丙氨酸转氨酶对FibroScan诊断慢性乙型肝炎肝纤维化分期的影响

目的 探讨慢性乙型肝炎(CHB)患者中,不同水平的ALT对FibroScan诊断不同肝纤维化分期准确性的影响.方法 回顾性分析213例慢性乙型肝炎患者,根据血清ALT水平分为ALT＜1×正常值上限(ULN)、1×ULN≤ALT＜2×ULN和ALT≥2×ULN 3组,分析3组采用FibroScan诊断不同肝纤维化分期的ROC曲线下面积,判断其诊断准确性.根据不同资料采用t检验、x2检验、受试者工作曲线或其曲线下面积(AUROC)进行统计学分析.结果在213例CHB患者中,FibroScan值与不同肝纤维化分期在3组患者中均有明显的相关性(rs值分别为0.773、0.889和0.412,P值均＜0.05).FibroScan诊断2级以上肝纤维化(F≥2,F0～1对比F2～4)和肝硬化(F=4,F0～3对比F4)的AUROC分别为0.916和0.971;其截断值分别为7.0kPa和13.0kPa;准确度分别为84.0%和93.4%.其诊断F≥2的AUROC和准确度均低于肝硬化.ALT＜1×ULN、1×ULN≤ALT＜2×ULN和ALT≥2×ULN 3组在诊断明显肝纤维化的AUROC分别为0.939、0.967和0.687,其敏感度分别为90.0%、89.7%和47.8%;准确度为90.5%、93.9%和68.4%.ALT≥2×ULN组的AUROC、敏感度和准确度明显低于另两组;而ALT＜2×ULN两组的AUROC和准确度相近.ALT＜1×ULN、1×ULN≤ALT＜2×ULN和ALT≥2×ULN 3组在诊断肝硬化的AUROC分别为0.970、0.985和0.952,其敏感度分别为93.8%、100%和100%;准确度分别为:88.9%、95.9%和92.1%.3组的AUROC、敏感度和准确度均较高,未随ALT升高而出现明显变化.结论 FibroScan是诊断2级以上肝纤维化,尤其是肝硬化可靠的检测方法; FibroScan诊断慢性乙型肝炎所致肝硬化的准确性可能受ALT升高的影响不明显;诊断2级以上肝纤维化的准确性对于ALT＜2×ULN的慢性乙型肝炎患者无明显影响,但是对ALT≥2×ULN的患者,其诊断的准确性降低.

Abstract：

Objective To analyze whether or not the accuracy of liver stiffness measurement (LSM)with transient elastography (FibroScan) for the diagnosis of liver fibrosis influenced by serum alanine aminotransferase (ALT) levels in patients with chronic hepatitis B. Methods 213 consecutive CHB patients who underwent liver biopsy and LSM were enrolled and divided into three groups by the criteria of ALT＜1×ULN, 1×ULN≤ALT＜2×ULN and ALT≥2×ULN. The areas under the receiver operating curve (AUC) were analyzed and the accuracy of FibroScan for the diagnosis of liver fibrosis were detected in the three groups. Results Significant correlation existed between the stages of liver fibrosis and LSM (rs=0.773,0.889 and 0.412, P＜0.05). AUCs of LSM in all patients for significant fibrosis (F≥2, F0-1 vs F2-4)and cirrhosis (F=4, F0-3 vs F4) were 0.916 and 0.971 respectively.The accuracy of diagnosis for significant fibrosis and cirrhosis were 84.0% and 93.4% respectively.AUCs of LSM in ALT＜1×ULN,1×ULN≤ALT＜2×ULN and ALT≥2×ULN groups for significant fibrosis were 0.939, 0.967 and 0.687 respectively.The sensitivity of the three groups was 90.0%, 89.7% and 47.8% respectively. The accuracies of the three groups was 90.5%, 93.9% and 68.4% respectively. The AUC, sensitivity and accuracy of ALT≥2×ULN group for significant fibrosis were significantly lower than the other two groups. AUCs of LSM in three groups for cirrhosis were 0.970, 0.985 and 0.952 respectively. The sensitivities of the three groups were 93.8%,100% and 100% respectively. The accuracies of the three groups were 88.9%, 95.9% and 92.1% respectively.The AUCs, sensitivity and accuracy for cirrhosis of the three groups didn't change with elevated ALT. Conclusion Transient elastography (FibroScan) is a reasonable noninvasive tool to diagnose significant fibrosis,especially liver cirrhosis in CHB patients. The accuracy of FibroScan for diagnosis of liver cirrhosis may not be influenced by elevated ALT. While in ALT≥2 ×ULN group, the accuracy of FibroScan for diagnosis of significant fibrosis was significantly lower as compared to the ALT≤2×ULN groups.     

