Relevance of liver function tests in pulmonary hypertension

Background: Pulmonary hypertension (PH) is a serious limitation of cardiovascular hemodynamics by increased pulmonary vascular resistance. Its prognosis is determined by right ventricular function as defined by right atrial pressure (RAP) and cardiac index (CI). Liver function tests (LFT) are well-established routine parameters. In PH reduced perfusion, congestion due to right heart failure and side effects of therapy with oral anticoagulants or endothelin receptor blockers may cause their elevation. In this study we investigated the prognostic relevance of these parameters for survival in patients with PH and their relation to hemodynamic parameters.

Methods: Blood samples were drawn during routine right heart catheterization in 65 patients with pulmonary arterial hypertension (PAH), lung disease associated PH (LD) and chronic thrombembolic PH (CTEPH). Alanine-aminotransferase (ALAT), aspartate-aminotransferase (ASAT), bilirubin, gamma-glutamyltransferase (GGT), lactate-dehyrogenase (LDH) and fibrinogen (FBG) were determined and data evaluated retrospectively. Variables were dichotomized for survival analysis based on maximal Youden's J.

Results: The median follow-up time was 10.48 years with all-cause mortality as primary end-point. GGT and bilirubin correlated negatively with CI and positively with RAP. Based on c-statistics, GGT was the best predictor for survival. Univariate cox regression confirmed predictive values for GGT (HR 3.30 [1.64 – 6.63], p = 0.0005), bilirubin (HR 2.57 [1.31 – 5.07], p = 0.0064) and LDH (HR 2.18 [1.08 – 4.38], 0.0287).

Conclusion: This study provides evidence for the clinical perception of elevated LFTs with decreased right ventricular function. Furthermore, it shows, that even GGT, LDH and bilirubin are useful parameters for evaluation of patients with PH beyond monitoring side effects of medication.