Rapid virological response in peripheral blood mononuclear cells with an increase of hepatitis C virus-specific interferon-gamma production predisposes to sustained virological response in patients with chronic hepatitis C genotype 1 undergoing treatment with pegylated-interferon alpha 2a plus ribavirin.
OBJECTIVE
Viral load evaluation in plasma, after 1 month of treatment, represents one of the most important parameters to predict treatment response during interferon (IFN) treatment in chronic hepatitis C (CHC). It has been proven that hepatitis C virus (HCV) RNA may be present in peripheral blood mononuclear cells (PBMCs) but few studies have investigated the viral load in PBMCs during treatment. The aim of this study was to evaluate HCV RNA in PBMCs during therapy with pegylated-IFN-alpha2a plus ribavirin and whether its clearance in PBMCs may induce a treatment response. Furthermore, we also analyzed the IFN-gamma and interleukin (IL)-4 responses of PBMCs during therapy.


METHODS
We studied 35 patients with CHC genotype 1 undergoing antiviral treatment with pegylated IFN-alpha2a 180 microg weekly plus ribavirin 1000 mg/daily. In these patients we evaluated HCV-RNA in plasma and PBMCs, IFN-gamma and IL-4 before treatment, after 1, 3 and 12 months of treatment and 6 months after the end of treatment.


RESULTS
We found that rapid virological clearance of HCV-RNA in PBMCs with a restored and improved HCV-specific IFN-gamma response was statistically significantly higher in those with a sustained virological response (SVR).


CONCLUSIONS
Patients having a rapid virological response in PBMCs with an improved Th1 network achieve a complete SVR, whereas those having viral clearance only in plasma without a restored Th1 network have a relapse.
Perrella
A
A
Department of Infectious Disease and Immunology, Hospital D Cotugno, Naples, Italy. alex.perrel@virgilio.it
Sbreglia
C
C
Atripaldi
L
L
Esposito
C
C
D'Antonio
A
A
Perrella
O
O
D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood / Q000378:metabolism; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D019562:Viral Load
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D015847:Interleukin-4; D011092:Polyethylene Glycols; D012254:Ribavirin; D007371:Interferon-gamma; C100416:peginterferon alfa-2a