title: Intrahepatic mRNA levels of interferon gamma and tumor necrosis factor alpha and response to antiviral treatment of chronic hepatitis C.
abstract: OBJECTIVE
  The impact of intrahepatic messenger RNA (mRNA) levels of interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) on the outcome of antiviral treatment of chronic hepatitis C was evaluated.
  
  
  METHODS
  Semiquantitative mRNA determination was performed on 36 pretreatment liver biopsies by reverse transcription/competitive polymerase chain reaction.
  
  
  RESULTS
  Sustained response (normal aminotransferase levels and negative hepatitis C virus [HCV] RNA for more than 6 months) was achieved in 13 patients, whereas 23 of 36 patients did not achieve sustained response (12 partial responders, 11 complete nonresponders). In sustained responders, pretreatment intrahepatic mRNA levels of IFN-gamma and TNF-alpha were lower than in nonsustained responders (IFN-gamma, 0.23 +/- 0.10 vs. 0.35 +/- 0.07, respectively; p = 0.024 and TNF-alpha, 1.2 +/- 0.7 vs. 2.3 +/- 1.4, respectively; p= 0.009); similarly, HCV viral load was lower in sustained responders than in nonresponders (663,424 +/- 756,389 copies/mL vs. 1,656,713 +/- 1,517,683 copies/mL, respectively; p = 0.037). In addition, TNF-alpha mRNA levels were correlated to HCV viral load and liver fibrosis scores.
  
  
  CONCLUSIONS
  Higher intrahepatic mRNA levels of IFN-gamma and TNF-alpha may reflect interferon resistance of HCV strains and may contribute to tissue damage in patients refractory to antiviral treatment.
authors.affiliation: Department of Medicine I, University of Bonn, Bonn, Germany. dumoulin@bonn.de
authors.forename: F L
authors.initials: FL
authors.lastname: Dumoulin
authors.forename: U
authors.initials: U
authors.lastname: Wennrich
authors.forename: H D
authors.initials: HD
authors.lastname: Nischalke
authors.forename: L
authors.initials: L
authors.lastname: Leifeld
authors.forename: H P
authors.initials: HP
authors.lastname: Fischer
authors.forename: T
authors.initials: T
authors.lastname: Sauerbruch
authors.forename: U
authors.initials: U
authors.lastname: Spengler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000187:drug effects / Q000302:isolation & purification / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000503:physiopathology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D008099:Liver / Q000276:immunology*; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D012367:RNA, Viral; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D012254:Ribavirin; D007371:Interferon-gamma