Obeticholic Acid Improves Aminotransferases Early during Treatment in Patients with Primary Biliary Cholangitis Not Responding to Ursodeoxycholic Acid: A Study in Clinical Practice

Sara Labanca,Giulia Pieri,Maria Plaz Torres,Valentina Cacciato,Edoardo Giannini,Paolo Borro,Antonino Picciotto,Simona Marenco

doi:10.3390/immuno1040033

Abstract

Obeticholic acid (OCA) improves cholestasis and is generally well tolerated in patients with primary biliary cholangitis (PBC) not responding, or intolerant, to ursodeoxycholic acid (UDCA). As PBC is mainly a cholestatic disorder, less attention is paid to aminotransferase behavior in the course of treatment. In this study we evaluated, in clinical practice, the efficacy of OCA treatment on both alkaline phosphatase (ALP) and alanine aminotransferase (ALT) using updated healthy ranges for aminotransferases. Fifteen PBC patients, non-responders to UDCA, were evaluated at baseline and during OCA treatment with serial measurement of cholestasis indexes and ALT, that were also assessed using updated normal ranges (<30 IU/L in males, <19 IU/L in females). Median ALP and ALT decreased from 2.16 to 1.27 × upper limit of normal (p = 0.003) and from 0.93 to 0.78 × upper limit of normal (p = 0.008), respectively, in the course of OCA treatment. At treatment day-15, median ALT decreased by 29.7% and ALP by 8.8%. Bilirubin and albumin were unmodified throughout treatment. Using updated normal ranges, ALT levels were normal in 6.7% of patients at baseline and in 33.3% of patients at 18 months of treatment. OCA treatment improves cholestasis and, also, indexes of hepatocyte necrosis, with a decline in necro-inflammatory activity even predating the improvement in cholestasis. Use of recalibrated healthy ranges for aminotransferases might be a useful tool to assess hepatic histological activity and its improvement with OCA treatment.

Highlights

Primary biliary cholangitis (PBC) is a rare autoimmune cholestatic liver disease, whose prevalence varies between 1.91 and 40.2 on 100,000 people and whose incidence is between0.3 and 5.8 on 100,000 cases per year, with highest figures observed in Northern Europe and Northern America [1]
We included in this study, among patients with PBC followed at our Unit, those eligible for a second-line treatment with Obeticholic acid (OCA) according to the indications set forth by the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA) when the drug was made available in Italy in 2017 [17]
This relatively rare disease often afflicts young and middle-aged patients and its course is life-long due to the absence of a definitive cure, treatment with ursodeoxycholic acid (UDCA)—if initiated at earlier stages of disease—is able to improve the cholestatic biochemical picture characterizing PBC, and to decrease the incidence of liver-related events, and eventually improve patients’ survival [21]

Summary

Introduction

Primary biliary cholangitis (PBC) is a rare autoimmune cholestatic liver disease, whose prevalence varies between 1.91 and 40.2 on 100,000 people and whose incidence is between0.3 and 5.8 on 100,000 cases per year, with highest figures observed in Northern Europe and Northern America [1]. PBC tends to affect middle-aged women, who often have comorbid autoimmune diseases, and its course is generally mild to moderate, with a slow progression to more advanced forms of liver disease in most cases, it may evolve to cirrhosis and end-stage liver disease, eventually leading to liver transplantation [1,2,3]. Prognostic assessment is essential, and adequate risk stratification is critical, for the management of patients with PBC [4,5] Several models such as the UK-PBC and GLOBE scores have recently been proposed, and validated, to assess the prognosis of PBC patients both at diagnosis and in the course of treatment [6,7,8]. If UDCA treatment is started during the early stages of the disease the drug is able to ensure a life expectancy similar to the general population [1,2,4,5]

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Results

Conclusion