title: Treatment optimization and prediction of HCV clearance in patients with acute HCV infection.
abstract: OBJECTIVE
  The lack of consensus on the optimal timing, regimen, and duration of treatment, in patients with acute HCV infection, stimulates the research on both favourable outcome predictors and individualized treatment regimens. This study aimed at investigating the impact of IL28B SNP rs12979860 alone or in combination with HLA class II alleles in both predicting spontaneous viral clearance and individualizing treatment strategies for patients with HCV persistence, after acute HCV exposure.
  
  
  METHODS
  178 patients with AHC, consecutively treated with interferon alone or in combination with ribavirin, starting within or after 48 weeks from the diagnosis of AHC, were tested for IL28B SNPs and HLA class II alleles.
  
  
  RESULTS
  Spontaneous viral clearance was achieved in 28% of 169 patients available for genetic testing. Factors associated with HCV elimination were jaundice (OR 2.75, 95% CI 1.31-5.77) and IL28B CC (OR 3.87, CI 1.71-8.51), but not HLA alleles. In CT/TT patients without jaundice, NPV for virus persistence was 98%. In patients with IL28B CT/TT, starting treatment 48 weeks after the onset was significantly associated with lower rates of response (28% vs. 100%, p=0.027). By contrast, no significant differences in the rate of SVR were observed for CC carriers who started treatment later (65% vs. 85%, p=1.0).
  
  
  CONCLUSIONS
  In patients with acute HCV hepatitis, lack of viral clearance may be predicted by absence of jaundice and IL28B CT/TT genotype; in patients with these characteristics, treatment needs to be started immediately.
authors.affiliation: Liver Unit, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy. a.mangia@tin.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mangia
authors.forename: Rosanna
authors.initials: R
authors.lastname: Santoro
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.forename: Marco
authors.initials: M
authors.lastname: Massari
authors.forename: Valeria
authors.initials: V
authors.lastname: Piazzolla
authors.forename: Enea
authors.initials: E
authors.lastname: Spada
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cappucci
authors.forename: Gabriele
authors.initials: G
authors.lastname: Missale
authors.forename: Leonardo
authors.initials: L
authors.lastname: Mottola
authors.forename: Ernesto
authors.initials: E
authors.lastname: Agostinacchio
authors.forename: Lazzaro di
authors.initials: Ld
authors.lastname: Mauro
authors.forename: Ornella
authors.initials: O
authors.lastname: Zuccaro
authors.forename: Patrizia
authors.initials: P
authors.lastname: Maio
authors.forename: Fabio
authors.initials: F
authors.lastname: Pellegrini
authors.forename: Antonella
authors.initials: A
authors.lastname: Folgori
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferrari
mesh_terms: D000208:Acute Disease; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005802:Genes, MHC Class II; D005838:Genotype; D059866:HLA-DQ beta-Chains / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D007565:Jaundice / Q000188:drug therapy / Q000821:virology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D019562:Viral Load / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D059866:HLA-DQ beta-Chains; D059811:HLA-DRB1 Chains; D007372:Interferons; D007378:Interleukins; C069051:HLA-DQB1 antigen; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: AHC; ALT; AUC; Acute hepatitis; HCV; HCV hepatitis; IL28B; Jaundice; LR; NPV; PI; PPV; RECPAM; SC; SVR; acute HCV infection; alanine aminotransferase; area under a curve; hepatitis C virus; likelihood ratio; negative predictive value; persistent infection; positive predictive value; recursive partitioning and amalgamation; spontaneous clearance; sustained virologic response