Intrahepatic mRNA levels of interferon gamma and tumor necrosis factor alpha and response to antiviral treatment of chronic hepatitis C.
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.
Dumoulin
F L
FL
Department of Medicine I, University of Bonn, Bonn, Germany. dumoulin@bonn.de
Wennrich
U
U
Nischalke
H D
HD
Leifeld
L
L
Fischer
H P
HP
Sauerbruch
T
T
Spengler
U
U
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
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