关注丙氨酸氨基转移酶水平正常的慢性乙型肝炎病毒感染者

血清ALT水平升高是存在组织坏死性炎症活动的标志之一,因此ALT水平正常一般被认为预示着肝脏组织正常或肝损害处于组织学静止状态.     

丙氨酸氨基转移酶正常的慢性乙型肝炎病毒感染者的处理建议

丙氨酸氨基转移酶（ALT）是确定慢性乙型肝炎病毒（HBV）感染患者是否需要治疗的重要指标。但最近的数据显示一些ALT水平正常的慢性HBV感染者中大多存在不同程度的肝脏组织学改变，甚至已发展至肝硬化和肝癌。本文结合HBV感染的自然史、国内外研究的最新进展及目前的慢性乙型肝炎患者抗病毒治疗现状就ALT正常的慢性HBV感染者提出合理的处理建议。     

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.     

慢性乙型肝炎患者丙氨酸氨基转移酶水平与HBV DNA转阴的相关性

目的 观察慢性乙型肝炎患者ALT高水平与HBV DNA转阴的相关性,以探讨抗病毒治疗CHB患者的时机,为更加合理应用抗病毒药物提供参考.方法 应用回顾性分析的方法,对本院就诊的HBV DNA＞1×104拷贝/ml且ALT＞800 U/L的177例CHB患者,分为未抗病毒组96例,抗病毒组81例,在4、8、12、24周,各检测1次HBV DNA、HBV标志物及ALT,随访时间为24～228周.两组间计量资料方差齐时采用t检验,率的比较采用x2检验或Fisher's确切概率法.结果 随访24周者,未抗病毒组71例,抗病毒组65例.24周内未抗病毒组和抗病毒组HBV DNA阴转者分别为62例(87.3%)和63例(96.9%);8周内HBV DNA阴转者分别为56例(78.9%)和60例(92.3%).24周内,两组HBV DNA阴转率比较,x2=0.058,P＞0.05,差异无统计学意义.未抗病毒组HBV DNA≤106拷贝/ml 43例,HBV DNA＞106拷贝/ml 28例.24周内,HBV DNA≤106拷贝/ml组HBV DNA阴转41例(95.3%),HBV DNA＞106拷贝/ml组HBV DNA阴转21例(75.0%),HBV DNA＞106拷贝/ml的患者HBV阴转率低,两组比较,x2=0.024,P＜0.05,差异有统计学意义.未抗病毒组HBeAg阴性41例,HBeAg阳性30例,24周内,HBV DNA分别阴转36例(87.8%)和26例(86.7%),两组比较,x2=1,P＞0.05,差异无统计学意义.HBeAg阳性30例中,发生HBeAg阴转10例,有4例发生在4周内.未抗病毒组71例中,HBV DNA阴转62例,有5例HBV DNA反弹(发生在24～72周),均伴有ALT再次升高(47～140 U/L).结论 ALT＞800 U/L的CHB患者有自发清除HBV倾向,可以考虑暂时不抗病毒治疗.HBV DNA的阴转与HBeAg状态无关,但与HBV载量相关.     

丙氨酸氨基转移酶轻度升高慢性乙型肝炎患者肝组织病理学改变

目的分析ALT轻度升高的慢性乙型肝炎患者肝组织病理学改变情况,以探讨ALT水平与肝脏炎症及纤维化分期的关系。方法选择216例ALT轻度升高的慢性乙型肝炎患者及83例慢性HBV携带者,进行肝活检,分析肝脏炎症分级（G）及纤维化分期（S）与ALT及年龄的关系。结果在肝炎组中,炎症分级≥G2者占55.6%,明显高于对照组（31.3%）;肝炎组纤维化分期≥S2者占62.1%,也明显高于对照组（28.9%,P〈0.01）,均有显著性差异;在慢性肝炎组中年龄大于40岁者,肝组织炎症分级≥G2及纤维化分期≥S2者分别为69.5%及75.0%,均明显高于年龄〈40岁组,差异具有统计学意义（P〈0.01）;在年龄大于40岁的患者中,ALT〉60U/L者G3＋4比例（52.9%）高于ALT〈60U/L者（31.7%,P〈0.05）;ALT〉60U/L者纤维化分级高（S3＋4）者比例也明显高于ALT〈60U/L者,差异具有统计学意义（P〈0.05）,ALT〉60U/L组有84.3%纤维化分级≥S2,明显高于ALT〈60U/L组（63.4%,P〈0.05）。结论部分ALT轻度升高的慢性乙型肝炎患者肝组织病变也处于活动期,其中年龄大于40岁而ALT又大于60U/L者,应开始抗病毒治疗,达不到这个标准的患者应行肝组织活检来决定是否需要抗病毒治疗。     

