Predictive factors for decompensating events in cirrhotic patients with primary biliary cholangitis under different lines of therapy

Background & Aims: The landscape in primary biliary cholangitis (PBC) has changed with the advent of second-line treatments. However, the use of obeticholic acid (OCA) and fibrates in PBC-related cirrhosis is challenging. We assessed the impact of receiving a second-line therapy as a risk factor for decompensated cirrhosis in a real-world cirrhotic PBC population, and identify the predictive factors for decompensated cirrhosis in these patients. Approach & Results: Multicenter study enrolling 388 PBC-cirrhotic patients from the Spanish ColHai registry. Biopsy (20%), ultrasound (59%), or transient elastography (21%) defined cirrhosis, and the presence of varices and splenomegaly defined clinically significant portal hypertension (CSPH). Paris-II and POISE criteria determined the response to ursodeoxycholic acid (UDCA), fibrates (n=93), and OCA (n=104). The incidence of decompensated cirrhosis decreased for UDCA versus OCA or fibrates in the real-world population, but they were similar considering the PS-matched cohort (UDCA 3.77 vs. second-line therapy 4.5 100 persons-year, respectively), as patients on second-line therapy exhibited advanced liver disease. Consequently, GGT, albumin, platelets, CSPH, and UDCA response were associated with a decompensating event. OCA response (achieved in 52% of patients) was associated with bilirubin [OR 0.21 (95%CI 0.06-0.73)] and AST [OR 0.97 (95%CI 0.95-0.99)], while fibrate response (achieved in 55% of patients) with AST [OR 0.96 (95%CI 0.95-0.98)]. In OCA-treated patients, drug response [sHR 0.23 (95%CI 0.08-0.64)], diabetes [sHR 5.62 (95%CI 2.02-15.68)], albumin [sHR 0.34 (95%CI 0.13-0.89)], and platelets [sHR 0.99 (95%CI 0.98-1.00)] were related to decompensation. In fibrate-treated patients, drug response [sHR 0.36 (95%CI 0.14-0.95)], albumin [sHR 0.36 (95%CI 0.16-0.81)], and CSPH [sHR 3.70 (95%CI 1.17-11.70)] were associated with decompensated cirrhosis. Conclusions: Advanced PBC, rather than OCA and fibrates, was found to be associated with decompensating events. Therefore, biochemical and clinical variables should be considered when making decisions about the management of these drugs. Moreover, a positive response to OCA and fibrates reduced the risk of decompensation.