title: Impact of Hepatic and Extrahepatic Insults on the Outcome of Acute-on-Chronic Liver Failure.
abstract: BACKGROUND
  To study the differences in outcome and predictors of mortality in acute-on-chronic liver failure (ACLF) precipitated by hepatic or extrahepatic insults.
  
  
  METHODS
  Consecutive patients of cirrhosis with acute decompensation were prospectively included and followed up for 90 days from admission. ACLF was defined based on chronic liver failure (CLIF) acute-on-chronic liver failure in cirrhosis (CANONIC study) criteria. Acute worsening due to acute viral hepatitis A and E, hepatitis B flare, alcoholic hepatitis, autoimmune hepatitis flare, or drug-induced liver injury were categorized as hepatic ACLF and that due to bacterial infection, upper gastrointestinal bleed or surgery as extrahepatic ACLF. Patients with both hepatic and extrahepatic insults were included in combined insult group.
  
  
  RESULTS
  Of 179 patients of acute decompensation, 122 had ACLF (hepatic insults 47 and extrahepatic insults 51). Alcohol (64.8%) was the most common etiology of cirrhosis while infection (36%) was the most common acute insult followed by alcoholic hepatitis (24.6%). Higher proportion of extrahepatic ACLF patients had history of prior decompensation than hepatic ACLF patients (62.7% vs. 27.7%,P< 0.001). There was no difference in mortality among hepatic and extrahepatic ACLF groups at 28 and 90 days (53.2% vs. 56.9%,P= 0.715 and 85% vs. 74.5%,P= 0.193, respectively). Area under receiver-operating curve (AUROC) for 28-day mortality in extrahepatic ACLF group was 0.788, 0.724, 0.718, 0.634, and 0.726 and in hepatic-ACLF group was 0.786, 0.625, 0.802, 0.761, and 0.648 for chronic liver failure-sequential organ failure assessment (CLIF-SOFA), model for end stage liver disease (MELD), integrated MELD score (iMELD), acute physiology and chronic health evaluation score (APACHE-II), and Child-Turcotte-Pugh score scores, respectively.
  
  
  CONCLUSIONS
  There is no difference in mortality among hepatic and extrahepatic ACLF groups at 28 and 90 days. iMELD and CLIF-SOFA have highest AUROC to predict 28-day mortality in hepatic and extrahepatic ACLF groups, respectively.
authors.affiliation: Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.
authors.forename: Tarana
authors.initials: T
authors.lastname: Gupta
authors.affiliation: Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.
authors.forename: Radha K
authors.initials: RK
authors.lastname: Dhiman
authors.affiliation: Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.
authors.forename: Sahaj
authors.initials: S
authors.lastname: Rathi
authors.affiliation: Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.
authors.forename: Swastik
authors.initials: S
authors.lastname: Agrawal
authors.affiliation: Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.
authors.forename: Ajay
authors.initials: A
authors.lastname: Duseja
authors.affiliation: Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.
authors.forename: Sunil
authors.initials: S
authors.lastname: Taneja
authors.affiliation: Department of Hepatology, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Chawla
keywords: ACLF, acute-on-chronic liver failure; APACHE-II, acute physiology and chronic health evaluation score; APASL, Asian Pacific Association for the Study of Liver; AUROC, area under receiver-operating characteristics; CANONIC study, chronic liver failure (CLIF) acute-on-chronic liver failure in cirrhosis; CLIF-SOFA, chronic liver failure-sequential organ failure assessment; CTP, Child–Turcotte–Pugh score; EASL, European Association for the Study of Liver; HE, hepatic encephalopathy; MELD, model for end-stage liver disease; SBE, spontaneous bacterial empyema; SBP, spontaneous bacterial peritonitis; SIRS, systemic inflammatory response syndrome; UTI, urinary tract infection; acute-on-chronic liver failure; extrahepatic insult; hepatic insult; iMELD, integrated MELD score; mortality; organ failure