Low Bilirubin, Normal Alkaline Phosphatase Tied To Better Outcomes Of Biliary Cholangitis

Treatment targets for improved survival in primary biliary cholangitis should include low-normal bilirubin and normal alkaline phosphatase levels, a new study suggests.

Various surrogate markers have been proposed to predict clinical outcomes of primary biliary cholangitis (PBC), including bilirubin and alkaline phosphatase (ALP).

Dr. Bettina E. Hansen of the University Health Network and University of Toronto, in Canada, and colleagues used the GLOBAL PBC Study Group database to evaluate whether bilirubin or ALP levels within the normal range (at or below the upper limit of normal, or ULN) are associated with survival in patients with PBC.

Compared with the lowest quartile of bilirubin concentrations at time zero, the risk of liver transplantation or death was 83% higher with bilirubin concentrations in the highest quartile (P = 0.003). Similarly, bilirubin concentrations in the highest quartile at one year were associated with a 2.2-fold increased risk of liver transplantation or death (P < 0.001).

The bilirubin threshold at 1 year with the highest ability to predict liver transplantation or death was 0.6 times ULN. The 10-year survival of patients was 91.3% with a normal bilirubin 0.6 times ULN or lower, 79.2% with normal bilirubin above 0.6 times ULN, and 37.3% with abnormal bilirubin at 1 year.

A reduction to 0.6 times ULN or lower at 1 year following treatment with ursodeoxycholic acid was associated with a 10.5% improvement in 10-year survival, compared with bilirubin that remained above this threshold, the researchers report in The American Journal of Gastroenterology.

Among patients whose bilirubin was normal at 1 year, the optimal ALP threshold was 1.0 times ULN, which was associated with significantly higher survival at 10 years and 15 years, compared with higher ALP levels.

When both levels were combined, the prognosis of patients with bilirubin above 0.6 times ULN was dependent on ALP normalization. Such patients had similar survival rates to those with bilirubin 0.6 times ULN or lower when their ALP levels were normal, but their survival was significantly diminished when their ALP levels were above the ULN.

"These findings suggest that the interpretation of not being at risk if bilirubin is within the normal range needs to be revised," the authors note.

"Our proposed thresholds of 0.6 times ULN for bilirubin and normalization for ALP represent a refinement of previous criteria with an aim to optimize survival and identify patients at risk for poor outcome," they conclude. "Moreover, their implementation can broaden the patient population included in intervention studies who may benefit from therapeutic agents."

Dr. Hansen did not respond to a request for comments.

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