Karbannek Henrik, Reichert Matthias C, Greinert Robin, Zipprich Alexander, Lammert Frank, Ripoll Cristina
Department of Internal Medicine IV, Jena University Hospital, Jena, Germany.
Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.
Liver Int. 2025 Apr;45(4):e16143. doi: 10.1111/liv.16143. Epub 2024 Oct 29.
NOD2 mutations are associated with impaired gut mucosal barrier function. According to the systemic inflammation hypothesis, bacterial translocation is central in the development of decompensation. The aim was to evaluate whether the presence of NOD2 variants is associated with the development of first decompensation.
Secondary analysis of prospectively collected consecutive patients with compensated cirrhosis, who were screened between 2014 and 2018. Patients with and without NOD2 variants were compared and stratified analysis according to the presence of varices was performed.
360 patients [239 (66%) men, median age 61 (53-69) years, 70 (19%) with NOD2 variants, 90 (25%) with varices] were followed for a median of 9 (4-16) months. Similar baseline characteristics were observed across NOD2 status groups, except for beta-blocker use (45% vs. 32% amongst variant carriers vs. non-carriers, p = 0.05). During follow-up, 34 patients (12%) developed their first decompensation, with no differences according to NOD2 status [HR 1.75 (95% CI 0.84-3.67)]. On multivariate analysis, only MELD remained an independent predictor of decompensation. Amongst patients with varices (n = 90), 18 (24.4%) carried a NOD2 variants, with a higher incidence of first decompensation [HR 3.00 (95% CI 1.08-8.32)], primarily due to ascites [HR 3.32 (95% CI 1.07-10.32)]. In this subgroup, MELD [HR 1.18 (95% CI 1.06-1.32)] and NOD2 variants [HR 2.91 (95% CI 0.95-8.89)] were determined to be independent predictors of decompensation.
The presence of NOD2 risk variants leads to a greater incidence of first decompensation only in compensated patients with varices.
NOD2突变与肠道黏膜屏障功能受损有关。根据全身炎症假说，细菌移位在失代偿发展过程中起核心作用。本研究旨在评估NOD2变异体的存在是否与首次失代偿的发生有关。
对2014年至2018年间前瞻性收集的连续代偿期肝硬化患者进行二次分析。比较有无NOD2变异体的患者，并根据静脉曲张的存在进行分层分析。
360例患者[239例（66%）男性，中位年龄61岁（53 - 69岁），70例（19%）有NOD2变异体，90例（25%）有静脉曲张]，中位随访时间为9个月（4 - 16个月）。除β受体阻滞剂使用情况外（变异体携带者与非携带者分别为45%和32%，p = 0.05），各NOD2状态组的基线特征相似。随访期间，34例患者（12%）发生首次失代偿，根据NOD2状态无差异[风险比（HR）1.75（95%置信区间0.84 - 3.67）]。多因素分析显示，只有终末期肝病模型（MELD）评分仍然是失代偿的独立预测因素。在有静脉曲张的患者（n = 90）中，18例（24.4%）携带NOD2变异体，首次失代偿发生率更高[HR 3.00（95%置信区间1.08 - 8.32）]，主要是由于腹水[HR 3.32（95%置信区间1.07 - 10.32）]。在该亚组中，MELD评分[HR 1.18（95%置信区间1.06 - 1.32）]和NOD2变异体[HR 2.91（95%置信区间0.95 - 8.89）]被确定为失代偿的独立预测因素。
仅在有静脉曲张的代偿期患者中，NOD2风险变异体的存在会导致首次失代偿的发生率更高。
