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Keywords:

  • angiogenesis;
  • cirrhosis;
  • hepatopulmonary syndrome;
  • ICAM3;
  • VCAM1

Abstract

Background & Aims

Hepatopulmonary syndrome is a complication of chronic liver disease resulting in increased morbidity and mortality. It is caused by intrapulmonary vascular dilations and arteriovenous connections with devastating influence on gas exchange. The pathogenesis is not completely understood but evidence mounts for angiogenesis. Aims of this study were [1] to identify angiogenic factors in serum of patients with hepatopulmonary syndrome and [2] to study the possibility to predict its presence by these factors.

Methods

Multiplex assays were used to measure the concentration of angiogenic factors in patients with (n = 30) and without hepatopulmonary syndrome (n = 30). Diagnosis was based on the presence of gas exchange abnormality and intrapulmonary vasodilations according to published guidelines.

Results

Patients with and without hepatopulmonary syndrome had similar MELD scores (median: 11.2 vs. 11.6; P = 0.7), Child–Pugh score (P = 0.7) and PaCO2 values (median: 35 vs. 37; P = 0.06). PaO2 and P(A-a) O2 gradient were significantly different (respectively median of 80 vs. 86, P = 0.02; and 24 vs. 16, P = 0.004). Based on area under the curve (AUC) data and P-values, the best predictors were vascular cell adhesion molecule 1 (VCAM1) (AUC = 0.932; P < 0.001) and intercellular adhesion molecule 3 (ICAM3) (AUC = 0.741; P = 0.003). Combining these factors results in an AUC of 0.99 (after cross-validation still 0.99).

Conclusions

VCAM1 and ICAM3 might be promising biomarkers for predicting hepatopulmonary syndrome. Combining these factors results in an AUC of 0.99 and a negative predictive value of 100%. Determining the concentration of these biomarkers might be a screening method to detect hepatopulmonary syndrome. The use of these biomarkers should be validated in larger groups of patients.