乙型肝炎病毒基因突变后的修复及其肝细胞损伤变化

Relationship between repair of mutated HBV gene and hepatic cell damage

目的观察有YMDD基因突变的乙型肝炎病毒携带者停用拉米夫定后YMDD突变的修复及其肝细胞损伤变化。方法分别采用速率法、放免法和流式细胞术监测38例乙型肝炎病毒携带者血清肝功能酶学指标(ALT、AST和CHE)、肝纤维化指标(HA、LN、PⅢ、Ⅳ.C)和细胞免疫活性指标(CD4/CD8),应用阵列技术(UniArray)和核酸杂交技术监测血清乙型肝炎病毒YMDD突变基因。结果停药1～2年后有6例(15.8%)YMDD变异得到修复;变异前、变异后与修复后肝功酶学指标、肝纤维化指标和细胞免疫活性指标分别对应比较,差异无统计学意义(P>0.05)。YMDD变异时ALT活性与变异前和修复后比较有显著性差异(P<0.01)。结论停药后体内肝细胞内环境得到恢复,15.8%YMDD突变的乙型肝炎病毒携带者变异株被野生株替代,或乙型肝炎病毒DNA修复酶不断地对DNA进行扫描并替换或纠正变异核苷酸;YMDD变异可导致肝细胞早期轻微损伤。

Objective To study the relationship between repair of mutated HBV gene and hepatic cell damage in 38 HBV carriers with YMDD variation after withdrawal of lamivudine.Melhods Speed, RIA, and flow cytometry were used to investigate the liver function indexes （ALt,ASt,CHE）,Iiver fibrosis indexes （HA,LN,PⅢ, IV,C）,and immunologically competent cells indexes（ CD4, CDS） in 38 HBV carders＇ serum. Uniarray technique and nucleic acid molecular hybridization technique were applied to detect the YMDD mutational gene of hepatitis B vires.Results YMDD mutation was repaired in six pationts （15.8%）1- 2 years after withdrawal of lamivudine . The results of Asr, CHE, HA, LN, P m, iv. c, CD4/CD8 were compared among three different groups before and after gene variation, and after gene repair; there were no significant differences （ P 〉 0.05）. In the case of YMDD mutation, ALT actinity before gene variation differed significantly from that after gene repair（ P 〈 0.01）. Conclusions After the withdrawal of lamivudine,the internal- envimment of liver cells was recovered. In 16.7% of 38 carriers with YMDD mutation HBV gene was replaced by wildtype gene, or the repair enzyme of HBV scan ned the DNA and replaced or corrected variant nuclectide. YMDD variation can induce early minimal damage to hepatic cells.