PNPLA3 gene predicts clinical recovery after sustained virological response in decompensated hepatitis C cirrhosis
PNPLA3 gene predicts clinical recovery after sustained virological response in decompensated hepatitis C cirrhosis
复制标题
DOI：
10.1136/bmjgast-2018-000241
复制
发表时间：
2019-01-01
影响因子：
3.1
通讯作者：
Weinman, Steven A.
中科院分区：
文献类型：
--
作者：
Dunn, Winston;Vittal, Anusha;Weinman, Steven A.
背景：失代偿丙型肝炎病毒（HCV）肝硬化患者在持续病毒学反应（SVR）后经历各种结果，从临床恢复到进一步恶化。我们假设脂肪变性的遗传风险，即Patatin-like Phospholipase - containing 3 （PNPLA3）多态性rs738409、Transmembrane-6-Superfamily-2 （TM6SF2）多态性rss58542926和膜结合o -酰基转移酶- containing 7 （MBOAT7）多态性rs641738，可以预测恢复。方法前瞻性纳入56例接受抗病毒治疗的Child-Pugh (CPT) B/C型肝硬化患者。主要结局是SVR后12周、24周和48周CPT评分的变化。我们采用线性混合效应模型进行分析。结果45例患者（PNPLA3: 21例CC， 19例CG， 5例GG）存活至第一终点，未进行肝移植。PNPLA3 CC基因型患者的CPT评分在12、24和48周时的平均变化分别为-1.57 （SE=0.30）、-1.76 （SE=0.32）和-2.0 (SE=0.36)，其他24例患者的CPT评分分别为-0.50 （SE=0.20）、-0.41 （SE=0.25）和-0.24 （SE=0.27）。调整基线特征后，PNPLA3 CG/GG基因型与1.29 (SE=0.30, p
Background Patients with decompensated hepatitis C virus (HCV) cirrhosis experience various outcomes after sustained virological response (SVR), ranging from clinical recovery to further deterioration. We hypothesised that the genetic risk for steatosis, namely the polymorphisms rs738409 of Patatin-like Phospholipase Domain-Containing 3 (PNPLA3), rs58542926 of Transmembrane-6-Superfamily-2 (TM6SF2), and rs641738 of Membranebound O-acyltransferase Domain-Containing 7 (MBOAT7), is predictive of recovery.Methods We prospectively enrolled 56 patients with Child-Pugh (CPT) B/C cirrhosis who underwent antiviral therapy. The primary outcome was change in CPT score at 12, 24, and 48 weeks after SVR. We used a linear mixed-effects model for analysis.Results Forty-five patients (PNPLA3: 21 CC, 19 CG, 5 GG) survived to the first endpoint without liver transplantation. The mean change in CPT score at 12, 24, and 48 weeks was -1.57 (SE=0.30), -1.76 (SE=0.32), and -2.0 (SE=0.36), respectively, among the patients with the PNPLA3 CC genotype and -0.50 (SE=0.20), -0.41 (SE=0.25), and -0.24 (SE=0.27), respectively, among the other 24 patients. After adjustment for baseline characteristics, the PNPLA3 CG/GG genotypes were associated with a 1.29 (SE=0.30, p