The association of histological progression with biochemical response to ursodeoxycholic acid in primary biliary cholangitis

Primary biliary cholangitis (PBC) is currently diagnosed at an early stage; therefore, the number of patients with PBC without symptoms at the time of diagnosis is increasing. However, up to 30% of patients with PBC exhibit the suboptimal response to ursodeoxycholic acid (UDCA) and are at high risk of end-stage liver disease. Obeticholic acid is an approved second-line therapy for patients with PBC that are refractory to UDCA. Novel surrogate endpoints are required to identify individuals eligible for second-line therapies. An inadequate biochemical response to UDCA is a useful predictor of poor outcomes in patients with PBC. In addition to UDCA effects on biochemical parameters, histological outcomes could be considered as candidate surrogate endpoints. Alterations in liver histology are used as surrogate endpoints in clinical studies. However, current staging systems are insufficient to determine PBC disease severity and progression because of the pathological heterogeneity of the disease. Histological features at baseline and biochemical response to UDCA treatment can affect the disease course of PBC. Therefore, novel surrogate endpoints must be represented by parameters characterized by histological outcomes and treatment responses in PBC. In this review, we discuss the existing histological parameters and newly created factors to identify patients with PBC who are at a high risk of developing end-stage liver disease and, consequently, the potential need for additional treatments.

Automated summary

PBC patients with suboptimal response to UDCA are at high risk for end-stage liver disease, requiring new surrogate endpoints to identify candidates for second-line therapies, as current staging systems are insufficient in determining disease severity and progression.