丙氨酸转氨酶正常的慢性乙型肝炎病毒感染者的肝脏病理学分析

目的 了解ALT正常的慢性HBV感染者的肝脏病理学改变及其影响因素.方法 观察632例ALT正常的慢性HBV感染者,采用超声定位穿刺取肝组织,行HE染色、纤维Masson染色,HBsAg和HBcAg免疫组织化学染色,观察Knodell坏死炎症评分和Ishak纤维化评分,并分析它们与年龄、ALT水平、血清HBV DNA载量、HBsAg和HBcAg肝组织表达的关系.两均数比较采用t检验,多均数比较采用单因素方差分析及q检验,计数资料采用x2检验.结果 632例ALT正常的HBV感染者中,中度炎症坏死167例,占26.4%,重度炎症坏死26例,占4.1%,中度纤维化217例,占34.3%,重度纤维化(肝硬化)52例,占8.2%.Knodell坏死炎症评分和Ishak纤维化评分在高ALT层次组比低ALT层次组高,在女性高ALT层次组比男性高ALT层次组高,在年龄＞40岁组比年龄≤20岁组高(q=19.63,P＜0.05).肝组织损伤程度在HBV DNA载量≤5×105拷贝/L组明显轻于HBV DNA 5×105～1×107拷贝/L、1×107～1×109拷贝/L和＞1×109拷贝/L组(Knodell评分,q=3.87、2.87、6.34;Ishak评分,q=2.64、2.64、5.54;均P＜0.05),在不同HBV DNA载量复制组之间差异无统计学意义(F=1.35,P＞0.05).HBsAg(F=1.65、0.73,均P＞0.05)和HBcAg(F=0.17、1.29,均P＞0.05)肝组织表达与Knodell坏死炎症评分和Ishak纤维化评分差异均无统计学意义.结论 可检测到HBV DNA的ALT持续正常的慢性HBV感染患者应考虑进行肝组织活检,特别是年龄＞40岁且ALT在(0.75～1.00)×正常值上限者.     

丙氨酸转氨酶正常的慢性乙型肝炎病毒感染者的肝脏病理学分析

Objective To study the liver histological changes in chronic hepaitits B (CHB) patients with normal serum alanine aminotransferase (ALT) levels and the related factors. Methods Six hundred and thirty-two CHB patients with normal ALT levels had undergone ultrasound guided percutaneous liver biopsies. All specimen were examined by HE staining, collagen fiber Masson staining and immunohistochemical staining for hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg). The Knodell inflammation score and Ishak fibrosis score were both calculated and the relationship with age, serum levels of ALT and hepatitis B virus (HBV) DNA, hepatic expressions of HBsAg and HBcAg were analyzed. The means between two groups were compared by t test and those among groups were compared by one-factor analysis of variance and q test. Enumeration data were analyzed by x2 test. Results Among 632 CHB patients with normal ALT levels, 167 (26.4%) showed moderate necrotic inflammation in liver tissues and 26 (4.1%) showed severe necrotic inflammation; 217 (34. 3 % ) showed moderate fibrosis and 52 (8. 2 % ) showed severe fibrosis (cirrhosis). The Knodell inflammation score and Ishak fibrosis score in high ALT group were higher than low ALT group, those in female high ALT group were higher than male high ALT group and those in patients ＞ 40 years old were higher than ≤20 years old (q= 19.63, P＜0. 05). The liver injuries in patients with active HBV replication were more severe than those with undetectable HBV DNA levels (Knodell score, q=3.87, 2.87, 6.34; Ishak score, q=2.64,2. 64,5.54, all P＜0. 05),while there was no significant difference between patients with high levels and low levels of HBV DNA (F= 1.35, P＞0. 05). There was no significant difference between expressions of HBsAg (F= 1.65,0. 73,respectively; both P＞0. 05) and HBcAg in liver tissues and Knodell inflammation score and Ishak fibrosis score (F=0. 17, 1.29, respectively; both P＞0. 05). Conclusions Liver biopsies should be considered in CHB patients with normal ALT levels and detectable HBV DNA levels, especially those ＞ 40 years old and with ALT of (0.75-1.00) × upper limits of normal (ULN).     

