Immunological and mutagenic actions of ribavirin monotherapy preceding combination therapy with interferon for patients with chronic hepatitis C.
BACKGROUND
We aimed to investigate the effects of ribavirin on hepatitis C virus (HCV). Immunological and virological effects were analysed in patients undergoing treatment with ribavirin monotherapy prior to the initiation of combination therapy with interferon-alpha.


METHODS
A total of 25 patients with chronic HCV infection were enrolled in this study. All patients received ribavirin for 4 weeks during monotherapy; subsequently, interferon-alpha2b was additionally given as combined therapy. Patients were divided into two groups according to virological response. A rapid viral responder (RVR) was defined as a patient in whom HCV RNA became undetectable within 4 weeks after combination therapy. The changes of the T-helper (Th)1/Th2 subset of peripheral blood CD4(+) T-cells, serum cytokine levels and the alignment of the interferon sensitivity-determining region (ISDR) during ribavirin monotherapy were analysed by flow cytometry, ELISAs and sequencing methods.


RESULTS
A total of 17 patients were classed as RVR. In the RVR group, the mean +/-sd serum alanine aminotransferase levels significantly decreased (before treatment 103 +/-92 IU/l and after treatment 57 +/-46 IU/l; P<0.05) during ribavirin monotherapy. The mean +/-sd Th1/Th2 ratio significantly increased (before treatment 13.9 +/-5.1 and after treatment 16.7 +/-6.2; P<0.05), but did not change in the non-RVR group. The levels of Th2 cytokines (interleukin-10 and soluble CD30) significantly decreased, especially in the RVR group. The mean +/-sd mutation rates of ISDR at the nucleotide level increased in the RVR group (before treatment 2.6 +/-0.9 sites/clone and after treatment 3.9 +/-1.6 sites/clone; P<0.05), but did not change in the non-RVR group.


CONCLUSIONS
Ribavirin administration might increase the efficacy of interferon therapy for patients with chronic hepatitis C by stimulating the host immune system and promoting HCV gene mutation.
Ogawa
Koji
K
Department of Gastroenterology, Hakodate Municipal Hospital, Hakodate, Japan. shuhei-h@med.hokudai.ac.jp
Hige
Shuhei
S
Nakanishi
Mitsuru
M
Yamamoto
Yoshiya
Y
Chuma
Makoto
M
Nagasaka
Atsushi
A
Asaka
Masahiro
M
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D012254:Ribavirin