慢性乙型肝炎患者肝组织病理特征及其相关因素分析

目的探讨慢性乙型肝炎患者肝脏组织病理特征,筛选与显著性组织学损伤相关的常规临床生化指标。方法分析221例慢性乙型肝炎患者在不同ALT水平的病理特征。进一步分析组织学变化与常规临床生化指标的关系。结果 (1)CHB患者221例,不同ALT水平的显著性炎症发生率为ALT≤1 ULN组18.6%(8/43)、ALT1~2×ULN组40.26%(31/77)、ALT2×ULN组81.19%(82/101);而显著性纤维化发生率为ALT≤1 ULN组20.93%(9/43)、ALT1~2×ULN组37.66%(29/77)、ALT2×ULN组62.38%(63/101)。ALT2×ULN组患者显著性肝脏炎症和肝纤维化发生率均较ALT≤1 ULN组和ALT1~2×ULN组的显著增高(P均≤0.001);(2)单因素及多因素分析ALT、AST、Alb与显著性肝脏炎症相关,ALT、AST预测显著性肝脏炎症ROC曲线下面积为(0.829~0.854±0.03);而AST、GGT、AKP和PLT与显著性肝纤维化相关。APAG(AST、PLT、AKP、GGT)模型及APRI指数预测显著性肝纤维化ROC曲线下面积为(0.835~0.874±0.03)。结论 1.ALT正常或ALT轻度升高的慢性乙型肝炎患者中肝组织显著性改变较常见。2.APAG(APAG=0.034×AST-0.02×PLT+0.02×AKP-0.016×GGT)是预测HBV相关性肝纤维化的标志物。     

丙氨酸转氨酶低于2倍正常值上限的慢性乙型肝炎患者的肝脏病理学特征及其影响因素

目的分析丙氨酸转氨酶(ALT)低于2倍正常值上限(ULN)的慢性乙型肝炎(CHB)患者的肝脏病理学特征及其影响因素, 探讨启动抗病毒治疗ALT阈值的优化策略。方法回顾性收集2010年1月—2019年12月行肝穿刺活体组织学检查的CHB初治患者及其临床资料。利用多元回归模型探讨ALT水平和显著肝组织学改变(≥G2/S2)的风险。采用受试者操作特征曲线评价不同模型诊断肝组织炎症≥G2或纤维化≥S2的价值。结果共纳入447例符合要求的CHB患者, 中位数年龄为38.0岁, 72.9%为男性。ALT水平在正常范围时, 分别有66.9%和53.0%的患者存在显著的肝脏炎症(≥G2)和纤维化(≥S2);ALT为1～2×ULN时, 肝脏炎症≥G2和纤维化≥S2的比例上升为81.2%和60.0%。调整混杂因素后, 发现较高的ALT水平(> 29 U/L)与显著的肝脏炎症(OR:2.30, 95%置信区间:1.11～4.77)以及纤维化(OR:1.84, 95%置信区间:1.10～3.09)有关。引入γ-谷氨酰转移酶-血小板比值(GPR)后, 不同ALT治疗阈值标准下的CHB患者出现≥G2/S2的...     

