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Background <p>Hepatopulmonary syndrome (HPS) is a severe complication in cirrhotic patients and characterized by abnormal intrapulmonary vasodilation (IPVD), resulting in impaired oxygenation. Recent studies highlight the pivotal role and clinical merit of Reticulocalbin 3 (RCN3) in interstitial pulmonary remodeling.</p> Objectives <p>This study aimed to investigate the clinical value of plasma RCN3 for early diagnosis of HPS in cirrhotic patients.</p> Methods <p>This prospective observational study on a cohort including 41 healthy control subjects and 247 cirrhotic patients with/without HPS, in which most HPS occurs in the mild stage. Plasma levels of RCN3 and key HPS-associated vasoactive factors are compared between patients with and without HPS/IPVD. The predictive value of RCN3 for the diagnosis of HPS is further analyzed.</p> Results <p>Patients with HPS had a severe condition. Plasma RCN3 was decreased in cirrhotic patients versus health control, but it is significantly higher in patients with HPS/IPVD than without non-HPS/IPVD. Notably, RCN3 level is positively correlated with <i>P</i>(A−a)O<sub>2</sub> and MELD scores as well as plasma levels of angiogenetic factors VEGF and AngII. Although the plasma levels of vasoactive factors were significantly different between HPS and non-HPS patients, only plasma RCN3 and albumin are independently associated with HPS in cirrhotic patients. Plasma RCN3 exhibits better predictive value in HPS diagnosis (RCN3, AUC = 0.657, 95% CI 0.571–0.744, <i>p</i> &lt; 0.001). Interestingly, the combination of RCN3 and albumin achieves more efficiency in HPS prediction (AUC = 0.711, 95% CI 0.630–0.792, <i>p</i> &lt; 0.0001).</p> Conclusions <p>Circulating RCN3 is likely a relatively specific earlier biomarker for the prediction of early or latent HPS in cirrhotic patients, and the combination of RCN3-ALB can achieve more efficiency in HPS prediction.</p>

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Plasma Reticulocalbin 3 (RCN3) is a Novel Biomarker for the Early Diagnosis of Hepatopulmonary Syndrome in Cirrhotic Patients

  • 期刊论文

  • 发表日期：

    2025年3月20日

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  • Fangping Ding,
  • Liu Yang,
  • Wenhui Cao,
  • Jie Sun,
  • Fengwei Shi,
  • Yingfei Wang,
  • Caixia Hu,
  • Weiwei Kang,
  • Jing Han,
  • Qingkun Song,
  • Yingmin Ma,
  • Jiawei Jin

摘要

Background

Hepatopulmonary syndrome (HPS) is a severe complication in cirrhotic patients and characterized by abnormal intrapulmonary vasodilation (IPVD), resulting in impaired oxygenation. Recent studies highlight the pivotal role and clinical merit of Reticulocalbin 3 (RCN3) in interstitial pulmonary remodeling.

Objectives

This study aimed to investigate the clinical value of plasma RCN3 for early diagnosis of HPS in cirrhotic patients.

Methods

This prospective observational study on a cohort including 41 healthy control subjects and 247 cirrhotic patients with/without HPS, in which most HPS occurs in the mild stage. Plasma levels of RCN3 and key HPS-associated vasoactive factors are compared between patients with and without HPS/IPVD. The predictive value of RCN3 for the diagnosis of HPS is further analyzed.

Results

Patients with HPS had a severe condition. Plasma RCN3 was decreased in cirrhotic patients versus health control, but it is significantly higher in patients with HPS/IPVD than without non-HPS/IPVD. Notably, RCN3 level is positively correlated with P(A−a)O2 and MELD scores as well as plasma levels of angiogenetic factors VEGF and AngII. Although the plasma levels of vasoactive factors were significantly different between HPS and non-HPS patients, only plasma RCN3 and albumin are independently associated with HPS in cirrhotic patients. Plasma RCN3 exhibits better predictive value in HPS diagnosis (RCN3, AUC = 0.657, 95% CI 0.571–0.744, p < 0.001). Interestingly, the combination of RCN3 and albumin achieves more efficiency in HPS prediction (AUC = 0.711, 95% CI 0.630–0.792, p < 0.0001).

Conclusions

Circulating RCN3 is likely a relatively specific earlier biomarker for the prediction of early or latent HPS in cirrhotic patients, and the combination of RCN3-ALB can achieve more efficiency in HPS prediction.