OBJECTIVES Common nucleotide-binding oligomerization domain containing 2 (NOD2) gene variants have been associated with bacterial infections (BIs) in cirrhosis, in particular, spontaneous bacterial peritonitis, and mortality. Our aim was to evaluate the independent association of NOD2 variants with BI according to the decompensation stage. METHODS Consecutive patients with cirrhosis in 2 academic medical centers were included and genotyped for the NOD2 variants p.R702W, p.G908R, and c.3020insC. Electronic medical records were screened for BI (requiring antibiotic therapy) and past and present decompensation (as defined by variceal bleeding, encephalopathy, ascites, and/or jaundice). Clinically significant portal hypertension (CSPH) was assessed with liver stiffness and/or hepatic venous pressure gradient measurements. RESULTS Overall, 735 patients were recruited (men 65%; interquartile age range 53-68 years). Alcoholic cirrhosis was the predominant etiology (n = 406, 55%), and most patients were in the decompensated stage (n = 531, 72%). In total, 158 patients (21%) carried at least one NOD2 variant. BIs were detected in 263 patients (36%), and NOD2 variants were associated with BI (odds ratio = 1.58; 95% confidence interval 1.11-2.27; P = 0.02). In compensated patients, the combination of NOD2 variants and presence of CSPH was the best independent predictors of BI, whereas other factors, such as spleen size and hemoglobin, and decompensations including hepatic encephalopathy or jaundice, gained relevance in decompensated patients. CONCLUSIONS NOD2 risk variants are associated with BI in cirrhosis. The genetic effect on BI is strongest in compensated patients, whereas in decompensated patients their presence is less relevant. In this situation, CSPH becomes an independent factor associated with BI.

中文翻译：

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常见的NOD2风险变异性是代偿性肝硬化细菌感染的主要易感性因素。

目的常见的包含2个（NOD2）基因变异的核苷酸结合寡聚域与肝硬化中的细菌感染（BI）有关，特别是与自发性细菌性腹膜炎有关，并与死亡率相关。我们的目的是根据失代偿阶段评估NOD2变体与BI的独立关联。方法纳入2个学术医学中心的连续性肝硬化患者，并对NOD2变体p.R702W，p.G908R和c.3020insC进行基因分型。筛选电子病历以检查BI（需要抗生素治疗）以及过去和现在的代偿失调（如静脉曲张破裂出血，脑病，腹水和/或黄疸定义）。临床上显着的门静脉高压症（CSPH）通过肝硬度和/或肝静脉压力梯度测量进行评估。结果总体而言，招募了735名患者（男性65％；四分位数年龄范围53-68岁）。酒精性肝硬化是主要病因（n = 406，55％），大多数患者处于失代偿期（n = 531，72％）。总共158名患者（21％）携带至少一种NOD2变异体。在263例患者中检测到BI（36％），并且NOD2变异与BI相关（几率= 1.58； 95％置信区间1.11-2.27； P = 0.02）。在有补偿的患者中，NOD2变异和CSPH的存在是BI的最佳独立预测指标，而其他因素，如脾脏大小和血红蛋白以及失代偿（包括肝性脑病或黄疸）与失代偿患者相关性更高。结论NOD2风险变异与肝硬化中的BI有关。有补偿的患者对BI的遗传效应最强，而在失代偿患者中，它们的存在意义不大。在这种情况下，CSPH成为与BI相关的独立因素。