ALT水平正常或轻度升高慢性乙型肝炎的肝组织学改变及临床特征分析

目的研究ALT水平正常或轻度升高的慢性乙型肝炎(CHB)患者肝组织学改变与临床指标的关系,为指导抗病毒治疗提供依据。方法回顾性收集四川省人民医院2011年10月-2018年8月行肝穿刺活检的CHB患者903例,比较性别、年龄、血清HBeAg状态、血清ALT、HBV DNA水平与ALT 2倍正常值上限(ULN) CHB患者肝脏炎症活动度和纤维化程度的关系,计数资料两组间比较采用χ~2检验。结果 903例CHB患者肝脏炎症活动度分级在G1～G4之间,其中以G2为主,占67. 6%,G≥2的患者有831例(92. 0%);肝纤维化分期在S0～S4之间,以S1为主,占78. 2%,S≥2的患者有159例(17. 6%)。男性患者的肝脏炎症活动度分级和纤维化分期明显高于女性患者(χ~2=6. 120、15. 098,P值均0. 05)。ALT 1×ULN、1×ULN≤ALT 1. 5×ULN、ALT≥1. 5×ULN患者显著肝脏炎症坏死(G≥2)所占比例分别为91. 2%、92. 1%、94. 8%,差异有统计学意义(χ~2=28. 125,P 0. 05);三组患者的显著肝纤维化(S≥2)所占比例分别为12. 7%、22. 9%、24. 4%,差异亦有统计学意义(χ~2=18. 004,P 0. 05)。随着CHB患者年龄增大,肝脏炎症活动度和纤维化程度均加重,差异均有统计学意义(χ~2=65. 768、56. 056,P值均0. 05)。随着血清HBV DNA水平降低,肝脏炎症活动度和纤维化程度均加重,差异均有统计学意义(χ~2=21. 712、29. 461,P值均0. 05)。HBeAg阴性患者肝脏炎症活动度分级和纤维化分期均明显高于HBeAg阳性患者(χ~2=30. 798、26. 380,P值均0. 05)。年龄≥30岁且1. 5×ULN≤ALT 2×ULN的HBeAg阳性和HBeAg阴性患者显著肝脏炎症坏死的比例分别为100%(40/40)和97. 8%(45/46)。结论 ALT水平正常或轻度升高的CHB患者中大多数具有显著的肝脏炎症和不同程度的肝纤维化,特别是年龄≥30岁的男性患者,建议完善肝组织病理学检查评估抗病毒治疗指征,以免延误治疗。     

慢性乙型肝炎肝纤维化进展与丙氨酸氨基转移酶演变关联性的探讨

目的探讨慢性乙型肝炎(chronic hepatitis B,CHB)患者肝纤维化进展与丙氨酸氨基转移酶(ALT)演变规律的相关性。方法选取深圳市第三人民医院2000年1月至2011年1月住院并行肝脏组织活检的510例慢性乙型肝炎患者,经肝组织活检术明确其纤维化程度,根据纤维化的进展分为两个阶段,早中期阶段(S0→S1→S2)与中后期阶段(S2→S3→S4),两阶段均按ALT分成A[ALT≤正常值上限(ULN,ULN=40 U/L)]、B(ULNALT≤2×ULN)、C(ALT2×ULN)3组。探讨两个阶段纤维化进展与ALT各组之间的相关性。结果 510例患者中,男性391例(76.67%),女性119例(23.33%),纤维化早中期患者404例(S0期28例,S1期261例,S2期115例),随着纤维化进展(S0→S1→S2),纤维化与ALT之间的差异有统计学意义(χ~2=25.377,P=0.00)。三组ALT经过χ~2分割法(即Bonferroni法)比较,检验水准调整为0.05/3(即0.017),各组之间的ALT水平差异均有统计学意义(P值均0.017)。经Spearman等级相关分析r=0.137,即随着纤维化进展,血清ALT呈逐渐上升趋势。纤维化中后期患者221例(S2期115例,S3期67例,S4期39例),随着肝纤维化进展(S2→S3→S4),纤维化与ALT之间的差异无统计学意义(χ~2=6.365,P=0.173)。三组ALT经过χ~2分割法比较,检验水准调整为0.05/3(即0.017),各组之间的ALT水平差异亦无统计学意义(P值均0.017)。结论在CHB肝纤维化进展过程中,肝纤维化早中期阶段对应的ALT呈现逐渐升高的趋势,而中后期阶段与ALT无相关性。     

