Longitudinal Relationship Between Elevated Liver Biochemical Tests and Negative Clinical Outcomes in Primary Biliary Cholangitis: A Population-Based Study

Abstract

Background: Elevated liver biochemistries are associated with increased risk of negative outcomes in patients with primary biliary cholangitis (PBC).

Aims: To evaluate whether longitudinal monitoring of liver biochemistries and fibrosis scores provides additional prognostic value and to assess the relationship between the degree of elevation of multiple biomarkers within different alkaline phosphatase (ALP) strata.

Methods: Adults with PBC were identified from Komodo's Healthcare Map. A Cox proportional hazards model examined time to first occurrence of hospitalisation due to hepatic decompensation, liver transplantation, or death as a function of the proportion of time during follow-up that liver biochemistries and fibrosis scores exceeded thresholds. Within ALP strata (ALP ≤ upper limit of normal [ULN]; ALP>ULN to ≤ 1.67 × ULN; ALP > 1.67 × ULN), separate multivariate Cox hazard models assessed the association between time-varying covariates and the composite endpoint.

Results: Overall, 3974 patients were included; 88.2% were female, with a mean age of 59.4 years. The median follow-up was 2.5 years. Increasing magnitude and duration beyond established thresholds of ALP, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), AST/platelet ratio index (APRI) and fibrosis-4 (FIB-4) were associated with increased risk of negative outcomes. Elevated ALT, AST, TB, APRI and FIB-4 were associated with increased risk of negative outcomes across all ALP strata.

Conclusions: Prolonged elevation of multiple hepatic biomarkers and fibrosis scores is associated with a greater risk of negative clinical outcomes, underscoring the importance of ongoing monitoring beyond the guideline-recommended initial treatment response to guide timely treatment decisions and improve PBC management.

Keywords: clinical outcomes; hepatic failure; liver function test; primary biliary cholangitis; risk factor.

FIGURE 1

Flow diagram of patient selection criteria. ALP, alanine phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; PBC, primary biliary cholangitis; PLT, platelet; TB, total bilirubin.

FIGURE 2

Impact of magnitude and time spent beyond clinical thresholds for (A) hepatic biomarkers and (B) fibrosis scores on the risk of hospitalisation for hepatic decompensation, liver transplantation or death. ALP ULN defined as 120 U/L; ALT ULN defined as 40 U/L; APRI ULN defined as 0.5; AST ULN defined as 35 U/L for males and 30 U/L for females; TB ULN defined as 1 mg/dL. ALP, alanine phosphatase; ALT, alanine aminotransferase; APRI, aspartate aminotransferase to platelet ratio index; AST, aspartate aminotransferase; FIB‐4, fibrosis 4 score; HR, hazard ratio; TB, total bilirubin; ULN, upper limit of normal.

FIGURE 3

HRs for the risk of hospitalisation for hepatic decompensation, liver transplantation, or death as a function of time above (A) serum hepatic biomarkers and (B) fibrosis score thresholds within each ALP strata. ALP ULN defined as 120 U/L; ALT ULN defined as 40 U/L; AST ULN defined as 35 U/L for males and 30 U/L for females; TB ULN defined as 1 mg/dL. ALP, alanine phosphatase; ALT, alanine aminotransferase; APRI, aspartate aminotransferase to platelet ratio index; AST, aspartate aminotransferase; FIB‐4, fibrosis 4 score; HR, hazard ratio; TB, total bilirubin; ULN, upper limit of normal.

FIGURE 4

Risk of hospitalisation for hepatic decompensation, liver transplantation, or death by proportion of 5‐year follow‐up with ALP ≥ ULN and TB ≥ 0.6 × ULN. ALP, alkaline phosphatase; HR, hazard ratio; TB, total bilirubin; ULN, upper limit of normal.