Inter-α-inhibitor heavy chain 4 levels in incident and prevalent patients with primary biliary cholangitis

Primary biliary cholangitis (PBC) is an autoimmune liver disease characterised by progressive bile duct injury. We recently showed that inter-α-inhibitor heavy chain 4 (ITIH4) levels are elevated in patients with PBC. Here, we investigated the potential of ITIH4 as a biomarker for disease severity and treatment response.

We included 237 patients with primary biliary cholangitis, 80 incident (newly diagnosed), 157 prevalent (with established disease) and 100 healthy controls. All patients were followed for 12 months during initiation or continuation of ursodeoxycholic acid (UDCA). Associations with treatment response, patient type, autoimmune hepatitis (AIH-PBC) and sex were assessed using linear mixed-effects models. The prognostic value of baseline ITIH4 for following response was assessed using logistic regression.

ITIH4 levels were significantly higher in both PBC cohorts compared with healthy controls (incident: 274 µg/ml, prevalent: 283 µg/ml, controls: 221 µg/ml; p < .0001). In a mixed-effects model, treatment response, prevalent (vs. incident) disease and AIH-PBC (vs. PBC alone) were each independently associated with lower ITIH4 (p = .003, p = .034 and p = .013). Correlations between ITIH4 and markers of disease severity were generally weak. Baseline ITIH4 was not significantly associated with treatment response (OR 0.994, p = .14).

ITIH4 was consistently elevated in patients with PBC compared with healthy individuals. Baseline ITIH4 levels did not independently predict response and correlations with established severity markers remained weak. These findings do not support its use as a prognostic marker or as an addition to existing clinical biomarkers.