血清高尔基体蛋白73联合AST对慢性乙型肝炎患者显著肝脏炎症损伤的诊断效能

目的探讨血清高尔基体蛋白73(Golgi protein 73,GP73)与慢性乙型肝炎(chronic hepatitis B,CHB)患者的肝脏炎症的相关性,评估GP73联合AST的无创诊断模型对显著肝脏炎症(≥G2)的诊断效能。方法选取CHB初治患者422例,ALT2倍正常值上限(upper limit of normal value,ULN)的患者222例,ALT≥2倍ULN患者200例,全部进行GP73、AST、ALT及其他实验室指标检测。ALT2×ULN的患者进行肝活检,分析GP73与肝组织病理炎症的相关性,采用二元Logistic回归方法建立无创诊断模型并绘制受试者工作特征(ROC)曲线评价对于显著肝脏炎症(≥G2)的诊断效能。结果 ALT2×ULN的患者GP73水平显著低于ALT≥2×ULN的患者,中位数分别为50.68 ng/mL和110.6 ng/mL (P0.01)。ALT2×ULN的患者具有显著肝脏炎症(≥G2)及显著纤维化(≥S2)者分别为57例(25.7%)和110例(49.5%),显著肝脏炎症组(≥G2)的GP73水平高于无明显肝脏炎症组(G0-G1)(P0.01),伴随肝脏炎症程度的增加,GP73水平逐渐升高且与肝组织病理的炎症呈正相关,相关系数为0.405(P0.01)。Logistic回归构建的GP73联合AST的无创诊断模型诊断显著肝脏炎症的效能(≥G2)明显优于单独应用GP73、ALT以及AST,AUROC为0.836(95%CI:0.781～0.882),敏感度、特异度分别为75.44%、80.61%(P0.01)。新模型采用≤2.88以及≥4.2的诊断界值可以使80.6%(175/222)的CHB患者避免行肝活检。结论血清GP73与CHB患者的肝脏炎症密切相关,应用GP73联合AST的无创诊断模型能够准确预测显著肝脏炎症,替代肝穿刺,用以判定ALT在2倍正常值以下的患者是否须进行抗病毒治疗,值得临床推广。     

肝组织炎症与纤维化预测抗HBV疗效比较与探讨

目的评估并比较CHB患者肝组织炎症及纤维化等级,预测抗病毒疗效的能力。方法将ALT≥4倍正常上限(ULN)和(或)HBV DNA≤6.55 log10拷贝/ml设定为具备预测抗HBV有效的能力指标,纳入365例资料完整的CHB患者,根据患者肝组织炎症及纤维化程度不同分为四组,Ⅰ组(炎症G2,纤维化S2),Ⅱ组(炎症≥G2,纤维化S2),Ⅲ组(炎症G2,纤维化≥S2),Ⅳ组(炎症≥G2,纤维化≥S2),统计各组与ALT、HBV DNA两个指标的相关性。结果 365例患者根据不同肝组织炎症及纤维化程度分为Ⅰ组(167例)、Ⅱ组(48例)、Ⅲ组(107例)、Ⅳ组(43例),4组ALT≥4 ULN例数分别为18、7、11、17例;4组HBV DNA≤6.55 log10拷贝/ml例数分别为38、8、54、17例;4组满足ALT≥4 ULN和(或)HBV DNA≤6.55 log10拷贝/ml的比例分别为31.7%、22.9%、57.0%、65.1%。经χ2检验,Ⅰ组与Ⅱ组、Ⅲ组与Ⅳ组差异均无统计学意义,其余各组间差异均有统计学意义(P均0.001)。结论 CHB肝组织显著纤维化指标比肝组织炎症指标具备更突出的预测抗病毒疗效能力。     

瞬时弹性扫描检测慢性乙型肝炎病情严重程度的研究

目的 探讨瞬时弹性扫描(TE)诊断慢性乙型肝炎(CHB)肝纤维化状态的临床价值.方法 969例CHB患者纳入研究,均接受TE检查,其中258例还接受肝活检,117例接受胃镜检查食管静脉曲张情况.结果 35例患者因TE检查成功率低于60%或肝脏弹性值(LSM)四分位偏差值/LSM比值高于0.3而被剔除.影响LSM的因素包括胆红素、AST、肝纤维化分期、炎症分级、超声波评分及血白蛋白水平.TE预测肝硬化Child-PughC级、B/C级、肝纤维化分期S4、≥S3、≥S2的接受者操作特征(ROC)曲线下面积分别为0.907、0.920、0.871、0.852及0.807.LSM＜32.2 kPa时排除Child-Pugh C级的可能性为99.4%,LSM≥35.3 kPa时诊断Child-Pugh B/C级的可能性为82.0%.对于代偿性CHB,LSM临界值23.3、15.2及10.8 kPa诊断肝硬化、肝纤维化分期≥S3及≥S2的阳性似然比均接近10.0;LSM临界值8.8、6.6 kPa排除肝硬化、肝纤维化分期≥S3的阴性似然比接近0.1.LSM与食管静脉曲张分期的等级相关系数仅为0.180,TE预测食管静脉曲张的ROC曲线下面积似无临床意义.结论 TE可较准确预测CHB患者肝纤维化严重性及Child-Pugh等级,LSM≥10.8 kPa的患者应考虑抗病毒治疗.

