Department of Internal Medicine II, Division of Gastroenterology, Hepatology, and Infectious Diseases, Jena University Hospital, Jena, Germany.
Liver Int. 2012 Feb;32(2):223-30. doi: 10.1111/j.1478-3231.2011.02561.x. Epub 2011 Jun 13.
Spontaneous bacterial peritonitis (SBP) is considered as result of bacterial translocation from the gastrointestinal lumen to the mesenteric lymph nodes and subsequent circulation. Variants of the NOD2 gene contribute to bacterial translocation and were associated with SBP in a recent study.
We determined common NOD2 variants by TaqMan polymerase chain reaction and analysed the ascitic fluid neutrophil count and bacterial culture results in 175 prospectively characterized hospitalized patients with decompensated cirrhosis who underwent diagnostic paracentesis in two German centres.
Ten patients presented with culture-positive SBP, 19 with culture-negative SBP and six had bacterascites. Minor allele frequencies for R702W, G908R and 1007fs in subjects with sterile non-neutrocytic ascites were 3.2, 2.5 and 2.5% respectively. Patients with SBP [odds ratio (OR) 2.7; P=0.036], culture-positive SBP (OR 6.0; P=0.012) and bacterascites (OR 6.0; P=0.050) were more often carriers of NOD2 variants than patients with sterile non-neutrocytic ascites. The mutations 1007fs and G908R were associated with culture-positive SBP (P ≤ 0.005) and R702W with bacterascites (P=0.014). There was no significant association of NOD2 variants with culture-negative SBP (OR 1.6; P=0.493). In logistic regression, previous SBP, a higher model for end-stage liver disease (MELD) score and the presence of a NOD2 variant were independent predictors of ascitic fluid infection. The median survival was insignificantly shorter in patients with NOD2 variants (268 vs. 339 days; P=0.386). In patients without hepatocellular carcinoma at study entry (N=148), NOD2 was a predictor of survival after adjustment for the MELD score and age (hazard ratio 1.89; P=0.045).
NOD2 variants increase the risk for culture-positive SBP and bacterascites in cirrhosis and may affect survival.
自发性细菌性腹膜炎（SBP）被认为是细菌从胃肠道腔转移到肠系膜淋巴结并随后循环的结果。最近的一项研究表明，NOD2 基因的变体有助于细菌易位，并与 SBP 相关。
我们通过 TaqMan 聚合酶链反应确定常见的 NOD2 变体，并分析了在两个德国中心进行诊断性腹腔穿刺的 175 例代偿性肝硬化住院患者的腹水中性粒细胞计数和细菌培养结果。
10 例患者培养阳性 SBP，19 例培养阴性 SBP，6 例菌血症。在无菌非中性粒细胞性腹水患者中，R702W、G908R 和 1007fs 的次要等位基因频率分别为 3.2%、2.5%和 2.5%。SBP 患者（比值比[OR]2.7；P=0.036）、培养阳性 SBP 患者（OR6.0；P=0.012）和菌血症患者（OR6.0；P=0.050）携带 NOD2 变体的频率高于无菌非中性粒细胞性腹水患者。1007fs 和 G908R 突变与培养阳性 SBP 相关（P≤0.005），R702W 与菌血症相关（P=0.014）。NOD2 变体与培养阴性 SBP 无显著相关性（OR1.6；P=0.493）。在逻辑回归中，既往 SBP、较高的终末期肝病模型（MELD）评分和 NOD2 变体的存在是腹水感染的独立预测因素。携带 NOD2 变体的患者中位生存期无显著缩短（268 天 vs. 339 天；P=0.386）。在研究开始时无肝细胞癌的患者（N=148）中，NOD2 是 MELD 评分和年龄调整后的生存预测因素（危险比 1.89；P=0.045）。
NOD2 变体增加肝硬化患者培养阳性 SBP 和菌血症的风险，并可能影响生存。
