HBV PC区和BCP区变异与Peg-IFNα-2b疗效的关系及治疗前后的变化

目的:探讨乙型肝炎病毒(HBV)前核心区(PC区)G1896A和基本核心启动子区(BCP区)A1762T/G1764A突变与聚乙二醇化干扰素α-2b(Peg-IFNα-2b)治疗应答的关系及相关变异在治疗前后的变化。方法:69例HBeAg阳性慢性乙型肝炎(CHB)患者,接受48周Peg-IFNα-2b治疗并随访24周。PCR扩增每位患者第0周和第72周HBV PC和BCP区并测序分析突变情况,同时监测患者第0、4、8、12、24、36、48、60和72周HBsAg、HBeAg、丙氨酸转氨酶(ALT)和HBV的DNA水平。结果:共14例患者检测为野生型(20.29%),55例患者检测为突变型(79.71%)。野生型较突变型HBeAg基线水平更高(P=0.024)。患者基线和72周时野生型、PC突变型、BCP突变型和PC+BCP突变型所占构成比发生明显变化(P=0.004)。野生型、PC突变型、BCP突变型和PC+BCP突变型患者在72周的HBeAg血清转换率和联合应答率差异均无统计学意义。结论:PC区和BCP区突变对HBeAg阳性B/C基因型CHB患者Peg-IFNα-2b治疗应答无明显影响,但治疗前后各突变所占构成比发生明显变化。

Relationship between precore/basal core promoter mutations of hepatitis B virus and therapeutic effect of peginterferon α-2b,and changes of mutations before and after treatment

AIM:To investigate the relationship between therapeutic effect of peginterferon α-2b (Peg-IFNα-2b) and precore (PC) region G1896A and basal core promoter (BCP) region A1762T/G1764A mutations of hepatitis B virus (HBV), and the changes of the mutations before and after treatment. METHODS:The patients with HBeAg-positive chronic hepatitis B (CHB) (n=69) were treated with Peg-IFNα-2b for 48 weeks and followed up for 24 weeks. The PC and BCP sequences at baseline and the 72th week were determined using polymerase chain reaction (PCR) and direct sequencing. Serum HBsAg, HBeAg, alanine aminotransferase (ALT) and HBV DNA was quantified in the samples taken at baseline (week 0), during the treatment period (weeks 4, 8, 12, 24, 36 and 48), and during follow-up (weeks 60 and 72). RESULTS:Within the total cohort, wild-type (WT) virus was detectable in only 14 patients (20.29%), and mutants were detected in 55 patients (79.71%). The serum HBeAg level in the patients with mutant virus was significantly lower than that in the patients with WT virus (P=0.024). The proportion of WT, PC mutant, BCP mutant and PC+BCP mutant was significantly changed at baseline and week 72 (P=0.004). No significant difference of HBeAg seroconversion and combined response between patients with WT virus or mutants (PC, BCP and PC+BCP) was observed. CONCLUSION:PC and BCP mutations have no effect on the response of HBeAg-positive CHB patients to Peg-IFNα-2b. The proportion of each mutation was significantly changed before and after treatment.