儿童慢性乙肝肝组织病理与相关标志物的研究

目的 分析乙肝病毒核内共价闭合环状DNA（HBV cccDNA）、肝纤维化血清标志物、乙肝病毒基因型与肝脏纤维化和炎症活动度的相关性,以了解其在乙肝诊断中的价值,指导治疗和预后.方法 2008年4月至2011年8月于甘肃省人民医院儿科和兰州大学第一医院感染科门诊就诊和住院的乙肝及HBV携带患儿为慢性乙肝组和HBV携带组,选择同期健康查体儿童为对照组.检测慢性乙肝组、HBV携带组和对照组血清HA、LN、PCⅢ和CⅣ.依据病情严重程度,慢性乙肝组进一步分为轻度、中度和重度亚组;慢性乙肝组和HBV携带组检测血清HBV cccDNA和HBV基因型;分析HBV cccDNA、肝纤维化血清标志物、HBV基因型与肝脏纤维化和炎症活动度的相关性.结果 46例患儿进入分析,男34例,女12例,年龄1～16岁,平均年龄（11.8±3.7）岁.HBV携带组20例,慢性乙肝组26例（轻度13例、中度8例、重度5例）,对照组20例.①随乙肝临床分度加重,血清HA、LN、PCⅢ和CⅣ呈升高趋势,以重度乙肝亚组上升最为明显;②随肝组织纤维化程度与炎症活动度的增加,血清HA、LN、PCⅢ和CⅣ呈升高趋势;③血清HBV cccDNA阳性组与阴性组在肝组织炎症活动度〈G2级比例的差异无统计学意义（29/35 vs 9/11,P=0.963）;在肝组织纤维化〈S2期比例的差异无统计学意义（31/35 vs 9/11,P=0.736）;④HBV B基因型患儿肝炎症活动度和纤维化程度显著高于C基因型.结论 血清HBV cccDNA水平与肝纤维化和炎症活动度无相关性;血清HA、LN、PCⅢ和CⅣ,HBV基因型与肝纤维化和炎症活动度有较好的相关性.临床可结合病毒复制水平、丙氨酸氨基转移酶、肝纤维化血清标志物及HBV基因分型综合判断肝损害程度.

Study on chronic hepatitis B related markers and liver tissue pathology in children

Objective To investigate the relationship between serum HBV cccDNA, serum fibrosis markers and genotypes of hepatitis B virus and liver tissue pathology to guide the treatment and prognosis. Methods Outpatient and inpatient children with chronic hepatitis B and HBV carriers in the People＇s Hospital of Gansu Province and the First Hospital of Lanzhou University from April 2008 to August 2011 were recruited as chronic hepatitis B group and HBV carriers group, healthy children receiving physical examination in the same hospital in the same period were chosen as control group. Serum HA, LN, PC Ⅲ and C Ⅳ were examined in three groups. Based on the severity of the disease, chronic hepatitis B group was further divided into mild, moderate and severe subgroups. Serum HBV cccDNA and HBV genotypes were also detected in chronic hepatitis B group and HBV carriers group. The correlation of HBV cccDNA, liver fibrosis markers, HBV genotypes and degree of liver fibrosis and inflammatory activity was analyzed. Results A total of 46 HBV-DNA positive chidren with chronic hepatitis B were enrolled, including 20 cases in HBV carriers group, 26 cases in chronic hepatitis B group （mild in 13 cases, moderate in 8 cases and severe in 5 cases） , and 20 children in control group. In chronic hepatitis B group the serum hepatic fibrosis indicator levels were higher than that in the carriers and the mild groups, with the liver tissue inflammation grade and fibrosis degree increased, four liver fiber indexes increased gradually, especially in over grade 2 patients. HA, PC Ⅲ levels in the carrier group were higher than the normal group, there was no obvious correlation between serum HBV cccDNA and the liver tissue inflammatory activity or fibrosis. Liver tissue inflammatory activity and fibrosis degree were more severe in C genotype than in B genotype. Conclusions There is no significant direct correlation between the serum HBV cecDNA levels and grade of inflammation or degree of fibrosis. There is good relation between the index of liver fibrosis or hepatitis B virus genotypes and grade of inflammation or degree of fibrosis. The levels of viral replication, alanine transaminase, liver fibrosis and hepatitis B virus genotypes may be very important for the assessment of liver damage.