Stopping rule based on baseline anti-NS4a antibody levels and early on-treatment virological response in treatment-naive genotype 1

European Journal of Gastroenterology & Hepatology:
December 2010 - Volume 22 - Issue 12 - p 1443–1448
doi: 10.1097/MEG.0b013e32833ef6e3
Original Articles: Hepatitis

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, Hans

Abstract
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.