Research ArticleEarly primary biliary cirrhosis: Biochemical response to treatment and prediction of long-term outcome
Introduction
Primary biliary cirrhosis (PBC) is a slowly progressive cholestatic disease associated with the development of cirrhosis and liver failure that may justify liver transplantation. Ursodeoxycholic acid (UDCA) is currently the only drug approved specifically for the treatment of PBC [1], [2]. UDCA improves liver biochemistry, delays histological progression, as well as the development of portal hypertension and its complications [3], [4], [5], [6]. However, the transplant-free survival of patients treated with UDCA remains lower than that of an age and sex-matched population [7], [8], [9] indicating that new therapeutic options are warranted. To evaluate efficacy of new treatments, surrogate end-points of disease progression are required [10]. Observational studies in PBC have shown that the biochemical response to UDCA correlates with the long-term outcome [11], [12], [13], [14] and thus could have a role in clinical practice and future therapeutic trials by identifying the patients with a poor prognosis. Different definitions of the biochemical response as a surrogate marker of survival without transplantation have been proposed and currently the so-called Paris criteria have been recognized as the most relevant [10]. However, since most patients are nowadays diagnosed and treated at an early stage, traditional hard end-points, such as the occurrence of death or liver transplantation, are no longer thought to be realistic [10]. Accordingly, more extended end-points and stringent criteria in homogeneous cohorts of patients are required to define clinically relevant criteria of biochemical response in early PBC.
The aim of the present study was, therefore, to determine in patients with initially early histological stage of PBC the best biochemical criteria of response to UDCA able to predict the absence of adverse outcome, as defined not only by liver-related death, liver transplantation, or referral to a transplant unit, but also by complications of cirrhosis or histological evidence of cirrhosis development during follow-up.
Section snippets
Patient population
All the patients included in the study had serologically and histologically proven early-stage PBC, were treated with UDCA at the daily dose of 13–15 mg/kg of body weight and had documented biochemical analyses (that is: serum bilirubin and albumin concentrations; serum activities of alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT)) before and after 1 year of treatment with UDCA. The histological stage was
Descriptive data
Among a cohort of 292 patients with PBC, whose long-term outcome was described previously [13], a total of 165 patients (94% females; age, 51 ± 12 years) complied with the inclusion criteria. The biochemical characteristics of the patients at baseline and after 1 year of UDCA therapy are shown in Table 1. After 1 year of UDCA treatment, the serum activities of ALP, GGT, AST, and ALT were decreased by about 50% (p <0.0001) and the serum concentration of total bilirubin by 30% (p <0.01), as compared to
Discussion
The identification of PBC patients with a poor long-term prognosis among those treated with UDCA at the daily dose of 13–15 mg/kg is an important issue in clinical practice as well as in the design of trials aimed at assessing new therapeutic approaches. Serum bilirubin, albumin, and prothrombin time are the traditional independent predictors of survival in patients with advanced PBC. These variables are now of less utility since most patients are diagnosed at an early stage and treated with
Conflict of interest
The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.
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