Gane E J, Naoumov N V, Qian K P, Mondelli M U, Maertens G, Portmann B C, Lau J Y, Williams R
Institute of Liver Studies, King's College School of Medicine and Dentistry, Denmark Hill, London, England.
Gastroenterology. 1996 Jan;110(1):167-77. doi: 10.1053/gast.1996.v110.pm8536853.
BACKGROUND & AIMS: The pathogenesis of graft injury in liver transplant recipients with recurrent hepatitis C virus (HCV) infection remains poorly understood. In this study, the relationship between HCV replication, genotype, and the evolution of graft damage was investigated.
HCV RNA was quantified in 184 protocol sera from 25 patients transplanted for HCV cirrhosis. HCV isolates were genotyped, and hepatic expression of core and NS4 antigens was sought in protocol allograft biopsy specimens.
Acute lobular hepatitis was accompanied by a steep increase in HCV RNA levels and the appearance of core and NS4 antigens in the graft. Methylprednisolone treatment for acute rejection led to a 4-100-fold increase in serum HCV RNA. At the end of follow-up, HCV RNA levels were 3-112 times pretransplant levels and were higher in patients with more severe hepatitis. Progressive liver damage developed in 7 of 14 patients with HCV genotype 1b and in 1 of 11 patients infected with other genotypes (P = 0.03).
Peak viremia levels and the initial detection of HCV antigens in hepatocytes suggests increased viral replication at the time of acute HCV hepatitis in the graft. Genotype 1b and higher viremia levels were associated with more severe chronic graft damage.
复发性丙型肝炎病毒（HCV）感染的肝移植受者发生移植物损伤的发病机制仍知之甚少。本研究调查了HCV复制、基因型与移植物损伤进展之间的关系。
对25例因HCV肝硬化接受移植患者的184份常规血清进行HCV RNA定量检测。对HCV分离株进行基因分型，并在常规移植肝活检标本中检测核心抗原和NS4抗原的肝内表达。
急性小叶性肝炎伴有HCV RNA水平急剧升高以及移植物中核心抗原和NS4抗原的出现。针对急性排斥反应的甲泼尼龙治疗导致血清HCV RNA升高4至100倍。随访结束时，HCV RNA水平为移植前水平的3至112倍，且在肝炎更严重的患者中更高。14例HCV基因型1b患者中有7例出现进行性肝损伤，11例感染其他基因型的患者中有1例出现进行性肝损伤（P = 0.03）。
病毒血症峰值水平以及肝细胞中HCV抗原的初次检测提示移植肝急性HCV肝炎时病毒复制增加。基因型1b和更高的病毒血症水平与更严重的慢性移植物损伤相关。
