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Title: An IL28B genotype-based clinical prediction model for treatment of chronic hepatitis C.
Authors: O'Brien TR,  Everhart JE,  Morgan TR,  Lok AS,  Chung RT,  Shao Y,  Shiffman ML,  Dotrang M,  Sninsky JJ,  Bonkovsky HL,  Pfeiffer RM,  HALT-C Trial Group,  Szabo G,  Banner BF,  Cormier M,  Giansiracusa D,  Borders G,  Kelley M,  Di Bisceglie AM,  Bacon B,  Neuschwander-Tetri B,  Brunt EM,  King D,  Dienstag JL,  Reid AE,  Bhan AK,  Molchen WA,  Gooch CC,  Everson GT,  Trouillot T,  Kugelmas M,  Nash SR,  DeSanto J,  McKinley C,  Hoefs JC,  Craig JR,  Jamal MM,  Sheikh M,  Park C,  Lee WM,  Rogers TE,  Malet PF,  Shelton J,  Crowder N,  Elbein R,  Liston N,  Lindsay KL,  Govindarajan S,  Jones CB,  Milstein SL,  Fontana RJ,  Greenson JK,  Richtmyer PA,  Bonham RT,  Sterling RK,  Contos MJ,  Mills AS,  Hofmann C,  Smith P,  Ghany MG,  Liang TJ,  Kleiner D,  Park Y,  Rivera E,  Haynes-Williams V,  Seeff LB,  Robuck PR,  Hoofnagle JH,  Wright EC,  Morishima C,  Gretch DR,  Apodaca MC,  Shankar R,  Antonov N,  Snow KK,  Naishadham D,  Curto TM,  Goodman ZD,  Davis GL,  Garcia-Tsao G,  Kutner M,  Lemon SM,  Perrillo RP,  Catanese J,  Ross D,  Chen S,  Check D
Journal: PLoS One
Date: 2011
Branches: BB, IIB
PubMed ID: 21760886
PMC ID: PMC3132753
Abstract: BACKGROUND: Genetic variation in IL28B and other factors are associated with sustained virological response (SVR) after pegylated-interferon/ribavirin treatment for chronic hepatitis C (CHC). Using data from the HALT-C Trial, we developed a model to predict a patient's probability of SVR based on IL28B genotype and clinical variables. METHODS: HALT-C enrolled patients with advanced CHC who had failed previous interferon-based treatment. Subjects were re-treated with pegylated-interferon/ribavirin during trial lead-in. We used step-wise logistic regression to calculate adjusted odds ratios (aOR) and create the predictive model. Leave-one-out cross-validation was used to predict a priori probabilities of SVR and determine area under the receiver operator characteristics curve (AUC). RESULTS: Among 646 HCV genotype 1-infected European American patients, 14.2% achieved SVR. IL28B rs12979860-CC genotype was the strongest predictor of SVR (aOR, 7.56; p<.0001); the model also included HCV RNA (log10 IU/ml), AST:ALT ratio, Ishak fibrosis score and prior ribavirin treatment. For this model AUC was 78.5%, compared to 73.0% for a model restricted to the four clinical predictors and 60.0% for a model restricted to IL28B genotype (p<0.001). Subjects with a predicted probability of SVR <10% had an observed SVR rate of 3.8%; subjects with a predicted probability >10% (43.3% of subjects) had an SVR rate of 27.9% and accounted for 84.8% of subjects actually achieving SVR. To verify that consideration of both IL28B genotype and clinical variables is required for treatment decisions, we calculated AUC values from published data for the IDEAL Study. CONCLUSION: A clinical prediction model based on IL28B genotype and clinical variables can yield useful individualized predictions of the probability of treatment success that could increase SVR rates and decrease the frequency of futile treatment among patients with CHC.