Abstract：

Objective To evaluate the value of transient elastography (TE) for predicting severity of liver fibrosis in patients with chronic hepatitis B (CHB).Methods A total of 969 patients with CHB was enrolled and recruited for analysis,which had been received TE scan,including 258 patients of liver biopsy,and 117 patients of gastric endoscopy.Results A total of 35 patients was excluded from analysis due to TE failure or unreliable TE.Liver stiffness measurement (LSM) was independently influenced by bilirubin,AST,liver fibrosis and inflammation,ultrasonic score and albumin.TE predicted Child-Pugh C,B/C,liver fibrosis S4,≥S3 and ≥ S2 with respective area under receiver operating characteristics curves (AUROC)0.907 (95% CI 0.886-0.928 ),0.920 ( 95% CI 0.899-0.940 ),0.871 ( 95% CI 0.819-0.923 ),0.852(95%CI0.805-0.899) and 0.807(95% CI0.749-0.865),respectively.While LSM ＜32.2 kPa excluded Child-Pugh C with 99.4% probability,LSM ≥35.3 kPa determined Child-Pugh B/C with positive predictive value (PPV) 0.820.For compensated CHB,cut-offs of LSM 23.3,15.2 and 10.8 kPa diagnosed cirrhosis,liver fibrosis ≥S3 and ≥S2 with positive likelihood ratio nearly 10.0 and PPV 0.692,0.882 and 0.980,respectively; and cut-offs 8.8 kPa,6.6 kPa excluded cirrhosis,liver fibrosis ≥ S3 with negative likelihood ration nearly 0.1 and negative predictive value 0.977 and 0.903,respectively.Correlation coefficient between LSM and grades of esophageal varices was only 0.180,and AUROC for TE predicting EV was of no clinical value.ConclusionTE relatively make accurate prediction in the severity of liver fibrosis and classification of Child-Pugh.Patients with LSM ≥ 10.8 kPa should be considered for receiving antivirus treatment.     

Diagnostic value of FIB-4, aspartate aminotransferaseto-platelet ratio index and liver stiffness measurement in hepatitis B virus-infected patients with persistently normal alanine aminotransferase

AIM To assess the diagnostic value of FIB-4, aspartate aminotransferase-to-platelet ratio index(APRI), and liver stiffness measurement(LSM) in patients with hepatitis B virus infection who have persistently normal alanine transaminase(PNALT).METHODS We enrolled 245 patients with chronic hepatitis B: 95 in PNALT group, 86 in intermittently elevated alanine transaminase(PIALT1) group [alanine transaminase(ALT) within 1-2 × upper limit of normal value(ULN)], and 64 in PIALT2 group(ALT 2 × ULN). All the patients received a percutaneous liver biopsy guided by ultrasonography. LSM, biochemical tests, and complete blood cell counts were performed.RESULTS The pathological examination revealed moderate inflammatory necrosis ratios of 16.81%(16/95), 32.56%(28/86), and 45.31%(28/64), and moderate liverfibrosis of 24.2%(23/95), 33.72%(29/86), and 43.75%(28/64) in the PNALT, PIALT1, and PIALT2 groups, respectively. The degrees of inflammation and liver fibrosis were significantly higher in the PIALT groups than in the PNALT group(P 0.05). No significant difference was found in the areas under the curve(AUCs) between APRI and FIB-4 in the PNALT group; however, significant differences were found between APRI and LSM, and between FIB-4 and LSM in the PNALT group(P 0.05 for both). In the PIALT1 and PIALT2 groups, no significant difference(P 0.05) was found in AUCs for all comparisons(P 0.05 for all). In the overall patients, a significant difference in the AUCs was found only between LSM and APRI(P 0.05).CONCLUSION APRI and FIB-4 are not the ideal noninvasive hepatic fibrosis markers for PNALT patients. LSM is superior to APRI and FIB-4 in PNALT patients because of the influence of liver inflammation and necrosis.     

