전호수 (이화여자대학교 의과대학)

한빛사논문

조회435

이화여자대학교 의과대학

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J. Hepatol., Sep 19 2023, S0168-8278(23)05096-1 | https://doi.org/10.1016/j.jhep.2023.09.011 PAGE-B incorporating moderate HBV DNA levels predicts risk of HCC among patients entering into HBeAg-positive chronic hepatitis B.

Ho Soo Chun ^1,2,a, George V. Papatheodoridis ^3,a, Minjong Lee ^1,2*, Hye Ah Lee ⁴, Yeong Hwa Kim ¹, Seo Hyun Kim ¹, Yun-Seo Oh ¹, Su Jin Park ¹, Jihye Kim⁵, Han Ah Lee ^1,2, Hwi Young Kim ^1,2, Tae Hun Kim ^1,2, Eileen L. Yoon ⁶, Dae Won Jun ⁶, Sang Hoon Ahn ^7,8, Vana Sypsa ³, Cihan Yurdaydin ⁹, Pietro Lampertico ¹⁰, Jose Luis Calleja¹¹, Harry LA. Janssen¹², George N. Dalekos ¹³, John Goulis ¹⁴, Thomas Berg ¹⁵, Maria Buti ¹⁶, Seung Up Kim ^7,8*, Yoon Jun Kim ^5*

¹Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea;

²Department of Internal Medicine, Ewha Womans University Medical Center, Seoul, Korea;

³Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens "Laiko", Athens, Greece;

⁴Clinical Trial Center, Ewha Womans University Seoul Hospital, Seoul, Korea;

⁵Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea

⁶Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea;

⁷Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea;

⁸Yonsei Liver Center, Severance Hospital, Seoul, Korea;

⁹Department of Gastroenterology & Hepatology, Koc University Medical School, Istanbul, Turkey;

¹⁰Division of Gastroenterology and Hepatology, CRC “A. M. and A. Migliavacca” Center for Liver Disease, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy;

¹¹Hospital U Puerta de Hierro, IDIPHIM CIBERehd, Madrid, Spain;

¹²Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands;

¹³Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece;

¹⁴4th Department of Internal Medicine, Αristotle University of Thessaloniki Medical School, Thessaloniki, Greece;

¹⁵Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany;

¹⁶Hospital General Universitario Vall Hebron and Ciberehd, Barcelona, Spain

^aHo Soo Chun and George V. Papatheodoridis contributed equally to this work.

^*Corresponding authors : Minjong Lee, Seung Up Kim, Yoon Jun Kim

Abstract

Recent studies reported that moderate hepatitis B virus (HBV) DNA levels are significantly associated with hepatocellular carcinoma (HCC) risk in hepatitis B e antigen (HBeAg)-positive, non-cirrhotic patients with chronic hepatitis B (CHB). We aimed at developing and validating a new risk score to predict HCC development using baseline moderate HBV DNA levels in patients entering into HBeAg-positive CHB from chronic infection. This multicenter cohort study recruited 3,585 HBeAg-positive, non-cirrhotic patients who started antiviral treatment with entecavir or tenofovir disoproxil fumarate at phase change into CHB from chronic infection in twenty-three tertiary university-affiliated hospitals of South Korea (2012-2020). A new HCC risk score (PAGED-B) was developed (training cohort, n=2,367) based on multivariable Cox models. Bootstrap for internal validation and external validation (validation cohort, n=1,218) were performed. Sixty (1.7%) patients developed HCC (median follow-up, 5.4 years). In the training cohort, age, gender, platelets, diabetes and moderate HBV DNA levels (5.00-7.99 log ₁₀ IU/mL) were independently associated with HCC development. PAGED-B score with five predictors for HCC development (platelets, age, gender, diabetes, and moderate HBV DNA) showed a time-dependent area under the receiver operating characteristics curve (AUROC) of 0.81 for 5-year HCC development. In the validation cohort, the AUROC of PAGED-B at 5-years was 0.85, significantly higher than the other scores (PAGE-B, mPAGE-B, CAMD, and REAL-B). When stratified by the PAGED-B score, the HCC risk was significantly higher in high-risk patients than in low-risk patients (sub-distribution hazard ratio= 8.43 in the training and 11.59 in the validation cohorts, all P<0.001). The newly established PAGED-B score may enable risk stratification for HCC at the time of change into HBeAg-positive CHB. This study developed and validated a new risk score to predict HCC development in patients entering into HBeAg-positive CHB from chronic infection, and suggested that newly established PAGED-B score included baseline moderate HBV DNA levels (5-8 log ₁₀ IU/ml) could improve the predictive performance. A PAGED-B score, which is based on a patient's age, gender, diabetic status, platelet counts, and moderate DNA levels (5-8 log ₁₀ IU/ml) at the phase change into CHB from chronic infection, represents a reliable and easily available risk score to predict HCC development during the first five years of antiviral treatment in HBeAg- positive patients entering into CHB. With a scoring range from 0 to 12 points, a PAGED-B score differentiates the HCC risk. A PAGED-B score significantly differentiates the 5-year HCC risk: low <7 points and high ≥7 points.

논문정보

형식Research article
게재일2023년 09월 (BRIC 등록일 2023-09-26)
연구진국내 연구진
분야 의약학 > 종양의학

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