CAJ | 학술논문

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.
목적 탐토ALT지속정상적HBeAg음충만성HBV감염자병독학인소여간장조직학개변적관계.방법 창측52례연구대상적HBV DNA수평、기인형、기본핵심계동료(BCP)여전C구변이,분석각병독학인소대간장조직학개변적영향.지태분포수거량조간균수비교채용t검험,다조균수비교채용단인소방차분석;비정태분포수거비교채용Mann-Whitney I검험;량양본솔적비교용χ2검험급Fisher정학개솔법;HBV DNA여간장조직학적관계등비삼수쌍변량상관분석채용Spearman상관계수방법;채용수시자T작특정곡선하이적평개HBV DNA수평대간장병리개변적진단개치. 결과 BCP여전C구연합돌변조적병독재량고우비연합돌변조[(4.9±1.4)10g10고패/ml비(4.1±1.1)log10고패/ml,t=2.308,P<0.05];연합돌변조32.1%적환자HAI≥4분、14.3%적환자F≥3분.전C구혹BCP야독주적감염자중,HBV DNA여간장염증정정상관(r치분별위0.626화0.592,P치균<0.01)、여섬유화개변야정정상관(r치분별위0.730화0.641,P치균<0.01).재왕연합돌변적연구대상중,HBV DNA용우예측기F≥3분적간장병리개변유현저의의(수시자공작특정곡선하면적위0.905,95%가신구간위0.771～1.039,P<0.05),림계치위4.5 log10고패/ml(민감도1.000,특이도0.778,아I성예측치위42.9%,음성예측치위100.0%).기인B형적HBV DNA고우C형[(5.1±1.5)log10고패/ml비(4.3±1.0)lOg10고패/ml],차이유통계학의의(t= 2.059,P<0.05);단량자재현저간장병리개변방면적차이왕통계학의의. 결론 HBV연합돌변주적복제능력최강,행차부분연합돌변주감염자출현현저간조직학개변,차류환자유필요접수항병독치료.재전C구혹BCP변이야독주감염자중,HBVDNA여간장적염증、섬유화개변정정상관,병독재량용우예측저부분감염자F≥3분적간장병리개변유현저의의.
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).