@article{c58994079e184b85a55fb41289850080,
title = "Impact of HBeAg on Hepatocellular Carcinoma Risk During Oral Antiviral Treatment in Patients With Chronic Hepatitis B",
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 patients with chronic hepatitis B 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 9143 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 patients with chronic hepatitis B without cirrhosis, but not in those with cirrhosis.",
keywords = "Cumulative Incidence, DNA, Hepatitis B Virus, Liver Cancer, Neoplasm",
author = "Heejoon Jang and Yoon, {Jun Sik} and Park, {Soo Young} and Lee, {Han Ah} and Jang, {Myoung jin} and Kim, {Seung Up} and Sinn, {Dong Hyun} and Seo, {Yeon Seok} and Kim, {Hwi Young} and Kim, {Sung Eun} and Jun, {Dae Won} and Yoon, {Eileen L.} and Sohn, {Joo Hyun} and Ahn, {Sang Bong} and Shim, {Jae Jun} and Jeong, {Soung Won} and Cho, {Yong Kyun} and Kim, {Hyoung Su} and Nam, {Joon Yeul} and Lee, {Yun Bin} and Kim, {Yoon Jun} and Yoon, {Jung Hwan} and Fabien Zoulim and Pietro Lampertico and Dalekos, {George N.} and Ramazan Idilman and Vana Sypsa and Thomas Berg and Maria Buti and Calleja, {Jose Luis} and John Goulis and Spilios Manolakopoulos and Janssen, {Harry LA} and Papatheodoridis, {George V.} and Lee, {Jeong Hoon}",
note = "Funding Information: Funding The trial was supported by grants from Liver Research Foundation of Korea as part of Bio Future Strategies Research Project, Seoul National University Hospital Research Fund (grant number 03-2016-0380), and from the National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIP) (grant number NRF-2019R1A2C2010311). Funding Information: Funding The trial was supported by grants from Liver Research Foundation of Korea as part of Bio Future Strategies Research Project, Seoul National University Hospital Research Fund (grant number 03-2016-0380), and from the National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIP) (grant number NRF-2019R1A2C2010311). Conflicts of interest These authors disclose the following: Seung Up Kim reports receiving grants from Yuhan Pharmaceuticals, and lecture fees from Bristol-Myers Squibb, Gilead Science, and Yuhan Pharmaceuticals; Yoon Jun Kim reports receiving research grants from Bristol-Myers Squibb, Roche, JW Creagene, Bukwang Pharmaceuticals, Handok Pharmaceuticals, Hanmi Pharmaceuticals, Yuhan Pharmaceuticals, and Pharmaking, and lecture fees from Bayer HealthCare Pharmaceuticals, Gilead Science, MSD Korea, Yuhan Pharmaceuticals, Samil Pharmaceuticals, CJ Pharmaceuticals, Bukwang Pharmaceuticals, and Handok Pharmaceuticals; Jung-Hwan Yoon reports receiving research grant from Bayer HealthCare Pharmaceuticals, Bukwang Pharmaceuticals, and Daewoong Pharmaceuticals; George V. Papatheodoridis has served as advisor/lecturer for Abbvie, Dicerna, Gilead, GlaxoSmithKline, Ipsen, Janssen, Merck Sharp & Dohme, Roche, and Spring Bank and has received research grants from Abbvie, Gilead; Jeong-Hoon Lee reports receiving lecture fees from GreenCross Cell, Daewoong Pharmaceuticals, and Gilead Korea. The remaining authors declare no confilcts. Publisher Copyright: {\textcopyright} 2022 AGA Institute",
year = "2022",
month = jun,
doi = "10.1016/j.cgh.2021.09.001",
language = "English",
volume = "20",
pages = "1343--1353.e16",
journal = "Clinical Gastroenterology and Hepatology",
issn = "1542-3565",
publisher = "W.B. Saunders Ltd",
number = "6",
}