肝脏硬度值检测诊断慢性乙型肝炎患者肝组织纤维化的效能分析*

目的 探讨采用肝脏硬度测定（LSM）诊断慢性乙型肝炎（CHB）患者肝纤维化分期的效能。方法 2016年1月~2018年7月我院收治的112例CHB患者和选择同期健康志愿者30例,使用肝脏瞬时弹性检测仪（FT）检测LSM,所有患者均接受肝活检,采用Ishak评分系统行肝组织纤维化分期。结果 本组112例CHB患者经Ishak评分诊断为肝组织无肝纤维化（S0期）16例（14.3%）,轻度肝纤维化（S1期）40例（35.7%）,中度肝纤维化（S2~S3期）40例（35.7%）,重度肝纤维化和肝硬化（S4期）16例（14.3%）;肝组织纤维化S0期、S1期、S2~S3期和S4期LSM值分别为（5.4±0.8） kPa、（7.1±2.1） kPa、（9.9±2.5） kPa和（15.8±3.4） kPa,而正常志愿者LSM值为（5.3±0.9）kPa;分别以LSM=5.90、LSM=7.61、LSM=9.25和LSM=14.84为诊断S0期、S1期、S2~S3和S4期的截断点,诊断的曲线下面积分别为0.943、0.800、0.568和1.000,其诊断的灵敏度和特异度分别为100.0%和89.6%、100.0%和69.4%、100.0%和52.1%,和100.0%和100.0%。结论 使用FT检测LSM值对CHB患者肝组织纤维化分期有一定的诊断价值,值得在临床上进一步验证。     

The clinical significance of persistently normal ALT in chronic hepatitis B infection

BACKGROUND/AIMS: Chronic hepatitis B virus (HBV) disease is caused by both necroinflammation and active viral replication. The role of ALT levels as a predictor of liver injury has recently been questioned. The aim of the study was to determine whether normal ALT is associated with liver injury in a cohort of HBV patients undergoing liver biopsy. METHODS: This is a retrospective review of chronic HBV patients divided into 3 groups; (1) persistently normal ALT (PNALT); (2) ALT 1-1.5X ULN and (3) ALT>1.5X ULN. Multiple clinical, biochemical, virological variables were evaluated. RESULTS: One hundred and ninety-two patients met the inclusion criteria, 59 with PNALT, 26 with ALT 1-1.5X ULN, and 107 with ALT>1.5X ULN. Increasing age, higher ALT, higher grade of inflammation on biopsy, and HBeAg positivity predicted fibrosis. 18% of patients with PNALT had stage 2+ fibrosis and 34% had grade 2 or 3 inflammation. Overall 37% of patients with PNALT had significant fibrosis or inflammation. Subgroup analysis showed the majority with fibrosis belonged to the high normal ALT group and that only a minority who were young and immune tolerant had significant findings on biopsy. CONCLUSIONS: There is significant fibrosis and inflammation in 37% of patients with PNALT and a liver biopsy should be considered in patients older than 40 with high normal ALT.     

Significant changes in liver stiffness measurements in patients with chronic hepatitis B: 3-year follow-up study

Summary. For patients with chronic hepatitis B (CHB) infection, changes in liver stiffness measurement (LSM) over time are not known. We examined changes longitudinally in a cohort of patients. Four hundred and twenty‐six patients with CHB underwent transient elastography. Patients were followed regularly, and repeat elastography was performed at 3 years. Hepatitis serology, viral load and routine liver biochemistry were monitored. Of the 426 patients, 38 (9%) were hepatitis B e‐antigen (HBeAg)‐positive, 293 (69%) were HBeAg‐negative and 95 (22%) were patients with prior hepatitis B surface antigen (HBsAg) seroclearance. A total of 110 patients received oral antiviral therapy. There was a significant decline of LSMs at the follow‐up measurement compared to baseline (6.1 vs 7.8 kPa respectively, P = 0.002) in treated patients who had elevated alanine aminotransferase (ALT) at baseline and subsequent normalization after 3 years (normal ALT limit being 30 U/L for males and 19 U/L for females). In nontreated patients, only the patients with persistently normal ALT at both time points had significantly lower LSMs at the follow‐up measurement compared to baseline: 4.9 vs 5.3 kPa, respectively, in patients who remained positive for HBsAg (P = 0.005) and 5.1 vs 5.4 kPa, respectively, in patients who had HBsAg seroclearance (P = 0.026). In patients who remained positive for HBsAg, independent factors associated with a significant decline in LSM of ≥1 kPa included antiviral therapy (P = 0.011) and the ALT levels at the follow‐up time point (P = 0.024). Thus, in patients with CHB, a significant decline in LSM after 3 years was observed in treated patients with ALT normalization and in untreated patients who had persistently normal ALT. Antiviral therapy and follow‐up ALT levels were independent significant factors associated with a decline in LSM.     

