Rostaing L, Izopet J, Cisterne J M, Arnaud C, Duffaut M, Rumeau J L, Puel J, Durand D
Multi-Organ Transplant Unit, Toulouse University Hospital, France.
Transplantation. 1998 Apr 15;65(7):930-6. doi: 10.1097/00007890-199804150-00012.
The aim of this study was to evaluate the long-term impact of chronic hepatitis C virus (HCV) infection on the liver in renal transplant patients.
We studied 78 patients for whom at least one posttransplant liver biopsy (LB) was available and for whom the duration of HCV infection was precisely defined. The LB were graded according to a histological activity index, i.e., the Knodell score, divided into the activity score and the fibrosis score. They were also classified as either normal or showing evidence of chronic persistent hepatitis, chronic active hepatitis (CAH), or cirrhosis.
The study comprised 7 HCV-positive/hepatitis B surface antigen-positive patients (group 1); 4 HCV-positive/RNA-negative patients (group 2); and 67 HCV-positive/RNA-positive patients (group 3). The three groups were comparable according to demographic data and baseline immunosuppression. The median time from transplantation to LB was 38 months (range, 10-306 months). At that time, alanine aminotransferase (ALT) levels had increased in 71.4%, 0%, and 42% of patients from groups 1, 2, and 3, respectively (P=0.07). The total Knodell score showed significantly more severe lesions in group 1 patients (6.2+/-3.2) than in group 2 (1+/-1.2) or in group 3 (4.6+/-2.4) patients (P=0.007). The Knodell score also showed that the fibrosis score was significantly higher in group 1 (2.3+/-1.6) than in group 2 (0) or in group 3 (0.9+/-1.1) patients (P=0.007). Overall, there were 28 cases of CAH (36%) and 4 cases of cirrhosis (5%). We did not observe any correlation between liver histology and characteristics of HCV infection or the type of chronic immunosuppression (double-drug versus triple-drug therapy). However, liver histology (total Knodell score) and the activity score were significantly correlated with ALT levels. Multivariate analysis did identify (i) four independent variables that could explain the degree of liver fibrosis-the sex of the patient, the number of blood units received before transplantation, increased ALT levels at the time of LB, and the occurrence of at least one acute rejection episode (thus the receipt of methylprednisolone pulses); and (ii) two independent variables associated with the occurrence of CAH-the number of blood units before transplantation and increased ALT levels at the time of LB.
This study showed that renal transplant patients infected by HCV for more than 10 years, with a mean posttransplant follow-up of more than 5 years, showed more severe liver lesions when coinfected by hepatitis B virus. Overall, we observed only four cases of cirrhosis (5%) and evidence of histological CAH lesions in 36% of the patients.
本研究旨在评估慢性丙型肝炎病毒（HCV）感染对肾移植患者肝脏的长期影响。
我们研究了78例患者，这些患者至少有一次移植后肝活检（LB）资料，且HCV感染持续时间明确。根据组织学活动指数（即Knodell评分）对肝活检进行分级，该评分分为活动评分和纤维化评分。肝活检还被分类为正常或显示慢性持续性肝炎、慢性活动性肝炎（CAH）或肝硬化的证据。
该研究包括7例HCV阳性/乙型肝炎表面抗原阳性患者（第1组）；4例HCV阳性/RNA阴性患者（第2组）；以及67例HCV阳性/RNA阳性患者（第3组）。根据人口统计学数据和基线免疫抑制情况，这三组具有可比性。从移植到肝活检的中位时间为38个月（范围为10 - 306个月）。此时，第1组、第2组和第3组患者中谷丙转氨酶（ALT）水平升高的比例分别为71.4%、0%和42%（P = 0.07）。第1组患者的总Knodell评分（6.2±3.2）显示的病变明显比第2组（1±1.2）或第3组（4.6±2.4）患者严重（P = 0.007）。Knodell评分还显示，第1组患者的纤维化评分（2.3±1.6）明显高于第2组（0）或第3组（0.9±1.1）患者（P = 0.007）。总体而言，有28例CAH（36%）和4例肝硬化（5%）。我们未观察到肝脏组织学与HCV感染特征或慢性免疫抑制类型（双药与三药疗法）之间存在任何相关性。然而，肝脏组织学（总Knodell评分）和活动评分与ALT水平显著相关。多变量分析确实确定了：（i）四个可解释肝纤维化程度的独立变量——患者性别、移植前接受的血液单位数量、肝活检时ALT水平升高以及至少发生一次急性排斥反应（因此接受了甲泼尼龙冲击治疗）；以及（ii）两个与CAH发生相关的独立变量——移植前的血液单位数量和肝活检时ALT水平升高。
本研究表明，HCV感染超过10年且移植后平均随访超过5年的肾移植患者，在合并感染乙型肝炎病毒时肝脏病变更严重。总体而言，我们仅观察到4例肝硬化（5%），且36%的患者有组织学CAH病变的证据。
