Department of General, Visceral, and Transplant Surgery, Charité, Campus Virchow, Berlin, Germany.
Liver Transpl. 2011 Mar;17(3):289-98. doi: 10.1002/lt.22235.
Up to 30% of liver transplants will develop graft cirrhosis within 5 years after liver transplantation (LT) due to recurrent HCV-infection forwarding accelerated graft damage. Genetic variants of cytokines involved in the immune response may contribute to the degree of graft inflammation, fibrosis progression, and antiviral therapy outcome. The aim of our study was to analyze biochemical and histological inflammation extent based on protocol liver biopsies and to evaluate the role of genetic variants of IL-28b in HCV-related graft disease and antiviral treatment response. 183 patients, who underwent liver transplantation for HCV-induced liver disease, were genotyped for IL-28b (rs8099917, G ≥ T) by TaqMan Genotyping Assay. 56 of 159 patients have been successfully treated with interferon-based antiviral therapy. 605 protocol liver biopsies performed 0.5 to 10 and more than 10 years after transplantation were evaluated according to Desmet and Scheuer classification of inflammation and fibrosis. Prevalence of IL-28b-genotypes was correlated with histological severity of graft damage, levels of aminotransferases, occurrence of acute cellular rejection, pre-treatment viremia, and antiviral therapy outcome. Significant association of IL-28b-genotype distribution was observed to the median grade of inflammation (p < 0.001), mean levels of aminotransferases (ALT: p = 0.001, AST: p = 0.003), median pre-treatment viremia level within 1 year after LT (p = 0.046) and interferon-based antiviral therapy failure (p < 0.001). Among successfully treated patients, G-allele was significantly less frequent, and the genotype GG was not present at all. No differences were observed regarding acute cellular rejection (p = 0.798) and fibrosis stages (p = 0.586). IL-28b polymorphism seems to influence the degree of graft inflammation at biochemical and histological levels. G-allele might serve as a marker for graft inflammation and as a predictor for unfavorable antiviral therapy outcome in HCV-re-infected LT-population.
多达 30%的肝移植患者在肝移植（LT）后 5 年内会因 HCV 感染复发导致加速移植物损伤而发生移植肝肝硬化。细胞因子的遗传变异参与免疫反应，可能导致移植物炎症、纤维化进展和抗病毒治疗结果的不同。我们的研究目的是基于方案肝活检分析生物化学和组织学炎症程度，并评估 IL-28b 基因变异在 HCV 相关移植物疾病和抗病毒治疗反应中的作用。183 例因 HCV 相关性肝病接受肝移植的患者通过 TaqMan 基因分型检测 IL-28b（rs8099917，G≥T）进行基因分型。159 例患者中有 56 例成功接受了基于干扰素的抗病毒治疗。对移植后 0.5 年至 10 年及 10 年以上的 605 例方案肝活检进行评估，依据 Desmet 和 Scheuer 炎症和纤维化分类进行。IL-28b 基因型的流行率与移植物损伤的组织学严重程度、转氨酶水平、急性细胞排斥反应的发生、治疗前病毒血症以及抗病毒治疗结果相关。IL-28b 基因型分布与炎症的中位数等级（p<0.001）、转氨酶的平均水平（ALT：p=0.001，AST：p=0.003）、LT 后 1 年内治疗前病毒血症中位数水平（p=0.046）和基于干扰素的抗病毒治疗失败（p<0.001）显著相关。在成功治疗的患者中，G 等位基因明显较少，基因型 GG 根本不存在。在急性细胞排斥反应（p=0.798）和纤维化分期（p=0.586）方面无差异。IL-28b 多态性似乎影响移植物在生物化学和组织学水平的炎症程度。G 等位基因可能是移植物炎症的标志物，并可预测 HCV 再感染 LT 人群中不利的抗病毒治疗结果。