丙氨酸转氨酶正常的慢性乙型肝炎病毒感染者的肝脏病理学分析

Objective To study the liver histological changes in chronic hepaitits B (CHB) patients with normal serum alanine aminotransferase (ALT) levels and the related factors. Methods Six hundred and thirty-two CHB patients with normal ALT levels had undergone ultrasound guided percutaneous liver biopsies. All specimen were examined by HE staining, collagen fiber Masson staining and immunohistochemical staining for hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg). The Knodell inflammation score and Ishak fibrosis score were both calculated and the relationship with age, serum levels of ALT and hepatitis B virus (HBV) DNA, hepatic expressions of HBsAg and HBcAg were analyzed. The means between two groups were compared by t test and those among groups were compared by one-factor analysis of variance and q test. Enumeration data were analyzed by x2 test. Results Among 632 CHB patients with normal ALT levels, 167 (26.4%) showed moderate necrotic inflammation in liver tissues and 26 (4.1%) showed severe necrotic inflammation; 217 (34. 3 % ) showed moderate fibrosis and 52 (8. 2 % ) showed severe fibrosis (cirrhosis). The Knodell inflammation score and Ishak fibrosis score in high ALT group were higher than low ALT group, those in female high ALT group were higher than male high ALT group and those in patients ＞ 40 years old were higher than ≤20 years old (q= 19.63, P＜0. 05). The liver injuries in patients with active HBV replication were more severe than those with undetectable HBV DNA levels (Knodell score, q=3.87, 2.87, 6.34; Ishak score, q=2.64,2. 64,5.54, all P＜0. 05),while there was no significant difference between patients with high levels and low levels of HBV DNA (F= 1.35, P＞0. 05). There was no significant difference between expressions of HBsAg (F= 1.65,0. 73,respectively; both P＞0. 05) and HBcAg in liver tissues and Knodell inflammation score and Ishak fibrosis score (F=0. 17, 1.29, respectively; both P＞0. 05). Conclusions Liver biopsies should be considered in CHB patients with normal ALT levels and detectable HBV DNA levels, especially those ＞ 40 years old and with ALT of (0.75-1.00) × upper limits of normal (ULN).     

持续丙氨酸氨基转移酶正常乙型肝炎肝硬化的临床分析

目的探讨持续ALT正常乙型肝炎肝硬化患者的肝组织病理特征及其相关因素,为临床诊断及治疗提供参考。方法选取2005年1月-2012年12月住院的乙型肝炎肝硬化患者68例,对所有患者进行肝组织病理学检查,分析肝组织病理改变程度与患者年龄、HBV DNA载量、ALT水平的相关性。结果 30岁的肝组织病变以轻度为主,≥30岁且40岁者以中度病变为主,≥40岁者以重度病变为主(P0.05);当HBV DNA载量5×105拷贝/ml时,以重度改变为主(P0.05);ALT水平为0~20 U/L时肝组织以轻度病理改变为主,20~30 U/L以中度病理改变为主,30~40 U/L以重度病理改变为主(P0.05)。结论对ALT持续正常的肝硬化患者,应结合其年龄、HBV DNA载量及ALT水平综合评估,40岁以上、HBV DNA载量5×105拷贝/ml、ALT水平在30~40 U/L的患者,应行肝组织活检以明确疾病有无进展,即使不做肝组织活检,也应予以合理的抗病毒治疗。     

慢性乙型肝炎病毒感染者病毒载量与丙氨酸氨基转移酶水平的关系

用荧光定量聚合酶链反应(PCR)方法检测血清乙型肝炎病毒(HBV)DNA含量，对不同HBV感染状态患者血清HBV载量与丙氨酸氨基转移酶(ALT)水平的关系进行了探讨。     

