Ribavirin and IFN-alpha combination therapy induces CD4+ T-cell proliferation and Th1 cytokine secretion in patients with chronic hepatitis B.
OBJECTIVE
To investigate the anti-viral mechanism of combination therapy of interferon (IFN)-alpha and ribavirin in patients with chronic hepatitis B.


METHODS
Twenty patients were assigned to receive either IFN-alpha plus ribavirin (group A, n = 14) or no treatment as a control (group B, n = 6). Patients were analyzed for T-cell proliferative responses specific for hepatitis B virus (HBV)-antigen and cytokine production by peripheral blood mononuclear cells (PBMCs).


RESULTS
Combination therapy induced HBV-antigen specific CD4+ T-cell proliferative responses in four patients (28.6%). Production of high levels of HBV-specific IFN-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-12 by PBMCs was found in five patients (35.7%), who showed significantly lower HBV DNA levels in serum at 12 mo after treatment ended (P = 0.038) and at 24 mo of follow-up (P = 0.004) than those without high levels of cytokine production.


CONCLUSIONS
HBV-antigen specific CD4+ T cells may directly control HBV replication and secretion of anti-viral T helper 1 (Th1) cytokines by PBMCs during combination therapy of chronic hepatitis B with ribavirin and IFN-alpha.
Ren
Fen-Yu
FY
Department of Gastroenterology and Hepatology, Yanbian University Hospital, Yanji 133000, Jilin Province, China. fenyu65@yahoo.com.cn
Jin
Hai
H
Piao
Xi-Xu
XX
Piao
Feng-Shun
FS
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects*; D016207:Cytokines / Q000097:blood*; D004279:DNA, Viral / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D006511:Hepatitis B Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use*; D018417:Th1 Cells / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D016207:Cytokines; D004279:DNA, Viral; D006511:Hepatitis B Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D012254:Ribavirin; D007371:Interferon-gamma