Evaluation of early null response to pegylated interferon and ribavirin as a predictor of therapeutic nonresponse in patients undergoing treatment for chronic hepatitis C.
OBJECTIVE
Early viral kinetics accurately predicts sustained virological response (SVR) in genotype 1 patients with hepatitis C virus (HCV) undergoing therapy with pegylated interferon (PEG) and ribavirin (RBV). No baseline factor has a stronger predictive role. Early identification of patients unlikely to respond is equally important, allowing early treatment modification or discontinuation. The aim of this study was to determine whether 4-week null response (eNR) correlates directly with 12-week null response and inversely with SVR.


METHODS
A retrospective analysis of HCV patients treated at our institution was done. Patients were classified based on a 4-week viral log decline compared with baseline: <1 log, ≥ 1 log, <2 log, ≥ 2 log, <3 log, ≥ 3 log without rapid virological response (RVR) and with RVR. eNR was defined as less than a 1 log change from baseline.


RESULTS
A total of 159 patients had quantitative HCV-RNA PCR at treatment week 4, of whom 24% (38) experienced eNR. In all, 22 (58%) of the eNR patients were African American, 58% male, 32% cirrhotic, average age 53 years (range 36-71), 89% (33) genotype 1, and average baseline viral load was 5.9261 log (range 3.1492-7.3025). On-treatment response demonstrated failure to attain early virological response (EVR; 2-log decline at week 12) in 50% (19) and partial EVR (pEVR) in 39% (15). Three (8%) patients with eNR achieved SVR. In our patient population, eNR had 92% negative predictive value (confidence interval 83.5-100%) for SVR and was the strongest single predictor for treatment failure, including the baseline factors genotype and viral load.


CONCLUSIONS
eNR is strongly associated with null response or pEVR and accurately predicts failure to attain SVR. Consideration should be made to discontinue or modify therapy in patients with eNR who receive the appropriate weight-based PEG/RBV.
University of Chicago Medical Center, Center for Liver Disease, Chicago, Illinois 60637, USA. nreau@medicine.bsd.uchicago.edu
Nancy
N
Reau
Rohit
R
Satoskar
Helen
H
Te
Amanda
A
DeVoss
Carolyn
C
Elsen
Gautham
G
Reddy
Smruti
S
Mohanty
Donald
D
Jensen
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000302:isolation & purification; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
D000998:Antiviral Agents; D004337:Drug Carriers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a