T-helper cells and liver fibrosis in hepatitis C virus-monoinfected patients.
Limited data suggest that low T-helper cell levels may be observed in hepatitis C virus (HCV) monoinfected patients with decompensated liver disease. We sought to determine the distribution and relationship of T-helper cells (CD4) to liver fibrosis in HCV-monoinfected patients before and during pegylated interferon (PegIFN) therapy. CD4 populations were prospectively determined using flow cytometry. All subjects had compensated liver disease. Baseline and subsequent CD4 counts at treatment weeks 12, 24, 36 and 48 and at two time points following treatment discontinuation (weeks 60 and 72) were evaluated. Ishak score was determined by a central pathologist. At baseline, data from 267 subjects were available. Mean age was 50 and 68% were male/Caucasian. HCV viral load was >800 000 IU/mL in 55%. Nearly half (48%) were Ishak 4-6 with all stages represented. Mean CD4 count was 1004 cells/mm(3) + or - 400, and 6% had counts <500. There was a trend towards lower CD4 counts among cirrhotic subjects (P = 0.07). A CD4 decrease was noted following PegIFN initiation. Mean CD4 decline was 38.9% and was statistically significant for all fibrosis stages compared with baseline levels, but not between fibrosis levels. CD4 counts <500 cells/mm(3) are seen in <10% of HCV-monoinfected subjects. A trend towards lower CD4 counts in subjects with advanced fibrosis was observed. However, at baseline and during/after PegIFN therapy, no significant differences were observed between groups. CD4 counts declined during PegIFN treatment, but returned to baseline after completion. The significance of these findings in terms of disease progression and treatment response requires further evaluation.
Rashkin
S
S
Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Rouster
S
S
Goodman
Z D
ZD
Sherman
K E
KE
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D016174:Hepacivirus / Q000276:immunology; D006526:Hepatitis C / Q000150:complications* / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins; D012720:Severity of Illness Index; D016176:T-Lymphocyte Subsets / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D019562:Viral Load
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a