病毒学因素对ALT持续正常的e抗原阴性慢性乙型肝炎病毒感染者肝脏组织学改变的影响

目的 探讨ALT持续正常的HBeAg阴忡慢性HBV感染者病毒学因素与肝脏组织学改变的关系.方法 枪测52例研究对象的HBV DNA水平、基因型、基本核心启动了(BCP)与前C区变异,分析各病毒学因素对肝脏组织学改变的影响.止态分布数据两组间均数比较采用t检验,多组均数比较采用单因素方差分析;非正态分布数据比较采用Mann-Whitney I检验;两样本率的比较用χ2检验及Fisher精确概率法;HBV DNA与肝脏组织学的关系等非参数双变量相关分析采用Spearman相关系数方法;采用受试者T作特征曲线下而积评价HBV DNA水平对肝脏病理改变的诊断价值. 结果 BCP与前C区联合突变组的病毒载量高于非联合突变组[(4.9±1.4)10g10拷贝/ml比(4.1±1.1)log10拷贝/ml,t=2.308,P<0.05];联合突变组32.1%的患者HAI≥4分、14.3%的患者F≥3分.前C区或BCP野毒株的感染者中,HBV DNA与肝脏炎症呈正相关(r值分别为0.626和0.592,P值均<0.01)、与纤维化改变也呈正相关(r值分别为0.730和0.641,P值均<0.01).在尢联合突变的研究对象中,HBV DNA用于预测其F≥3分的肝脏病理改变有显著意义(受试者工作特征曲线下面积为0.905,95%可信区间为0.771～1.039,P<0.05),临界值为4.5 log10拷贝/ml(敏感度1.000,特异度0.778,阿I性预测值为42.9%,阴性预测值为100.0%).基因B型的HBV DNA高于C型[(5.1±1.5)log10拷贝/ml比(4.3±1.0)lOg10拷贝/ml],差异有统计学意义(t= 2.059,P<0.05);但两者在显著肝脏病理改变方面的差异尢统计学意义. 结论 HBV联合突变株的复制能力最强,行且部分联合突变株感染者出现显著肝组织学改变,此类患者有必要接受抗病毒治疗.在前C区或BCP变异野毒株感染者中,HBVDNA与肝脏的炎症、纤维化改变呈正相关,病毒载量用于预测这部分感染者F≥3分的肝脏病理改变有显著意义.     

慢性乙型肝炎丙氨酸转氨酶低于2倍正常上限者的肝组织学改变

目的 通过肝组织活检评价慢性乙型肝炎患者丙氨酸转氨酶(ALT)低于2倍正常上限(2×ULN)者的肝组织病理学特征,为临床抗病毒治疗提供客观依据。方法 2005年10月至2010年8月四川省人民医院感染科肝脏组织活检患者。肝脏组织活检纳入标准：①HBsAg阳性持续6个月以上;②HBeAg阳性者,HBV DNA≥103拷贝/ml,HBeAg阴性者,HBV DNA≥104拷贝/ml;③AIT＜2×UIN持续6个月以上,且未使用任何保肝降酶药;④既往未接受过任何抗病毒治疗,包括干扰素和核苷类似物;⑤愿意接受肝活检。肝脏组织活检前查血常规、凝血酶原时间、生化、乙型肝炎病毒标志物、HBV DNA定量,常规B型超声定位,肝组织活检评价炎症坏死分级范围和纤维化程度。比较各因素与肝脏炎症和纤维化之间的关系。结果 符合诊断标准病例共383例,其中男性240例,女性143例,年龄16～59岁,平均年龄28.0岁。肝脏炎症G0期2例(0.5％)、G1期165例(43.1％)、G2期191例(49.9％)、(3期25例(6.5％)、G4期0例(0.0％),≥G2期占56.4％。肝脏纤维化S0期103例(26.9％)、S1期265例(69.2％)、S2期13例(3.4％)、S3期2例(0.5％)、S4期0例(0.0％),肝脏纤维化≥S2期仅3.9％。不同年龄、AIT水平、HBV DNA水平和H BeAg状态与肝脏炎症严重程度发生率相关(P＜0.05)。肝纤维化程度仅与年龄、ALT水平及HBeAg状态相关(P＜0.05),HBV DNA水平与肝纤维化发生率无明显相关性(P＞0.05)。结论 ALT低于2×ULN患者大多数有明显的肝脏炎症和不同程度的肝纤维化,建议应通过肝活检了解肝损伤程度作为评价是否具有抗病毒治疗的指征。     

