Yeh Matthew M, Larson Anne M, Tung Bruce Y, Swanson Paul E, Upton Melissa P
Department of Pathology, University of Washington School of Medicine, Seattle, Washington 98195-6100, USA.
Am J Surg Pathol. 2006 Jun;30(6):727-33. doi: 10.1097/00000478-200606000-00008.
Endotheliitis is an important histologic feature of acute cellular rejection (ACR) in the liver allograft. This change is not specific, however, and has been suggested to be associated with various liver diseases. End-stage liver disease owing to chronic hepatitis C is the leading indication for transplantation in North America, and its recurrence in allograft recipients is common. Because the presence of endotheliitis remains a diagnostic and therapeutic dilemma in transplant pathology, we investigated the prevalence and severity of endotheliitis in chronic liver diseases including hepatitis C. Endotheliitis was evaluated in 128 nontransplant liver biopsies of chronic liver diseases before therapy, including hepatitis C (HCV, n=62), hepatitis B (HBV, n=17), and nonalcoholic steatohepatitis (NASH, n=49). Eighty posttransplant biopsies with ACR were also reviewed. Subendothelial and supraendothelial endotheliitis were separately scored in the portal and central regions using a semiquantitative scoring system from 0 to 4. Pathologists were blinded to the clinical histories, and each biopsy was independently scored by 2 pathologists. Histologic activity index was also scored subsequently for cases of chronic HCV and HBV, using the modified Knodell (Ishak) score. Mean endotheliitis scores>1 were seen in 60%, 35%, and 6% of HCV, HBV, and NASH patients, respectively. The scores for portal subendotheliitis and supraendotheliitis were significantly higher in the viral hepatitis group than in the NASH group (P<0.01). There was no significant difference in the scores of endotheliitis comparing HCV to HBV. ACR group showed significantly higher scores in both portal and central subendotheliitis than any other group (P<0.00005). In the HBV and HCV groups with mean scores of portal subendotheliitis>1 (n=44), mean Ishak scores for portal inflammation and periportal injury were 2.43 and 2.34, respectively; whereas in those with less severe portal subendotheliitis (<or=1, n=35), Ishak scores were 1.66 and 1.37, respectively (P=0.00001 for portal inflammation and P=0.00001 for periportal injury, respectively). Our results suggest that minimal to mild subendotheliitis is common in portal veins in chronic hepatitis C and B, but is significantly less intense than that seen in ACR. The degree of endotheliitis correlates with inflammatory activity. These observations may help minimize the risk of overdiagnosing ACR when the patient has recurrent viral hepatitis, and may help clinicians avoid exposing patients to unnecessary immunosuppressive regimens when patients do not have cellular rejection.
内皮细胞炎是肝移植中急性细胞排斥反应（ACR）的一项重要组织学特征。然而，这种变化并不具有特异性，有人认为它与多种肝脏疾病有关。在北美，丙型肝炎所致终末期肝病是肝移植的主要适应证，且在移植受者中该病复发很常见。由于内皮细胞炎的存在在移植病理学中仍是一个诊断和治疗难题，因此我们研究了包括丙型肝炎在内的慢性肝病中内皮细胞炎的发生率和严重程度。我们对128例慢性肝病患者治疗前的非移植肝活检标本进行了内皮细胞炎评估，这些患者包括丙型肝炎（HCV，n = 62）、乙型肝炎（HBV，n = 17）和非酒精性脂肪性肝炎（NASH，n = 49）。我们还回顾了80例发生ACR的移植后活检标本。使用0至4的半定量评分系统分别对门静脉和中央静脉区域的内皮下和内皮下以上内皮细胞炎进行评分。病理学家对临床病史不知情，每份活检标本由两名病理学家独立评分。随后还对慢性HCV和HBV病例的组织学活动指数进行了评分，采用改良的Knodell（Ishak）评分法。分别在60%、35%和6%的HCV、HBV和NASH患者中观察到平均内皮细胞炎评分>1。病毒性肝炎组门静脉内皮下和内皮下以上内皮细胞炎的评分显著高于NASH组（P<0.01）。比较HCV和HBV，内皮细胞炎评分无显著差异。ACR组门静脉和中央静脉内皮下内皮细胞炎的评分均显著高于其他任何组（P<0.00005）。在门静脉内皮下平均评分>1的HBV和HCV组（n = 44）中，门静脉炎症和门静脉周围损伤的平均Ishak评分分别为2.43和2.34；而在门静脉内皮下炎症较轻（≤1，n = 35）的患者中，Ishak评分分别为1.66和1.37（门静脉炎症P = 0.00001，门静脉周围损伤P = 0.00001）。我们的结果表明，轻度至中度内皮下内皮细胞炎在慢性丙型和乙型肝炎的门静脉中很常见，但比ACR中所见的炎症程度明显较轻。内皮细胞炎的程度与炎症活动相关。这些观察结果可能有助于降低患者发生病毒性肝炎复发时过度诊断ACR的风险，也可能有助于临床医生在患者没有细胞排斥反应时避免让患者接受不必要的免疫抑制治疗方案。
