title: Hepatic apoptotic markers are not predictors for the virological response to interferon-based therapy in chronic hepatitis C patients.
abstract: BACKGROUND
  Chronic hepatitis C virus (HCV) infection is a major health problem worldwide. The majority of cases involving HCV infection develop into chronic hepatitis because of a failure to develop an effective immune response. Apoptosis of the hepatocytes plays a significant role in the pathogenesis of HCV infection: the interaction between the Fas antigen on hepatocytes and the Fas ligand on T cells corresponds to the main mechanism for hepatocyte damage. Interferon (IFN)-α has antiviral, immunoregulatory, and antiproliferative properties, and apoptosis seems to be a critical event in the action mechanisms of both IFNs. In this study, we aimed to detect any relationship between apoptotic markers in the liver and the response to the treatment.
  
  
  METHODS
  The study included 180 chronic HCV patients treated with IFN and ribavirin in four centers. Apoptotic markers (Fas, Fas ligand, Fas-associated death domain, caspases 3, 8, and 9, and in-situ apoptosis) were studied in the liver. The age, sex of the patients, response to therapy, ALT level, viral load, and genotype were recorded.
  
  
  RESULTS
  The results of the study showed that the histological activity index and fibrosis correlated with CD95 staining density, caspase-8 intensiveness, and portal and parenchymal Fas ligand scores. The apoptotic parameters of the responsive cases were not significantly different from those of the unresponsive cases.
  
  
  CONCLUSIONS
  The apoptotic parameters studied in liver tissue are associated with inflammation and fibrosis; however, these parameters may not predict response to treatment.
authors.affiliation: Departments of aInfection bGastroenterology cPathology dMicrobiology, Cerrahpasa Medical School, Istanbul University eOkmeydani Research and Education Hospital fPathology Department gGastroenterology Department, Marmara University Medical School hPathology Department iInfection Department, Istanbul Research and Education Hospital, Istanbul, Turkey.
authors.forename: Resat
authors.initials: R
authors.lastname: Ozaras
authors.forename: Veysel
authors.initials: V
authors.lastname: Tahan
authors.forename: Gulsen
authors.initials: G
authors.lastname: Ozbay
authors.forename: Recep
authors.initials: R
authors.lastname: Ozturk
authors.forename: Necati
authors.initials: N
authors.lastname: Yenice
authors.forename: Çigdem A
authors.initials: ÇA
authors.lastname: Celikel
authors.forename: Kenan
authors.initials: K
authors.lastname: Midilli
authors.forename: Zuhal
authors.initials: Z
authors.lastname: Gucin
authors.forename: Muzaffer
authors.initials: M
authors.lastname: Fincanci
authors.forename: Nurdan
authors.initials: N
authors.lastname: Tozun
authors.forename: Hakan
authors.initials: H
authors.lastname: Senturk
authors.forename: Abdullah
authors.initials: A
authors.lastname: Osme
authors.forename: Fehmi
authors.initials: F
authors.lastname: Tabak
authors.forename: Ali
authors.initials: A
authors.lastname: Mert
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D014421:Turkey; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a