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.

[Guest guest]

Eur J Gastroenterol Hepatol. 2010 Dec;22(12):1443-8.

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 H, Desombere I, Hansen B, Van Vlierberghe H, Haagmans B, De Knegt RJ,

Schalm SW, Leroux-Roels G, Janssen HL.

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.

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 ¥ìg pegylated interferon (PEG-IFN)-¥á-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

¡Ã100.000 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-¥á-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-¥á-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.

PMID: 21389795 [PubMed - in process]

[Guest guest]

Eur J Gastroenterol Hepatol. 2010 Dec;22(12):1443-8.

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 H, Desombere I, Hansen B, Van Vlierberghe H, Haagmans B, De Knegt RJ,

Schalm SW, Leroux-Roels G, Janssen HL.

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.

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 ¥ìg pegylated interferon (PEG-IFN)-¥á-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

¡Ã100.000 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-¥á-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-¥á-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.

PMID: 21389795 [PubMed - in process]