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.