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.

Histological findings and its influencing factors of HBeAg-negative chronic hepatitis B virus-infected patients with persistently normal alanine aminotransferase levels

Objective To identify the histological features as well as factors influencing the course of HBeAg-negative chronic hepatitis B virus ( HBV)-infected patients with persistently normal alanine amino-transferase (ALT) levels (PNAL). Methods Ninety-eight HBeAg-negative chronic HBV-infected patients with PNAL who underwent percutaneous liver biopsy were recruited from October 2003 to March 2008. The ALT level, HBV markers, HBV DNA level and liver histological changes were detected. Comparison of means was done by t test and single factor analysis of variance. Nonparametric statistics was done by Marm-Whitey U test and Kruskal-Wallis test. Analysis of independent risk factor was done using Logistic model. The dianostic value of ALT level to significant liver histological changes was evaluated by receiver performance curve. Results Twenty-two point four percent and 17.3% of subjects had the histological activity index (HAI)≥4and fibrosis (F) score≥3 respectively. Subgroup analysis showed that subjects with ALT＞0.50 × upper limit of normal (ULN) had a significantly higher rate of HAI≥4 and F score≥3 than those with ALT≤0.50×ULN (HAI≥4:36.4% vs 11.1%, χ2 =8.881, P=0.003;F score≥3:27.3% vs 9.3%, χ2 =5.487, P= 0.019, respectively), and older subjects (more than 45 years old) had a higher proportion of HAI ≥4 than the younger (33.3% vs 13.4%, χ2 =4.923, P=0.027). Multivariate Logistic regression analysis revealed that a decade increase in age was the independent predictor of HAI≥4 (OR=2.410, P=0.023).Receive operating characteristic (ROC) curve showed that 87.0% and 90.7% of subjects with ALT＜0.50× ULN had histological changes of HAI＜4 and F score＜3 respectively. The proportions of HAI≥4 and F score≥3 in subjects with HBV DNA＜1×104 copy/mL were 14.9% and 12.8%, respectively. Conclusions Significant histological changes may be present in part of the subjects with persistently normal ALT and different HBV DNA levels, so that liver biopsy is very important, especially in those with age ＞45 years.Half time the ULN may serve as an appropriate cutoff value of normal ALT level for managing Chinese HBeAg-negative chronic HBV-int'ected patients.