title: Development of an accurate index for predicting outcomes of patients with acute liver failure.
abstract: OBJECTIVE
  Patients with acute liver failure (ALF) have high mortality and frequently require liver transplantation (LT); few reliable prognostic markers are available. Levels of M30, a cleavage product of cytokeratin-18 caspase, are significantly increased in serum samples from patients with ALF who die or undergo LT. We developed a prognostic index for ALF based on level of M30 and commonly measured clinical variables (called the Acute Liver Failure Study Group [ALFSG] index) and compared its accuracy with that of the King's College criteria (KCC) and Model for End Stage Liver Disease (MELD). We also validated our model in an independent group of patients with ALF.
  
  
  METHODS
  Serum levels of M30 and M65 antigen (the total cytokeratin-18 fragment, a marker of apoptosis and necrosis) were measured on 3 of the first 4 days following admission of 250 patients with ALF. Logistic regression was used to determine whether the following factors, measured on day 1, were associated with LT or death: age, etiology; coma grade; international normalized ratio (INR); serum pH; body mass index; levels of creatinine, bilirubin, phosphorus, arterial ammonia, and lactate; and log(10) M30 and log(10) M65. The area under the receiver operating characteristic (AUROC) was calculated for the ALFSG and other indices.
  
  
  RESULTS
  Coma grade, INR, levels of bilirubin and phosphorus, and log(10) M30 value at study entry most accurately identified patients who would require LT or die. The ALFSG index identified these patients with 85.6% sensitivity and 64.7% specificity. Based on comparison of AUROC values, the ALFSG Index (AUROC, 0.822) better identified patients most likely to require LT or die than the KCC (AUROC, 0.654) or MELD (AUROC, 0.704) (P = .0002 and P = .0010, respectively). We validated these findings in a separate group of 250 patients with ALF.
  
  
  CONCLUSIONS
  The ALFSG index, a combination of clinical markers and measurements of the apoptosis biomarker M30, better predicts outcomes of patients with ALF than the KCC or MELD.
authors.affiliation: Department of Internal Medicine, Brigham & Women's Hospital, Boston, MA; Division of Gastroenterology, Hepatology & Endoscopy, Brigham & Women's Hospital, Boston, MA.
authors.forename: Anna
authors.initials: A
authors.lastname: Rutherford
authors.affiliation: Department of Internal Medicine, Brigham & Women's Hospital, Boston, MA; Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA.
authors.forename: Lindsay Y
authors.initials: LY
authors.lastname: King
authors.affiliation: Departments of Clinical Sciences (Division of Biostatistics) and Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Linda S
authors.initials: LS
authors.lastname: Hynan
authors.affiliation: Harvard Medical School, Boston, MA.
authors.forename: Chetan
authors.initials: C
authors.lastname: Vedvyas
authors.affiliation: Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Lin
authors.affiliation: Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
authors.affiliation: Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA. Electronic address: RTChung@partners.org.
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D001663:Bilirubin / Q000097:blood; D016009:Chi-Square Distribution; D003128:Coma / Q000209:etiology; D058625:End Stage Liver Disease / Q000601:surgery; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D053538:Keratin-18 / Q000097:blood*; D017114:Liver Failure, Acute / Q000097:blood* / Q000150:complications / Q000601:surgery; D016031:Liver Transplantation; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D012372:ROC Curve; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D053538:Keratin-18; C561463:M30 cytokeratin-18 peptide, human; C577325:M65 antigen, human; D010446:Peptide Fragments; D001663:Bilirubin