NOD2 and TLR1 Polymorphisms Predict Spontaneous Bacterial Peritonitis and Mortality in Cirrhotic Patients With Ascites

ABSTRACT Objectives Spontaneous bacterial peritonitis (SBP) is a severe infectious complication of cirrhosis associated with high morbidity and mortality. Genetic variations in innate immune receptors may influence susceptibility to infection. This study evaluated the association of TLR1 (rs4833095, rs5743551) and NOD2 (rs2066844, rs2066845, rs2066847) polymorphisms with SBP development and mortality in patients with decompensated cirrhosis and ascites. Methods This prospective cohort study included 280 cirrhotic patients at a tertiary gastroenterology center. After exclusions, 242 patients were analyzed. SBP was diagnosed according to international guidelines. TLR1 and NOD2 polymorphisms were determined using real-time polymerase chain reaction. Logistic regression identified risk factors for SBP development, and Cox proportional hazards models evaluated predictors of mortality. Results SBP occurred in 70 patients (28.9%). Mean follow-up was 16.78 ± 11.67 months. The three-year survival rate was 45.1%, and one-year mortality was 43.8%. Patients with SBP had higher one-year mortality than those without SBP (64.3% vs. 35.5%, p < 0.001). TLR1 rs4833095 and NOD2 polymorphisms (rs2066844, rs2066845, rs2066847) were significantly associated with SBP risk. NOD2 rs2066844, NOD2 rs2066847, and TLR1 rs4833095 were independent SBP predictors. Advanced age, higher MELD score, HCC, and SBP independently predicted mortality. In SBP patients, NOD2 rs2066844 and rs2066847 independently predicted one-year mortality. Conclusion NOD2 and TLR1 variants are linked to SBP and mortality in cirrhosis, highlighting potential genetic risk stratification.摘要 研究目的：自发性细菌性腹膜炎（Spontaneous bacterial peritonitis, SBP）是肝硬化的严重感染性并发症，伴随较高的发病率与死亡率。固有免疫受体的基因变异可能影响感染易感性。本研究旨在评估toll样受体1（TLR1）的rs4833095、rs5743551位点与核苷酸结合寡聚化结构域2（NOD2）的rs2066844、rs2066845、rs2066847位点的基因多态性，与失代偿期肝硬化伴腹水患者发生SBP及死亡风险的关联。 方法：本前瞻性队列研究纳入某三级消化内科中心的280例肝硬化患者，经排除后最终纳入242例患者进行分析。SBP的诊断参照国际指南标准。采用实时聚合酶链反应（real-time polymerase chain reaction）检测TLR1与NOD2的基因多态性。通过logistic回归分析确定SBP发生的危险因素，采用Cox比例风险模型评估死亡预测因素。 结果：共70例患者（28.9%）发生SBP。平均随访时长为16.78±11.67个月。三年生存率为45.1%，一年死亡率为43.8%。合并SBP的患者一年死亡率显著高于未合并SBP者（64.3% vs. 35.5%，p<0.001）。TLR1 rs4833095位点及NOD2的rs2066844、rs2066845、rs2066847位点的基因多态性与SBP发病风险显著相关。NOD2 rs2066844、NOD2 rs2066847及TLR1 rs4833095位点是SBP发生的独立预测因素。高龄、更高的终末期肝病模型（MELD）评分、合并肝细胞癌（HCC）及SBP本身均为患者死亡的独立预测因素。在SBP患者亚组中，NOD2 rs2066844与rs2066847位点可独立预测一年死亡率。 结论：NOD2与TLR1的基因变异与肝硬化患者发生SBP及死亡风险相关，该结果提示可通过基因检测实现潜在的遗传风险分层。