Author information

¹Hospital Universitario Virgen del Rocío, Sevilla, Spain.

²Instituto de Biomedicina de Sevilla, Spain.

³Universidad de Sevilla, Spain.

⁴CIBERehd, Spain.

⁵Hepatology and Liver Transplantation Unit, IISLaFe, La Fe University Hospital, Valencia, Spain.

⁶University of Valencia, Dept of Medicine, Valencia, Spain.

⁷Hospital Universitario de Canarias, Spain.

⁸Hospital Clinico Universitario de Santiago, Spain.

⁹Complejo Asistencial Universitario de Burgos, Spain.

¹⁰Hospital Universitario Reina Sofía, Córdoba, Spain.

¹¹Hospital Universitario 12 de Octubre, Madrid, Spain.

¹²Unidad de Aparato Digestivo, Hospital Universitario Torrecardenas, Almería, Spain.

¹³Hospital Universitario Central de Asturias, Oviedo, Spain.

¹⁴Servicio de Aparato Digestivo, Complejo Asistencial Universitario de León, León, Castilla y León, Spain.

¹⁵Gastroenterology Department, Hospital Universitario La Princesa, IIS-IP, Universidad Autónoma de Madrid, Spain.

¹⁶Servicio de Gastroenterología y Hepatología. Grupo de Investigación Clínica y Traslacional en Enfermedades Digestivas, Instituto de Investigación Valdecilla (IDIVAL), Hospital Universitario Marqués de Valdecilla, Santander, Spain.

¹⁷Liver Section, Hospital Universitari Germans Trias i Pujol, IGTP, Badalona, Spain.

¹⁸Universitat Autònoma de Barcelona, Spain.

¹⁹Hospital del Mar, Barcelona, Spain.

²⁰Complexo Hospitalario Universitario de Pontevedra. Instituto de Investigación Sanitaria Galicia Sur (IISGS).

²¹Servicio de Aparato Digestivo, Hospital Clínico Universitario, Zaragoza, Spain.

²²Instituto de Investigacion Sanitaria de Aragon (IIS Aragón), Universidad de Zaragoza, Spain.

²³Hospital Universitario Ramón y Cajal, Madrid, Spain.

²⁴Hospital Universitario Donostia, San Sebastián, Spain.

²⁵Liver Unit, Hospital Clínic Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), University of Barcelona, Barcelona, Spain.

²⁶Hospital Universitario La Paz, Madrid, Spain.

²⁷Hospital Universitario Fundación Alcorcon, Universidad Rey Juan Carlos, Madrid, Spain.

Abstract

Background and 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 population with cirrhosis and PBC, and identify the predictive factors for decompensated cirrhosis in these patients.

Approach and results: Multicenter study enrolling 388 patients with PBC-cirrhosis 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 PBC OCA international study of efficacy 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 propensity score-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, clinically significant portal hypertension, 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 patients treated with OCA, 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 patients treated with fibrate, drug response (sHR 0.36 (95% CI: 0.14-0.95]), albumin (sHR 0.36 (95% CI: 0.16-0.81]), and clinically significant portal hypertension (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.