Seehofer Daniel, Rayes Nada, Tullius Stefan G, Schmidt Christian A, Neumann Ulf P, Radke Cornelia, Settmacher Utz, Müller Andrea R, Steinmüller Thomas, Neuhaus Peter
Department of General, Visceral, and Transplant Surgery, Charité Campus Virchow, Humboldt University of Berlin, Berlin, Germany.
Liver Transpl. 2002 Dec;8(12):1138-46. doi: 10.1053/jlts.2002.36732.
Cytomegalovirus (CMV) hepatitis is described as the most frequent manifestation of CMV tissue invasive disease after liver transplantation. Its correlation with HLA-matching, hepatic artery thrombosis, and chronic rejection is still controversial. Risk factors, incidence, clinical course, and complications of CMV hepatitis were retrospectively analyzed in a 12-year series of 1,146 consecutive liver transplantations in 1,054 patients. All patients received only low-dose acyclovir but no gancyclovir prophylaxis. CMV infection was diagnosed by viral culture, pp65 antigenemia, or by polymerase chain reaction (PCR). CMV hepatitis was proven by liver biopsy. Treatment of CMV disease consisted of intravenous ganciclovir for a minimum of 14 days. Long-term follow-up of patients included monthly routine laboratory values and routine liver biopsies 1, 3 and 5 years after transplantation. CMV hepatitis was a rare event after liver transplantation, with a total incidence of 2.1% (24 cases). It was significantly more frequent in CMV seronegative (5.2%) than in seropositive recipients (0.7%). The leading indication in patients with CMV hepatitis was HCV cirrhosis (n = 8). The maximum number of pp65 positive white blood cells was 82 +/- 23 per 10,000 cells. Most courses manifested as isolated hepatitis; only 2 patients had disseminated disease. Nine of 24 patients had received OKT3 monoclonal antibodies because of steroid-resistant rejection before CMV hepatitis. In seronegative patients with CMV hepatitis, 71% revealed 1 or 2 HLA DR matches, in contrast to 32% in patients without CMV hepatitis. One-, 3-, and 5-year graft survival was 78%, 65%, and 59% in patients with CMV hepatitis compared with 88%, 81%, and 79% in patients without. Chronic rejection was observed in one patient, but already before onset of CMV hepatitis. Beneath D+R-constellation and OKT3 treatment as risk factors, HLA DR-matched grafts and HCV seem to favor manifestation of CMV hepatitis after liver transplantation. Long-term complications of CMV hepatitis were not observed, and especially no correlation with chronic rejection was found.
巨细胞病毒（CMV）肝炎被认为是肝移植后CMV组织侵袭性疾病最常见的表现形式。其与人类白细胞抗原（HLA）匹配、肝动脉血栓形成及慢性排斥反应之间的相关性仍存在争议。我们对1054例患者连续进行的1146例肝移植手术的12年系列病例进行回顾性分析，以研究CMV肝炎的危险因素、发病率、临床病程及并发症。所有患者仅接受低剂量阿昔洛韦治疗，未进行更昔洛韦预防性治疗。通过病毒培养、pp65抗原血症或聚合酶链反应（PCR）诊断CMV感染。通过肝活检证实为CMV肝炎。CMV疾病的治疗包括静脉注射更昔洛韦至少14天。对患者的长期随访包括移植后1年、3年和5年每月的常规实验室检查结果及常规肝活检。CMV肝炎在肝移植后是一种罕见事件，总发病率为2.1%（24例）。在CMV血清阴性受者中（5.2%）比血清阳性受者中（0.7%）明显更常见。CMV肝炎患者的主要指征是丙型肝炎病毒（HCV）肝硬化（n = 8）。每10000个细胞中pp65阳性白细胞的最大数量为82±23。大多数病程表现为孤立性肝炎；只有2例患者有播散性疾病。24例患者中有9例在发生CMV肝炎之前因激素抵抗性排斥反应接受了OKT3单克隆抗体治疗。在CMV肝炎的血清阴性患者中，71%显示1或2个HLA DR匹配，而无CMV肝炎患者中这一比例为32%。CMV肝炎患者1年、3年和5年的移植物存活率分别为78%、65%和59%，而无CMV肝炎患者分别为88%、81%和79%。在1例患者中观察到慢性排斥反应，但在CMV肝炎发病之前就已出现。除了D+R-组合和OKT3治疗作为危险因素外，HLA DR匹配的移植物和HCV似乎有利于肝移植后CMV肝炎的表现。未观察到CMV肝炎的长期并发症，尤其未发现其与慢性排斥反应之间的相关性。
