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).     

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

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).     

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).     

Treatment of patients with chronic hepatitis C and normal ALT levels

A certain group of patients with chronic hepatitis C have normal serum alanine aminotransferase (ALT) levels, despite the replication of hepatitis C virus (HCV) in infected liver cells and detection of HCV RNA in serum. These patients are usually asymptomatic and are discovered fortuitously, generally after a volunteer blood donation. A standard definition for this group of patients is obviously needed, which should include the presence of anti-HCV, detectable serum HCV RNA by polymerase chain reaction and persistently normal ALT levels. These patients have minimal or mild necroinflammatory lesions in liver tissue specimens and cirrhosis is rare. The natural course of the disease in this epidemiologic setting is unknown, but the progression is probably good. Alpha-interferon has been administered in small pilot studies and three controlled studies. Overall, the end of treatment response was 35% and the sustained virologic response 15%. These response rates are similar to those reported in patients with elevated ALT levels. More important, serum ALT levels became abnormal during therapy in 47% of the patients and levels remained elevated in some patients after therapy. Prospective studies on the long-term natural history of HCV infection in this setting are needed and well designed randomized controlled trials are necessary to determine whether these patients would benefit from IFN or a combination treatment with ribavirin regimen. Currently, there is no rationale to treat these patients.     

Alanine aminotransferase (ALT) levels in a normal population and interferon therapy in chronic hepatitis C patients with normal ALT

BACKGROUND/AIMS: The aims of this study were to determine the distribution of serum alanine aminotransferase levels in a normal population and to clarify whether interferon treatment is justified in HCV-infected patients with persistently normal alanine aminotransferase levels. METHODOLOGY: The distribution of alanine aminotransferase levels was examined among 949 normal subjects who were negative for hepatitis viruses, denied regular alcohol use. Nineteen patients with chronic hepatitis C and persistently normal alanine aminotransferase levels were treated with alpha interferon (six or ten million units thrice weekly for six months). RESULTS: Peaks of alanine aminotransferase distribution among the normal subjects were seen at 16-20 IU/L and 11-15 IU/L in males and females, respectively. Fourteen of the 19 patients who received interferon treatment had favorable factors of response to interferon (eight with low pretreatment virus load, four with HCV genotype 2 and two with both). A sustained virological response was achieved in eight (57%) of 14, and alanine aminotransferase levels decreased significantly to within the normal range after interferon treatment in six of eight. CONCLUSIONS: Patients with chronic hepatitis C and persistently normal alanine aminotransferase levels should be treated with high doses of interferon if they have favorable factors of response to interferon treatment.     

ALT持续正常及持续或间断升高的慢性乙型肝炎患者肝脏硬度值分析

目的目前ALT持续正常(PNALT)以及持续或间断升高(PIEALT)的慢性乙型肝炎(CHB)患者肝脏硬度值(LSM)的数据十分有限。本研究对该组患者LSM范围及其影响因素进行了探讨,以供临床应用参考。方法将在2012年9月-2013年3月于本院就诊的208例初治CHB患者纳入研究,均接受瞬时弹性扫描仪(FS)检查。PNALT组:在最近1 a随访至少3次,每次间隔2个月以上,ALT水平均正常,入组时ALT正常;PIEALT组进一步分为ALT轻度升高(过去1 a随访中ALT水平至少有1次升高但2×ULN)以及ALT明显升高(过去1 a随访中ALT水平至少有1次升高2×ULN),入组时ALT2×ULN。根据现有的研究结果,当ALT2×ULN时,用于诊断以及排除进展性肝纤维化的标准分别为LSM≥10.6 kPa和LSM7.4 kPa。计量资料分析采用t检验、方差分析和秩和检验,计数资料采用χ2检验,相关因素采用双变量相关分析及Logistic回归分析。结果受试人群平均LSM为(6.2±2.9)kPa。在PNALT患者中,LSM≥7.4 kPa占14.3%(18/126),LSM≥10.6 kPa占2.4%(3/126)。在总体PIEALT患者中,这个比例分别是35.4%(29/82)以及13.4%(11/82)。多元回归分析中,ALT1×ULN(OR=2.63,P=0.037)、男性(OR=5.29,P=0.012)是LSM≥7.4 kPa的独立影响因素;HBV DNA定量5 log10拷贝/ml是LSM≥10.6 kPa唯一的独立影响因素(OR=13.84,P=0.046)。结论在PIEALT和PNALT的CHB患者中,分别有35%及14%的患者不能排除进展性肝纤维化的可能;大约13%的PIEALT患者根据LSM结果可判断为进展性肝纤维化。对于ALT1×ULN、HBV DNA拷贝数的对数值大于5的男性CHB患者,建议对其进行密切随访。     

