LAUSR

To the Editor: Wewould like to thank the authors for their interest in our study. Overall, our study was not aimed at looking for a fifth element of MELD score but investigating the role of copeptin as biomarker of circulatory dysfunction, disease progression, and prognosis in cirrhosis. The main finding our study was that copeptin was not only an independent predictive factor of mortality but also of acute decompensation during a 3-month follow-up period. Moreover, the study showed that copeptin, as a good surrogate marker of vasopressin (AVP), likely reflected the progressive impairment of circulatory function of patients with decompensated cirrhosis [1]. The main results of our study were internally and externally validated, which supports the robustness of the findings. Indeed, our results are in keeping with a previous study from the authors of this letter in which for the first time they showed that copeptin levels increased with liver disease severity and that were an independent predictive factor of 1-year mortality [2]. Therefore, considering their previous results and the fact that our results were externally validated, it appears that the prognostic value of copeptin is reliable. We agree with the authors that ideally, it would have been better to use a larger sample size for external validation, however, this population was selected using a 1:2 ration from the population of the study, and rather than being single-centre it includes patients from different European hospitals. Finally, of the 120 patients from the validation series, 25 died (20%) and 11 were transplanted (9%) during the 3-month followup period, which is a similar proportion of outcomes to that of patients from the study cohort [1]. While in our study, the prognostic model included copeptin together with MELD and leukocyte count, in the previous study from these authors the model included copeptin, MELD score and CRP. As indicated by the authors, CRP has already been shown as a marker of prognosis in cirrhosis [3–5]. Unfortunately, we did not measure CRP in our study so it could not be compared to the prognostic value of copeptin. Nevertheless, we agree with the authors that it would have been an interesting analysis. However, it is probable that copeptin and CRP (or leukocyte count in our study) reflect different aspects related to the prognosis of patients with cirrhosis. Results of our study suggest that copeptin reflects circulatory dysfunction of patients with cirrhosis. However, it is important to note that both CRP and leukocyte count are markers of inflammation. Moreover, in recent years there has been increasing evidence indicating that a systemic inflammatory reaction may play an important role in the progression of cirrhosis, development of complications and prognosis together with the impairment of circulatory function [6]. Therefore, it appears that prognostic models of both studies included three variables representing the most relevant factors affecting prognosis in cirrhosis (1) MELD score, (2) copeptin as a marker of circulatory dysfunction and (3) a marker or inflammation (either CRP or leukocytes). Whether copeptin has better accuracy than CRP to predict prognosis should be investigated in future studies.