title: A diagnostic score for the prediction of spontaneous resolution of acute hepatitis C virus infection.
abstract: OBJECTIVE
  IL28B polymorphisms, jaundice, decline in HCV-RNA, IP-10, and gender have been proposed to be indicative of spontaneous clearance of acute hepatitis C virus infection. The aim of this study was to define a score enabling the discrimination of patients with spontaneous clearance of HCV from those with development of viral persistence and need for early antiviral treatment.
  
  
  METHODS
  136 patients (74 male; 35 ± 15 years) were analyzed. From variables predictive of spontaneous clearance, calculated by univariate analysis, three scores were built. Analogous cut-offs were evaluated by computing area under the receiver operating characteristic curves. Candidate variables and cut-offs were: (I) presence of IL28B C/C (p=0.027), (II) age (p=0.031; cut-off: 35 years), (III) peak-bilirubin (p=0.018; cut-off: 6 mg/dl), (IV) HCV-RNA decline within 4 weeks (p<0.001;cut-off: >2.5 log), (V) serum IP-10 (p=0.003; cut-off: 546 pg/ml), (VI) presence of CD4(+) Th1 cells (p=0.024). Each variable was allocated to 0 or 1 point, an HCV-RNA decline of ≥ 1 log 10 but <2.5 log 10 to 1 point, a decline of ≥ 2.5 log 10 to 2 points. Three scores were evaluated (Score 1: I-IV; Score 2: I-V; Score 3: I-VI).
  
  
  RESULTS
  A cut-off of ≥ 3 points out of 5 in Score 1 (AUROC: 0.82; DeLong 95% CI: 0.76-0.93) predicted spontaneous clearance with a sensitivity of 71% (95% CI: 0.53-0.86) and specificity of 87% (95% CI: 0.73-0.95). PPV and NPV were 79% and 82%. Corresponding findings for Score 2 including IP-10 (AUROC: 0.93; DeLong 95% CI: 0.86-0.93) at a cut-off of ≥ 4 were: sensitivity 81%, specificity 95% (PPV: 100%; NPV: 77%). A cut-off of ≥ 5 in Score 3 (AUROC: 0.98; DeLong 95% CI: 0.95-1.0) predicted spontaneous resolution with a sensitivity of 75% and specificity of 100% (PPV: 100%; NPV: 88%).
  
  
  CONCLUSIONS
  The scores enable a reliable discrimination between AHC-patients with high potential for spontaneous clearance from candidates for early therapeutic intervention due to marginal chance of spontaneous resolution.
authors.affiliation: Internal Medicine III, Department of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Sandra
authors.initials: S
authors.lastname: Beinhardt
authors.forename: Berit Anna
authors.initials: BA
authors.lastname: Payer
authors.forename: Christian
authors.initials: C
authors.lastname: Datz
authors.forename: Michael
authors.initials: M
authors.lastname: Strasser
authors.forename: Andreas
authors.initials: A
authors.lastname: Maieron
authors.forename: Livia
authors.initials: L
authors.lastname: Dorn
authors.forename: Evelyn
authors.initials: E
authors.lastname: Grilnberger-Franz
authors.forename: Emina
authors.initials: E
authors.lastname: Dulic-Lakovic
authors.forename: Rudolf
authors.initials: R
authors.lastname: Stauber
authors.forename: Hermann
authors.initials: H
authors.lastname: Laferl
authors.forename: Judith H
authors.initials: JH
authors.lastname: Aberle
authors.forename: Heidemarie
authors.initials: H
authors.lastname: Holzmann
authors.forename: Christoph
authors.initials: C
authors.lastname: Krall
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Vogel
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.forename: Harald
authors.initials: H
authors.lastname: Hofer
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D001663:Bilirubin / Q000097:blood; D054357:Chemokine CXCL10 / Q000097:blood; D005260:Female; D016174:Hepacivirus / Q000235:genetics; D006526:Hepatitis C / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood; D012075:Remission, Spontaneous; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D057832:Watchful Waiting; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D001663:Bilirubin; D054357:Chemokine CXCL10; D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: AHC; ALT; AUROC; DAA; GT; HCV; HIV; IL28B; IP-10; NPV; Newly acquired HCV; PPV; SC; SNP; Score; Spontaneous clearance; acute hepatitis C; alanine aminotransferase; area under the receiver operating curve; direct acting antivirals; genotype; hepatitis C virus; human immunodeficiency virus; interferon-gamma inducible protein; negative predictive value; positive predictive value; single nucleotide polymorphism; spontaneous clearance