Bilirubin Levels May Reveal Severity, Predict Progression of IPF, Study Finds

The amount of bilirubin in the blood might predict the progression of idiopathic pulmonary fibrosis (IPF), according to a recent study.

If validated in larger studies, bilirubin levels in the blood — or serum bilirubin — could offer a cheaper, simpler, and more convenient blood test than other prognostic markers of IPF.

The study, “Correlation between serum bilirubin levels and the severity as well as the prognosis of idiopathic pulmonary fibrosis,” was published in the journal Chronic Respiratory Disease.

A link between serum bilirubin and pulmonary diseases — such as chronic obstructive pulmonary disease, asthma, and lung cancer — has been reported. However, it is not clear if a link also exists between serum bilirubin levels and IPF.

To address this question, researchers from Nanjing University Medical School, in China, conducted a retrospective study of IPF patient records.

In total, records of 146 IPF patients and 69 randomly-selected healthy controls were analyzed to identify associations between serum bilirubin and the progression of lung dysfunction and survival.

A separate set of 40 IPF patient records was also analyzed to validate the predictive value of serum bilirubin levels — the validation group.

Results showed that IPF patients tended to be older and had lower total and direct bilirubin levels than their healthy counterparts. Total bilirubin is composed of direct and indirect bilirubin. Indirect bilirubin is bound to a protein called albumin, while direct bilirubin is not.

Total bilirubin correlated with DLCO-SB, a measure of the lungs’ ability to transfer oxygen to the blood, but it was not associated with other measures of lung function, namely the P/F ratio, forced vital capacity (FVC), or forced expiratory volume in one second (FEV1).

Among the IPF patients analyzed, 23 experienced acute exacerbations, which is the rapid worsening of one’s condition that can result in lung function decline and raises the risk of mortality. These patients had significantly lower total and indirect bilirubin than patients with stable disease.

The team established cutoff values of 10.65 micromol/l for total serum bilirubin and 7.95 micromol/l for indirect bilirubin concentrations for predicting the incidence of acute exacerbations in IPF.

The researchers then assessed the potential link between bilirubin levels and survival.

Follow-up data was available for 98 of the initial 146 patients. Of these, 25 died during the study, which included data up to April 2020.

Patients with total bilirubin of 8.8 micromol/l or less were defined as the lower bilirubin group (43 patients), while those with more than that were defined as the higher group (55 patients).

Results showed that significantly more patients in the lower bilirubin group survived than did those in the higher group. Applying this cutoff value to the validation cohort revealed similar results.

After adjusting the results for several factors, serum total bilirubin level was identified as an independent prognostic factor for survival among people with IPF.

“Serum TBIL [total bilirubin] levels might be useful for reflecting the severity and predicting the survival of patients with IPF,” the researchers wrote.

Among the patients analyzed, 34 were receiving the approved IPF treatment Esbriet (pirfenidone).

After one year of treatment, the researchers found no significant association between serum bilirubin at baseline (study start) and Esbriet’s efficacy, suggesting that bilirubin levels do not predict the patient’s response to treatment.

Overall, the data “shows serum bilirubin concentration is associated with the severity and prognosis of IPF patients [and] offers the advantages of convenience, ease of accessibility and low cost,” the researchers wrote.

“Further studies are required to … explore the mechanism underlying the association of bilirubin with the prognosis of IPF patients,” they added.