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Gastroenterology. 2012 Sep;143(3):608-618.e5. doi: 10.1053/j.gastro.2012.05.011. Epub 2012 May 21.

Factors that predict response of patients with hepatitis C virus infection to boceprevir.

Author information

1
Cedars-Sinai Medical Center, Los Angeles, California. Electronic address: poordad@txliver.com.
2
INSERM 954, Centre Hospitalier Universitaire de Nancy, Université Henri Poincaré, Vandoeuvre les Nancy, France.
3
Henry Ford Hospital, Detroit, Michigan.
4
J.W. Goethe University Hospital, Frankfurt, Germany.
5
Weill Cornell Medical College, New York, New York.
6
Johns Hopkins University School of Medicine, Baltimore, Maryland.
7
Assistance Publique Hôpitaux de Paris-University Pierre et Marie Curie Liver Center, Paris, France.
8
VA Long Beach Healthcare System, Long Beach, California.
9
Merck Sharp & Dohme, Corp, Whitehouse Station, New Jersey.
10
Saint Louis University School of Medicine, St. Louis, Missouri.

Abstract

BACKGROUND & AIMS:

Little is known about factors associated with a sustained virologic response (SVR) among patients with hepatitis C virus (HCV) infection to treatment with protease inhibitors.

METHODS:

Previously untreated patients (from the Serine Protease Inhibitor Therapy 2 [SPRINT-2] trial) and those who did not respond to prior therapy (from the Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 [RESPOND-2] trial) received either a combination of peginterferon and ribavirin for 48 weeks or boceprevir, peginterferon, and ribavirin (triple therapy) after 4 weeks of peginterferon and ribavirin (total treatment duration, 28-48 wk). A good response to interferon was defined as a ≥ 1 log(10) decrease in HCV RNA at week 4; a poor response was defined as a <1 log(10) decrease. We used multivariate regression analyses to identify baseline factors of the host (including the polymorphism interleukin [IL]-28B rs12979860) associated with response. The polymorphism IL-28B rs8099917 also was assessed.

RESULTS:

In the SPRINT-2 trial, factors that predicted a SVR to triple therapy included low viral load (odds ratio [OR], 11.6), IL-28B genotype (rs 12979860 CC vs TT and CT; ORs, 2.6 and 2.1, respectively), absence of cirrhosis (OR, 4.3), HCV subtype 1b (OR, 2.0), and non-black race (OR, 2.0). In the RESPOND-2 trial, the only factor significantly associated with a SVR was previous relapse, compared with previous nonresponse (OR, 2.6). Most patients with rs12979860 CC who received triple therapy had undetectable levels of HCV RNA by week 8 (76%-89%), and were eligible for shortened therapy. In both studies, IL-28B rs12979860 CC was associated more strongly with a good response to interferon than other baseline factors; however, a ≥ 1 log(10) decrease in HCV-RNA level at week 4 was associated more strongly with SVR than IL-28B rs12979860. Combining the rs8099917 and rs12979860 genotypes does not increase the association with SVR.

CONCLUSIONS:

The CC polymorphism at IL-28B rs12979860 is associated with response to triple therapy and can identify candidates for shorter treatment durations. A ≥ 1 log(10) decrease in HCV RNA at week 4 of therapy is the strongest predictor of a SVR, regardless of polymorphisms in IL-28B.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00705432 NCT00708500.

PMID:
22626609
DOI:
10.1053/j.gastro.2012.05.011
[Indexed for MEDLINE]

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