总结分析肝移植术后早期人类微小病毒B19(HPV-B19)宏基因组二代测序(mNGS)筛查阳性受者HPV-B19感染特点及临床诊疗经验。

回顾性分析2021年6月至2022年2月于江西省人民医院器官移植科接受肝移植且术后早期(术后第5~10天)mNGS检测HPV-B19阳性的21例受者临床资料，21例受者同期完善定量聚合酶链反应(qPCR)检测，当HPV-B19 DNA>1×10³拷贝/mL时则为qPCR检测阳性。对21例受者检测结果、感染情况、发病特点和诊疗方法等进行总结分析。正态分布计量资料采用配对t检验进行比较，计数资料采用卡方检验进行比较，P<0.05为差异有统计学意义。

21例受者均抽取静脉血行mNGS检测，其中3例因术后存在肺部感染，另行支气管镜检查取肺泡灌洗液标本进行mNGS检测，余18例留取深部痰标本行mNGS检测。21例受者中7例qPCR检测阳性，占33.3%。21例受者在接受干预性治疗前均有不同程度的贫血表现，期间血红蛋白最低值为(75±11)g/L。21例受者中20例mNGS检测阳性后即予降低免疫抑制强度处理，余1例未调整免疫抑制方案，仅作观察处理。21例受者中9例移植后血红蛋白水平持续下降，予输血治疗；9例受者中4例除予输注红细胞悬液外，还给予静脉注射免疫球蛋白(IVIG)治疗。21例受者治疗前CD4⁺/CD8⁺ T细胞为(1.12±0.47)，治疗后1个月为(1.51±0.72)，差异有统计学意义(t＝－2.106，P<0.05)；治疗前CD4⁺和CD8⁺ T细胞计数分别为(236±130)个/μL和(212±98)个/μL，治疗后1个月分别为(284±252)个/μL和(174±108)个/μL，前后差异均无统计学意义(t＝－0.779和1.182，P均>0.05)。21例受者术后1、3个月血红蛋白水平分别为(108±15)g/L和(130±15)g/L；术后3个月HPV-B19 DNA qPCR复查均为阴性。随访至2022年5月，所有肝移植受者贫血症状均得到改善，不需要输注红细胞悬液或IVIG治疗。

对于肝移植术后mNGS早期筛查HPV-B19阳性受者，通过予降低免疫抑制强度为主的治疗方案，大部分受者贫血症状可得到有效控制；对于持续性贫血受者采用降低免疫抑制强度联合输血的治疗方案，效果不佳时予小剂量IVIG治疗效果好；对于qPCR检测阳性的肝移植受者，单纯降低免疫抑制强度治疗效果不佳。

To summarize and analyze the infectious characteristics of early human parvovirus B19 (HPV-B19) positive liver transplant recipients with metagenomic next-generation sequencing (mNGS) detection after transplantation and the relevant clinical experience of diagnosis and treatment.

The clinical data of 21 recipients who underwent liver transplantation in the Department of Organ Transplantation of Jiangxi Provincial People′s Hospital from June 2021 to February 2022 and were early HPV-B19 positive with mNGS detection after transplantation (postoperative days 5 to 10) were retrospectively analyzed. Quantitative polymerase chain reaction (qPCR) was used to detect the HPV-B19 in 21 recipients during the same period, and HPV-B19 DNA > 1×10³ copies/mL was considered as HPV-B19 positive. The detection results, infection status, disease characteristics, diagnosis and treatment methods of 21 recipients were summarized and analyzed. Normally distributed measurement data were compared using the paired t-test, and enumeration data were compared using the Chi-square test. P<0.05 was considered statistically significant.

Venous blood samples of all 21 recipients were detected, of which 3 were additionally examined by bronchoscopy for mNGS from bronchoalveolar lavage fluid samples due to the presence of pulmonary infection after transplantation, and the remaining 18 deep sputum samples were detected by mNGS. Seven (33.3%) of 21 recipients were positive with qPCR for HPV-B19. All recipients had varying degrees of anemia before treatment, during which the lowest hemoglobin value was (75±11) g/L. the dosage of immune drugs of 20 among the 21 recipients was reduced immediately after mNGS, and the remaining 1 case was only observed. Nine of the 21 recipients with a continuous decrease in hemoglobin levels after transplantation and were treated with blood transfusion. Four of the nine recipients were treated with intravenous immunoglobulin (IVIG) in addition to having to transfuse red blood cell suspension. CD4⁺ /CD8⁺ T cells in 21 recipients were (1.12±0.47) and (1.51±0.72) before and 1 month after treatment, respectively, and the difference was statistically significant (t=-2.106, P<0.05). CD4⁺ and CD8⁺ counts were (236±130)/μL and (212±98)/μL before treatment, and (284±252)/μL and (174±108)/μL 1 month after treatment, respectively, and the differences were not statistically significant (t=-0.779 and 1.182, all P>0.05). Hemoglobin was (108±15) and (130±15) g/L at 1 and 3 months after transplantation in 21 recipients, respectively. HPV-B19 DNA qPCR reexamination was negative at 3 months after surgery for all recipients. During follow-up until May 2022, 21 recipients showed significant improvement in anemia symptoms and did not require red blood cell transfusion or IVIG therapy.

For HPV-B19 positive recipients screened early by mNGS after liver transplantation, anemia symptoms could be effectively controlled in most recipients by giving a treatment regimen based on reducing the intensity of immunosuppression. For recipients with persistent anemia, a treatment regimen of reducing the intensity of immunosuppression combined with blood transfusion can be considered, and low-dose IVIG was effective when the effect was poor. For liver transplant recipients tested positive for HPV-B19 via qPCR, the treatment effect of reducing the intensity of immunosuppression alone can not be satisfied.