Macrophage Migration Inhibitory Factor as a Novel Biomarker of Portopulmonary Hypertension

Abstract

Portopulmonary hypertension (POPH) is a poorly understood complication of liver disease associated with significant morbidity and mortality. We sought to identify novel biomarkers of POPH disease presence and severity. We performed a prospective, multicenter, case-control study involving patients with liver disease undergoing right heart catheterization. POPH cases were defined as a mean pulmonary arterial pressure (mPAP) ≥25 mmHg and pulmonary vascular resistance (PVR) >240 dynes˙s˙cm. Plasma samples were collected from the systemic and pulmonary circulation, and antibody microarray was used to identify biomarkers. Characterization and validation of a candidate cytokine, macrophage migration inhibitory factor (MIF), was performed using enzyme-linked immunosorbent assay. Continuous variables were compared using a Mann-Whitney U test and correlated with disease severity using Spearman correlation. MIF levels were elevated in both the systemic and pulmonary circulation in patients with POPH compared with controls .53], P = 0.002). In patients with POPH, MIF levels were positively correlated with PVR (r = 0.58, P = 0.006) and inversely correlated with cardiac output (r = −0.57, P = 0.007). MIF >60 ng/mL or tricuspid regurgitation gradient >50 mmHg had a 92% sensitivity and specificity for the diagnosis of POPH, with a positive predictive value of 86% and a negative predictive value of 96%. MIF is a promising novel biomarker of POPH disease presence and severity in patients with liver disease and portal hypertension.

The Myths and Realities of Portopulmonary Hypertension

“…(8) In another study, patients with POPH had higher circulating levels of macrophage migration inhibitory factor, a proinflammatory cytokine. (9) MIF levels were correlated with PVR and were associated with worse survival. Higher levels of endothelin-1, a potent vasoconstrictor and therapeutic target of endothelin receptor antagonists, have also been reported in patients with POPH.…”

Pulmonary Complications of Liver Cirrhosis: A Concise Review

“…High levels of MIF were associated with an increased risk of death and MIF production may play a role in disease pathogenesis of PPH [31]. MIF can be an ideal novel biomarker in detecting disease presence and severity [31].…”

“…Hence, it will be useful to develop a sensitive biomarker which can detect disease presence, predict the severity, and treatment response. A recent prospective multicentre case-control study which studied the plasma level of macrophage migration inhibitory factor (MIF) in PPH patients seemed to show promising results [31]. It showed that MIF was higher in both the systemic and pulmonary circulations of patients with PPH compared with controls and correlated with hemodynamic indices of disease severity [31].…”

“…A recent prospective multicentre case-control study which studied the plasma level of macrophage migration inhibitory factor (MIF) in PPH patients seemed to show promising results [31]. It showed that MIF was higher in both the systemic and pulmonary circulations of patients with PPH compared with controls and correlated with hemodynamic indices of disease severity [31]. High levels of MIF were associated with an increased risk of death and MIF production may play a role in disease pathogenesis of PPH [31].…”

“…It showed that MIF was higher in both the systemic and pulmonary circulations of patients with PPH compared with controls and correlated with hemodynamic indices of disease severity [31]. High levels of MIF were associated with an increased risk of death and MIF production may play a role in disease pathogenesis of PPH [31]. MIF can be an ideal novel biomarker in detecting disease presence and severity [31].…”