丙型肝炎基因型影响肝移植术后的预后。
Hepatitis C genotype influences post-liver transplant outcomes.
作者信息
Campos-Varela Isabel, Lai Jennifer C, Verna Elizabeth C, O'Leary Jacqueline G, Todd Stravitz R, Forman Lisa M, Trotter James F, Brown Robert S, Terrault Norah A
机构信息
1 Division of Gastroenterology and Hepatology, University of California-San Francisco, San Francisco, CA. 2 Division of Gastroenterology and Hepatology, New York Presbyterian Hospital-Columbia, New York, NY. 3 Baylor Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX. 4 Section of Hepatology and Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, VA. 5 Division of Hepatology, University of Colorado, Denver, CO.
出版信息
Transplantation. 2015 Apr;99(4):835-40. doi: 10.1097/TP.0000000000000413.
BACKGROUND
In nontransplant patients with chronic hepatitis C virus (HCV), HCV genotype has been linked with a differential response to antiviral therapy, risk of steatosis and fibrosis, as well as all-cause mortality, but the role of HCV genotypes in posttransplant disease progression is less clear.
METHODS
Using the multicenter CRUSH-C cohort, genotype-specific rates of advanced fibrosis, HCV-specific graft loss and response of antiviral therapy were examined.
RESULTS
Among 745 recipients (605 [81%] genotype 1, 53 [7%] genotype 2, and 87 [12%] genotype 3), followed for a median of 3.1 years (range, 2.0-8.0), the unadjusted cumulative rate of advanced fibrosis at 3 years was 31%, 19%, and 19% for genotypes 1, 2, and 3 (P = 0.008). After multivariable adjustment, genotype remained a significant predictor, with genotype 2 having a 66% lower risk (P = 0.02) and genotype 3 having a 41% lower risk (P = 0.07) of advanced fibrosis compared to genotype 1 patients. The cumulative 5-year rates of HCV-specific graft survival were 84%, 90%, and 94% for genotypes 1, 2, and 3 (P = 0.10). A total of 37% received antiviral therapy, with higher rates of sustained virologic response in patients with genotype 2 (hazard ratios, 5.10; P = 0.003) and genotype 3 (hazard ratios, 3.27; P = 0.006) compared to patients with genotype 1.
CONCLUSION
Risk of advanced fibrosis and response to therapy are strongly influenced by genotype. Liver transplantation recipients with HCV genotype 1 have the highest risk of advanced fibrosis and lowest sustained virologic response rate. These findings highlight the need for genotype-specific management strategies.
背景
在非移植的慢性丙型肝炎病毒（HCV）患者中，HCV基因型与抗病毒治疗的差异反应、脂肪变性和纤维化风险以及全因死亡率有关，但HCV基因型在移植后疾病进展中的作用尚不清楚。
方法
利用多中心CRUSH-C队列，研究了特定基因型的晚期纤维化发生率、HCV特异性移植物丢失率和抗病毒治疗反应。
结果
在745例接受者中（605例[81%]为1型基因型，53例[7%]为2型基因型，87例[12%]为3型基因型），中位随访时间为3.1年（范围为2.0 - 8.0年），1、2和3型基因型在3年时未经调整的晚期纤维化累积发生率分别为31%、19%和19%（P = 0.008）。多变量调整后，基因型仍然是一个显著的预测因素，与1型基因型患者相比，2型基因型发生晚期纤维化的风险降低66%（P = 0.02），3型基因型降低41%（P = 0.07）。1、2和3型基因型的HCV特异性移植物5年累积生存率分别为84%、90%和94%（P = 0.10）。共有37%的患者接受了抗病毒治疗，与1型基因型患者相比，2型基因型患者（风险比，5.10；P = 0.003）和3型基因型患者（风险比，3.27；P = 0.006）的持续病毒学应答率更高。
结论
晚期纤维化风险和治疗反应受基因型的强烈影响。HCV 1型基因型的肝移植受者发生晚期纤维化的风险最高，持续病毒学应答率最低。这些发现凸显了制定特定基因型管理策略的必要性。
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