低水平丙氨酸氨基转移酶慢性乙型肝炎病毒感染者肝组织病理学变化研究

目的研究血清ALT≤3ULN的乙型肝炎病毒感染者肝组织病理学改变情况。方法选取血清ALT≤3ULN的乙型肝炎病毒感染者71例,在B超引导下行肝穿刺活检术,进行肝组织炎症活动度和肝纤维化程度检查。结果在71例HBV感染者,HBeAg阳性54例,HBeAg阴性17例。血清HBV DNA定量在1×103~105copies/ml 19例(26.8%),106~107copies/ml 34例(47.9%),≥108copies/ml 18例(25.3%)。ALT≤40U/L17例(23.9%),40U/L相似文献   

乙型肝炎e抗原阴性慢性乙型肝炎和肝硬化患者病毒基因型及丙氨酸氨基转移酶水平分析

目的观察乙型肝炎e抗原(HBeAg)阴性慢性乙型肝炎(CHB)及肝硬化患者的乙型肝炎病毒(HBV)基因型及丙氨酸氨基转移酶(ALT)水平。方法采用酶联免疫吸附法检测62例CHB和41例肝硬化患者HBV标志物和血清ALT水平,用聚合酶链反应法检测其HBV基因型。结果CHB患者中,21 例(33.9%)为HBeAg阴性,41例(66.1%)为HBeAg阳性;肝硬化患者中,28例(68.3%)为HBeAg阴性,13例(31.7%)为HBeAg阳性。CHB患者中,53例(85.5%)为C基因型,9例(14.5%)为B基因型; 肝硬化患者中39例(95.1%)为C基因型,2例(4.9%)为B基因型。HBeAg阴性CHB患者ALT>40 U/L 者的比例低于HBeAg阳性组(分别为47.6%和85.4%),差异有统计学意义(P<0.01)。HBeAg阴性肝硬化患者ALT>40 U/L者的比例低于HBeAg阳性组(分别为64.3%和92.3%)但差异无统计学意义。结论CHB 和肝硬化患者中,HBeAg阴性者的比例较高,此类患者的ALT水平较低,以C基因型占优势。     

病毒学因素对ALT持续正常的e抗原阴性慢性乙型肝炎病毒感染者肝脏组织学改变的影响

Objective To investigate the correlation between viral factors and liver histological changes of HBeAg-negative chronic hepatitis B patients with persistently normal serum ALT levels (PNAL). Methods HBV DNA level, HBV genotype, basal core promoter (BCP) and precore mutation were exam- ined in 52 HBeAg-negative chronic hepatitis B patients with PNAL (defined as normal ALT measured on at least 3 occasions in the intervals of about two months over a period of 12 months or more prior to the biopsy). Viral factors influencing histological changes of HBeAg-negative chronic hepatitis B patients with per-Results Subjects with both BCP and precore mutations had significantly higher HBV DNA levels than those without mutations [(4.9±1.4) vs (4.1±1.1) log10copies/ml, t = 2.308, P < 0.05]. A higher proportion of patients with histological activity index (HA1)≥ 4 was found in patients with both mutations (32.1% vs 16.7%) than in patients without mutation, however, the proportion of patients with histological activity index (HAl)≥ 3 in patients with mutations was not significantly different from that in patients without mutations (14.3% vs. 12.5%, χ2 = 0.000, P > 0.05). In patients without precore or BCP mutations, there was a strong positive correlation between viral load and liver inflammation as well as fibrosis (precore: r = 0.626, 0.592, P < 0.01; BCP: r = 0.730, 0.641, P < 0.01). In patients without both mutations, HBV DNA has shown a high accuracy for predecting fibrosis (F≥3) (AUC = 0.905, 95% CI: 0.771±1.039, P < 0.05) with the cutoff value of 4.5 log10copies/ml (sensitivity = 1.000, specificity = 0.778, PPV = 42.9%, NPV = 100.0%). Results of both genotypes and mutations were successfully obtained in 40 samples with HBV DNA≥ 104 copies/ml. The higher viral load was observed in the patients with genotype B than genotype C (5.1 vs 4.3 Iog,0copies/ml, t = 2.059, P < 0.05), but no difference was seen of liver pathologic changes between these two genotypes. Conclusions Virus harboring both BCP and precore mutants has the higher replication level than wild type virus. 32.1% and 14.3% of the patients with both mutations have moderate or severe inflammation and fibrosis. There was a strong positive correlation between viral load and liver histological changes in patients without precore or BCP mutations, and viral load shows a high accuracy for predecting sig-nificant fibrosis (F ≥ 3).     

