Role of anti-interferon antibodies in breakthrough occurrence during alpha 2a and 2b therapy in patients with chronic hepatitis C.
OBJECTIVE
Alpha interferon induces aminotransferase normalization in about 50% of patients with chronic viral hepatitis C. However, some patients who initially respond experience a relapse during the treatment period (breakthrough phenomenon). The aim of this study was to evaluate the prevalence of breakthrough and its relationship with the emergence of neutralizing anti-interferon antibodies.


METHODS
We studied 172 patients with histologically proven chronic hepatitis C, treated with interferon alpha 2a or 2b 3 mega units three times a week for 6 months. For each patient, HCV RNA level (polymerase chain reaction and bDNA) and anti-interferon antibodies dosage were determined during therapy.


RESULTS
Among 84 patients with initial response, 13 (15.5%) experienced breakthrough. The kinetics of alanine aminotransferase and HCV RNA levels were strongly correlated, suggesting that breakthrough is not due to a random alanine aminotransferase fluctuation during treatment, but to the reappearance of viral replication. Neutralizing anti-interferon antibodies emergence was observed in 38.5% in patients with breakthrough, as compared to 9.0% and 2.8% of non-responder and complete-responder patients, respectively (p<0.0005). By multivariate analysis, the only factor predictive of breakthrough was the emergence of neutralizing anti-interferon antibodies 3 months after the onset of therapy.


CONCLUSIONS
Our results suggest that the emergence of neutralizing anti-interferon antibodies during treatment may explain breakthrough in about one third of cases. Other causes may also be responsible for this phenomenon and they remain to be determined.
Leroy
V
V
Département d'Hépato-gastroentérologie, CHU Grenoble, France.
Baud
M
M
de Traversay
C
C
Maynard-Muet
M
M
Lebon
P
P
Zarski
J P
JP
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000906:Antibodies / Q000502:physiology*; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005544:Forecasting; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000453:epidemiology / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons / Q000276:immunology*; D008297:Male; D015995:Prevalence; D012367:RNA, Viral / Q000032:analysis; D011994:Recombinant Proteins; D012008:Recurrence; D012727:Sex Characteristics
D000906:Antibodies; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D007372:Interferons; D000410:Alanine Transaminase