Reply to: Do fatigue and UDCA therapy truly have independent effects on mortality in PBC?
Authors: David Jones, Julia Newton
Journal: Journal of Hepatology (2011)

Do fatigue and UDCA therapy truly have independent effects on mortality in PBC?Journal of HepatologyVol. 55Issue 3PreviewTo the Editor: Full-Text PDF Open Access We thank Drs. Yousuf and Yeoman for their appreciation of our work and interest in our recent paper [[1]Jones D.E. Al-Rifai A. Frith J. Patanwala I. Newton J.L. The independent effects of fatigue and UDCA therapy on mortality in primary biliary cirrhosis: results of a 9 year follow-up.J Hepatol. 2010; 53: 911-917Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar] regarding the impact of fatigue and ursodeoxycholic acid (UDCA) treatment on mortality in PBC. Although they raise some interesting points, we believe they may not fully understand the conclusions we made in our paper. This is the largest series of patients with PBC followed up for a considerable period of time, and this cohort has provided important insights into the true impact that fatigue has on not only quality of life but also length of life. Yousuf and Yeoman are correct, COX models can theoretically be limited in their interpretation as the number of variables is increased. If we had used this as our only analysis, we may have agreed with them; however, combined with the Kaplan Meier and Log Rank Test Analysis, which confirm the relationship between fatigue and mortality, we believe this enhances the power of the COX models considerably and should be interpreted as underlining our findings. In order to perform the Kaplan Meier analysis it was necessary to dicotomise the groups into those with and without fatigue. The rationale for this was described fully in the original description of the cohort [[2]Goldblatt J. Taylor P.J.S. Lipman T. Prince M.I. Baragiotta A. Bassendine M.F. et al.The true impact of fatigue in primary biliary cirrhosis: a population study.Gastroenterology. 2002; 122: 1235-1241Abstract Full Text Full Text PDF PubMed Google Scholar]. The COX model allowed us to explore the absolute level of FIS score. Both analyses confirmed the relationship between fatigue and mortality and, therefore, we cannot understand how Yousaf and Yeoman can now suggest “how the presence (or otherwise) of fatigue affects mortality in an independent model is not certain”. The authors are correct, in the COX model UDCA therapy was not independently predictive of improved mortality and on the basis of this they refute our conclusions regarding UDCA. We believe inclusion of categorical data into a COX model is a blunt instrument and we would direct Yousuf and Yeoman to the other analyses in the results section which clearly show that the effect that UDCA response has upon mortality is clearly independent of the effect that fatigue status has. This is an important message for clinicians managing patients with PBC in that it confirms that non-fatigued patients who are UDCA responders are at very low risk. This is one of the key messages from the paper. In summary, we question what further data the authors consider required to confirm to them that it has now gone from beyond the “possible that fatigue is independently associated with increased mortality in PBC” if they believe that our well characterised comprehensively collected geographically defined cohort does not “prove that this is the case in respect of the presence or otherwise of fatigue”. Furthermore we would suggest that we clearly show, albeit in a small cohort, that response to UDCA therapy has an effect on mortality. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.