BCP/前C及A1846T变异与HBV导致的慢加急性肝衰竭发病相关研究

Basal core promoter/precore and A1846T mutations are associated with hepatitis B-related acute-on-chronic liver failure

目的调查中国广东地区HBV基因型、C基因调控区和前C终止密码子变异与慢加急性肝衰竭(ACLF)发病的关系。方法选取39例ACLF患者、38例严重肝炎活动患者和44例慢性乙肝(CHB)患者,应用PCR扩增测序HBV前C基因和C基因区;用PCR-RFLP的方法鉴定HBV基因型。结果 BCP的变异率在ACLF中明显高于CHB组(56.7%vs 32.4%,P=0.046),PC的变异率在ACLF中也显著高于CHB组(50.0%vs 15.9%,P=0.003)。在BCP-/PC+和BCP+/PC+模式中HBeAg阴性率明显高于BCP+/PC-和BCP-/PC-。nt1846位点A-T的变异比率在ACLF组明显高于CHB组[80.6%vs 11.1%,P<0.001]。结论 BCP、前C和A1846T高变异与ACLF发病相关,BCP-/PC+和BCP+/PC+模式导致的HBeAg阴性与ACLF发病相关。

Objective The study was undertaken to investigate the features of HBV genotypes, PC and C gene mutations in ACLF. Methods Thirty-nine patients with ACLF and 38 with SHB were involved in this study. SHB was defined as ALT ≥ 600 U/L associated with TB ≥ 3.0 mg/dl and PTA ≤ 50%. Forty-four CHB patients with ALT level within the range of 80- 400 U/L and TB ≤ 1.0 mg/dl were enrolled as control. BCP/PC mutations were determined by direct sequencing. HBV genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. Results The prevalence of BCP mutations were found significantly higher in ACLF than in CHB （56.7% vs 32.4%, P=0.046）. The rate of PC mutation was higher in ACLF than in CHB （50.0% vs 15.9%, P=-0.003 ）. Compared with the distribution of BCP/PC mutation patterns, the patterns of BCP-/PC＋ and BCP＋/PC＋ occurred more frequently in ACLF than that in CHB. The prevalence of A1846T was found significantly higher in ACLF than in CHB [80.6% vs 11.1%, P〈0.001 ]. The BCP/PC mutations were found to be associated with increased HBeAg negativity. The distribution of genotype B was statistically higher in SHB than that in CHB （72% vs 50%, P=0.044）. Genotype B was found more often in ACLF compared with in CHB, however the difference was not significant （P=0.069）. Conclusion HBV BCP/PC and A1846T mutations were associated with development of ACLF. The loss of HBeAg caused by BCP/PC mutations was more likely related with the pathogenesis of ACLF.