Effect of in vitro interferon-beta administration on hepatitis C virus in peripheral blood mononuclear cells as a predictive marker of clinical response to interferon treatment for chronic hepatitis C.
OBJECTIVE
To test whether in vitro incubation of peripheral blood mononuclear cells (PBMC) with interferon (IFN) could efficiently decrease hepatitis C virus-RNA (HCV-RNA) amount and to analyze whether this effect was associated with clinical response to IFN.


METHODS
Twenty-seven patients with histologically proven chronic hepatitis C were given intravenous administration of 6 million units (MU) IFN-beta daily for 6 weeks followed by three times weekly for 20 weeks. PBMC collected before IFN therapy were incubated with IFN-beta and HCV-RNA in PMBC was semi-quantitatively determined.


RESULTS
Twenty-five patients completed IFN therapy. Eight patients (32%) had sustained loss of serum HCV-RNA with normal serum ALT levels after IFN therapy (complete responders). HCV-RNA in PBMC was detected in all patients, whereas it was not detected in PBMC from healthy subjects. In vitro administration of IFN-beta decreased the amount of HCV-RNA in PMBC in 18 patients (72%). Eight of these patients obtained complete response. On the other hand, none of the patients whose HCV-RNA in PBMC did not decrease by IFN-beta was complete responders. Multiple logistic regression analysis revealed that the decrease of HCV-RNA amount in PBMC by IFN-beta was the only independent predictor for complete response (P<0.05).


CONCLUSIONS
The effect of in vitro IFN-beta on HCV in PBMC reflects clinical response and would be taken into account as a predictive marker of IFN therapy for chronic hepatitis C.
Department of Internal Medicine, Division of Gastroenterology, Tokai University School of Medicine, Bohseidai, Isehara 259-1193, Japan.
Kaori
K
Mochizuki
Tatehiro
T
Kagawa
Shinji
S
Takashimizu
Kazuya
K
Kawazoe
Sei-Ichiro
S
Kojima
Naruhiko
N
Nagata
Atsushi
A
Nakano
Yasuhiro
Y
Nishizaki
Koichi
K
Shiraishi
Masaru
M
Itakura
Norihito
N
Watanabe
Tetsuya
T
Mine
Shohei
S
Matsuzaki
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D024882:Drug Resistance, Viral; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D006801:Humans; D066298:In Vitro Techniques; D016899:Interferon-beta / Q000008:administration & dosage*; D007963:Leukocytes, Mononuclear / Q000821:virology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000378:metabolism
D000998:Antiviral Agents; D012367:RNA, Viral; D016899:Interferon-beta