摘要
目的探讨乙型肝炎病毒前C区／BCP区变异与乙型肝炎相关性慢加急性肝衰竭（ACLF）的关系。方法收集44例ACLF患者和28例慢性乙型肝炎患者（CHB）的血清及临床资料，并对其中10例ACLF患者进行随访，每周收集血清1次。依据MELD评分对患者的病情进行判断。采用巢氏PCR方法扩增HBVDNA，扩增产物直接测序。序列比对采用BioEdit（7．0．9．0）生物分析软件。采用荧光定量PCR法检测HBVDNA含量。数据采用SPSS13．0软件分析，两组间比较采用t检验及t’检验。结果44例ACLF患者基因型均为C型，28例CHB患者中仅两例基因型为B型，其余均为C型。ACLF组患者A1762T、G1764A、T1753V、G1896A、G1899A变异频率分别为88．6％（39／44）、93．2％（41／44）、61．4％（27／44）、63．60／0（28／44）和29．5％（13／44），CHB组分别为64．3％（18／28）、67．9％（19／28）、14．3％（4／28）、21．40／0（6／28）和3．6％（1／28），两组比较，疋。值分别为6．152、7．901、15．468、12．331和7．370，P值均〈0．05，差异均有统计学意义。ACLF组内MELD评分〈20、20～25、〉25组间差异均无统计学意义。CHB组前C区、BCP区均未发生变异的频率为17．9％（5／28），ACLF组为2．3％（1／44），CHB组前C区、BCP区均未发生变异的频率高于ACLF组，x2=5．440，P=0．020，差异有统计学意义。ACLF组前C区、BCP区同时发生变异的频率为79．6％（35／44），CHB组为39．3％（11／28），两组比较，x2=12．021，P〈0．01，差异有统计学意义。CHB组仅BCP区有变异的发生频率为42．9％（12／28），ACLF组为20．5％（9／44），x2=4．157，P=0．041，差异有统计学意义。两组均未出现单独的前C区变异。10例ACLF患者均出现3个或3个以上的联合变异位点。G1896A、T1753C、A1846T变异随着病情好转而恢复。结论乙型肝炎病毒前C区／BCP区变异可能与ACLF的发生相关。
Objective To analyze the relationship between hepatitis B virus （HBV） precore （PC） and basal core promoter （BCP） mutations and HBV-related acute-on-chronic liver failure （HB-ACLF）. Methods Forty-four patients with HB-ACLF and 28 patients with chronic hepatitis B （CHB; used as controls） were enrolled and venous blood samples were collected from all individuals. The PC and BCP gene fragments were amplified by nested PCR. HBV genotype and BCP/PC mutations were determined by direct sequencing and analysis by BioEdit （version 7.0.9.0）. Ten of the HB-ACLF patients were selected for follow-up （range： 2-8 weeks）, which included once weekly sera collection to determine the realtion of mutations and treatmentresponse. Serum levels of HBV DNA were measured by real-time PCR assay, and alanine aminotransferase, total bilirubin, creatinine and albumin were measured by standard biochemical assay and used to determine the MELD score. Results All 44 HB-ACLF patients were infected with HBV genotype C. In the CHB group, 26 patients were infected with genotype C and two with genotype B. Single mutations （A1762T, G1764A, T1753V, G1896A, and G1899A） and combined mutations （A1762T ＋ G1764A, G1896A ＋ G1899A, T1753V ＋ A1762T ＋ G1764A, G1896A ＋ G1899A ＋ A1762T ＋ G1764A, and A1762T ＋ G1764A ＋ G1896A） were more lYequently detected in HB-ACLF patients than in CHB patients （P 〈 0.05）. A significantly higher proportion of PC/BCP wild-type sequences was found in patients with CI-IB than in patients with HB-ACLF （17.9% vs. 2.3%;2~ = 5.440, P = 0.020）. The proportion of patients carrying both PC and BCP mutations was significantly higher in HB-ACLF patients than in CHB patients （79.6% vs. 39.3%;2,2 = 12.021, P = 0.001）. The proportion of patients carrying only BCP mutation was 42.9% in the CHB group and 20.5% in the HB- ACLF group （x2 = 4.157, P = 0.041）. No occurences of only PC mutation were detected in either the CHB or HB-ACLF group. The combined mutations were present in all 10 of the HB-ACLF follow-up patients. Mutations G 1899A, T 1753V, and A 1846T were correlated with disease recovery. Significant decreses in the MELD score were accompanied by decreases in the A1846T mutation. Conclusion Significantly more HB-ACLF patients carried HBV with mutations in the PC and BCP than CHB patients. Moreover, more HB-ACLF patients carried HBV with PC ＋ BCP combined mutations and PC mutation only. The G1899A, T1753C, and A1846T mutations were associated with HB-ACLF response to treatment and improvement in liver ruction.
出处
《中华肝脏病杂志》
CAS
CSCD
北大核心
2012年第9期644-648,共5页
Chinese Journal of Hepatology
基金
国家重点基础研究发展规划基金资助项目（2007CB512801）,“十一五”科技重大专项（2008ZX10002-005）,天津市卫生局重点攻关资助项目（07KG9）
关键词
肝炎病毒
乙型
突变
肝炎
乙型
慢性
慢加急肝性衰竭
Hepatitis B virus
Mutation
Hepatitis B, chronic
Acute-on-chronic liver failure
