Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea.
Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea.
Am J Gastroenterol. 2023 Aug 1;118(8):1373-1380. doi: 10.14309/ajg.0000000000002185. Epub 2023 Jan 13.
This prospective study aimed to investigate the efficacy and safety of preemptive antiviral therapy with tenofovir disoproxil fumarate (TDF) for HBsAg-positive patients with newly diagnosed diffuse large B-cell lymphoma receiving rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy.
We enrolled 73 patients from 20 institutions. The primary end point was the absolute risk of hepatitis B virus (HBV)-related hepatitis during preemptive TDF therapy and for 24 weeks after withdrawal from TDF. Hepatitis was defined as a more than 3-fold increase in serum alanine aminotransferase from baseline or an alanine aminotransferase level of ≥100 U/L. HBV-related hepatitis was defined as hepatitis with an increase in serum HBV-DNA to >10 times that of the pre-exacerbation baseline or an absolute increase of ≥20,000 IU/mL compared with the baseline.
No patient developed HBV reactivation or HBV-related hepatitis during preemptive antiviral therapy (until 48 weeks after completion of R-CHOP chemotherapy) with TDF. All adverse events were grade 1 or 2. HBV reactivation was reported in 17 (23.3%) patients. All HBV reactivation was developed at a median of 90 days after withdrawal from TDF (range, 37-214 days). Six (8.2%) patients developed HBV-related hepatitis at a median of 88 days after withdrawal from TDF (range, 37-183 days).
Preemptive TDF therapy in HBsAg-positive patients with diffuse large B-cell lymphoma receiving R-CHOP chemotherapy was safe and effective for preventing HBV-related hepatitis. However, a long-term maintenance strategy of preemptive TDF therapy should be recommended because of the relatively high rate of HBV-related hepatitis after withdrawal from TDF ( ClinicalTrials.gov ID: NCT02354846).
本前瞻性研究旨在探讨替诺福韦酯（TDF）预防性抗病毒治疗对接受利妥昔单抗联合环磷酰胺、多柔比星、长春新碱和泼尼松（R-CHOP）化疗的新诊断弥漫性大 B 细胞淋巴瘤 HBsAg 阳性患者的疗效和安全性。
我们从 20 个机构共招募了 73 名患者。主要终点是预防性 TDF 治疗期间以及停止 TDF 后 24 周内乙型肝炎病毒（HBV）相关肝炎的绝对风险。肝炎定义为血清丙氨酸氨基转移酶（ALT）基线值升高 3 倍以上或 ALT 水平≥100 U/L。HBV 相关肝炎定义为血清 HBV-DNA 增加>10 倍于基线值或与基线值相比绝对增加≥20,000 IU/ml 的肝炎。
在 TDF 预防性抗病毒治疗期间（直至 R-CHOP 化疗完成后 48 周），没有患者发生 HBV 再激活或 HBV 相关肝炎。所有不良事件均为 1 级或 2 级。17 名（23.3%）患者报告发生 HBV 再激活。所有 HBV 再激活均在停止 TDF 后中位时间 90 天（范围 37-214 天）发生。6 名（8.2%）患者在停止 TDF 后中位时间 88 天（范围 37-183 天）发生 HBV 相关肝炎。
接受 R-CHOP 化疗的弥漫性大 B 细胞淋巴瘤 HBsAg 阳性患者的 TDF 预防性治疗安全有效，可预防 HBV 相关肝炎。然而，由于停止 TDF 后 HBV 相关肝炎的发生率相对较高，应推荐长期维持 TDF 预防性治疗策略（ClinicalTrials.gov ID：NCT02354846）。
