Primary Biliary Cholangitis
Primary Biliary Cholangitis (PBC) is a chronic and usually slowly progressive liver disease with autoimmune features, histologically characterized by destruction of the small intrahepatic bile ducts. The disease is primarily diagnosed based on an otherwise unexplained chronic elevation of serum alkaline phosphatase levels and the presence of anti-mitochondrial antibodies. The disease predominantly affects women and is typically diagnosed at middle age. Early identification of individuals with PBC is clinically challenging as symptoms are frequently absent. Identifying and managing patients with PBC is important, however, as the disease may silently progress towards cirrhosis at which stage patients are at risk of liver failure and hepatocellular carcinoma.
Ursodeoxycholic acid (UCDA), a choleretic and hydrophilic endogenous bile acid, is the standard treatment for PBC and is associated with a reduced risk of liver transplantation and death, especially when adequately dosed (13-15 mg/kg). Treatment with UDCA is relevant for all patients, irrespective of disease stage or biochemical response. Yet, up to 40% of the patients respond incompletely to UDCA and are in need for additional therapy to improve their prognosis. Recent research has identified a number of new therapeutic agents, of which obeticholic acid (a farnesoid X receptor agonist) and bezafibrate (a peroxisome proliferator-activated receptor agonist) showed a reduction of alkaline phosphatase in phase 3 randomized clinical trials. Currently, obeticholic acid is the only approved second-line therapy, although it is currently (January 2021) not available in the Netherlands. Bezafibrate may serve as an adequate off-label alternative, particularly in patients with pruritus. Despite adequate treatment, a small proportion of patients continue to develop end-stage liver disease and liver failure. For these patients, liver transplantation is the only therapeutic option that can prevent early death.
Current studies (January 2021)
Dutch PBC Cohort Study
In 2019 the Dutch PBC Cohort Study (DPCS) has started. This national retrospective cohort study aims to include all patients with PBC in the Netherlands. The study is coordinated by the Erasmus MC in Rotterdam on behalf of a broad steering committee, including hepatologists from all regions of the country. This unique study will provide unbiased real-world data on the clinical course, treatment and prognosis of PBC. In addition, it will provide insight into the necessity of second-line therapy, and the potential impact of new drugs from both a clinical and financial perspective in the Netherlands. The study is supported by the Dutch Cholestasis task force of the Netherlands Association for the Study of the Liver (NASL).
Retrospective PBC Biobank
For this project the cholestasis team in the Erasmus MC is assembling a retrospective biobank of serum samples of patients with PBC. Besides our center in Rotterdam, other Dutch centers will be invited to share stored samples, which can be aligned with the clinical dataset of the DPCS. The aim of this translational study is to assess biomarkers in the circulation of patients with PBC in relation to the clinical characteristics of their disease in order to better understand the pathophysiology of PBC, to improve diagnostics and to monitor disease activity and progression.
Health-related Quality of Life and Disease Awareness
ogether with the Dutch Liver Patient Federation a health-related quality of life (HRQoL) and disease awareness study was initiated in 2020. The goal of the project was to validate a Dutch translation of the PBC-40, which is an English PBC-specific measure of the HRQoL. A validated translation would enable further PBC studies with patient-reported outcomes in the Netherlands and Belgium. This is relevant considering the many drug development programs in the field of PBC, and the increasing recognition of the relevance of patient-reported outcomes measures. This project will further assess the HRQoL in relation to the disease awareness of the individual patient and their objective medical parameters. The results of this study are expected in 2021.
Global PBC Cohort Study
In 2012 the Global PBC study group was founded (www.globalpbc.com). The group started with combining individual data of patients with PBC from available long-term follow-up cohorts in a single database. This initiative has resulted in multiple landmark papers in the field of PBC. The cholestasis team of the Erasmus MC actively participates in this international network of medical centers conducting research in PBC. The study group meets bi-annually to discuss progress and propose new projects.
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