病毒学因素对ALT持续正常的e抗原阴性慢性乙型肝炎病毒感染者肝脏组织学改变的影响

Objective To investigate the correlation between viral factors and liver histological changes of HBeAg-negative chronic hepatitis B patients with persistently normal serum ALT levels (PNAL). Methods HBV DNA level, HBV genotype, basal core promoter (BCP) and precore mutation were exam- ined in 52 HBeAg-negative chronic hepatitis B patients with PNAL (defined as normal ALT measured on at least 3 occasions in the intervals of about two months over a period of 12 months or more prior to the biopsy). Viral factors influencing histological changes of HBeAg-negative chronic hepatitis B patients with per-Results Subjects with both BCP and precore mutations had significantly higher HBV DNA levels than those without mutations [(4.9±1.4) vs (4.1±1.1) log10copies/ml, t = 2.308, P < 0.05]. A higher proportion of patients with histological activity index (HA1)≥ 4 was found in patients with both mutations (32.1% vs 16.7%) than in patients without mutation, however, the proportion of patients with histological activity index (HAl)≥ 3 in patients with mutations was not significantly different from that in patients without mutations (14.3% vs. 12.5%, χ2 = 0.000, P > 0.05). In patients without precore or BCP mutations, there was a strong positive correlation between viral load and liver inflammation as well as fibrosis (precore: r = 0.626, 0.592, P < 0.01; BCP: r = 0.730, 0.641, P < 0.01). In patients without both mutations, HBV DNA has shown a high accuracy for predecting fibrosis (F≥3) (AUC = 0.905, 95% CI: 0.771±1.039, P < 0.05) with the cutoff value of 4.5 log10copies/ml (sensitivity = 1.000, specificity = 0.778, PPV = 42.9%, NPV = 100.0%). Results of both genotypes and mutations were successfully obtained in 40 samples with HBV DNA≥ 104 copies/ml. The higher viral load was observed in the patients with genotype B than genotype C (5.1 vs 4.3 Iog,0copies/ml, t = 2.059, P < 0.05), but no difference was seen of liver pathologic changes between these two genotypes. Conclusions Virus harboring both BCP and precore mutants has the higher replication level than wild type virus. 32.1% and 14.3% of the patients with both mutations have moderate or severe inflammation and fibrosis. There was a strong positive correlation between viral load and liver histological changes in patients without precore or BCP mutations, and viral load shows a high accuracy for predecting sig-nificant fibrosis (F ≥ 3).     

