Diabetes Linked to Worse Transplant-Free Survival in Primary Biliary Cholangitis

Diabetes is associated with an increased risk of poor clinical outcomes, including transplant-free survival, in patients with primary biliary cholangitis (PBC), according to findings from a recent study.¹

The research was presented at The Liver Meeting 2024 from the American Association for the Study of Liver Diseases (AASLD) in San Diego, California, by Ellen Werner, a PhD student at Erasmus University Medical Center, and suggests diabetes is an independent predictor of unfavorable transplant-free survival in patients with PBC.¹

Recent US Food and Drug Administration accelerated approvals of elafibranor (Iqirvo) and seladelpar (Livdelzi) have helped reshape PBC care, greatly expanding the treatment options available to patients. Understanding which patients are at the greatest risk of adverse disease outcomes is important for appropriate disease management.^2,3

Citing the increasing presence of metabolic comorbidities in patients with primary liver diseases, Werner and colleagues sought to assess the relationship between diabetes and clinical outcomes in patients with PBC by analyzing data from the Dutch PBC Cohort Study (DPCS), a retrospective study including every identifiable patient with PBC in the Netherlands from 1990 up to last data collection (2019-2022) in 71 Dutch hospitals.¹

Investigators obtained clinical data through medical chart review. The study’s primary endpoint was liver transplantation or all-cause mortality, and the secondary liver-specific endpoint was the first occurrence of either decompensated cirrhosis, liver transplant, or liver-related death.¹

In total, 4256 patients with PBC were followed for a median duration of 8.9 years (IQR, 4.2-14.8). Among the cohort, the median age at diagnosis was 56.7 years (IQR 48.4-66.2), 88.2% of participants were female, and 9.8% had diabetes at baseline. Investigators noted patients with diabetes were older (63.6 years vs 56.0 years; P <.001), were more often male (17.7% vs 11.3%; P <.001), and more frequently had cirrhosis at baseline (14.6% vs 5.8%; P <.001).¹

The Paris-2 response rate, defined as alkaline phosphatase (ALP) and aspartate transferase (AST) <1.5ULN as well as bilirubin <ULN, after 1 year of ursodeoxycholic acid (UDCA) was 55.2% among patients with diabetes compared with 57.6% among those without diabetes (P = .447). The 10-year transplant-free survival was 70.7% (95% CI, 65.2-76.2) among patients with diabetes compared with 87.0% (95% CI, 85.8-88.2) in those without diabetes (P <.001).¹

After 10 years, investigators noted the cumulative liver-specific event rate was 14.6% (95% CI, 10.3-18.9) vs 6.9% (95% CI, 5.9-7.9) in those with and without diabetes, respectively (P <.001). After adjusting for age; gender; cirrhosis; calendar time; and biochemical parameters of liver disease severity, diabetes was independently associated with an increased risk of liver transplant or death (adjusted hazard ratio [aHR], 1.7; 95% CI, 1.3-2.2; P <.001) and with liver-specific events (aHR, 1.6; 95% CI, 1.0-2.5; P = .040).¹

“In this nationwide cohort, diabetes was an independent predictor of unfavorable liver transplant-free survival in patients with PBC. This is partly explained by an increase in progression to end-stage liver disease,” investigators concluded.¹

References

1. ^{Werner E, Weijsters GHX, van Hooff MCB, et al. Diabetes mellitus is associated with worse clinical outcomes in patients with primary biliary cholangitis. Paper presented at: AASLD’s The Liver Meeting 2024. San Diego, California. November 15-19, 2024.}
2. ^{Brooks, A. FDA Grants Accelerated Approval to Elafibranor (Iqirvo) for PBC. HCPLive. June 10, 2024. Accessed November 18, 2024. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-elafibranor-iqirvo-for-pbc}
3. ^{Brooks, A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. HCPLive. August 14, 2024. Accessed November 18, 2024. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis}