终止替诺福韦治疗后慢性乙型肝炎患者的复发率及其预测因素

Incidence and predictors of HBV relapse in patients with chronic hepatitis B after discontinuation of tenofovir therapy

目的探讨停止替诺福韦(TDF)治疗后慢性乙型肝炎患者的复发率和预测因素。方法选择2015年1月至2017年6月收治的197例慢性乙型肝炎患者作为研究对象,采用Cox模型分析影响患者96周病毒学复发的因素,最佳截断值采用受试者工作特征(ROC)曲线计算。结果197例慢性乙型肝炎患者中,HBeAg阳性61例,HBsAg阴性136例,两组患者年龄、HBVDNA、HBV基因型、基线HBsAg、治疗时间、治疗12个月时HBsAg、治疗结束时HBsAg水平比较差异均有统计学意义(P<0.05),2组患者性别、基线ALT水平、总胆红素水平比较差异均无统计学意义(P>0.05)。61例HBeAg阳性患者12、24、48、72、96周时病毒复发率分别为26.23%(16/61)、45.90%(28/61)、55.74%(34/61)、57.38%(35/61)、72.13(44/61),临床复发率分别为13.11%(8/61)、27.87%(17/61)、40.98%(25/61)、44.26%(27/61)、57.38%(35/61)。多因素分析显示,治疗结束时HBsAg水平是TDF停药96周内病毒学复发的风险因素。136例HBeAg阴性患者12、24、48、72、96周时病毒复发率分别为18.38%(25/136)、43.38%(59/136)、61.03%(83/136)、67.65%(92/136)、72.06%(98/136),临床复发率分别为11.03%(15/136)、27.94%(38/136)、40.44%(55/136)、53.68%(73/136)、58.09%(79/136)。多因素分析显示,治疗结束时HBsAg水平是TDF停药96周内病毒学复发的风险因素。ROC显示,治疗结束时HBsAg预测病毒学复发的最佳截断值为92IU/mL。结论HBeAg阳性和阴性患者停止TDF治疗后48周内复发率较高,治疗结束时HBsAg水平与病毒复发率相关,有可能是预测慢性乙型肝炎患者TDF治疗后复发的有效因子。

Objective To investigate the incidence and predictive factors of hepatitis B virus(HBV)relapse in patients with chronic hepatitis B(CHB)after discontinuation of tenofovir(TDF).Methods A total of 197 patients with CHB admitted to our hospital from January 2015 to June 2017 were selected as the study subjects.The Cox model was used to analyze the factors affecting viral relapse at week 96.The best cut-off value was calculated by the receiver operating characteristic(ROC)curve.Results There were correlations between the age,HBV deoxyribonucleic acid,HBV genotype,baseline hepatitis B surface antigen(HBsAg),treatment time,HBsAg level at 12 months of treatment and HBsAg level at the end of treatment in CHB patients(P<0.05).There was no significant difference in sex,baseline ALT level and total bilirubin level between the hepatitis B envelope antigen(HBeAg)positive and negative CHB patients(P>0.05).The viral relapse rates of HBeAg positive patients at week 12,24,48,72 and 96 were 26.23%(16/61),45.90%(28/61),55.74%(34/61),57.38%(35/61)and 72.13(44/61),respectively,and the clinical relapse rates were 13.11%(8/61),27.87%(17/61),40.98%(25/61),44.26%(27/61)and 57.38%(35/61),respectively.The viral relapse rates of HBeAg negative patients at week 12,24,48,72 and 96 were 18.38%(25/136),43.38%(59/136),61.03%(83/136),67.65%(92/136)and 72.06%(98/136),respectively,and the clinical relapse rates were 11.03%(15/136),27.94%(38/136),40.44%(55/136),53.68%(73/136)and 58.09%(79/136),respectively.Besides,the multivariate analysis showed that HBsAg level at the end of treatment was an independent risk factor for viral relapse within 96 weeks after TDF withdrawal for both HBeAg positive and negative CHB patients.ROC curve showed that the best cut-off value of HBsAg at the end of treatment was 92 IU/mL for HBeAg negative patients.Conclusion The relapse rate of CHB patients within 48 weeks after termination of TDF treatment is high.The level of HBsAg at the end of treatment is related to the relapse rate,which may be an effective factor for predicting the relapse in CHB patients after discontinuation of TDF treatment.