Histological improvement of long‐term antiviral therapy in chronic hepatitis B patients with persistently normal alanine aminotransferase levels

The aim of this study was to evaluate the histological outcomes of chronic hepatitis B (CHB) patients with persistently normal alanine aminotransferase (ALT) levels after long‐term antiviral therapy. Paired liver biopsies before and after lamivudine (LAM) treatment in CHB patients with normal and elevated ALT levels were compared. Histological response was defined as a 1‐point decrease according to the Scheuer scoring system, without worsening of fibrosis between pretreatment and posttreatment biopsies. Among the 48 patients who underwent paired liver biopsies, 17 had persistently normal baseline ALT level and 31 had elevated ALT level. The median age of the patients was 44 years and 72.9% of the patients were male. The median duration of antiviral treatment was 44.5 months (range 14–104). Long‐term follow‐up of liver biopsies revealed that 82.4% of patients in the normal ALT group and 61.3% in the elevated ALT group had a baseline fibrosis score of 4, which was reduced to 17.6% and 38.7% after long‐term therapy, respectively, indicating reversal of cirrhosis in a large proportion of both groups, especially in patients with normal baseline ALT levels. Long‐term antiviral treatment could achieve significant histological improvement in CHB patients with fibrosis or cirrhosis, regardless of ALT level.     

Hepatocellular proliferation in patients with chronic hepatitis C and persistently normal or abnormal aminotransferase levels

BACKGROUND/AIMS: Some patients chronically infected with the hepatitis C virus (HCV) have persistently normal alanine aminotransferase (ALT) levels while progressive liver damage is observed histologically. In the present study, we compared the rate of proliferation, apoptosis, and necrosis in liver biopsy specimens of patients with persistently normal or elevated ALT levels. METHODS: Fourteen patients with persistently normal and 14 age- and sex-matched patients with elevated ALT levels were enrolled. Proliferation was detected using anti-Ki 67 in 10-microm liver biopsy specimens of the patients. Apoptosis was measured by TUNEL-assay and by monoclonal anti-M30 directed against caspase-cleaved cytokeratin 18 filaments. RESULTS: The mean number of anti-Ki 67 positive hepatocytes was lower in patients with persistently normal aminotransferases (3.1 +/- 2.8/10(3) vs 10.8 +/- 8.8/10(3) hepatocytes, p<0.0011) and was correlated with serum ALT (r=0.86, p<0.01) and aspartate aminotransferase levels (r=0.83, p<0.01). The rate of apoptosis detected by TUNEL assay was low and not different between patients with persistently normal and elevated aminotransferases. Staining with anti-M30 revealed a granular staining pattern and showed a trend towards higher cell death rates in patients with elevated aminotransferase levels (apoptotic hepatocytes with >75% staining: 3.97 +/- 6.24/10(3) hepatocytes vs 13.65 +/- 19.41/10(3) hepatocytes; p=0.08). CONCLUSIONS: Patients with chronic hepatitis C and normal aminotransferases have significantly lower hepatocyte proliferation rates and show a trend towards lower apoptosis rates compared with patients with elevated aminotransferases.     

Liver histology and progression of fibrosis in individuals with chronic hepatitis C and persistently normal ALT

OBJECTIVE: The natural history of hepatitis C virus (HCV) infection in patients with normal liver biochemistry remains poorly characterized. We performed a retrospective review of patients with chronic HCV infection and persistently normal ALT to compare clinical and histological features with those in patients with abnormal liver biochemistry. METHODS: Ninety-one HCV RNA-positive patients with persistently normal ALT who had a liver biopsy between 1993 and 1999 were identified. Clinical, histological, and epidemiological features in this group were compared with those found in 94 patients with abnormal ALT. Biopsies were assessed using Ishak's scoring system and fibrosis progression rate calculated from the likely time of infection. RESULTS: Although overall necroinflammatory score and fibrosis were significantly lower in those with normal ALT, none had normal liver histology, and 15 (16%) patients with normal ALT were found to have significant necroinflammation with a score of 5 or greater and/or significant fibrosis staged at 3 or 4. No clinical, epidemiological, or virological predictors of severe histological disease were found. CONCLUSIONS: One in six patients with HCV infection and persistently normal ALT will have evidence of significant, progressive liver disease that can only be identified on liver biopsy.