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.     

乙型肝炎病毒相关肝硬化的抗病毒治疗

慢性乙型肝炎（CHB）患者每年约有2．1％～6．0％进展为肝硬化。年龄、病毒复制程度、乙型肝炎病毒（HBV）基因型、合并丙型肝炎病毒（HCV）感染等都影响HBV感染后进展至肝硬化的速率。而进展至肝硬化后HBV仍可持续存在，血清乙型肝炎e抗原（HBeAg）或HBV DNA阳性，这些患者还处在进展至肝硬化失代偿和肝癌（HCC）的危险中，只有抗病毒治疗，即清除或持续抑制HBV，才能减少这些并发症的发生，延长生存率，提高生活质量。     

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).     

HBsAg阴性伴抗-HBc阳性淋巴瘤患者化疗后乙型肝炎病毒再激活一例

患者,男性,50岁,已婚,公务员,江苏江都人,2006年3月起无明显诱因出现发热,体温38℃～39℃,伴咽痛,无盗汗、咳嗽、畏寒、寒战、腹痛和腹泻.既往每年体检均示HBAg阴性,抗-HBc阳性,肝功能正常.     

肝病患者医院感染特点分析

肝病患者免疫功能低下,免疫调节机制异常,同时由于住院患者病情危重、合并基础疾病、治疗措施复杂以及侵入性操作增多,医院感染已成为肝病患者十分突出的医疗问题。为此,本研究通过随机抽取我院感染科2004年1月～2006年3月期间肝病患者住院资料,总结医院感染特点,以期提高临床医师对感染科医院感染的认识和重视,并提出应对策略。     

干扰素治疗慢性病毒性肝炎发生甲状腺功能异常的临床特征和危险因素

目的 探讨IFN治疗慢性病毒性肝炎患者发生甲状腺功能异常的临床特征,并结合生物化学、病毒学等因素分析其危险因素.方法 选择2007年1月至2010年3月间采用IFN治疗的慢性乙型和丙型肝炎患者385例,在抗病毒治疗前2周内及治疗中每4～12周检测血常规、肝功能和病毒载量,并观察甲状腺功能的血清学指标和甲状腺自身抗体变化,治疗结束后继续随访48周.Logistic分析甲状腺功能异常发生的危险因素.结果 IFN治疗后发生甲状腺功能异常者共32例,发生率为8.3％,其中甲状腺功能亢进及减退各占一半,依次为桥本甲状腺炎10例,Graves病和破坏性甲状腺炎各8例,非自身免疫性甲状腺功能减退6例.10例甲状腺功能异常者有明显临床症状;9例进行内分泌治疗,3例停用IFN.发生甲状腺功能异常的中位时间为治疗第7个月(最早于治疗第2个月,最迟于治疗结束后7个月),甲状腺功能异常持续时间中位数为4个月(1～11个月).治疗结束后随访1年,所有患者甲状腺功能均恢复正常.女性(OR=3.656)和预存的抗甲状腺过氧化物酶抗体(OR=1.006)是发生甲状腺功能异常的独立危险因素.结论 Graves病、桥本甲状腺炎、破坏性甲状腺炎和非自身免疫性甲状腺功能减退是IFN致甲状腺功能异常的主要类型,前两者通常伴有明显症状,可能需停用IFN并予内分泌治疗.接受IFN治疗的慢性病毒性肝炎患者在治疗前、中及后均应密切监测甲状腺功能和甲状腺自身抗体,尤其是女性及有预存甲状腺自身抗体者.     

肝脏瞬时弹性超声在药物性肝损伤患者肝纤维化诊断中的作用

目的 探讨肝脏瞬时弹性超声(Fibroscan)在评估药物性肝损伤(DILI)患者肝纤维化程度的价值.方法 上海交通大学医学院附属瑞金医院感染科2009年7月至2011年4月临床诊断为DILI患者54例,在肝活组织检查前1周内运用Fibroscan检测肝平均瞬时弹性超声硬度值(Stiffness),并与按照Ishak评分进行纤维化分期的患者肝组织病理检查结果比对,使用Spearman 等级相关系数方法进行统计学分析,以肝组织检查病理结果为标准绘制Fibroscan受试者工作特征(ROC)曲线,计算ROC曲线下面积(AUC),并计算相应的诊断界值.结果 54例DILI患者中,S0期4例、S1期13例、S2期18例、S3期8例、S4期7例、S5期4例和S6期0例.肝脏纤维化程度与ALT、AST和PLT无明显的统计学关联,而与碱性磷酸酶和TBil水平呈正相关.诊断为DILI患者的肝脏纤维化S0～S5的Stiffness值分别为(6.23±1.78)、(7.24±2.86)、(8.80±5.21)、(20.36±8.73)、(23.14±12.85)和(36.60±30.87) kPa.Stiffness值与其肝纤维化分期呈显著正相关(r=0.633,P＜0.01).以Stiffness值13.25 kPa作为中重度肝纤维化的诊断界值,AUC为0.954,灵敏度为84.2％,特异度为94.3％,阳性预测值为88.89％,阴性预测值为91.67％.结论 Fibroscan可将DILI患者无或轻度肝脏纤维化与中重度纤维化较好地予以区分.     

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.     

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).     

淋巴瘤化疗致乙型肝炎病毒再激活的临床特点

HBV再激活是合并HBV感染的肿瘤患者接受细胞毒性化学治疗(化疗)期间常见的并发症,可造成肝脏不同程度的损伤,严重者可致肝功能衰竭而死亡.