乙型肝炎病毒pgRNA在慢性乙型肝炎患者抗病毒治疗停药抉择中的临床意义

Clinical significance of hepatitis B virus pgRNA for deciding antiviral therapy discontinuation in patients with chronic hepatitis B

目的探索乙型肝炎前基因组RNA(pgRNA)在慢性乙型肝炎(CHB)患者抗病毒治疗停药抉择中的临床意义。方法收集2019年1月至2019年12月在四川大学华西医院感染性疾病中心就诊的长期抗病毒治疗的CHB患者资料,经高敏HBV DNA及HBV pgRNA评估后停药(HBV DNA≤20 IU/ml且HBV pgRNA<150拷贝/ml),对纳入的91例HBeAg阴性CHB患者进行前瞻性观察性研究,随访停药后3个月、6个月、12个月的临床情况,分析HBV pgRNA等因素与停药后复发的关系。组间比较应用χ2检验。停药后累积复发率以Kaplan-Meier分析计算。结果观察至停药后12个月,共有34例(37.4%)患者出现复发并恢复抗病毒治疗,停药12个月累积复发率为46.8%。复发患者中,有14例(41.2%)患者伴随出现了生物化学突破,恢复抗病毒治疗后均实现良好的生物化学及病毒学应答。运用Cox多因素比例风险回归分析发现停药前HBV pgRNA水平及服用的抗病毒药物种类与停药后复发有关。HBV pgRNA≤50拷贝/ml组停药后出现复发的风险是HBV pgRNA阴性组的2.316倍(HR=2.316,95%CI:1.047~5.126,P=0.038)。而HBV pgRNA>50拷贝/ml组停药后出现复发的风险是HBV pgRNA阴性组的3.45倍(HR=3.450,95%CI:1.338~8.892,P=0.010)。结论HBV pgRNA可以用于预测CHB患者抗病毒治疗停药后的复发风险。停药前血清中HBV pgRNA阴性的患者停药后复发风险相对较低,对于HBV pgRNA>50拷贝/ml的患者不建议停药。

Objective To explore the clinical significance of hepatitis B pregenomic RNA(pgRNA)for deciding antiviral therapy discontinuation in patients with chronic hepatitis B(CHB).Methods Data of patients with CHB who were treated with long-term antiviral therapy in the Center for Infectious Diseases,West China Hospital of Sichuan University from January 2019 to December 2019 were collected.Drug discontinuity after evaluation of high-sensitivity HBV DNA and HBV pgRNA(HBV DNA≤20 IU/ml and HBV pgRNA<150 copies/ml)was observed.The prospective observational study on 91 patients with HBeAg-negative CHB was conducted.The clinical conditions were followed up 3,6 and 12 months after the drug discontinuation.The relationship between HBV pgRNA and relapse after drug discontinuation was analyzed.Results From observation to 12 months after drug discontinuation,a total of 34 patients(37.4%)had developed recurrence and resumed antiviral therapy,and the cumulative recurrence rate within 12 months of drug discontinuation was 46.8%.Among the relapsed patients,14(41.2%)had biochemical breakthroughs,and all achieved good biochemical and virological responses after the resumption of antiviral therapy.The Cox multivariate proportional hazards regression analysis showed that the level of HBV pgRNA before drug discontinuation and the type of antiviral drugs taken were associated with recurrence after drug discontinuation.The risk of recurrence after drug withdrawal in the HBV pgRNA≤50 copies/ml group was 2.316 times higher than that in the HBV pgRNA negative group(HR=2.316,95%CI:1.047-5.126,P=0.038).The risk of recurrence after drug withdrawal in the HBV pgRNA>50 copies/ml group was 3.45 times higher than that in the HBV pgRNA negative group(HR=3.450,95%CI:1.338-8.892,P=0.010).Conclusion HBV pgRNA can be used to predict the risk of recurrence after antiviral therapy discontinuation in patients with CHB.Patients with negative serum HBV pgRNA before drug discontinuation have a relatively low risk of relapse after drug discontinuation,and drug discontinuation is not recommended for patients with HBV pgRNA>50 copies/ml.