Department of Experimental Medicine, Tor Vergata University, Rome, Italy.
Department of Microbiology and Virology, University of Milan, Milan, Italy.
J Viral Hepat. 2019 Jul;26(7):846-855. doi: 10.1111/jvh.13101. Epub 2019 May 14.
The study was undertaken in order to provide a snapshot from real clinical practice of virological presentation and outcome of patients developing immunosuppression-driven HBV reactivation. Seventy patients with HBV reactivation were included (66.2% treated with rituximab, 10% with corticosteroids and 23.8% with other immunosuppressive drugs). Following HBV reactivation, patients received anti-HBV treatment for a median (IQR) follow-up of 31(13-47) months. At baseline-screening, 72.9% of patients were HBsAg-negative and 27.1% HBsAg-positive. About 71.4% had a diagnosis of biochemical reactivation [median (IQR) HBV DNA and ALT: 6.9 (5.4-7.8) log IU/mL and 359 (102-775) U/L]. Moreover, 10% of patients died from hepatic failure. Antiviral prophylaxis was documented in 57.9% and 15.7% of HBsAg-positive and HBsAg-negative patients at baseline-screening (median [IQR] prophylaxis duration: 24[15-33] and 25[17-36] months, respectively). Notably, HBV reactivation occurred 2-24 months after completing the recommended course of anti-HBV prophylaxis in 35.3% of patients. By analysing treatment outcome, the cumulative probability of ALT normalization and of virological suppression was 97% and 69%, respectively. Nevertheless, in patients negative to HBsAg at baseline-screening, only 27% returned to HBsAg-negative status during prolonged follow-up, suggesting the establishment of chronic infection. In conclusion, most patients received a diagnosis of HBV reactivation accompanied by high ALT and 10% died for hepatic failure, supporting the importance of strict monitoring for an early HBV reactivation diagnosis. Furthermore, HBV reactivation correlates with high risk of HBV chronicity in patients negative for HBsAg at baseline-screening, converting a silent into a chronic infection, requiring long-term antiviral treatment. Finally, a relevant proportion of patients experienced HBV reactivation after completing the recommended course of anti-HBV prophylaxis, suggesting the need to reconsider proper duration of prophylaxis particularly in profound immunosuppression.
本研究旨在提供从真实临床实践中观察到的免疫抑制驱动的乙型肝炎病毒（HBV）再激活患者的病毒学表现和结局的快照。共纳入 70 例 HBV 再激活患者（66.2%接受利妥昔单抗治疗，10%接受皮质类固醇治疗，23.8%接受其他免疫抑制剂治疗）。HBV 再激活后，患者接受抗 HBV 治疗，中位（IQR）随访时间为 31（13-47）个月。基线筛查时，72.9%的患者 HBsAg 阴性，27.1%的患者 HBsAg 阳性。约 71.4%的患者诊断为生化再激活[中位（IQR）HBV DNA 和 ALT：6.9（5.4-7.8）log IU/mL 和 359（102-775）U/L]。此外，10%的患者死于肝功能衰竭。在基线筛查时，57.9%和 15.7%的 HBsAg 阳性和 HBsAg 阴性患者有抗病毒预防治疗记录（中位（IQR）预防持续时间：24[15-33]和 25[17-36]个月）。值得注意的是，35.3%的患者在完成推荐疗程的抗 HBV 预防治疗后 2-24 个月发生 HBV 再激活。通过分析治疗结局，ALT 正常化和病毒学抑制的累积概率分别为 97%和 69%。然而，在基线筛查时 HBsAg 阴性的患者中，只有 27%在长期随访中恢复为 HBsAg 阴性，提示发生慢性感染。总之，大多数患者被诊断为 HBV 再激活，伴有高 ALT，10%的患者因肝功能衰竭死亡，这支持了严格监测以早期诊断 HBV 再激活的重要性。此外，HBV 再激活与 HBsAg 阴性患者发生 HBV 慢性感染的风险相关，使潜伏感染变为慢性感染，需要长期抗病毒治疗。最后，相当一部分患者在完成推荐疗程的抗 HBV 预防治疗后发生 HBV 再激活，这提示需要重新考虑特别是在深度免疫抑制患者中预防治疗的适当持续时间。
