Primary Biliary Cholangitis—The Changing Biomarker Paradigms for Staging Fibrosis

Primary biliary cholangitis (PBC) is an autoimmune-mediated disease characterized by chronic, non-suppurative, small-duct lymphocytic cholangitis. The prognosis largely depends on early disease recognition and treatment. Suboptimal response to first-line therapy (ursodeoxycholic acid) is associated with risk for disease progression. Reliable biomarkers are also required to enhance risk stratification. The traditional gold standard for assessing fibrosis is liver biopsy, but it is invasive and unsuitable for serial evaluations. Hence, trends are towards non-invasive surrogate biomarkers (blood-based and imaging biomarkers respectively) which have a much better safety profile. Blood-based biomarkers include: (i) Fibrosis-4 Fib-4, (ii) Aspartate Aminotransferase to Platelet Ratio Index APRI, (iii) Enhanced Liver Fibrosis score ELF, and (iv) total bile acid to platelet ratio TPR. They show much potential but are not particularly sensitive tests. Ultrasound-based imaging biomarkers are increasingly being utilized for liver stiffness measurement (LSM), with vibration-controlled transient elastography (VCTE) emerging as the preferred technique. However, despite its growing popularity, VCTE is limited by technical issues. Hence, currently, none of the non-invasive tests fulfill the prerequisites to be the new gold standard as defined by the FDA. Nonetheless, there may be value to combining LSM with various serum biomarkers such as Fib-4, APRI, as aforementioned. The hope is to create nomograms for predicting liver-related events and decision tree algorithms. Newer studies are investigating microbiota in the gut-liver axis, biomolecules such as nanovesicles/nanofibers, and metabolic reprogramming as it pertains to e.g., proteomics and lipidomics. These approaches hold much promise, and if validated, could significantly change the management of PBC.