Hindawi Publishing Corporation BioMed Research International Volume 2013, Article ID 139763, 6 pages http://dx.doi.org/10.1155/2013/139763 Research Article Ursodeoxycholic Acid Improves Bilirubin but Not Albumin in Primary Biliary Cirrhosis: Further Evidence for Nonefficacy Emmanuel A. Tsochatzis, 1 Maurille Feudjo, 2 Cristina Rigamonti, 1 Jiannis Vlachogiannakos, 1 James R. Carpenter, 2 and Andrew K. Burroughs 1 1 he Royal Free Sheila Sherlock Liver Centre, Royal Free Hospital and UCL Institute of Liver and Digestive Health, London NW3 2QG, UK 2 UK Medical Statistics Unit, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK Correspondence should be addressed to Emmanuel A. Tsochatzis; mtsochatzis@med.uoa.gr and Andrew K. Burroughs; andrew.burroughs@nhs.net Received 30 April 2013; Accepted 7 July 2013 Academic Editor: Senthil K. Venugopal Copyright © 2013 Emmanuel A. Tsochatzis et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background/Aim. In randomised controlled trials (RCTs) of ursodeoxycholic acid (UDCA), although serum bilirubin is frequently reduced, its efect on disease progression and mortality is unclear. As serum albumin is an established independent prognostic marker, one might expect less deterioration of serum albumin values in a UDCA-treated group. We therefore modelled the typical evolution of serum bilirubin and albumin levels over time in UDCA-untreated patients and compared it with the observed levels in UDCA RCTs. Methods. Multilevel modelling was used to relate the evolution of serum albumin to serum bilirubin and time since patient referral. For each considered RCT, the derived model was used to predict the relationship between inal mean serum albumin and bilirubin concentration, adjusted for mean serum albumin at referral and followup duration. Results. Five RCTs were eligible in terms of available data, of which two had long followup. In all trials, serum albumin did not signiicantly difer between UDCA- and placebo-treated patients, despite the UDCA efect on serum bilirubin. herefore, there is no evidence over time for changes or maintenance of albumin levels for UDCA-treated patients above the levels predicted for placebo-treated patients. Conclusions. Our indings suggest that UDCA does not alter serum albumin in a way that is consistent with its efect on serum bilirubin. herefore, reductions in serum bilirubin of UDCA-treated PBC do not parallel another validated and independent prognostic marker, further questioning the validity of serum bilirubin reduction with UDCA as a surrogate therapeutic marker. 1. Introduction Primary biliary cirrhosis (PBC) is a slowly progressive disease characterised by the destruction of smaller size bile ducts leading to hepatic ibrosis, cirrhosis, and eventually liver fail- ure [1]. Currently, the only approved treatment is ursodeoxy- cholic acid (UDCA), which is claimed to modify disease progression [2]. However, separate meta-analyses have not shown beneit of UDCA in terms of survival, transplantation rates, or complications of disease [3–5]. Serum bilirubin and albumin levels are well-established and important prognostic markers for time to death or trans- plantation in untreated patients, being universally present in all disease prognostic models [6–8]. However, in the presence of treatment, an objective assessment of their quality and reliability as surrogate endpoints for survival has not been carried out despite adequate published methodology [9–11]. Although a serum bilirubin rise is clearly linked to shortened survival, the efect of a UDCA-mediated decrease is unclear [3–5], as patient survival and disease progression are not demonstrably improved. herefore, it can be considered premature and possibly unreliable to draw conclusions on the eicacy of treatment based solely on serum bilirubin. his would be particularly pertinent when considering UDCA, as other surrogate endpoints have not been shown to be diferent between UDCA and placebo or no treatment in randomised trials. In order to further assess the beneit of UDCA as a speciic therapy in PBC, we considered the relationship between serum bilirubin and albumin over time in a cohort of un- treated patients, with the expected rise in bilirubin being associated with a fall in serum albumin. We then evaluated