Early-Stage Primary Biliary Cholangitis: Progression and Outcomes

Primary biliary cholangitis (PBC) is a slowly progressive cholestatic liver disease which may cause cirrhosis and liver failure. Approximately half of patients with early-stage PBC progress to a more severe stage of the disease within 5 years, according to a study published in Clinical Gastroenterology and Hepatology. Disease progression is associated with an increased risk of experiencing a clinical event such as liver failure, requiring liver transplantation, indicating that careful surveillance is crucial in the early stages of PBC.

A diagnosis of PBC is based on biochemical analyses and usually given at an early stage in disease progression. This subgroup analysis of early-stage PBC patients from the Global PBC Study Group database (N=1615; mean age, 55.4 years) evaluated the proportion of patients who had progressed to a moderate or advanced stage of the disease and the factors associated with disease progression and outcomes. Data were collected from clinical evaluations on progression to moderate PBC, defined as an abnormal level of albumin or bilirubin, and to advanced PBC, defined as an abnormal level of both. The study end points were disease progression to moderate or advanced stage, and progression to composite clinical end points including liver transplantation, hepatic encephalopathy, hepatocellular carcinoma, ascites, variceal bleeding, or death, for whichever occurred first. The median (IQR, range) total follow-up time was 7.9 (4.3-12.5, 0.5-25) years.

Of the 1615 patients, 904 progressed to moderate PBC and 201 patients progressed to advanced PBC over the course of the study. The proportion of patients transitioning to moderate-stage PBC at 1 year was 12.9%, compared with 30.2% at 3 years and 45.8% at 5 years. The proportion transitioning to advanced-stage PBC at 1 year was 3.4%, compared with 12.5% at 3 years and 16% at 5 years. The median transition time from early- to moderate-stage PBC was 2.5 (IQR 1-5, range 0.5-15) years, and the median transition time from moderate- to advanced-stage PBC was 1.5 (IQR 0.5-3.5, range 0.5-11.5) years.

During follow-up, 236 participants experienced at least one clinical event. There were 18 instances of liver transplantation, 87 decompensations, 19 hepatocellular carcinomas, and 112 deaths; 21 of these deaths were liver-related. The proportions of patients with moderate-stage PBC and clinical event-free survival at 1, 3, and 5 years were 97.9%, 95.1%, and 91.5%, respectively, and the proportions of patients with advanced-stage PBC and clinical event-free survival at 1, 3, and 5 years were 90.6%, 71.2%, and 58.3%, respectively. In univariate and multivariate cox-regression with biochemical transition modeled as a time-dependent covariate, an increased risk for a clinical event was found for participants transitioning from early- to moderate-stage PBC (time-dependent hazard ratios [HR], 3.0; 95% CI, 2.0-4.5), from moderate- to advanced-stage PBC (HR, 4.6; 95% CI, 3.5-6.2), and overall from early- to advanced-stage PBC (HR, 14.1; 95% CI, 9.3-21.4, P <.001).

Limitations of the study include that a few laboratory data were missing, and no data on co-factors (e.g. alcohol consumption or obesity) were available in the GPBSCG database. Furthermore, a question which remains is how often one should perform laboratory exams in early PBC patients.

Study investigators concluded, “our internationally representative study provides a comprehensive overview of the natural history of PBC patients with early disease stage, showing that almost one out of two patients with early biochemical disease will transit to moderately advanced disease and, approximately one-sixth of them can progress to advanced stage. These transitions are associated with an increased probability of clinical events. The findings underline the importance of clinical surveillance in PBC patients with early biochemical disease stage.”

Disclosure: This clinical trial was supported by Intercept Pharmaceuticals. Please see the original reference for a full list of authors’ disclosures.

Reference

Gatselis NK, Goet JC, Zachou K, et al. Factors associated with progression and outcomes of early-stage primary biliary cholangitis [published online August 13, 2019]. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2019.08.013