULN的慢性HBV感染者,在超声引导下行肝穿刺活组织检查术,判断肝组织炎症活动度及纤维化程度,同期化验肝功能、乙型肝炎血清标志物、HBV DNA等指标,应用Logistic回归分析法探索该类患者的一般临床指标对其肝脏病理结果的预测作用。结果 122名患者中有明显炎症或纤维化(G≥2或S≥2)者共94例(77.0%),早期肝硬化者5例(4.1%)。G2组与G≥2组相比,除HBV DNA外,其余各指标间差异均无统计学意义;S2组与S≥2组相比,年龄、HBeAg、HBV DNA、AST、血小板差异均有统计学意义;Logistic回归分析提示,年龄、HBeAg和AST是肝脏明显纤维化(S≥2)的独立预测因子。结论对血清ALT2×ULN的慢性HBV感染者,年龄40岁、HBeAg阴性、AST40U/L者应积极进行肝穿刺活组织检查术,必要时尽早抗病毒治疗。     

Transient elastography for patients with chronic hepatitis B and C virus infection: Non-invasive, quantitative assessment of liver fibrosis

Aim/Methods: The aim of the present study was to compare the diagnostic performance of transient elastography (FibroScan) with that of serum fibrosis markers and stages of hepatic fibrosis by biopsy in 68 patients with chronic hepatitis B virus (HBV) and in 161 patients with hepatitis C virus (HCV) infection. Results: The serum levels of hyaluronic acid (r = 0.601) and type IV collagen (r = 0.663) significantly positively associated with the FibroScan values (all P < 0.05). Classified by fibrosis stages, the median values of FibroScan were 3.5 kPa for F0, 6.4 kPa for F1, 9.5 kPa for F2, 11.4 kPa for F3, and 15.4 kPa forF4 in patients with chronic HBV infection, and were 6.3 kPa for F0, 6.7 kPa for F1, 9.1 kPa for F2, 13.7 kPa for F3, and 26.4 kPa for F4 in those with chronic HCV infection. The values were significantly correlated with fibrosis stage for both (HBV, r = 0.559, P = 0.0093, and HCV, r = 0.686, P < 0.0001). Conclusion: These results suggest that FibroScan is an efficient and simple method for evaluating liver fibrosis in patients with chronic infection, both for HBV and HCV.     

Serum measures of iron status and HFE gene mutations in patients with hepatitis B virus infection

Aim: We tested associations between HFE mutations and hepatitis B virus (HBV) infection. We also explored measures of total body iron status and their association with chronic HBV infection. Methods: Serum measures of iron status and HFE mutations (C282Y, H63D, and S65C) were assessed in 344 Iranian patients with chronic HBV infection (214 asymptomatic carriers, 130 patients with chronic progressive liver disease [CPLD]) and 302 controls. Results: Frequencies of HFE mutations did not differ between patients with chronic HBV infection and controls (C282Y: P=0.9, H63D: P= 0.8, S65C: P=0.9). By logistic regression, advanced hepatic fibrosis was associated with HFE H63D mutation (OR=13.1, P=0.006; 95% CI=2.0-84.1). Higher levels of serum ferritin and transferrin saturation were observed in patients with CPLD than in healthy controls (P=0.0001 and 0.01, respectively, adjusted for age and sex). None of the serum iron measures was related to liver fibrosis stage or necroinflammatory grade. Conclusion: Serum iron measures are associated with chronic progressive hepatitis B. Carriage of HFE mutations is not associated with the presence of chronic HBV infection or values of serum iron measures in this population, although HFE H63D is associated with more advanced hepatic fibrosis.     

γ-谷氨酰转肽酶/血小板比值对血清转氨酶正常的慢性HBV感染者肝纤维化的预测价值分析*

目的 探讨γ-谷氨酰转肽酶/血小板比值(GPR)预测转氨酶正常的慢性HBV感染者肝纤维化分期的价值。方法 2010年~2016年我院诊治的血清转氨酶正常的慢性HBV感染者202例,经肝活检诊断肝纤维化,计算GPR、AST与PLT比值指数（APRI）和基于4因素的肝纤维化指数（FIB-4）预测明显肝纤维化（≥F2）、进展期肝纤维化（≥F3）和早期肝硬化（F4）的效能。应用ROC曲线下面积（AUC）判断诊断效能。结果 经肝组织病理学检查,本组发现F1、F2、F3和F4 分别为82例、60例、39例和21例;F4组GPR、APRI和FIB-4分别为0.4（0.2,1.0）、（0.6±0.2）和1.6（0.9,1.8）,而F3组分别为0.2（0.2,0.4）、（0.6±0.2）和0.9（0.9,1.2）,F2组则分别为0.2（0.1,0.3）、0.4±0.2和0.9（0.7,1.3）,差异显著（P<0.05）;GPR预测明显肝纤维化（≥F2）、进展期肝纤维化（≥F3）和早期肝硬化（F4）的AUC分别是0.739、0.790和0.824,显著高于APRI（分别为0.547、0.731和0.736,P<0.05）;GPR预测肝纤维化≥F3的AUC为0.790,显著高于FIB-4（0.748,P<0.05）,而FIB-4预测肝纤维化≥F2的AUC为0.777,显著高于GPR（0.739,P<0.05）,FIB-4和GPR预测肝硬化（F4）的效能之间无显著性差异（分别为0.824和0.792,P>0.05）。结论 GPR可以预测转氨酶正常的慢性HBV感染者肝纤维化分期,其效能优于APRI,而与FIB-4相比,各有优缺点。GPR可以作为对转氨酶正常的慢性HBV感染者肝纤维化一个无创生化预测指数。     

FibroScan and ultrasonography in the prediction of hepatic fibrosis in patients with chronic viral hepatitis

Background  The aim of this study was to assess the diagnostic performances of liver stiffness measurement (LSM), ultrasonography (US) and their combined use in predicting the extent of hepatic fibrosis. Methods  Consecutive patients with chronic hepatitis B (HBV) or hepatitis C virus (HCV) infections, with indications for liver biopsy, were prospectively enrolled. LSM was performed on the same day as biopsy. US scores, including assessment of liver surface, liver parenchyma, intrahepatic vessels and spleen index, were used to assess the degree of hepatic fibrosis. The pathological findings were used as a reference standard and diagnostic accuracy was assessed and compared. Results  Three-hundred and twenty patients, including 199 men and 121 women, with a mean age of 50.8 years, were analyzed. There were 214 (66.9%) HCV patients, 88 (27.5%) HBV patients and 18 (5.6%) patients with both HCV and HBV. LSM correlated significantly with the hepatic fibrosis (F) scores, necro-inflammatory activity and US scores in multivariate analysis. The diagnostic accuracy of LSM is significantly superior to US, and equal to combined LSM with US, in the prediction of all HCV-related fibrosis scores. The cut-off value of LSM is 6 kPa for diagnosing F > =1, with a positive predictive value of 91%. Also, the cut-off value is 12 kPa for the prediction of cirrhosis, with a negative predictive value of 94%. Conclusions  LSM is useful for predicting hepatic fibrosis and excluding cirrhosis. A combination of LSM and US does not improve the accuracy in assessing hepatic fibrosis.