Larger biopsies evaluation of transient elastography for detecting advanced fibrosis in patients with compensated chronic hepatitis B

Background and Aim: Although larger biopsies sample had been recommended for the study of non‐invasive liver fibrosis assessment, few studies with larger biopsies for transient elastography (TE) detecting liver fibrosis had been reported. The present study tries to re‐evaluate the performance of TE for detecting advanced fibrosis (≥F3) with larger biopsies in patients with compensated chronic hepatitis B. Methods: A total of 375 compensated patients were analyzed, who had undergone liver biopsy, reliable TE and routine blood tests. Results: The area under the receiver operating characteristic curve (AUC) was influenced by liver biopsy sample: 0.873 (95% confidence interval 0.838–0.909) in total patients, 0.880 (0.844–0.917) in length ≥ 15 mm, 0.897 (0.863–0.932) in length ≥ 20 mm and 0.911 (0.874–0.949) in length ≥ 25 mm. In patients with sample length ≥ 20 mm, the cutoffs to exclude and confirm advanced fibrosis were 7.1 kPa and 12.7 kPa, respectively. Stratified by alanine aminotransferase of two times the upper limit of normal (ALT 2 × ULN), transient elastography detecting advanced fibrosis with the most efficiency by 72.5% of patients obviated from liver biopsy. In patients with normal bilirubin and ALT < 2 × ULN, the area was 0.921 (0.860–0.982), and cutoffs for excluding and confirming diagnosis were 7.4 kPa and 10.6 kPa, respectively; 80% of patients could be classified with or without advanced fibrosis (AF). In patients with normal bilirubin and ALT ≥ 2 × ULN, the corresponding numbers were 0.885 (0.824–0.947), 7.5 kPa, 12.7 kPa and 79.2%, respectively. Conclusions: Inadequate sample study would underestimate the efficiency of TE on detecting advanced fibrosis. With ALT 2 × ULN stratified cutoffs, TE determined nearly 80% of patients with normal bilirubin as AF or non‐AF and obviated them from liver biopsies.     

慢性乙型肝炎236例肝组织病理分析

目的探讨不同年龄段不同HBeAg状态的慢性乙型肝炎患者肝组织炎症及纤维化程度。方法以236例在我院做过肝穿刺活体组织检查术（肝活检）、ALT〈2倍正常值上限（upper limit of normal，ULN）的慢性乙型肝炎患者为研究对象，分为HBeAg阳性组123例，HBeAg阴性组113例，各组所有病例按年龄段分为3组：年龄〈30岁组，30～40岁组，340岁组。分析不同年龄段不同HBeAg状态与肝组织病理炎症及纤维化程度的关系。结果相同HBeAg状态患者，年龄越大，肝组织炎症及纤维化程度越重；相同年龄段，HBeAg阴性患者肝组织炎症及纤维化程度重。结论HBeAg阴性、高年龄段（≥40岁）、ALT〈2×ULN的慢性乙型肝炎患者肝组织病理改变程度较重。这些患者若无条件行肝活检，可以考虑直接抗病毒治疗。     

