Modified PAGE-B score predicts the risk of hepatocellular carcinoma in Asians with chronic hepatitis B on antiviral therapy
Author(s): ,
Dae Hee Choi
Affiliations:
Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, Republic of Korea
Corresponding authors. Addresses: Department of Internal Medicine, Kangwon National University Hospital, 156, Baengnyeong-ro, Chuncheon-si, Gangwon-do 24289, Republic of Korea, Tel.: +82 33 258 2454, fax: +82 33 258 2404 (M. Lee), or Department of Interna
,
Soon Koo Baik
Affiliations:
Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
,
Dong Joon Kim
Affiliations:
Department of Internal Medicine, Hallym University College of Medicine, Chuncheon Sacred Heart Hospital, Chuncheon, Republic of Korea
,
Gab Jin Cheon
Affiliations:
Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Republic of Korea
,
Moon Young Kim
Affiliations:
Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
,
Seong Hee Kang
Affiliations:
Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
,
Ki Tae Suk
Affiliations:
Department of Internal Medicine, Hallym University College of Medicine, Chuncheon Sacred Heart Hospital, Chuncheon, Republic of Korea
,
Tae Suk Kim
Affiliations:
Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, Republic of Korea
,
Baek Gyu Jun
Affiliations:
Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Republic of Korea
,
Minjong Lee
Affiliations:
Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, Republic of Korea
Corresponding authors. Addresses: Department of Internal Medicine, Kangwon National University Hospital, 156, Baengnyeong-ro, Chuncheon-si, Gangwon-do 24289, Republic of Korea, Tel.: +82 33 258 2454, fax: +82 33 258 2404 (M. Lee), or Department of Interna
,
Young Don Kim
Affiliations:
Department of Internal Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Republic of Korea
Ji Hyun Kim
Affiliations:
Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, Republic of Korea
EASL LiverTree™. CHOI D. Nov 1, 2018; 234541
DAEHEE CHOI
DAEHEE CHOI
Contributions
Journal Abstract
References
Graphical abstract

Graphical abstract

A risk score was developed that predicted HCC in Asian patients with chronic hepatitis B under antiviral therapy. Modified PAGE-B scores required easily available information on age, gender, platelet counts, and serum albumin levels. Modified PAGE-B scores significantly differentiated the 5-year HCC risk: low ≤8 and high ≥13.

Background & Aims

Recently, the PAGE-B score and Toronto HCC risk index (THRI) have been developed to predict the risk of hepatocellular carcinoma (HCC) in Caucasian patients with chronic hepatitis B (CHB). We aimed to validate PAGE-B scores and THRI in Asian patients with CHB and suggested modified PAGE-B scores to improve the predictive performance.

Methods

From 2007 to 2017, we examined 3,001 Asian patients with CHB receiving entecavir/tenofovir therapy. We assessed the performances of PAGE-B, THRI, CU-HCC, GAG-HCC, and REACH-B for HCC development. A modified PAGE-B score (mPAGE-B) was developed (derivation set, n = 2,001) based on multivariable Cox models. Bootstrap for internal validation and external validation (validation set, n = 1,000) were performed.

Results

The five-year cumulative HCC incidence rates were 6.6% and 7.2% in the derivation and validation datasets after entecavir/tenofovir onset. In the derivation dataset, age, gender, serum albumin levels, and platelet counts were independently associated with HCC. The mPAGE-B score was developed based on age, gender, platelet counts, and serum albumin levels (time-dependent area under receiver operating characteristic curves [AUROC] = 0.82). In the validation set, the PAGE-B and THRI showed similar AUROCs to CU-HCC, GAG-HCC, and REACH-B at five years (0.72 and 0.73 vs. 0.70, 0.71, and 0.61 respectively; all p >0.05 except REACH-B), whereas the AUROC of mPAGE-B at five years was 0.82, significantly higher than the five other models (all p <0.01). HCC incidence rates after initiation of entecavir/tenofovir therapy in patients with CHB were significantly decreased in all risk groups in long-term follow-up periods.

Conclusion

Although PAGE-B and THRI are applicable in Asian patients with CHB receiving entecavir/tenofovir therapy, mPAGE-B scores including additional serum albumin levels showed better predictive performance than the PAGE-B score.

Lay summary

PAGE-B scores and Toronto HCC risk index were developed to predict the risk of hepatocellular carcinoma (HCC) in Caucasian patients with CHB under potent antiviral therapy. This study validated these two scores in Asian patients with CHB and suggested that modified PAGE-B scores could improve the predictive performance. A modified PAGE-B score, which is based only on a patient’s age, gender, baseline platelet counts, and serum albumin levels at treatment initiation, represents a reliable and easily available risk score to predict HCC development during the first five years of antiviral treatment in Asian patients with CHB. With a scoring range from 0 to 21 points, a modified PAGE-B score differentiates the HCC risk. A modified PAGE-B score significantly differentiates the five-year HCC risk: low ≤8 points and high ≥13 points.

