背景:在没有抗病毒预防的情况下,接受利妥昔单抗治疗的乙型肝炎病毒感染已解决的患者有乙型肝炎病毒再激活的风险。然而,此类患者接受以利妥昔单抗为基础的治疗膜性肾病的风险尚不清楚.我们评估了在没有抗病毒预防的情况下接受基于利妥昔单抗的治疗方案的膜性肾病患者中乙型肝炎病毒再激活的风险。
方法:回顾性分析51例膜性肾病患者的临床资料,其中乙型肝炎病毒感染已解决,接受基于利妥昔单抗的方案,而无需抗病毒预防。其中,利妥昔单抗停药后随访21例患者超过1年。收集的临床数据旨在评估患者的反应和乙型肝炎病毒再激活期间和利妥昔单抗治疗后的风险。
结果:30/51(58.8%)患者在12个月时达到完全或部分缓解。在利妥昔单抗治疗期间,没有患者经历HBsAg血清逆转。丙氨酸转氨酶,天冬氨酸转氨酶,γ-谷氨酰转肽酶和总胆红素水平,以及超过碱性磷酸酶和凝血酶原时间正常上限的患者人数,在以利妥昔单抗为基础的治疗期间,未显示任何统计学上的显著差异。也没有反HBs水平,保护性抗HBs滴度超过10U/L的患者人数,CD19+B细胞的水平,CD4+T细胞,CD8+T细胞,和自然杀伤细胞。在利妥昔单抗停药后随访12个月(12至19个月)的21例患者中,未观察到乙型肝炎病毒再激活。平均抗-HBs水平和抗-HBs滴度超过10U/L的患者人数在33个患者年的延长随访期间没有显示任何统计学上的显着差异。CD4+T细胞也没有,CD8+T细胞,自然杀伤细胞也不计数.一名患者的ALT水平超过基线值三倍,达到100U/L以上,伴随着AST的升高,GGT,ALP水平。同时,抗-HBs效价为816.09U/L,HBsAg阴性。
结论:对膜性肾病患者给予以利妥昔单抗为基础的治疗方案,在没有抗病毒预防的情况下,乙型肝炎病毒再激活的风险较低。患者的免疫状态,药物组合,在考虑抗病毒预防治疗时,应充分评估利妥昔单抗策略。
BACKGROUND: Patients with resolved hepatitis B virus infection undergoing rituximab are at risk of hepatitis B virus reactivation without antiviral prophylaxis. However, the risk in such patients treated with rituximab-based regimens for membranous nephropathy is not clear. We evaluated the risk of hepatitis B virus reactivation in membranous nephropathy patients with resolved infection undergoing rituximab-based regimens without antiviral prophylaxis.
METHODS: Clinical data of 51 membranous nephropathy patients with resolved hepatitis B virus infection undergoing rituximab-based regimens without antiviral prophylaxis were retrospectively analyzed. Among these, 21 patients were followed for more than 1 year after rituximab discontinuation. The clinical data collected aimed to assess patients\' responses and the risk of hepatitis B virus reactivation during and after rituximab treatment.
RESULTS: 30/51 (58.8 %) patients reached complete or partial remission at 12 months. None of the patients experienced HBsAg seroreversion during rituximab treatment. Alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase and total bilirubin levels, as well as the numbers of patients who exceeded the upper limits of normal for alkaline phosphatase and prothrombin time, did not show any statistically significant difference during rituximab-based therapy. Neither did the anti-HBs level, the number of patients with protective anti-HBs titers exceeding 10 U/L, nor the levels of CD19+ B cells, CD4+ T cells, CD8+ T cells, and natural killer cells. Among the 21 patients followed for 12 (ranging from 12 to 19) months after rituximab discontinuation, no hepatitis B virus reactivation was observed. The mean anti-HBs level and the number of patients with anti-HBs titers over 10 U/L did not show any statistically significant difference during the extended follow-up of 33 patient-years. Neither did the CD4+ T cell, CD8+ T cell, nor the natural killer cell counts. One patient presented with an ALT level that exceeded the baseline value by three times and reached above 100 U/L, accompanied by elevations in AST, GGT, and ALP levels. Meanwhile, the anti-HBs titer was 816.09 U/L, and HBsAg was negative.
CONCLUSIONS: The administration of rituximab-based regimens in membranous nephropathy patients with hepatitis B virus resolved infection leads to a low risk of hepatitis B virus reactivation without antiviral prophylaxis. Patient\'s immune status, drug combination, rituximab strategy should be fully evaluated when considering antiviral prophylaxis therapy.