Whether liver EPZ-5676 molecular weight failure is a prerequisite for defining ACLF, we analyzed the characteristics of ACLF in patients with liver failure and patients with PX-478 web extra-hepatic organ failures. Of the 340 patients with ACLF according to either the AARC or CLIF-C definition, we compared the 160 patients who had liver failure according to the AARC definition (bilirubin 5mg/dL and INR 1.5) to the remaining 180 j.addbeh.2012.10.012 patients who had extra-hepatic organ failure but without liverFig 7. Ninety-day survival curves according to previous acute decompensation. (A) Without previous AD vs. with previous AD and (B) without previous AD vs. AD more than 1 year prior vs. AD within 1 year. Abbreviation: AD, acute decompensation doi:10.1371/journal.pone.0146745.gPLOS ONE | DOI:10.1371/journal.pone.0146745 January 20,12 /Acute-on-Chronic Liver FailureFig 8. Kaplan-Meier survival curves of ACLF according to the definition of organ failure (liver failure as a prerequisite vs. extra-hepatic organ failure). (A) 28-day and (B) 90-day survival according to liver failure as defined by the AARC definition, (C) 28-day and (D) 90-day survival according to bilirubin level. Abbreviations: ACLF, acute-on-chronic liver failure; AARC, Asian Pacific Association for the Study of the Liver ACLF Research Consortium doi:10.1371/journal.pone.0146745.gfailure (Fig 8A and 8B). Kaplan Meier analysis showed that the 28-day and 90-day cumulative survival rates of those who had extra-hepatic organ failure without liver failure were similar to those of patients who had liver failure as a prerequisite (28-day survival: 68.3 vs. 72.5 , P = 0.305; 90-day survival: 57.0 vs. 60.6 , P = 0.391). Because the CLIF-C criterion for liver failure is bilirubin 12 mg/dL, we performed survival analysis of 3 groups divided by serum bilirubin level (group 1: < 5 mg/dL, group 2: 5?2 mg/dL, and group 3: 12 mg/dL). The 28-day and 90-day survival rates of group 3 were significantly lower than those of group 1 (50.0 vs. 77.2 , P = 0.001 and 31.1 vs. 71.8 , P < 0.001) and group 2 (50.0 vs. 79.0 , P < 0.001 and 31.1 vs. 67.8 , P < 0.001), whereas there was no significant difference between the rates of groups 1 and 2 (P = 0.599 and P = 0.726) (Fig 8C and 8D).DiscussionACLF, which results in rapidly deteriorating liver function in patients with underlying CLD, is associated with poor prognosis. Eastern (AARC) and Western (CLIF-C) countries have proposed definitions of ACLF to identify these patients at a high risk of short-term mortality[5, 6]. However, the two definitions of ACLF differ from each journal.pone.0158910 other in many ways. This study demonstrated resultant differences in prevalence and mortality of ACLF patients according to the two definitions. In addition, we compared short-term mortality rates according to different criteriaPLOS ONE | DOI:10.1371/journal.pone.0146745 January 20,13 /Acute-on-Chronic Liver Failureamong the two definitions: predisposition (CLD vs. cirrhosis only, and first AD only vs. any previous AD) and organ dysfunction (liver failure as a prerequisite vs. extra-hepatic organ failure). In this study, among 1470 acutely deteriorated CLD patients, the prevalence of ACLF was 9.5 vs. 18.6 , according to the AARC and CLIF-C definitions, respectively. Prevalence based on the CLIF-C definition is somewhat lower than that seen in the CANONIC study (22.6 )[6] and the single center validation study by Silva et al. (24 )[16]. This might be because of the criterion of acute deterioration. This study included jaundic.Whether liver failure is a prerequisite for defining ACLF, we analyzed the characteristics of ACLF in patients with liver failure and patients with extra-hepatic organ failures. Of the 340 patients with ACLF according to either the AARC or CLIF-C definition, we compared the 160 patients who had liver failure according to the AARC definition (bilirubin 5mg/dL and INR 1.5) to the remaining 180 j.addbeh.2012.10.012 patients who had extra-hepatic organ failure but without liverFig 7. Ninety-day survival curves according to previous acute decompensation. (A) Without previous AD vs. with previous AD and (B) without previous AD vs. AD more than 1 year prior vs. AD within 1 year. Abbreviation: AD, acute decompensation doi:10.1371/journal.pone.0146745.gPLOS ONE | DOI:10.1371/journal.pone.0146745 January 20,12 /Acute-on-Chronic Liver FailureFig 8. Kaplan-Meier survival curves of ACLF according to the definition of organ failure (liver failure as a prerequisite vs. extra-hepatic organ failure). (A) 28-day and (B) 90-day survival according to liver failure as defined by the AARC definition, (C) 28-day and (D) 90-day survival according to bilirubin level. Abbreviations: ACLF, acute-on-chronic liver failure; AARC, Asian Pacific Association for the Study of the Liver ACLF Research Consortium doi:10.1371/journal.pone.0146745.gfailure (Fig 8A and 8B). Kaplan Meier analysis showed that the 28-day and 90-day cumulative survival rates of those who had extra-hepatic organ failure without liver failure were similar to those of patients who had liver failure as a prerequisite (28-day survival: 68.3 vs. 72.5 , P = 0.305; 90-day survival: 57.0 vs. 60.6 , P = 0.391). Because the CLIF-C criterion for liver failure is bilirubin 12 mg/dL, we performed survival analysis of 3 groups divided by serum bilirubin level (group 1: < 5 mg/dL, group 2: 5?2 mg/dL, and group 3: 12 mg/dL). The 28-day and 90-day survival rates of group 3 were significantly lower than those of group 1 (50.0 vs. 77.2 , P = 0.001 and 31.1 vs. 71.8 , P < 0.001) and group 2 (50.0 vs. 79.0 , P < 0.001 and 31.1 vs. 67.8 , P < 0.001), whereas there was no significant difference between the rates of groups 1 and 2 (P = 0.599 and P = 0.726) (Fig 8C and 8D).DiscussionACLF, which results in rapidly deteriorating liver function in patients with underlying CLD, is associated with poor prognosis. Eastern (AARC) and Western (CLIF-C) countries have proposed definitions of ACLF to identify these patients at a high risk of short-term mortality[5, 6]. However, the two definitions of ACLF differ from each journal.pone.0158910 other in many ways. This study demonstrated resultant differences in prevalence and mortality of ACLF patients according to the two definitions. In addition, we compared short-term mortality rates according to different criteriaPLOS ONE | DOI:10.1371/journal.pone.0146745 January 20,13 /Acute-on-Chronic Liver Failureamong the two definitions: predisposition (CLD vs. cirrhosis only, and first AD only vs. any previous AD) and organ dysfunction (liver failure as a prerequisite vs. extra-hepatic organ failure). In this study, among 1470 acutely deteriorated CLD patients, the prevalence of ACLF was 9.5 vs. 18.6 , according to the AARC and CLIF-C definitions, respectively. Prevalence based on the CLIF-C definition is somewhat lower than that seen in the CANONIC study (22.6 )[6] and the single center validation study by Silva et al. (24 )[16]. This might be because of the criterion of acute deterioration. This study included jaundic.
