Smoking Aggravates Inflammation, Fibrogenesis, Angiogenesis and Cancer Risk in Patients With Cirrhosis

IF 5.2 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Liver International Pub Date : 2025-09-03 DOI:10.1111/liv.70314

Nina Dominik, Benedikt Simbrunner, Bernhard Scheiner, Michael Schwarz, Lukas Hartl, Mathias Jachs, Lorenz Balcar, Georg Semmler, Georg Kramer, Christian Sebesta, Michael Trauner, Matthias Pinter, Mattias Mandorfer, Thomas Reiberger, Benedikt Silvester Hofer

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Abstract

Background and Aims

Smoking induces a proinflammatory state, yet its role in advanced chronic liver disease (ACLD) remains understudied. This study evaluated its impact on disease-driving mechanisms and clinical outcomes in ACLD patients.

Methods

ACLD patients undergoing hepatic venous pressure gradient measurements from 2017 to 2021 were included. The association of smoking with biomarkers of inflammation, fibrogenesis, angiogenesis and the incidence of hepatocellular carcinoma (HCC), extrahepatic malignancies and mortality was examined.

Results

Among 339 ACLD patients (66.1% men, median age: 56.8 years, MELD: 11, HVPG: 17 mmHg), 62% (n = 210) were ever-smokers (n = 78 former, n = 132 active). Compared to never/former smokers, active smokers exhibited significantly higher white blood cell counts (5.49 vs. former: 4.74 vs. never: 4.25 G/L; p < 0.001) and C-reactive protein levels (CRP: 0.36 vs. former: 0.29 vs. 0.21 mg/dL; p = 0.035). Active smokers showed upregulated fibrogenic (TIMP-1: 364 vs. former: 324 vs. never: 278 ng/mL, p < 0.001; P3NP: 20.9 vs. former: 15.6 vs. never: 17.2 μg/L, p = 0.008) and angiogenic (PLGF: 21.7 vs. former: 18.2 vs. never: 19.0 pg/mL, p = 0.004) activity markers. Over a median follow-up of 30.4 months, ever-smokers exhibited a higher incidence of extrahepatic malignancies (SHR: 11.30; p = 0.019) and numerically higher HCC incidence (SHR: 2.27 p = 0.150; mostly evident in Child-Pugh A patients: SHR: 7.44, p = 0.053). All-cause or liver-related mortality risk did not differ significantly between ever-smokers and never-smokers.

Conclusion

Smoking is linked to an upregulation of inflammatory, fibrogenic and angiogenic processes in ACLD and increases the risk of extrahepatic malignancies. These findings underscore the importance of strategies supporting smoking cessation in ACLD patients.

Trial Registration

NCT03267615

Abstract Image

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吸烟加重肝硬化患者的炎症、纤维生成、血管生成和癌症风险

背景和目的吸烟诱导促炎状态，但其在晚期慢性肝病（ACLD）中的作用仍未得到充分研究。本研究评估了其对ACLD患者疾病驱动机制和临床结果的影响。方法纳入2017 - 2021年接受肝静脉压梯度测量的ACLD患者。研究了吸烟与炎症、纤维生成、血管生成、肝细胞癌（HCC）、肝外恶性肿瘤和死亡率等生物标志物的关系。结果在339例ACLD患者中（66.1%为男性，中位年龄56.8岁，MELD: 11, HVPG: 17 mmHg）， 62% （n = 210）为既往吸烟者（n = 78例戒烟者，n = 132例活跃者）。与从不吸烟者或戒烟者相比，积极吸烟者的白细胞计数（5.49 vs.戒烟者；4.74 vs.从不吸烟者：4.25 G/L; p < 0.001）和c反应蛋白水平（CRP: 0.36 vs.戒烟者；0.29 vs. 0.21 mg/dL; p = 0.035）明显更高。活跃吸烟者表现出纤维生成（TIMP-1: 364比戒烟者；324比从不戒烟者：278 ng/mL， p < 0.001; P3NP: 20.9比戒烟者：15.6比从不戒烟者：17.2 μg/L, p = 0.008）和血管生成（PLGF: 21.7比戒烟者：18.2比从不戒烟者：19.0 pg/mL, p = 0.004）活性指标上调。在30.4个月的中位随访中，吸烟者表现出更高的肝外恶性肿瘤发生率（SHR: 11.30; p = 0.019）和更高的HCC发生率（SHR: 2.27 p = 0.150；在Child-Pugh a患者中最为明显：SHR: 7.44, p = 0.053）。吸烟和不吸烟的全因或肝脏相关的死亡风险没有显著差异。结论：吸烟与ACLD中炎症、纤维化和血管生成过程的上调有关，并增加肝外恶性肿瘤的风险。这些发现强调了支持ACLD患者戒烟策略的重要性。试验注册编号NCT03267615

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来源期刊

Liver International 医学-胃肠肝病学

CiteScore

13.90

自引率

4.50%

发文量

348

审稿时长

2 months

期刊介绍： Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.