title: A systematic review on prognostic indicators of acute on chronic liver failure and their predictive value for mortality.
abstract: BACKGROUND
  An early and proper diagnosis of acute on chronic liver failure (ACLF), together with the identification of indicators associated with disease severity is critical for outcome prediction and therapy.
  
  
  OBJECTIVE
  To systematically identify and summarize prognostic indicators for patients with ACLF and to evaluate the predictive value of these indicators.
  
  
  METHODS
  Embase and Ovid-Medline were searched for English-language articles. The search criteria focused on identifying clinical trials and observational studies reporting on indicators used for prediction of mortality in patients with ACLF.
  
  
  RESULTS
  Of 2382 studies identified, 19 were included for detailed analysis. Thirteen different definitions of ACLF were found. The main differences were related to acute deterioration in liver function, coagulopathy and hyperbilirubinaemia/jaundice. Seventy three prognostic indicators and their association with mortality were extracted and categorized into seven categories: general markers (n = 13), viral markers (n = 6), bio-markers (n = 22), hemodynamics (n = 1), morphology/histology (n = 17), scoring systems (n = 10) and treatments (n = 4).
  
  
  CONCLUSIONS
  The ambiguity and variability in the definition of ACLF and in its predictive indicators hampers comparability among studies. There is a need for a single uniform definition of ACLF. Also absence of a gold standard is an obstacle to render one indicator superior to another. The age, hepatic encephalopathy, model for end-stage liver disease score, total bilirubin and International normalized ratio (prothrombin time) appeared to be promising candidates for evaluation in future studies. The result of this review may be useful as a starting point in developing a standard list of indicators for clinical outcome that concur with the clinicians' subjective views on prognosis in ACLF.
authors.affiliation: Department of Medical Informatics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. k.a.wlodzimirow@amc.uva.nl
authors.forename: Kama A
authors.initials: KA
authors.lastname: Wlodzimirow
authors.forename: Saeid
authors.initials: S
authors.lastname: Eslami
authors.forename: Ameen
authors.initials: A
authors.lastname: Abu-Hanna
authors.forename: Martin
authors.initials: M
authors.lastname: Nieuwoudt
authors.forename: Robert A F M
authors.initials: RA
authors.lastname: Chamuleau
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D002648:Child; D018450:Disease Progression; D042241:Early Diagnosis; D058625:End Stage Liver Disease / Q000145:classification / Q000175:diagnosis* / Q000401:mortality*; D005260:Female; D006305:Health Status Indicators; D006801:Humans; D017114:Liver Failure, Acute / Q000145:classification / Q000175:diagnosis* / Q000401:mortality*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D009626:Terminology as Topic; D055815:Young Adult
chemical_list: D015415:Biomarkers