Factors predictive of sustained virological response following 72 weeks of combination therapy for genotype 1b hepatitis C.
BACKGROUND
Treatment of genotype 1b chronic hepatitis C virus (HCV) infection has been improved by extending peg-interferon plus ribavirin combination therapy to 72 weeks, but predictive factors are needed to identify those patients who are likely to respond to long-term therapy.


METHODS
We analyzed amino acid (aa) substitutions in the core protein and the interferon sensitivity determining region (ISDR) of nonstructural protein (NS) 5A in 840 genotype 1b chronic hepatitis C patients with high viral load. We used logistic regression and classification and regression tree (CART) analysis to identify predictive factors for sustained virological response (SVR) for patients undergoing 72 weeks of treatment.


RESULTS
When patients were separately analyzed by treatment duration using multivariate logistic regression, several factors, including sex, age, viral load, and core aa70 and ISDR substitutions (P = 0.0003, P = 0.02, P = 0.01, P = 0.0001, and P = 0.0004, respectively) were significant predictive factors for SVR with 48 weeks of treatment, whereas age, previous interferon treatment history, and ISDR substitutions (P = 0.03, P = 0.01, and P = 0.02, respectively) were the only significant predictive factors with 72 weeks of treatment. Using CART analysis, a decision tree was generated that identified age, cholesterol, sex, treatment length, and aa70 and ISDR substitutions as the most important predictive factors. The CART model had a sensitivity of 69.2% and specificity of 60%, with a positive predictive value of 68.4%.


CONCLUSIONS
Complementary statistical and data mining approaches were used to identify a subgroup of patients likely to benefit from 72 weeks of therapy.
Department of Medical and Molecular Science, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. chayama@hiroshima-u.ac.jp
Kazuaki
K
Chayama
C Nelson
CN
Hayes
Kentaro
K
Yoshioka
Hisataka
H
Moriwaki
Takashi
T
Okanoue
Shotaro
S
Sakisaka
Tetsuo
T
Takehara
Makoto
M
Oketani
Joji
J
Toyota
Namiki
N
Izumi
Yoichi
Y
Hiasa
Akihiro
A
Matsumoto
Hideyuki
H
Nomura
Masataka
M
Seike
Yoshiyuki
Y
Ueno
Hiroshi
H
Yotsuyanagi
Hiromitsu
H
Kumada
D000328:Adult; D000367:Age Factors; D000368:Aged; D019943:Amino Acid Substitution; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D057225:Data Mining; D003663:Decision Trees; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; 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; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D011237:Predictive Value of Tests; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D012737:Sex Factors; D013997:Time Factors; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C417083:peginterferon alfa-2b
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