title: Liver follicular helper T-cells predict the achievement of virological response following interferon-based treatment in HCV-infected patients.
abstract: BACKGROUND
  Here, we assessed the presence of intrahepatic follicular helper T-cells (T(FH)) in a cohort of consecutive genotype 1 (G1) chronic hepatitis C (CHC) patients comprising non-responders (NRs), relapsers (RRs) or those with sustained virological response (SVR) to pegylated interferon and ribavirin, and tested their relation with the response to antiviral treatment.
  
  
  METHODS
  A total of 78 patients with G1 CHC (30 SVR, 15 RR and 33 NR), comparable for sex, age, viral load and fibrosis were evaluated by immunohistochemistry for liver content of PD1+Bcl6+ T(FH) cells. The number of T(FH) cells in the immunostained sections was counted out of five representative high-power microscopic fields (400×) relative to areas involved by the inflammatory infiltrate. IL28B rs12979860 and rs8099917 polymorphisms were also evaluated.
  
  
  RESULTS
  The absolute number of liver T(FH) progressively increased from NR to RR to a maximum in SVR patients (14.2 ±12.5 versus 24.5 ±12.5 versus 59.2 ±27.1; P<0.001). The mean absolute number of liver T(FH) was 24.3 ±21.1 in 18 TT polymorphism patients, 31.7 ±29.5 in 43 TC and 47.8 ±27.8 in 17 CC (P=0.01). SVR was achieved in 27/35 (77.1%) of patients with T(FH)≥28 and in only 3/43 (6.9%) of those with T(FH)<28. Similarly, 15/17 (88.2%) CC patients achieved SVR, compared with 15/61 (24.6%) TT/TC subjects. With the combination of T(FH) at the threshold of 28 and the rs12979860 polymorphism, the ability to predict SVR strongly increased.
  
  
  CONCLUSIONS
  In G1 CHC patients, T(FH) cells are present in the hepatic inflammatory infiltrate. Their amount is proportional to the ultimate likelihood of SVR, with a progressive increase from NR to RR to SVR. Quantification of T(FH) cells in the liver biopsy of these patients adds useful prognostic information.
authors.affiliation: Cattedra di Anatomia Patologica, University of Palermo, Palermo, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Tripodo
authors.forename: Salvatore
authors.initials: S
authors.lastname: Petta
authors.forename: Carla
authors.initials: C
authors.lastname: Guarnotta
authors.forename: Rosaria
authors.initials: R
authors.lastname: Pipitone
authors.forename: Daniela
authors.initials: D
authors.lastname: Cabibi
authors.forename: Mario P
authors.initials: MP
authors.lastname: Colombo
authors.forename: Antonio
authors.initials: A
authors.lastname: Craxì
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000032:analysis; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012367:RNA, Viral / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000187:drug effects; D019562:Viral Load / Q000187:drug effects; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D054316:Biomarkers, Pharmacological; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a