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Low ALP, bilirubin levels increased transplant-free survival rate in PBC patients

Serum alkaline phosphatase and bilirubin levels were accurate in predicting transplant-free survival and mortality rates among patients with primary biliary cirrhosis, according to study results.

“This study represents the largest international collaboration in [primary biliary cirrhosis] and provided us with a wealth of data supporting the use of this biochemical endpoint for therapeutic clinical trials,” researcher Bettina Hansen, PhD, of the department of gastroenterology and Hepatology at Erasmus University Medical Center in Rotterdam, the Netherlands, said in a press release. “The key take away from this analysis for everyday clinical practice is that the lower a patient’s [alkaline phosphatase] level and having a normal bilirubin level correlate with an improved prognosis for patients with [primary biliary cirrhosis].”

Hansen and colleagues from the Global Primary Biliary Cirrhosis (PBC) Study Group, a collaboration between 15 liver centers throughout the United States and Europe, analyzed data of 4,845 patients with PBC from long-term follow-up cohorts. A majority of the data collected included patients who were starting therapy with ursodeoxycholic acid (UDCA; 85%). The median follow-up was 7.3 years and researchers sought to determine any correlation between patient outcomes, including liver transplantation and death, and alkaline phosphatase (ALP) and bilirubin levels.

During follow-up, 729 patients died and 389 underwent transplantation. Analyses showed that levels of ALP and bilirubin were highly associated with transplantation and mortality. Lower levels of both serums were associated with a longer transplant-free survival. ALP serum levels two times the upper limit of normal (ULN) were the most accurate way in predicting patient survival outcome (c-statistic=0.71; 95% CI, 0.69-0.73), whereas bilirubin serum levels one time the ULN best predicted survival (c-statistic=0.79; 95% CI, 0.77-0.8). Eighty-four percent of patients with normal levels of ALP survived for 10 years compared with 62% of patients with ALP levels two times the ULN (P<.0001), 1 year after study enrollment. Also, more patients with bilirubin levels less than one time the ULN survived for 10 years after enrollment compared with patients with bilirubin levels one time greater the ULN (86% vs. 41%; P<.0001). When combined, both serum levels increased researchers’ ability to predict patient survival times, according to the research.

Among the entire cohort, 5-year transplant-free survival was 88%; 77% for 10-year survival; and 63% for 15-year survival. In patients who received UDCA therapy, 5-year transplant-free survival was 90% compared with 79% of untreated patients; 78% at 10 years compared with 59% of untreated patients; and 66% at 15 years compared with 32% of untreated patients.  

“We unequivocally show that both increased serum [ALP] and bilirubin levels are strongly associated with reduced transplant-free survival in patients with PBC and that a combination of both variables improves prognostic prediction for patients,” the researchers concluded. “These data support that both [ALP] and bilirubin provide meaningful surrogate end points in PBC that can be reasonably used in clinical trials.”

Disclosure: The study was funded by unrestricted grants from Intercept Pharmaceuticals and Zambon Nederland BV and funded by the Foundation for Liver and Gastrointestinal Research. See the study for a full list of researchers’ relevant financial disclosures.