Keyword(s)
Chronic hepatitis B, Hepatocellular carcinoma, PAGE-B, Risk prediction model
[1]. N.A. Terrault - AASLD guidelines for treatment of chronic hepatitis B
[2]. G.V. Papatheodoridis - Risk of hepatocellular carcinoma in chronic hepatitis B: assessment and modification with current antiviral therapy
[3]. G.L. Wong - Risk prediction of hepatitis B virus-related hepatocellular carcinoma in the era of antiviral therapy
[4]. V.W. Wong - Can we use HCC risk scores to individualize surveillance in chronic hepatitis B infection?
[5]. J.Y. Cho - Patients with chronic hepatitis B treated with oral antiviral therapy retain a higher risk for HCC compared with patients with inactive stage disease
[6]. G. Papatheodoridis - PAGE-B predicts the risk of developing hepatocellular carcinoma in Caucasians with chronic hepatitis B on 5-year antiviral therapy
[7]. S.A. Sharma - Toronto HCC risk index: a validated scoring system to predict 10-year risk of HCC in patients with cirrhosis
[8]. W. Sohn - Risk score model for the development of hepatocellular carcinoma in treatment-naive patients receiving oral antiviral treatment for chronic hepatitis B
[9]. H.J. Cho - Development of risk prediction model for hepatocellular carcinoma progression of indeterminate nodules in hepatitis B Virus-related cirrhotic liver
[10]. H.L. Chan - High viral load and hepatitis B virus subgenotype ce are associated with increased risk of hepatocellular carcinoma
[11]. G.L. Wong - Liver stiffness-based optimization of hepatocellular carcinoma risk score in patients with chronic hepatitis B
[12]. H.S. Kim - Association between level of fibrosis, rather than antiviral regimen, and outcomes of patients with chronic hepatitis B
[13]. K.S. Jung - Risk assessment of hepatitis B virus-related hepatocellular carcinoma development using liver stiffness measurement (FibroScan)
[14]. D.Y. Kim - Usefulness of FibroScan for detection of early compensated liver cirrhosis in chronic hepatitis B
[15]. J. Bruix - American Association for the Study of Liver Disease. Management of hepatocellular carcinoma: an update
[16]. H.J. Seo - A comparison of the cancer incidence rates between the national cancer registry and insurance claims data in Korea
[18]. S. Chevaliez - Performance of version 2.0 of the Cobas AmpliPrep/Cobas TaqMan real-time PCR assay for hepatitis B virus DNA quantification
[19]. J. Saldanha - An international collaborative study to establish a World Health Organization international standard for hepatitis B virus DNA nucleic acid amplification techniques
[20]. P.J. Heagerty - Time-dependent ROC curves for censored survival data and a diagnostic marker
[21]. E.R. DeLong - Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach
[22]. V.W. Wong - Clinical scoring system to predict hepatocellular carcinoma in chronic hepatitis B carriers
[23]. H.I. Yang - Risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B): development and validation of a predictive score
[24]. M.F. Yuen - Independent risk factors and predictive score for the development of hepatocellular carcinoma in chronic hepatitis B
[25]. L.M. Sullivan - Robustness and power of analysis of covariance applied to ordinal scaled data as arising in randomized controlled trials
[26]. Y.S. Seo - Validation of risk prediction models for the development of HBV-related HCC: a retrospective multi-center 10-year follow-up cohort study
[27]. M.N. Kim - Validation of PAGE-B model in Asian chronic hepatitis B patients receiving entecavir or tenofovir
[28]. S. Mittal - Role of age and race in the risk of hepatocellular carcinoma in veterans with hepatitis B virus infection
[29]. M.N. Kim - Validation of PAGE-B model in Asian chronic hepatitis B patients receiving entecavir or tenofovir
[30]. C.J. Liu - Global perspective on the natural history of chronic hepatitis B: role of hepatitis B virus genotypes A to
[31]. W.G. Cooksley - Do we need to determine viral genotype in treating chronic hepatitis B?
[32]. J.H. Kao - Hepatitis B genotypes correlate with clinical outcomes in patients with chronic hepatitis B
[34]. S.Y. Kim - MRI With Liver-Specific Contrast for Surveillance of Patients With Cirrhosis at High Risk of Hepatocellular Carcinoma
[35]. G.V. Papatheodoridis - The risk of hepatocellular carcinoma is decreasing after the first 5 years of entecavir or tenofovir in Caucasians with chronic hepatitis B
[36]. M.H. Lee - Prediction models of long-term cirrhosis and hepatocellular carcinoma risk in chronic hepatitis B patients: risk scores integrating host and virus profiles
[37]. T.C. Tseng - High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies