Wieczorek-Godlewska Renata, Płoski Rafał, Perkowska-Ptasińska Agnieszka, Tronina Olga, Sadowska Anna, Pacholczyk Marek, Lisik Wojciech, Durlik Magdalena
Department of Transplantation Medicine and Nephrology, Medical University of Warsaw, Poland.
Medical Genetics Unit, Medical University of Warsaw, Poland.
Clin Exp Hepatol. 2017 Sep;3(3):152-158. doi: 10.5114/ceh.2017.68401. Epub 2017 Jun 12.
Aim of the study was to assess the impact of the recipient and donor interferon lambda-3 (IFNL3) single-nucleotide polymorphisms (SNPs) rs12979860 and rs8099917 on the course of hepatitis C virus (HCV) reinfection following liver transplantation.
The study involved 141 subjects after liver transplantation for HCV-induced cirrhosis, performed between 2000 and 2015. It assessed the impact of both SNPs on the outcomes of interferon/ribavirin (IFN/RBV) treatment following transplantation, HCV viral load, laboratory test results, histological lesions in the liver graft, the risk of acute rejection, and the development of hepatocellular carcinoma (HCC) in patient's own liver.
In the case of rs12979860, SVR was achieved in 58.8% of recipients with the CC genotype, and only 12% of recipients with the TT genotype ( = 0.016). Recipients with the rs12979860 CC variant had lower viral load and lower alanine transaminase (ALT) activity than recipients with a non-CC variant. Opposite effects were demonstrated in the analysis of the donors' genotype. Recipients with the unfavorable variants (rs12979860 TT and rs8099917 GG) had a lower risk of graft rejection and tended to have a higher risk of developing HCC in their own liver.
The IFNL3 rs12979860 polymorphism may be considered a predictor for IFN/RBV effectiveness following liver transplantation. The course of HCV reinfection following liver transplantation may be more aggressive if an unfavorable variant in the recipient coexists with a promising variant in the donor. Particularly careful monitoring for HCC in recipients with unfavorable IFNL3 variants is warranted.
本研究旨在评估受体和供体干扰素λ-3（IFNL3）单核苷酸多态性（SNP）rs12979860和rs8099917对肝移植后丙型肝炎病毒（HCV）再感染病程的影响。
本研究纳入了2000年至2015年间因HCV诱导的肝硬化接受肝移植的141名受试者。评估了这两个SNP对移植后干扰素/利巴韦林（IFN/RBV）治疗结局、HCV病毒载量、实验室检查结果、肝移植组织学病变、急性排斥反应风险以及患者自身肝脏肝细胞癌（HCC）发生情况的影响。
对于rs12979860，CC基因型受体的持续病毒学应答（SVR）率为58.8%，而TT基因型受体仅为12%（P = 0.016）。rs12979860 CC变异型受体的病毒载量和丙氨酸转氨酶（ALT）活性低于非CC变异型受体。对供体基因型的分析显示出相反的效应。具有不利变异型（rs12979860 TT和rs8099917 GG）的受体发生移植排斥的风险较低，且其自身肝脏发生HCC的风险倾向于较高。
IFNL3 rs12979860多态性可被视为肝移植后IFN/RBV疗效的预测指标。如果受体中的不利变异型与供体中的有前景变异型同时存在，肝移植后HCV再感染的病程可能更具侵袭性。对于具有不利IFNL3变异型的受体，有必要特别仔细地监测HCC。
