Long-term follow-up after successful interferon therapy of acute hepatitis C.
Early treatment of acute hepatitis C infection with interferon alfa-2b (IFN-alpha-2b) prevents chronicity in almost all patients. So far, no data are available on the long-term outcome after interferon (IFN) therapy of acute hepatitis C. The aim of this study was to assess the clinical, virological, and immunological long-term outcome of 31 successfully treated patients with acute hepatitis C infection who were followed for a median of 135 weeks (52-224 weeks) after end of therapy. None of the individuals had clinical evidence of liver disease. Alanine aminotransferase (ALT) levels were normal in all but 1 patient. Serum hepatitis C virus (HCV) RNA was negative throughout follow-up, even when investigated with the highly sensitive transcription-mediated amplification (TMA) assay (cutoff 5-10 IU/mL). In addition, no HCV RNA was detected in peripheral blood mononuclear cells (PBMC) of 15 cases tested. The patients' overall quality-of-life scores as determined by the SF-36 questionnaire did not differ from the German reference control cohort. Ex vivo interferon gamma (IFN-gamma) ELISPOT analysis detected HCV-specific CD4(+) T-helper cell reactivity in only 35% of cases, whereas HCV-specific CD8(+) T-cell responses were found in 4 of 5 HLA-A2-positive individuals. Anti-HCV antibody levels decreased significantly during and after therapy in all individuals. In conclusion, early treatment of symptomatic acute hepatitis C with IFN-alpha-2b leads to a long-term virological, biochemical, and clinical response. Waning of anti-HCV humoral immunity and presence of HCV-specific CD8(+) (but not CD4(+)) T cells highlights the complexity of T-cell and B-cell memory to HCV, which might be significantly altered by IFN treatment.
Wiegand
Johannes
J
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany.
Jäckel
Elmar
E
Cornberg
Markus
M
Hinrichsen
Holger
H
Dietrich
Manfred
M
Kroeger
Julian
J
Fritsch
Wolfgang P
WP
Kubitschke
Anne
A
Aslan
Nuray
N
Tillmann
Hans L
HL
Manns
Michael Peter
MP
Wedemeyer
Heiner
H
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral; D000917:Antibody Formation; D000918:Antibody Specificity; D000998:Antiviral Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D016896:Treatment Outcome
D000914:Antibodies, Viral; D000998:Antiviral Agents; D000949:Histocompatibility Antigens Class II; D016898:Interferon-alpha; D012367:RNA, Viral