Objective: The utility of risk scores to predict the development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with nucleos(t)ide analogue (NA) remains to be elucidated. Methods: CU-HCC (The Chinese University of Hong Kong-HCC) and GAG-HCC (Guide with Age, Gender, HBV DNA, Core promoter mutations and Cirrhosis) scores of 225 Japanese patients treated with NAs for at least 2 years were calculated before and 2 years after the NA treatment. According to the cutoff values, the patients were categorized into high-score or low-score groups. Results: Sixteen of 225 patients developed HCC. Patients with a high score before the NA treatment showed a significantly higher HCC incidence than those with a low score using both score models (p < 0.001). Time-dependent receiver operating characteristic analyses based on scores before and 2 years after the NA treatment showed that both models exhibited moderate accuracy in predicting HCC development. The HCC incidence was significantly lower in the patients whose scores decreased below the cutoff values in response to the NA treatment than in those whose scores remained high using both models (p < 0.01). Conclusions: The predictive performance of the CU-HCC and GAG-HCC scores in the CHB patients treated with NAs is comparable to that in the NA-naive patients. The patients with sustained high scores after the NA treatment showed a higher incidence of HCC development.

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
Sherman M: Hepatocellular carcinoma: epidemiology, risk factors, and screening. Semin Liver Dis 2005;25:143-154.
Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP: The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 2006;45:529-538.
Chemin I, Zoulim F: Hepatitis B virus induced hepatocellular carcinoma. Cancer Lett 2009;286:52-59.
Di Bisceglie AM: Hepatitis B and hepatocellular carcinoma. Hepatology 2009;49:S56-S60.
El-Serag HB: Hepatocellular carcinoma. N Engl J Med 2011;365:1118-1127.
Gao J, Xie L, Yang WS, Zhang, W, Gao, S, Wang, J, Xiang YB: Risk factors of hepatocellular carcinoma - current status and perspectives. Asian Pac J Cancer Prev 2012;13:743-752.
Wong VW, Chan SL, Mo F, Chan TC, Loong HH, Wong GL, Lui YY, Chan AT, Sung JJ, Yeo W, Chan HL, Mok TS: Clinical scoring system to predict hepatocellular carcinoma in chronic hepatitis B carriers. J Clin Oncol 2010;28:1660-1665.
Yuen MF, Tanaka Y, Fong DY, Fung J, Wong DK, Yuen JC, But DY, Chan AO, Wong BC, Mizokami M, Lai CL: Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B. J Hepatol 2009;50:80-88.
Heidelbaugh JJ, Bruderly M: Cirrhosis and chronic liver failure: part I. Diagnosis and evaluation. Am Fam Physician 2006;74:756-762.
Bruix J, Sherman M; Practice Guidelines Committee, American Association for the Study of Liver Diseases: Management of hepatocellular carcinoma. Hepatology 2005;42:1208-1236.
Bruix J, Sherman M; American Association for the Study of Liver Diseases: Management of hepatocellular carcinoma: an update. Hepatology 2011;53:1020-1022.
Heagerty PJ, Lumley T, Pepe MS: Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics 2000;56:337-344.
Lok AS, McMahon BJ: Chronic hepatitis B: update 2009. Hepatology 2009;50:661-662.
Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J; Cirrhosis Asian Lamivudine Multicentre Study Group: Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004;351:1521-1531.
Matsumoto A, Tanaka E, Rokuhara A, Kiyosawa K, Kumada H, Omata M, Okita K, Hayashi N, Okanoue T, Iino S, Tanikawa K; Inuyama Hepatitis Study Group: Efficacy of lamivudine for preventing hepatocellular carcinoma in chronic hepatitis B: a multicenter retrospective study of 2,795 patients. Hepatol Res 2005;32:173-184.
Hosaka T, Suzuki F, Kobayashi M, Seko Y, Kawamura Y, Sezaki H, Akuta N, Suzuki Y, Saitoh S, Arase Y, Ikeda K, Kobayashi M, Kumada H: Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection. Hepatology 2013;58:98-107.
Yang HI, Yuen MF, Chan HL, Han KH, Chen PJ, Kim DY, Ahn SH, Chen CJ, Wong VW, Seto WK; REACH-B Working Group: Risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B): development and validation of a predictive score. Lancet Oncol 2011;12:568-574.
Lee MH, Yang HI, Liu J, Batrla-Utermann R, Jen CL, Iloeje UH, Lu SN, You SL, Wang LY, Chen CJ; REVEAL-HBV Study Group: Prediction models of long-term cirrhosis and hepatocellular carcinoma risk in chronic hepatitis B patients: risk scores integrating host and virus profiles. Hepatology 2013;58:546-554.
Tseng TC, Liu CJ, Yang HC, Su TH, Wang CC, Chen CL, Kuo SF, Liu CH, Chen PJ, Chen DS, Kao JH: High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load. Gastroenterology 2012;142:1140-1149.
Papatheodoridis GV, Dalekos GN, Yurdaydin C, Buti M, Goulis J, Arends P, Sypsa V, Manolakopoulos S, Mangia G, Gatselis N, Keskın O, Savvidou S, Hansen BE, Papaioannou C, Galanis K, Idilman R, Colombo M, Esteban R, Janssen HL, Lampertico P: Incidence and predictors of hepatocellular carcinoma in Caucasian chronic hepatitis B patients receiving entecavir or tenofovir. J Hepatol 2015;62:363-370.
Arends P, Sonneveld MJ, Zoutendijk R, Carey I, Brown A, Fasano M, Mutimer D, Deterding K, Reijnders JG, Oo Y, Petersen J, van Bömmel F, de Knegt RJ, Santantonio T, Berg T, Welzel TM, Wedemeyer H, Buti M, Pradat P, Zoulim F, Hansen B, Janssen HL; VIRGIL Surveillance Study Group: Entecavir treatment does not eliminate the risk of hepatocellular carcinoma in chronic hepatitis B: limited role for risk scores in Caucasians. Gut 2014;64:1289-1295.
Wong GL, Chan HL, Chan HY, Tse PC, Tse YK, Mak CW, Lee SK, Ip ZM, Lam AT, Iu HW, Leung JM, Wong VW: Accuracy of risk scores for patients with chronic hepatitis B receiving entecavir treatment. Gastroenterology 2013;144:933-944.
Locarnini S: Primary resistance, multidrug resistance, and cross-resistance pathways in HBV as a consequence of treatment failure. Hepatol Int 2008;2:147-151.
Ganem D, Prince AM: Hepatitis B virus infection - natural history and clinical consequences. N Engl J Med 2004;350:1118-1129.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.