Petrovic L M, Villamil F G, Vierling J M, Makowka L, Geller S A
Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
Liver Transpl Surg. 1997 Jul;3(4):398-406. doi: 10.1002/lt.500030407.
Recurrent hepatitis C infection after orthotopic liver transplantation (OLT) is frequent and may occur as early as a few weeks postoperatively. Early histopathological features of recurrent hepatitis C virus (HCV) infection may be modified by immunosuppressive therapy and can be difficult to differentiate from acute allograft rejection (AAR). Thus, we retrospectively compared histopathological features of liver biopsy specimens from two carefully selected patient groups: one with unequivocal recurrent hepatitis C, the other with unequivocal AAR. Index biopsy specimens obtained at the time of the appearance of liver test abnormalities after OLT and all serial liver biopsy specimens (2 to 13 per patient) were assessed under code and scored semiquantitatively for 44 histopathological variables. The index biopsy specimens from patients with recurrent HCV infection and AAR index biopsies (AAR-Ib) differed significantly (P < .05) for 11 features (10 features were statistically associated with AAR and 1 with early recurrence of HCV infection). Statistically significant features associated with AAR included bile duct injury with overlapping nuclei, lymphocytic infiltrates and necrosis, endothelialitis, portal inflammatory infiltrates containing eosinophils and polymorphonuclear leukocytes, hepatocyte mitoses, and zone 3 canalicular cholestasis. In contrast, the only statistically significant feature associated with early recurrent HCV was sinusoidal dilatation. Stepwise discriminant analysis showed that the presence of eosinophils in the portal inflammatory infiltrate, bile duct necrosis, and bile duct lymphocytic infiltrates were independently associated with AAR. However, serial biopsy specimens from patients with recurrent HCV infection showed statistically significant progression in scores for portal inflammation, portal lymphoid aggregates, and lobular inflammation. We conclude that (1) multiple histopathological features are associated with AAR; (2) early recurrent HCV infection is characterized by elevated alanine aminotransferase levels, positive HCV RNA by polymerase chain reaction (PCR), and absence of diagnostic histopathological features; and (3) serial biopsies are needed to demonstrate progression of histopathological features of recurrent hepatitis C.
原位肝移植（OLT）后丙型肝炎复发感染很常见，可能早在术后几周就会发生。复发性丙型肝炎病毒（HCV）感染的早期组织病理学特征可能会受到免疫抑制治疗的影响，难以与急性移植物排斥反应（AAR）区分开来。因此，我们回顾性比较了两组精心挑选患者的肝活检标本的组织病理学特征：一组为明确的复发性丙型肝炎患者，另一组为明确的AAR患者。对OLT后出现肝功能检查异常时获取的索引活检标本以及所有系列肝活检标本（每位患者2至13份）进行编码评估，并对44个组织病理学变量进行半定量评分。复发性HCV感染患者的索引活检标本与AAR索引活检（AAR-Ib）在11个特征上存在显著差异（P <.05）（10个特征与AAR有统计学关联，1个与HCV感染早期复发有关）。与AAR相关的具有统计学意义的特征包括细胞核重叠的胆管损伤、淋巴细胞浸润和坏死、内皮细胞炎、含有嗜酸性粒细胞和多形核白细胞的门静脉炎性浸润、肝细胞有丝分裂以及3区胆小管胆汁淤积。相比之下，与早期复发性HCV相关的唯一具有统计学意义的特征是肝血窦扩张。逐步判别分析表明，门静脉炎性浸润中嗜酸性粒细胞的存在、胆管坏死和胆管淋巴细胞浸润与AAR独立相关。然而，复发性HCV感染患者的系列活检标本显示门静脉炎症、门静脉淋巴样聚集和小叶炎症的评分有统计学意义的进展。我们得出结论：（1）多种组织病理学特征与AAR相关；（2）早期复发性HCV感染的特征是丙氨酸氨基转移酶水平升高、聚合酶链反应（PCR）检测HCV RNA呈阳性，且缺乏诊断性组织病理学特征；（3）需要进行系列活检以证明复发性丙型肝炎组织病理学特征的进展。
