Liver dysfunction in idiopathic pulmonary arterial hypertension: prevalence, characteristics and prognostic significance, a retrospective cohort study in China

Objectives: The aim was to elucidate the relationship between liver function and idiopathic pulmonary arterial hypertension (IPAH).

Design and setting: Retrospective, longitudinal study in urban tertiary care centre in Shanghai, China.

Participants: 407 IPAH consecutive incident patients age 18-65 years were retrospectively enrolled from January 2008 to December 2018.

Outcome measurements: The primary endpoint was all-cause mortality. The cut-off value was determined by receiver operating characteristic curve (ROC), which was validated by Cox proportional hazard model was internally validated by bootstrap analysis and used for survival analysis. The Cox model was (internally) validated and cross-validated areas under the curve (AUC) should be reported.

Results: The prevalence of abnormal liver function tests (LFTs) at baseline was 77.6%. Hyperbilirubinaemia is the most common abnormal biochemical liver test: abnormal total bilirubin (TBIL in 51.6% patients). During the follow-up, 160 patients died. Patients with mixed liver dysfunction have worse prognosis than those with normal LFTs or isolated abnormal bilirubin metabolism. Comparing with patients with hepatocellular injury, the survival of patients with abnormal bilirubin metabolism is lower. Multivariable Cox models revealed a positive association between TBIL, γ-glutamyltransferase (GGT) and mortality showing that each Ig increment in TBIL and GGT was associated with a higher all-cause mortality (TBIL: HR 4. 29 (95% CI 1. 21 to 15. 27), p=0. 02; GGT: HR 2. 76 (95% CI 1. 18 to 6. 45), p=0. 02). A novel formula named Liver Function Predict Index (LFPI) was constructed (LFPI=-0.002*6MWD+1.014*lg GGT+1.458*lg TBIL) to predict prognosis. ROC curve analysis did further identify 2.729 as the best cut-off value for LFPI (AUC 0.75, p<0.001, sensitivity 79%, specificity 70%).

Conclusions: Liver dysfunction is frequent in IPAH, and characterised by a predominantly cholestatic enzyme profile. LFTs abnormalities are associated with worse survival and LFPI was a new and simple predictor for prognosis of IPAH.