ALT小于2倍正常上限的HBeAg阴性慢性HBV感染者肝脏病理改变及相关因素分析

目的探讨ALT小于2倍正常值上限(upper limits of normal,ULN)的HBeAg阴性慢性HBV感染者中与肝脏病理学改变相关的临床指标。方法将60例ALT2×ULN的HBeAg阴性慢性HBV感染者按照不同肝脏炎症程度及纤维化程度分组,对比各组患者性别比例、年龄、血清ALT、HBV DNA定量、脾脏厚度、门静脉内径、肝脏瞬时弹性探测仪(FibroScan)测定肝硬度值(liver stiffness measurement,LSM)的变化情况。结果 60例患者肝脏炎症改变在G1~G3级,纤维化程度在S0~S2期,其中≥G2、达S2者分别为49例(81.7%)、19例(31.7%)。60例患者中,随着肝脏炎症及纤维化程度的加重,男性患者比例、年龄、脾脏厚度、门静脉内径、LSM值均明显增加,差异均有统计学意义(P均0.05);血清ALT水平、HBV DNA定量随肝脏炎症程度的加重亦明显增加,差异均有统计学意义(P均0.05),但以上两指标随肝脏纤维化程度的加重无明显变化。结论对于ALT2×ULN的HBeAg阴性慢性HBV感染者,仍然有相当部分患者的肝脏病变在G2或/和S2以上,对于这部分人群,尤其是男性患者,密切随访年龄、血清ALT、HBV DNA、脾脏厚度、门静脉内径、LSM值的变化对于协助了解肝脏病理变化有一定的提示作用。     

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。     

丙氨酸转氨酶持续正常的HBeAg阴性慢性乙型肝炎病毒感染者肝脏组织学改变及其影响因素

目的 分析ALT持续正常的HBeAg阴性慢性HBV感染者的肝脏组织学改变及其影响因素.方法 选择2003年10月至2008年3月经皮肝组织活检的ALT持续正常的HBeAg阴性慢性HBV感染者98例,检测其ALT水平、HBV标志物、HBV DNA水平和肝脏组织学改变.均数比较采用t检验和单因素方差分析,非参数统计采用Mann-Whitney U检验和Kruskal-Wallis检验.采用Logistic模型进行独立危险因素分析,采用受试者工作特征曲线评价ALT水平对显著肝脏病理改变的诊断价值.结果 98例患者中炎症活动指数(Hal)≥4、纤维化(F)评分≥3的患者分别占22.4%与17.3%.ALT为(0.51～1.00)×正常值上限(ULN)组发生上述病理改变的比例均高于(0～0.50)×ULN组(HAI≥4:36.4%比11.1%,χ2=8.881,P=0.003;F评分≥3:27.3%比9.3%,χ2=5.487,P=0.019).年龄每增长10岁是HAI≥4分的独立危险因素(OR=2.410,P=0.023);年龄>45岁者发生HAI≥4分的比例明显高于≤45岁者(33.3%比13.4%,χ2=4.923,P=0.027).HBV DNA＜1×104拷贝/mL时,仍有14.9%的患者Hal≥4分、12.8%的患者F评分≥3分.结论 部分ALT持续正常的HBeAg阴性慢性HBV感染者在不同HBV DNA水平存在一定程度的肝脏病理改变,肝组织活检对于年龄＞45岁的患者是十分重要的.0.50×ULN有望为中国HBeAg阴性的慢性HBV感染者的临床处理提供一个恰当的ALT"正常"参考值.     

血清ALT与慢性乙型肝炎、肝硬化FibroScan 弹性值动态检测结果的相关性

目的探讨肝脏弹性值（LSM）在慢性乙型肝炎发作过程中的变化及ALT对LSM影响。方法 43名慢性乙型肝炎感染者,包括慢性乙型肝炎（CHB）23人、肝炎肝硬化（LC）20人;入院时行腹部B超检查,住院期间每7～10天、出院后每1～3月行Fibroscan（FS）检测,同时行常规血液指标化验。结果 CHB组中LSM与ALT有显著相关性（r=0.324,P=0.004）,偏相关分析提示LSM与ALT无统计学相关性（r=0.190,P=0.098）;随ALT下降,LSM逐渐降至诊断肝硬化界值14.6 kPa以下,呈现持续下降、先升后降或下降后波动等三种模式。LC组中,LSM与ALT无统计学相关性;在ALT好转的11例中,LSM较入院当天下降（P=0.003）,但仍高于肝硬化临界值。结论在非肝硬化CHB患者中,LSM受ALT水平影响较大。动态观察单一患者ALT与LSM变化,可能提高LSM预测肝纤维化准确性。