Abstract：
Tenofovir disoproxil fumarate (TDF) is effectively used as the first-line antiviral for chronic hepatitis B virus (HBV) infection in adults and children older than 12 years. To date, no confirmed case of virologic breakthrough (VBT) in a pediatric case has been reported.
Here we describe a case of a 5-year old, asymptomatically infected with HBV infection two months after chemotherapy for precursor B acute lymphoblastic leukemia (ALL). Although the 5-year old male is South African, his family originated from Guinea. At the end of the one-year follow-up, the infection progressed to chronic HBV infection, with a high viral load. At 36 weeks (8 months) post-treatment with lamivudine (LAM), there was a partial virologic response (PVR) and after 61 weeks (14 months), he was switched to TDF rescue monotherapy. Even with TDF treatment, he still experienced VBT and subsequent PVR. The full-length genome of HBV isolated 78 weeks after the switch to rescue TDF monotherapy was sequenced and belonged to genotype E. In addition to the LAM mutations (rtS256G and rtM267L), missense mutations in B-cell, T-cell, HLA class I and II-restricted epitopes emerged, which were to evade and escape host surveillance, leading to delayed viral clearance, persistence and disease progression. Two further events of VBT occurred between weeks 113 and 141 of TDF rescue-therapy. Viral loads and liver enzymes are normalizing progressively with long-term therapy.
Although the host immune reconstitution may be delayed, prolonged TDF treatment was effective in treating this pediatric case of HBV infection with VBT and PVR.
Here we describe a case of a 5-year old, asymptomatically infected with HBV infection two months after chemotherapy for precursor B acute lymphoblastic leukemia (ALL). Although the 5-year old male is South African, his family originated from Guinea. At the end of the one-year follow-up, the infection progressed to chronic HBV infection, with a high viral load. At 36 weeks (8 months) post-treatment with lamivudine (LAM), there was a partial virologic response (PVR) and after 61 weeks (14 months), he was switched to TDF rescue monotherapy. Even with TDF treatment, he still experienced VBT and subsequent PVR. The full-length genome of HBV isolated 78 weeks after the switch to rescue TDF monotherapy was sequenced and belonged to genotype E. In addition to the LAM mutations (rtS256G and rtM267L), missense mutations in B-cell, T-cell, HLA class I and II-restricted epitopes emerged, which were to evade and escape host surveillance, leading to delayed viral clearance, persistence and disease progression. Two further events of VBT occurred between weeks 113 and 141 of TDF rescue-therapy. Viral loads and liver enzymes are normalizing progressively with long-term therapy.
Although the host immune reconstitution may be delayed, prolonged TDF treatment was effective in treating this pediatric case of HBV infection with VBT and PVR.
摘要：
富马酸替诺福韦酯（TDF）有效地用作成人和12岁以上儿童慢性乙型肝炎病毒（HBV）感染的一线抗病毒药物。迄今为止,尚未报道儿科病例中病毒学突破（VBT）的确诊病例。
这里我们描述一个5岁孩子的案例,在前体B急性淋巴细胞白血病（ALL）化疗后两个月，无症状感染HBV感染。虽然5岁的男性是南非人，他的家族起源于几内亚。在为期一年的随访结束时，感染进展为慢性HBV感染，病毒载量高.在拉米夫定（LAM）治疗后36周（8个月），有部分病毒学应答（PVR），61周后（14个月），他被切换到TDF抢救单一疗法。即使使用TDF治疗，他仍然经历了VBT和随后的PVR。在转换为拯救TDF单一疗法后78周，对HBV分离的全长基因组进行了测序，属于基因型E。除了LAM突变（rtS256G和rtM267L）之外，B细胞错义突变,T细胞,HLAI类和II类限制性表位出现，逃避和逃避主机监视，导致病毒清除延迟，持久性和疾病进展。在TDF抢救治疗的第113周和第141周之间发生了另外两个VBT事件。通过长期治疗，病毒载量和肝酶逐渐正常化。
尽管宿主的免疫重建可能会延迟，延长TDF治疗是有效的治疗这种儿童HBV感染的VBT和PVR。
这里我们描述一个5岁孩子的案例,在前体B急性淋巴细胞白血病（ALL）化疗后两个月，无症状感染HBV感染。虽然5岁的男性是南非人，他的家族起源于几内亚。在为期一年的随访结束时，感染进展为慢性HBV感染，病毒载量高.在拉米夫定（LAM）治疗后36周（8个月），有部分病毒学应答（PVR），61周后（14个月），他被切换到TDF抢救单一疗法。即使使用TDF治疗，他仍然经历了VBT和随后的PVR。在转换为拯救TDF单一疗法后78周，对HBV分离的全长基因组进行了测序，属于基因型E。除了LAM突变（rtS256G和rtM267L）之外，B细胞错义突变,T细胞,HLAI类和II类限制性表位出现，逃避和逃避主机监视，导致病毒清除延迟，持久性和疾病进展。在TDF抢救治疗的第113周和第141周之间发生了另外两个VBT事件。通过长期治疗，病毒载量和肝酶逐渐正常化。
尽管宿主的免疫重建可能会延迟，延长TDF治疗是有效的治疗这种儿童HBV感染的VBT和PVR。
