乙型肝炎相关慢加急性肝衰竭患者乙型肝炎病毒前C/C区联合突变特点分析

目的分析乙型肝炎相关慢加急性肝衰竭（HBV-ACLF）患者HBV前C/C区联合突变的特征。方法入选166名慢性HBV感染者,其中ACLF 49人,慢性乙型肝炎（CHB）45人,肝硬化（LC）45人,肝细胞癌（HCC）27人,对HBV前C/C区片段进行PCR扩增,分析突变数量及联合突变状况。结果 ACLF患者多联突变比例明显高于其他组患者。4组之中,ACLF组5联突变和7联突变者比例最高,分别是20.4%（10/49）和12.2%（6/49）,6联突变者与HCC组相近分别为14.3%（7/49）和14.8%（4/27）,明显高于CHB和LC组。联合突变组合形式的分析结果提示,ACLF组患者,含nt1846和nt1913突变的联合突变组合阳性率在4组患者中最高。结论 ACLF患者HBV前C/C区多联突变比例高于其他慢性HBV感染者;以nt1846和nt1913为基础的联合突变率最高。

Analysis of mutational patterns of the pre-C/C region of with hepatitis B virus in patients with HBV-associated acute-on-chronic liver failure

Objective To analyze the mutational patterns of the pre-C/C region of hepatitis B virus（HBV） in patients with HBV-associated acute-on-chronic liver failure（HBV-ACLF）.Methods A total of 166 patients with chronic HBV infection were enrolled in the study,including 49 cases of ACLF,45 cases of chronic hepatitis B（CHB）,45 cases of liver cirrhosis（LC）,and 27 cases of hepatocellular carcinoma（HCC）.The pre-C/C region of HBV was amplified by polymerase chain reaction and then analyzed to determine the number of mutations and mutational patterns.Results Multi-site mutations occurred significantly more frequently in ACLF patients than in other patients.Among the four groups of patients,those with ACLF had the highest rates of 5-site and 7-site mutations 20.4%（10/49） and 12.2%（6/49）];they had a similar rate of 6-site mutations as HCC patients 14.3%（7/49） vs.14.8%（4/27）],but this was significantly higher than patients with CHB and LC.The mutational pattern analysis showed that multi-site mutations that included those at nt 1846 and nt 1913 were more likely to occur in patients with ACLF than in the other groups.Conclusion Compared with other patient groups with chronic HBV infection,ACLF patients had a higher frequency of multi-site mutations in the pre-C/C region of HBV,with the highest rates of multi-site mutations containing mutations at nt 1846 and nt 1913.