한빛사논문
Heejoon Jang∗,‡,a, Jun Sik Yoon§,a, Soo Young Park∥,a, Han Ah Lee¶,#,a, Myoung-jin Jang∗∗, Seung Up Kim‡‡, Dong Hyun Sinn§§, Yeon Seok Seo¶, Hwi Young Kim∥∥, Sung Eun Kim¶¶, Dae Won Jun##, Eileen L. Yoon###, Joo Hyun Sohn∗∗∗, Sang Bong Ahn‡‡‡, Jae-Jun Shim§§§, Soung Won Jeong∥∥∥, Yong Kyun Cho¶¶¶, Hyoung Su Kim###, Joon Yeul Nam∗, Yun Bin Lee∗, Yoon Jun Kim∗, JungHwan Yoon∗, Fabien Zoulim∗∗∗∗, Pietro Lampertico‡‡‡‡,§§§§, George N. Dalekos∥∥∥∥, Ramazan Idilman¶¶¶¶, Vana Sypsa####, Thomas Berg∗∗∗∗∗, Maria Buti‡‡‡‡‡, Jose Luis Calleja§§§§§, John Goulis∥∥∥∥∥, Spilios Manolakopoulos¶¶¶¶¶, Harry LA. Janssen#####, George V. Papatheodoridis∗∗∗∗∗∗, Jeong-Hoon Lee∗
∗Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea;
‡Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
§Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea;
∥Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea;
¶Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea
#Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Republic of Korea
∗∗Medical Research Collaboration Center, Seoul National University Hospital, Seoul, Republic of Korea
‡‡Department of Internal Medicine and Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
§§Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
∥∥Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
¶¶Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang-si, Republic of Korea
##Department of Internal Medicine, Hanyang University Hospital, Hanyang University College of Medicine, Seoul, Republic of Korea
∗∗∗Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri-si, Republic of Korea
‡‡‡Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University College of Medicine, Seoul, Republic of Korea
§§§Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
∥∥∥Department of Internal Medicine, Soonchunhyang University College of Medicine, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea
¶¶¶Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
###Department of Internal Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea
∗∗∗∗Cancer Research Centre of Lyon, INSERM U∥∥¶‡, Lyon University, Hospices Civils de Lyon, Lyon, France
‡‡‡‡Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
§§§§CRC “A. M. and A. Migliavacca” Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
∥∥∥∥Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece
¶¶¶¶Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
####Department of Hygiene, Epidemiology & Medical Statistics, Medical School of National and Kapodistrian University of Athens, Athens, Greece
∗∗∗∗∗Division of Hepatology, Department of Medicine II, Leipzig University Medical Center, Leipzig, Germany
‡‡‡‡‡Hospital General Universitario Vall Hebron and Ciberehd, Barcelona, Spain
§§§§§Hospital U Puerta de Hierro, IDIPHIM CIBERehd, Madrid, Spain
∥∥∥∥∥ ∥th Department of Internal Medicine, Αristotle University of Thessaloniki Medical School, General Hospital of Thessaloniki “Hippokratio”, Thessaloniki, Greece
¶¶¶¶¶‡nd Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Hippokratio”, Athens, Greece
#####Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, ON, Canada
∗∗∗∗∗∗Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Laiko”, Athens, Greece
Correspondence to George V. Papatheodoridis, MD, PhD, Jeong-Hoon Lee, MD, PhD
aThese four authors contributed equally as co-first authors
Abstract
BACKGROUND & AIMS
Antiviral treatment from hepatitis B envelope antigen (HBeAg)-positive status may attenuate the integration of hepatitis B virus DNA into the host genome causing hepatocellular carcinoma (HCC). We investigated the impact of HBeAg status at the onset of antiviral treatment on the risk of HCC.
METHODS
The incidence of HCC was evaluated in Korean chronic hepatitis B (CHB) patients who started entecavir or tenofovir in either HBeAg-positive or HBeAg-negative phase. The results in the Korean cohort were validated in a Caucasian PAGE-B cohort.
RESULTS
A total of 9,143 Korean patients (mean age=49.2 years) were included: 49.1% were HBeAg-positive and 49.2% had cirrhosis. During follow-up (median=5.1 years), 916 patients (10.0%) developed HCC. Baseline HBeAg-positivity was not associated with the risk of HCC in the entire cohort or cirrhotic subcohort. However, in the non-cirrhotic subcohort, HBeAg-positivity was independently associated with a lower risk of HCC in multivariable (adjusted hazard ratio [aHR]=0.41, 95% confidence interval [CI]=0.26–0.66), propensity score matching (aHR=0.46, 95% CI=0.28–0.76), and inverse probability weighting analyses (aHR=0.44, 95% CI=0.28–0.70). In the Caucasian cohort (n=719, mean age=51.8 years, HBeAg-positive=20.3%, cirrhosis=34.8%), HBeAg-positivity was not associated with the risk of HCC either in the entire cohort or cirrhotic subcohort. In the non-cirrhotic subcohort, none of the HBeAg-positive group developed HCC, although the difference failed to reach statistical significance (aHR=0.21, 95% CI=0.00–1.67).
CONCLUSIONS
This multinational cohort study implies that HBeAg-positivity at the onset of antiviral treatment seems to be an independent factor associated with a lower risk of HCC in CHB patients without cirrhosis, but not in those with cirrhosis.
Keywords : Liver cancer, neoplasm, hepatitis B virus, DNA, cumulative incidence
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