巨细胞病毒 IgM 阳性相关胆道闭锁的辅助治疗：初步的疗效证据。
Adjuvant therapy of cytomegalovirus IgM + ve associated biliary atresia: Prima facie evidence of effect.
机构信息
Department of Paediatric Surgery, Denmark Hill, London, UK SE5 9RS; Department of Hepatology Kings College Hospital, Denmark Hill, London, UK SE5 9RS.
Department of Paediatric Surgery, Denmark Hill, London, UK SE5 9RS; Department of Hepatology Kings College Hospital, Denmark Hill, London, UK SE5 9RS.
出版信息
J Pediatr Surg. 2019 Sep;54(9):1941-1945. doi: 10.1016/j.jpedsurg.2018.12.014. Epub 2019 Jan 22.
AIM OF STUDY
CMV-IgM + ve associated biliary atresia (CMV-BA) is a distinct etiological subgroup characterized by older age at presentation and a greater degree of inflammation and hepatic fibrosis, leading to a worse outcome. We report our experience with adjuvant antiviral therapy after Kasai portoenterostomy (KPE).
METHODS
Single-center prospective database identification of CMV-IgM + ve associated BA managed between 2003 and 2017. Since 2011, IV ganciclovir (5 mg/kg b.d.) and/or oral valganciclovir (520 mg/m b.d.) were started in the early postoperative period in selected cases and continued until negativity of CMV DNA load [Anti-Viral Therapy (AVT) Group 1]. Clearance of jaundice was defined as achieving a total bilirubin ≤20 μmol/L in post-KPE period and tested with a Fisher test; native liver survival (NLS) and overall actuarial survival (OS) were compared with untreated BA CMV IgM + ve patients (Group 2) using a Log-Rank test. A P value of <0.05 was regarded as significant. Data are quoted as median (IQ range).
RESULTS
During the 14-year period, 376 infants with histologically confirmed BA were treated; of those 38(10%) were CMV IgM + ve at presentation. One child was considered too late at presentation for KPE and underwent primary liver transplantation while another only started AVT one month after KPE. Both were excluded from survival analysis. Therefore 36 underwent KPE [AVT Group 1 (n = 8) and Control Group 2 (n = 28)]. Overall age at surgery was 67(53-77) days. There was no difference in age at surgery (P = 0.26); bilirubin (P = 0.12); or AST (P = 0.15) between Group 1 and Group 2. Viral load data were available in 16 with a trend towards higher counts in the AVT group 1 [4935 (2668-18,817) vs. 1296 (253-10,471) c/ml; P = 0.06]. Clearance of jaundice was higher in AVT Group 1 (75% vs 21%, P = 0.009). There was no difference in OS (P = 0.24) but NLS was improved in the AVT Group 1 (75% vs. 25% at 2 years; P = 0.04).
CONCLUSIONS
Although this finding may be regarded as preliminary, adjuvant antiviral therapy appeared to improve outcome in infants with CMV IgM + ve BA.
LEVEL OF EVIDENCE
III.
研究目的
巨细胞病毒免疫球蛋白 M（CMV-IgM）阳性相关胆道闭锁（CMV-BA）是一个独特的病因亚组，其特征为发病年龄较大，炎症和肝纤维化程度更高，导致预后更差。我们报告了我们在胆肠吻合术后（KPE）辅助抗病毒治疗方面的经验。
方法
在 2003 年至 2017 年期间，我们对单中心前瞻性数据库中 CMV-IgM 阳性相关 BA 进行了识别。自 2011 年以来，在选定的病例中，术后早期开始静脉注射更昔洛韦（5mg/kg，每日两次）和/或口服缬更昔洛韦（520mg/m，每日两次），并持续至 CMV DNA 载量转阴[抗病毒治疗（AVT）组 1]。术后黄疸消退定义为 KPE 后总胆红素≤20μmol/L，并通过 Fisher 检验进行检测；采用 Log-Rank 检验比较无治疗 BA CMV IgM 阳性患者（组 2）的原发性肝存活率（NLS）和总体累积存活率（OS）。P 值<0.05 被认为具有统计学意义。数据以中位数（IQR 范围）表示。
结果
在 14 年期间，376 名经组织学证实患有 BA 的婴儿接受了治疗；其中 38 名（10%）在就诊时 CMV IgM 阳性。有 1 名患儿因就诊太晚而不适合 KPE，并接受了肝移植，另 1 名患儿在 KPE 后 1 个月才开始接受 AVT。这两名患儿均被排除在生存分析之外。因此，共有 36 名患儿接受了 KPE[AVT 组 1（n=8）和对照组 2（n=28）]。手术时的总体年龄为 67（53-77）天。组 1 和组 2 之间的手术年龄（P=0.26）、胆红素（P=0.12）或 AST（P=0.15）无差异。16 名患儿有病毒载量数据，AVT 组 1 的病毒载量有升高趋势[4935（2668-18817）vs. 1296（253-10471）copies/ml；P=0.06]。AVT 组 1 的黄疸消退率更高（75% vs. 21%，P=0.009）。两组的 OS 无差异（P=0.24），但 AVT 组 1 的 NLS 有所改善（2 年时 75% vs. 25%；P=0.04）。
结论
尽管这一发现可能被认为是初步的，但辅助抗病毒治疗似乎改善了 CMV-IgM 阳性 BA 婴儿的预后。
证据水平
III。
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