Reply to: “Acute-on-chronic liver failure – Its definition remains unclear”
Authors: Rajiv Jalan, Pere Gines, Jody C. Olson, Rajeshwar P. Mookerjee, Richard Moreau, Guadalupe Garcia-Tsao, Vicente Arroyo, Patrick S. Kamath
Journal: Journal of Hepatology (2013)

Acute-on-chronic liver failure – Its definition remains unclearJournal of HepatologyVol. 59Issue 1PreviewWe have read with interest the review by Jalan et al. [1] in which they focus on the current understanding of acute-on-chronic liver failure (ACLF) from the clinical, prognostic and pathophysiologic perspectives. In addition, they indicate potential biomarkers and therapeutic targets for intervention. The authors confirm that the condition remains undefined, but that two consensus working definitions for this syndrome exist: one put forward by the Asia-Pacific association for the study of liver disease (APASL) and the other based on an EASL-AASLD single topic symposium. Full-Text PDF Open AccessAcute-on chronic liver failureJournal of HepatologyVol. 57Issue 6PreviewAcute-on-chronic liver failure (ACLF) is an increasingly recognised entity encompassing an acute deterioration of liver function in patients with cirrhosis, which is usually associated with a precipitating event and results in the failure of one or more organs and high short term mortality. Prospective data to define this is lacking but there is a large body of circumstantial evidence suggesting that this condition is a distinct clinical entity. From the pathophysiologic perspective, altered host response to injury and infection play important roles in its development. Full-Text PDF Open Access We would like to thank Dr. Wlodzimirow and colleagues for their comments. We agree with them that a uniform definition of Acute on Liver Failure (ACLF) is essential [[1]Jalan R. Gines P. Olson J.C. et al.Acute-on chronic liver failure.J Hepatol. 2012; 57: 1336-1348Abstract Full Text Full Text PDF PubMed Scopus (472) Google Scholar]. It is with this aim that the CLIF Consortium initiated the CANONIC study, the results of which provide the framework for a definition of ACLF and its diagnostic criteria on the background of cirrhosis [2Moreau R. Gines P. Jalan R. et al.Diagnosis, prevalence, and prognosis of acute-on- chronic liver failure (ACLF): results of the EASL-chronic liver failure (CLIF) consortium canonic study.J Hepatol. 2012; 56: S552-S553Abstract Full Text PDF Google Scholar, 3Jalan R. Moreau R. Gines P. et al.Acute-on chronic liver failure (ACLF): a distinct clinical syndrome.Hepatology. 2012; 56: 249AGoogle Scholar]. The issue of liver failure that occurs on the background of chronic hepatitis is more difficult and without more data that include biopsies in this group of patients, will remain very difficult to define. Out of nearly 1343 patients included in this study from 30 European centers, almost all had cirrhosis; there were only a handful of non-cirrhotic cases related to hepatitis B virus (HBV) reactivation. Therefore, findings of the CANONIC study cannot be extrapolated to patients with HBV-related ACLF. Nevertheless, we believe that the PIRO (Predisposition, Injury, Response and Organ failure) concept as described in our paper provides the framework generate multimodal definitions which may include patients without underlying cirrhosis [4Moreno R.P. Metnitz B. Adler L. Hoechtl A. Bauer P. Metnitz P.G. SAPS 3 investigators. Sepsis mortality prediction based on predisposition, infection and response.Intensive Care Med. 2008; 34: 496-504Crossref PubMed Scopus (118) Google Scholar, 5Jalan R. Stadlbauer V. Sen S. et al.Role of predisposition, injury, response and organ failure in the prognosis of patients with acute-on-chronic liver failure: a prospective cohort study.Crit Care. 2012; 16: R227Crossref PubMed Scopus (92) Google Scholar]. It is clear that more data will be needed to determine whether this group is at similar risk as the patients with underlying cirrhosis. We encourage our colleagues who see this patient group to generate prospective data. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.