Successful resolution of severe graft versus host disease after liver transplantation correlating with disappearance of donor DNA from the peripheral blood
Successful resolution of severe graft versus host disease after liver transplantation correlating with disappearance of donor DNA from the peripheral blood
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DOI：
10.1111/j.1445-5994.1998.tb01563.x
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发表时间：
1998-12-01
期刊：
影响因子：
--
通讯作者：
Grigg, AP
中科院分区：
文献类型：
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作者：
Paizis, G;Tait, BD;Grigg, AP
虽然急性移植物抗宿主病（GVHD）是异基因骨髓移植的常见并发症，但在实体器官移植后很少见到。自1988年以来，只有13例肝移植后的报告。'.“然而，真实的发病率可能被低估，因为轻度病例可能仍然未被诊断，因为发烧，皮疹和腹泻的临床特征可能被误解为移植后环境中的感染源。毫不奇怪，报告病例的死亡率很高，因为这些患者通常患有严重的、有症状的和临床上明显的疾病。这些患者中的大多数在长期的疾病诱导的中性粒细胞减少和强效免疫抑制治疗的背景下死于机会性感染。本报告记录了肝移植后的一种严重形式的GVHD，其中迅速引入强化免疫抑制治疗以及生长因子支持导致了成功的结果。我们证明了供体DNA在患者外周血中的消失与GVHD的临床解决之间的密切相关性。一位56岁意大利背景的男性因继发于B、C和δ型肝炎的慢性肝病接受原位肝移植。术后开始常规三联免疫抑制治疗，泼尼松龙硫唑嘌呤1.5 mg/kg/d和环孢菌素10 mg/kg/d。第一周每天肌肉注射B型肝炎免疫球蛋白，然后每周两次。开始使用复方新诺明预防肺孢子虫病，患者于术后第18天出院。三天后，他因间歇性发烧至38 ℃而入院。败血症的调查，包括巨细胞病毒培养，是徒劳的，发烧未能响应广谱抗生素。第30天，出现斑丘疹性躯干皮疹，累及面部和四肢。由于药疹和血清病可能是病因，因此停用复方新诺明和B型肝炎免疫球蛋白。在第36天进行的皮肤活检显示表皮基底细胞的显著空泡化和分散的凋亡性坏死，表皮的淋巴细胞浸润，与GVHD一致。入院后2周内，患者出现重度溃疡性口腔粘膜炎，但无腹泻或腹痛，进行性全血细胞减少症（尽管第27天停用硫唑嘌呤），第38天血红蛋白最低值为5.7 g/dL，中性粒细胞计数为0.3 X 109 L（图1）。第50天血小板最低值为59 × 109 L，两周后恢复正常。在第36天开始为期10天的治疗疗程，最初每天使用OKT 3 5 mg和高剂量甲基强的松龙1000 mg，在一周内逐渐减少至100 mg。停用环孢菌素，并更换为他克莫司5 mg bd。摇摆热在给予高剂量类固醇后12小时内消退。第36天开始粒细胞集落刺激因子（G-CSF）5 pglkgl天，到第40天导致中性粒细胞计数增加，此后持续增加（图1）。给予更昔洛韦治疗CMV再激活。给予局部抗真菌药，并对他进行隔离护理。重新开始使用B型肝炎免疫球蛋白，并雾化喷他脒300 mg用于持续的肺孢子虫预防。
While acute graft versus host disease (GVHD) is a common complication of allogeneic bone marrow transplantation, it is seen rarely following solid organ transplantation. Since 1988, only 13 cases have been reported after liver transplantation.'.'The true incidence, however, is likely to be underestimated since mild cases may remain undiagnosed as the clinical features of fever, rash and diarrhoea can be misinterpreted as being of infectious origin in the post transplant setting. Not surprisingly, mortality in reported cases is high as these patients typically have severe, symptomatic and clinically apparent disease. Most of these patients have died of opportunistic infections in the context of prolonged disease-induced neutropenia and powerful immunosuppression therapy. Others who have su+ ived the disease have succumbed subsequently'to lymphoproliferative This report documents a severe form of GVHD following liver transplantation in which the prompt introduction of intensive immunosuppressive therapy together with growth factor support resulted in a successful outcome. We demonstrate a close correlation between the disappearance of donor DNA in the patient's peripheral blood and clinical resolution of the GVHD. A 56-year-old male of Italian background underwent orthotopic liver transplantation for chronic liver disease secondary to B, C and delta hepatitis. Routine triple immunosuppressive therapy was commenced post operatively with prednisolone azathioprine 1.5 mgilzgtday and cyclosporin 10 mg/kg/day. Intramuscular hepatitis B immunoglobulin was given daily for the first week and then twice weekly. Pneumocystis prophylaxis was commenced with cotrimoxazole and the patient was discharged on the 18th postoperative day. He was admitted three days later with intermittent fevers to 38 C. Investigations for sepsis, including CMV cultures, were unrewarding and the fever failed to respond to broad spectrum antibiotics. On day 30 a maculopapular truncal rash appeared which involved the face and extremities. Both cotrimoxazole and hepatitis B immunoglobulin were ceased, as a drug eruption and serum sickness were possible aetiologies. A skin biopsy performed on day 36 demonstrated marked vacuolation of epidermal basal cells and scattered apoptotic necrosis, with lymphocytic infiltration of the epidermis, consistent with GVHD. In the two weeks after admission, he developed severe ulcerative oral mucositis, although without diarrhoea or abdominal pain, and progressive pancytopenia (despite cessation of azothiaprine on day 27) with a nadir haemoglobin of 5.7 g/dL and neutrophil count of 0.3 X 109L on day 38 (Figure 1). The platelet nadir of 59X 1 0 9 L occurred on day 50 and normalised two weeks later. A ten day treatment course with OKT3 5 mg daily and high dose methylprednisolone 1000 mg daily initially, tapering to 100 mg over one week, was commenced on day 36. Cyclosporin was discontinued and replaced with tacrolimus 5 mg bd. The swinging fevers resolved within 12 hours of the administration of high dose steroids. Granulocyte-colony stimulating factor (G-CSF) 5 pglkglday was commenced on day 36 and resulted by day 40 in an increase in neutrophil count which persisted thereafter (Figure 1). Ganciclovir was given prophylactically for CMV reactivation. Topical antifungals were administered and he was nursed in isolation. Hepatitis B immunoglobulin was recommenced and nebulised pentamidine 300 mg given for ongoing pneumocystis prophylaxis.