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Baseline anti-NS4a antibodies in combination with on-treatment quantitative HCV-RNA reliably identifies nonresponders to pegylated interferon–ribavirin combination therapy after 4 weeks of treatment

Orlent, Hansa,d; Desombere, Isabelleb; Hansen, Bettinad,e; Van Vlierberghe, Hansc; Haagmans, Bartf; De Knegt, Robert J.d; Schalm, Solko W.d; Leroux-Roels, Geertb; Janssen, Harry L.A.d

European Journal of Gastroenterology & Hepatology: December 2010 - Volume 22 - Issue 12 - p 1443–1448
doi: 10.1097/MEG.0b013e32833ef6e3
Original Articles: Hepatitis
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Background Early detection of nonresponders to hepatitis C therapy limits unnecessary exposure to treatment and its side-effects. A recent algorithm combining baseline anti-NS4a antibodies and on-treatment quantitative PCR identified nonresponders to a combination of interferon and ribavirin after 1 week of treatment.

Aim To validate a stopping rule based on baseline anti-NS4a antibody levels and early on-treatment virological response in treatment-naive genotype 1 chronic hepatitis C patients treated with the current standard pegylated interferon and ribavirin combination therapy.

Methods Eighty-nine genotype 1 patients from the Dynamically Individualized Treatment of hepatitis C Infection and Correlates of Viral/Host dynamics Study treated for 48 weeks with standard 180 μg pegylated interferon (PEG-IFN)-α-2a (weekly) and ribavirin 1000–1200 mg (daily) were analysed. Baseline anti-NS4a antibody enzyme-linked immunosorbent assay (NS4a AA 1687–1718) was performed on pretreatment serum. Hepatitis C virus-RNA was assessed at days 0, 1, 4, 7, 8, 15, 22, 29, weeks 6, 7, 8, 10, 12 and 6 weekly thereafter until end of treatment. Multiple regression logistic analysis was performed.

Results Overall 54 of 89 (61%) patients achieved sustained virological response. A baseline anti-NS4a antibody titre less than 1/1250 correlated with absence of favourable initial viral decline according to variable response types (P=0.015). The optimal algorithm was developed using the combination of the absence of anti-NS4a Ab (<1/1250) at baseline and the presence of a viral load ≥100.000 IU/ml at week 4. This algorithm has a specificity of 43% and negative predictive value of 100% to detect nonresponse to standard PEG-IFN-α-2a and ribavirin therapy at fourth week of therapy (intention–to-treat analysis).

Conclusion The decision to stop the therapy in genotype 1 chronic hepatitis C patients treated with PEG-IFN-α-2a and ribavirin can be confidently made after 4 weeks of treatment based on the absence of baseline anti-NS4a Ab and a week-4 hepatitis C virus-RNA above 100.000 IU/ml.

aDepartment of Gastroenterology and Hepatology, AZ St Jan AV, Bruges

bCenter for Vaccinology, Ghent University and Hospital

cDepartment of Gastroenterology and Hepatology, University Hospital of Ghent, Ghent, Belgium

departments of dGastroenterology and Hepatology

eEpidemiology and Biostatistics

fInstitute of Virology, Erasmus MC University Medical Center, Rotterdam, The Netherlands

Correspondence to Hans Orlent, MD, Department of Gastroenterology and Hepatology, AZ ST Jan AV, Ruddershove 10, Brugge 8000, Belgium Tel: +32 50 452180; fax: +32 50 452179; e-mail: Hans.Orlent@azbrugge.be

*See Appendix for list of participating members.

Received May 12, 2010

Accepted August 2, 2010

© 2010 Lippincott Williams & Wilkins, Inc.