病毒学因素对ALT持续正常的e抗原阴性慢性乙型肝炎病毒感染者肝脏组织学改变的影响

Objective To investigate the correlation between viral factors and liver histological changes of HBeAg-negative chronic hepatitis B patients with persistently normal serum ALT levels (PNAL). Methods HBV DNA level, HBV genotype, basal core promoter (BCP) and precore mutation were exam- ined in 52 HBeAg-negative chronic hepatitis B patients with PNAL (defined as normal ALT measured on at least 3 occasions in the intervals of about two months over a period of 12 months or more prior to the biopsy). Viral factors influencing histological changes of HBeAg-negative chronic hepatitis B patients with per-Results Subjects with both BCP and precore mutations had significantly higher HBV DNA levels than those without mutations [(4.9±1.4) vs (4.1±1.1) log10copies/ml, t = 2.308, P < 0.05]. A higher proportion of patients with histological activity index (HA1)≥ 4 was found in patients with both mutations (32.1% vs 16.7%) than in patients without mutation, however, the proportion of patients with histological activity index (HAl)≥ 3 in patients with mutations was not significantly different from that in patients without mutations (14.3% vs. 12.5%, χ2 = 0.000, P > 0.05). In patients without precore or BCP mutations, there was a strong positive correlation between viral load and liver inflammation as well as fibrosis (precore: r = 0.626, 0.592, P < 0.01; BCP: r = 0.730, 0.641, P < 0.01). In patients without both mutations, HBV DNA has shown a high accuracy for predecting fibrosis (F≥3) (AUC = 0.905, 95% CI: 0.771±1.039, P < 0.05) with the cutoff value of 4.5 log10copies/ml (sensitivity = 1.000, specificity = 0.778, PPV = 42.9%, NPV = 100.0%). Results of both genotypes and mutations were successfully obtained in 40 samples with HBV DNA≥ 104 copies/ml. The higher viral load was observed in the patients with genotype B than genotype C (5.1 vs 4.3 Iog,0copies/ml, t = 2.059, P < 0.05), but no difference was seen of liver pathologic changes between these two genotypes. Conclusions Virus harboring both BCP and precore mutants has the higher replication level than wild type virus. 32.1% and 14.3% of the patients with both mutations have moderate or severe inflammation and fibrosis. There was a strong positive correlation between viral load and liver histological changes in patients without precore or BCP mutations, and viral load shows a high accuracy for predecting sig-nificant fibrosis (F ≥ 3).     

病毒学因素对ALT持续正常的e抗原阴性慢性乙型肝炎病毒感染者肝脏组织学改变的影响

Objective To investigate the correlation between viral factors and liver histological changes of HBeAg-negative chronic hepatitis B patients with persistently normal serum ALT levels (PNAL). Methods HBV DNA level, HBV genotype, basal core promoter (BCP) and precore mutation were exam- ined in 52 HBeAg-negative chronic hepatitis B patients with PNAL (defined as normal ALT measured on at least 3 occasions in the intervals of about two months over a period of 12 months or more prior to the biopsy). Viral factors influencing histological changes of HBeAg-negative chronic hepatitis B patients with per-Results Subjects with both BCP and precore mutations had significantly higher HBV DNA levels than those without mutations [(4.9±1.4) vs (4.1±1.1) log10copies/ml, t = 2.308, P < 0.05]. A higher proportion of patients with histological activity index (HA1)≥ 4 was found in patients with both mutations (32.1% vs 16.7%) than in patients without mutation, however, the proportion of patients with histological activity index (HAl)≥ 3 in patients with mutations was not significantly different from that in patients without mutations (14.3% vs. 12.5%, χ2 = 0.000, P > 0.05). In patients without precore or BCP mutations, there was a strong positive correlation between viral load and liver inflammation as well as fibrosis (precore: r = 0.626, 0.592, P < 0.01; BCP: r = 0.730, 0.641, P < 0.01). In patients without both mutations, HBV DNA has shown a high accuracy for predecting fibrosis (F≥3) (AUC = 0.905, 95% CI: 0.771±1.039, P < 0.05) with the cutoff value of 4.5 log10copies/ml (sensitivity = 1.000, specificity = 0.778, PPV = 42.9%, NPV = 100.0%). Results of both genotypes and mutations were successfully obtained in 40 samples with HBV DNA≥ 104 copies/ml. The higher viral load was observed in the patients with genotype B than genotype C (5.1 vs 4.3 Iog,0copies/ml, t = 2.059, P < 0.05), but no difference was seen of liver pathologic changes between these two genotypes. Conclusions Virus harboring both BCP and precore mutants has the higher replication level than wild type virus. 32.1% and 14.3% of the patients with both mutations have moderate or severe inflammation and fibrosis. There was a strong positive correlation between viral load and liver histological changes in patients without precore or BCP mutations, and viral load shows a high accuracy for predecting sig-nificant fibrosis (F ≥ 3).