Association of liver fibrosis with incident chronic obstructive pulmonary disease

The Fibrosis-4 (FIB-4) index, a noninvasive hepatic fibrosis marker reflecting systemic inflammation and metabolic dysfunction, is associated with adverse outcomes in established chronic obstructive pulmonary disease (COPD). However, its ability to predict incident COPD in the general population remains unknown.

We conducted a prospective cohort study using UK Biobank data from 444,376 participants without prevalent COPD at baseline. The FIB-4 index was calculated from age, aspartate aminotransferase, alanine aminotransferase, and platelet count. The primary outcome is incident COPD. Cox proportional-hazards models were used to estimate hazard ratios (HRs) for incident COPD across FIB-4 categories (low, intermediate, high).

During a median follow-up of 14.1 years, 18,515 incident COPD events occurred. Higher FIB-4 was associated with a graded increase in COPD risk. In the fully adjusted model, the HRs for the intermediate and high FIB-4 categories were 1.48 (95% confidence interval [CI], 1.43 to 1.53) and 1.72 (95% CI, 1.57 to 1.88), respectively, as compared with the low category. When FIB-4 was analyzed as a continuous variable via restricted cubic splines, a positive graded association with COPD risk was observed with significant non-linearity (P for non-linearity <0.001). Results were consistent in both sexes and across sensitivity analyses, including exclusion of participants with hypertension, diabetes, or liver disease and exclusion of early events. Competing-risk analysis with death as a competing event yielded similar findings.

In this large prospective cohort study, we found that a higher FIB-4 index was independently associated with an increased risk of incident COPD.