CAJ | 학술논문

目的探讨国产重组Ⅱ型肿瘤坏死因子(TNF)受体-抗体融合蛋白(rh TNFR: Fc)对不同乙型肝炎病毒(HBV)感染状态下脊柱关节炎(SPA)患者肝功能及HBV感染的影响.方法纳入2012年2月至2014年8月在中山大学孙逸仙纪念医院风湿免疫科就诊的活动期SpA患者,经rhTNFR:Fc单药或联合治疗至少12周,治疗前及治疗第4、12周(主要观察终点)评估SpA病情、肝功能及HBV感染指标.如患者同意,延长rh TNFR:Fc治疗并随访至第24周(次要观察终点).结果 81例患者完成12周随访,其中HBV携带组21例,既往HBV感染组25例,无HBV感染组35例.第4周时3组各1例丙氨酸转氨酶(ALT)升高但未超过3倍.治疗24周,既往感染组均无再激活,无感染组均无新感染,携带组4例出现再激活,均无伴ALT超过正常上限2倍,其中7例基线HBV-DNA阴性且未预防性抗病毒治疗者,2例患者分别于第10、24周时发生HBV再激活,HBV-DNA自行转阴或抗病毒治疗后转阴;1例rh TNFR:Fc联合沙利度胺12周后改沙利度胺维持,第16周发生HBV-DNA再激活,第24周自行转阴.4例基线HBV轻度复制的携带组患者均未发生再激活,9例基线HBV高复制者1例对预防性抗病毒药物耐药而出现再激活.结论 rh TNFR:Fc为基础的短期治疗可引起HBV再激活,但多不引起肝炎活动.
목적 탐토국산중조Ⅱ형종류배사인자(TNF)수체-항체융합단백(rh TNFR: Fc)대불동을형간염병독(HBV)감염상태하척주관절염(SPA)환자간공능급HBV감염적영향.방법 납입2012년2월지2014년8월재중산대학손일선기념의원풍습면역과취진적활동기SpA환자,경rhTNFR:Fc단약혹연합치료지소12주,치료전급치료제4、12주(주요관찰종점)평고SpA병정、간공능급HBV감염지표.여환자동의,연장rh TNFR:Fc치료병수방지제24주(차요관찰종점).결과 81례환자완성12주수방,기중HBV휴대조21례,기왕HBV감염조25례,무HBV감염조35례.제4주시3조각1례병안산전안매(ALT)승고단미초과3배.치료24주,기왕감염조균무재격활,무감염조균무신감염,휴대조4례출현재격활,균무반ALT초과정상상한2배,기중7례기선HBV-DNA음성차미예방성항병독치료자,2례환자분별우제10、24주시발생HBV재격활,HBV-DNA자행전음혹항병독치료후전음;1례rh TNFR:Fc연합사리도알12주후개사리도알유지,제16주발생HBV-DNA재격활,제24주자행전음.4례기선HBV경도복제적휴대조환자균미발생재격활,9례기선HBV고복제자1례대예방성항병독약물내약이출현재격활.결론 rh TNFR:Fc위기출적단기치료가인기HBV재격활,단다불인기간염활동.
Objective To investigate the influence of recombinant human tumor necrosis factor α receptor-antibody fusion protein (rhTNFR: Fc) to the Hepatitis B virus (HBV) infection status and liver function of Spondyloarthritis (SpA) patients under different HBV infection status.Methods Active SpApatients with normal liver function were enrolled in Sun Yat-sen Memorial hospital from February 2012 to August 2014.All were treated with rhTNFR : Fc based therapy (monotherapy or combined therapy) for at least 12 weeks.SpA disease activity, HBV infection status and liver function were evaluated at each interview(baseline, 4th and 12th week, as primary endpoint).Part of the patients were evaluated at 24th week with or withoutextendedrhTNFR: Fc treatment (as secondary endpoint) based on their choice.Results Eighty-one patientswho completed 12-week follow-up visit were divided into chronic HBV carrier group(n =21), past HBV exposure group(n =25) and free of HBV infection group(n =35).Alanine transaminase (ALT) elevated (no more than 3-fold of normal) in 3 patients from 3 groups respectively at 4th week.During 24-week follow-up, none in past HBV exposure group or in free of HBV infection group developed HBV reactivation or HBV infection;and 4 patients in chronic HBV carrier group developed HBV reactivation without more than 2-fold of normalelevation of ALT.Among 7 patients with negative baseline HBV-DNA and without antiviral prophylaxis, 2 patients developed HBV reactivation at 10th, 24th week of rhTNFR: Fc therapy respectively and 1 patient developed reactivation at 16th week (12-week rhTNFR: Fc + thalidomide therapy and following 4-week thalidomide monotherapy), whose HBV-DNA load returned to normal spontaneously or after antiviral therapy.Four chronic HBV carriers with low-load of baseline HBV-DNA did not develop reactivation.One of 9 chronic HBV carriers with high-load of baseline HBV-DNA developed reactivation due to resistance of antiviral prophylaxis.Conclusions Short-term rhTNFR : Fc based therapy may induce mild and transient HBV reactivation, usually without hepatitis.