Next generation sequencing screening for human parvovirus B19 infection after liver transplantation and the analysis of related risk factors
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摘要:
目的 总结肝移植术后人类细小病毒(HPV)B19感染的筛查方法并分析相关危险因素。 方法 回顾性分析86例受者的临床资料。根据二代测序(NGS) 结果 分为HPV B19感染组和对照组, 分析HPV B19感染患者的临床特点、治疗方案及预后, 采用单因素和多因素Logistic回归向前LR逐步法分析HPV B19感染的危险因素。结果86例受者中9例受者肝移植术后2周左右出现不明原因发热伴进行性贫血, NGS检测提示HPV B19阳性, 诊断为HPV B19感染引起的纯红细胞再生障碍性贫血(PRCA)。所有患者给予静脉注射用免疫球蛋白(IVIG)治疗及免疫抑制方案调整后, 血红蛋白水平明显回升。多因素分析结果显示, 患者术后7 d外周血清球蛋白水平低[比值比(OR)=0.749, P=0.040]、年轻患者(OR=0.937, P=0.038)是肝移植术后HPV B19感染的独立危险因素。 结论 对于肝移植术后早期出现不明原因的血红蛋白水平下降的相对年轻患者, 需考虑HPV B19感染。NGS筛查是早期诊断HPV B19感染的有效方法。患者术后7 d外周血清球蛋白水平低和年龄(年轻患者)可能是其发生的独立危险因素。 -
关键词:
- 肝移植 /
- 人类细小病毒B19 /
- 纯红细胞再生障碍性贫血 /
- 二代测序 /
- 危险因素 /
- 感染 /
- 免疫排斥反应 /
- 心脏死亡器官捐献 /
- 静脉注射用免疫球蛋白 /
- 人类疱疹病毒
Abstract:Objective To summarize the screening Methods for human parvovirus (HPV) B19 infection after liver transplantation and analyze the related risk factors. Methods Clinical data of 86 recipients were retrospectively analyzed. According to the Results of next generation sequencing (NGS), all recipients were divided into the HPV B19 infection group and control group. Clinical characteristics, treatment regime and clinical prognosis of patients infected with HPV B19 were analyzed. The risk factors of HPV B19 infection were analyzed using univariate and multivariate Logistic regression model by forward LR step method. Results Nine of the 86 recipients developed fever and progressive anemia with unexplained reasons at approximately 2 weeks after liver transplantation. NGS detection demonstrated that HPV B19 was positive and they were diagnosed with pure red cell aplasia (PRCA) caused by HPV B19 infection. After intravenous immunoglobulins (IVIG) was given and the immunosuppressant therapy was adjusted, the hemoglobin levels in all patients were significantly increased. The Results of multivariate analysis revealed that low serum globulin level in peripheral blood at postoperative 7 d [odds ratio (OR) =0.749, P=0.040] and young age (OR=0.937, P=0.038) were the independent risk factors of HPV B19 infection after liver transplantation. Conclusions HPV B19 infection should be considered in relatively young patients with unexplained hemoglobin decline early after liver transplantation. NGS screening is an effective method for early diagnosis of HPV B19 infection. Low serum globulin level in peripheral blood at postoperative 7 d and young age may be independent risk factors of the incidence of HPV B19 infection. -
表 1 肝移植术后HPV B19感染患者一般情况
Table 1. General situation of patients with HPV B19 infection after liver transplantation
例序 年龄(岁) 性别 合并感染情况 治疗前血常规 治疗后血常规 Hb(g/L) WBC(×109/L) PLT(×109/L) Hb(g/L) WBC(×109/L) PLT(×109/L) 1 39 男 HHV 5型 50 7 259 92 6 207 2 46 男 – 86 3 100 116 5 108 3 18 女 HHV 5型 64 2 81 116 5 150 4 39 男 – 71 2 187 120 6 253 5 38 男 HHV 6B型 85 3 212 110 9 224 6 35 女 – 54 10 70 96 14 235 7 51 男 HHV 5型 66 8 189 121 4 221 8 47 男 – 78 2 46 112 5 111 9 38 男 HHV 5型 77 9 113 122 10 182 –表示无; HHV为人类疱疹病毒; Hb为血红蛋白; WBC为白细胞; PLT为血小板 表 2 肝移植术后受者HPV B19感染的单因素分析
Table 2. Univariate analysis of HPV B19 infection in recipients after liver transplantation
变量 感染组(n=9) 对照组(n=77) P值 性别[n(%)] 男 7(78) 56(73) 1.000 a 女 2(22) 21(27) 年龄[M(R),岁] 39(10) 50(12) 0.003 c 术前消化道出血情况[n(%)] 有 1(11) 3(4) 0.363 b 否 8(89) 74(96) 术前胆红素水平[M(R),μ mol/L] 260(379) 31(123) 0.041 c 术前血清肌酐水平[M(R),μ mol/L] 63(18) 64(24) 0.849 c 术前PT-INR [M(R)] 2.1(1.4) 1.3(0.6) 0.034 c 术前PT [M(R),s] 22(14) 15(8) 0.061 c 术前淋巴细胞绝对值[M(R),×109/L] 1.3(0.5) 1.0(0.5) 0.076 c MELD评分[M(R),分] 25(21) 11(13) 0.043 c 手术时间[n(%)] ≥ 7 h 2(22) 33(43) 0.404 a < 7 h 7(78) 44(57) 术中出血量[n(%)] ≥ 1 L 7(78) 57(74) 1.000 a < 1 L 2(22) 20(26) 术中输血量[n(%)] ≥ 1.5 L 6(67) 35(45) 0.394 a <1.5 L 3(33) 42(55) 术后7 d外周血清球蛋白水平[M(R),g/L] 22(3) 23(5) 0.006 c 住院时间[n(%)] ≥ 30 d 6(67) 34(44) 0.353 a < 30 d 3(33) 43(56) a使用连续校正的χ2检验; b使用Fisher确切概率法; c使用Mann-Whitney U秩和检验; PT为凝血酶原时间 -
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