Martin P, Carter D, Fabrizi F, Dixit V, Conrad A J, Artinian L, Peacock V, Han S, Wilkinson A, Lassman C R, Danovitch G
Department of Medicine, UCLA School of Medicine, National Genetics Institute, Los Angeles, California, USA.
Transplantation. 2000 Apr 15;69(7):1479-84. doi: 10.1097/00007890-200004150-00045.
Although hepatitis C virus (HCV) infection is common in renal transplant candidates, its clinical significance remains unclear in this population. Little detailed information is available about the histological severity of HCV infection in these patients. We evaluated the liver biopsy features of chronic HCV in a large population of renal transplant candidates and investigated associations between histopathological changes and host- and virus-related factors.
Thirty-seven patients seropositive for anti-HCV with chronic renal failure (CRF) referred to UCLA Medical Center for kidney or kidney/liver transplantation during the period 1992-1997 were included. HCV genotype and viral load were measured. A multivariate analysis by logistic regression model was performed: age, gender, race, HCV load and genotype, CRF level, aspartate and alanine aminotransferase activity, duration of HCV infection, underlying nephropathy, and alcohol abuse were independent variables; liver histology score was assumed a dependent variable.
Liver disease was present in all HCV-infected patients. Logistic regression analysis revealed that histological damage was (P = 0.0017) independently associated with the CRF level; the severity of liver disease, as shown by univariate analysis, being significantly higher in CRF patients not requiring dialysis than among dialysis population. All patients on dialysis showed mild or moderate necroinflammatory activity; the majority (22/28 = 79%) of these individuals had fibrosis, three (3/28 = 11%) dialysis patients had established cirrhosis. Thirty-one (84%) of 37 patients were tested by polymerase chain reaction, 25 (81%) patients had detectable HCV RNA in serum, the mean HCV load among viremic patients was 10.9x10(5) copies/ ml. The most frequent HCV genotypes were la (8/24 = 33%) and 1b (7/24 = 29%), followed by genotype 2b (3/24 = 12%).
Pathological changes on liver biopsy were observed in all HCV-infected patients awaiting renal transplantation. The severity of histologic damage observed on liver biopsy was less in dialysis than predialysis CRF patients. All dialysis patients had mild or moderate necroinflammatory activity; fibrosis was frequent with 11% of them having cirrhosis. The HCV viral load was rather low; no relationship between liver histology changes and virological features of HCV or aminotransferase activity was apparent. Further studies with repeat liver biopsies after kidney transplantation to observe the evolution of HCV-related liver disease after immunosuppressive therapy are indicated. We suggest including liver biopsy in the evaluation of the HCV-infected renal transplant candidate.
尽管丙型肝炎病毒（HCV）感染在肾移植候选者中很常见，但其在该人群中的临床意义仍不明确。关于这些患者中HCV感染的组织学严重程度，几乎没有详细信息。我们评估了大量肾移植候选者中慢性HCV的肝活检特征，并研究了组织病理学变化与宿主及病毒相关因素之间的关联。
纳入了1992年至1997年间因慢性肾衰竭（CRF）前往加州大学洛杉矶分校医学中心进行肾脏或肝肾联合移植的37例抗-HCV血清学阳性患者。检测了HCV基因型和病毒载量。采用逻辑回归模型进行多变量分析：年龄、性别、种族、HCV载量和基因型、CRF水平、天冬氨酸和丙氨酸转氨酶活性、HCV感染持续时间、潜在肾病和酒精滥用为自变量；肝组织学评分作为因变量。
所有HCV感染患者均存在肝脏疾病。逻辑回归分析显示，组织学损伤（P = 0.0017）与CRF水平独立相关；单变量分析显示，不需要透析的CRF患者的肝脏疾病严重程度明显高于透析人群。所有透析患者均表现为轻度或中度坏死性炎症活动；其中大多数（22/28 = 79%）有纤维化，3例（3/28 = 11%）透析患者已发展为肝硬化。37例患者中的31例（84%）进行了聚合酶链反应检测，25例（81%）患者血清中可检测到HCV RNA，病毒血症患者的平均HCV载量为10.9×10⁵拷贝/毫升。最常见的HCV基因型为1a（8/24 = 33%）和1b（7/24 = 29%），其次是2b基因型（3/24 = 12%）。
在所有等待肾移植的HCV感染患者中均观察到肝活检中的病理变化。肝活检中观察到的组织学损伤严重程度在透析患者中低于透析前CRF患者。所有透析患者均有轻度或中度坏死性炎症活动；纤维化很常见，其中11%已发展为肝硬化。HCV病毒载量相当低；未发现肝组织学变化与HCV病毒学特征或转氨酶活性之间存在明显关系。有必要进行进一步研究，在肾移植后重复进行肝活检，以观察免疫抑制治疗后HCV相关肝病的演变。我们建议在评估HCV感染的肾移植候选者时进行肝活检。
