Inadequate response to UDCA among PBC patients under routine care in the US: Rising serum bilirubin even in the normal range is a risk factor and subsequent clinical follow-up differs based on treatment response

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Conference Proceeding

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J Hepatol


Background and aims: Ursodeoxycholic acid (UDCA)is a first line treatment in patients with primary biliary cholangitis (PBC)that is often followed by second-line therapy if there is inadequate response (IR). Previous analyses by the Fibrotic Liver Disease Consortium showed that pre-treatment total bilirubin, even within the normal range, is associated with increased risk of mortality. In the present study, we analyzed the effect of pre-treatment bilirubin and other covariates associated with the risk of IR, and compared follow-up care between patients with/without IR. Method: Baseline data were collected for PBC patients at time of UDCA initiation between 2006 and 2015. Total bilirubin was categorized as > 2, 2 > 1.5, 1.5 > 1.0, 1.0 > 0.7, 0.7 > 0.4, and ≤ 0.4 mg/dL. IR was defined using Paris II criteria 12 months after UDCA initiation. Logistic regression was used to estimate the adjusted risk for IR; model accuracy was assessed using area under the receiver operator characteristic curve (AUROC). Z-statistic was used to compare rates of follow-up care and treatment modification per person-year (PPY)between IR and non-IR patients. Results: Among 1578 UDCA treated patients (13% men; 8% African American, 9% Asian American/American Indian/Pacific Islander (ASINPI); 25% Hispanic), 706 (45%)had IR to UDCA at 12 months post-baseline. The multivariate model (AUROC = 0.79)showed that younger age, increasing alkaline phosphatase (ALP), low albumin, and a ratio of aspartate to alanine aminotransferase (AST/ALT)> 1.1 were independently associated with an increased risk of IR. Bilirubin—even in the high-normal (1.0 > 0.7)and mid-normal (0.7 > 0.4 mg/dL)ranges—was also significantly associated with increased risk of IR compared to low-normal levels (≤ 0.4 mg/dL; Figure). A sensitivity analysis that defined IR as ALp > 1.67xULN yielded similar results. Compared to responders, patients with IR were more likely to: discontinue UDCA (0.08 vs 0.04 PPY; p < 0.01); add obeticholic acid (0.023 vs 0.004 PPY; p < 0.01); and were more likely to see a specialist (5.12 vs 3.16 visits PPY; p < 0.01), undergo liver imaging (1.23 vs 0.56 tests PPY; p < 0.01), have liver-related laboratory testing (18.4 vs 10.2 tests PPY; p < 0.01), be hospitalized (0.11 vs 0.07 PPY; p < 0.01), and seek emergency care (0.13 vs 0.08 PPY; p < 0.01). Conclusion: Almost half of PBC patients (45%)in a routine clinical care cohort showed IR to UDCA. Baseline bilirubin > 0.4 mg/dL is associated with increasing risk of IR. Patients with IR had higher rates of specialist follow-up and health care utilization.





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