Impact of HBeAg on Hepatocellular Carcinoma Risk During Oral Antiviral Treatment in Patients With Chronic Hepatitis B

Heejoon Jang; Jun Sik Yoon; Soo Young Park; Han Ah Lee; 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; Jung Hwan 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

doi:10.1016/j.cgh.2021.09.001

Impact of HBeAg on Hepatocellular Carcinoma Risk During Oral Antiviral Treatment in Patients With Chronic Hepatitis B

Heejoon Jang, Jun Sik Yoon, Soo Young Park, Han Ah Lee, 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 LeeYoon Jun Kim, Jung Hwan 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

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1343-1353.e16
Journal	Clinical Gastroenterology and Hepatology
Volume	20
Issue number	6
DOIs	https://doi.org/10.1016/j.cgh.2021.09.001
Publication status	Published - 2022 Jun

Bibliographical 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:
© 2022 AGA Institute

All Science Journal Classification (ASJC) codes

Hepatology
Gastroenterology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cgh.2021.09.001

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Jang, H., Yoon, J. S., Park, S. Y., Lee, H. A., Jang, M. J., Kim, S. U., Sinn, D. H., Seo, Y. S., Kim, H. Y., Kim, S. E., Jun, D. W., Yoon, E. L., Sohn, J. H., Ahn, S. B., Shim, J. J., Jeong, S. W., Cho, Y. K., Kim, H. S., Nam, J. Y., ... Lee, J. H. (2022). Impact of HBeAg on Hepatocellular Carcinoma Risk During Oral Antiviral Treatment in Patients With Chronic Hepatitis B. Clinical Gastroenterology and Hepatology, 20(6), 1343-1353.e16. https://doi.org/10.1016/j.cgh.2021.09.001

@article{7e6f69a080a944fdbc6509cf3de08680,

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.",

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",

}

Jang, H, Yoon, JS, Park, SY, Lee, HA, Jang, MJ, Kim, SU, Sinn, DH, Seo, YS, Kim, HY, Kim, SE, Jun, DW, Yoon, EL, Sohn, JH, Ahn, SB, Shim, JJ, Jeong, SW, Cho, YK, Kim, HS, Nam, JY, Lee, YB, Kim, YJ, Yoon, JH, Zoulim, F, Lampertico, P, Dalekos, GN, Idilman, R, Sypsa, V, Berg, T, Buti, M, Calleja, JL, Goulis, J, Manolakopoulos, S, Janssen, HLA, Papatheodoridis, GV & Lee, JH 2022, 'Impact of HBeAg on Hepatocellular Carcinoma Risk During Oral Antiviral Treatment in Patients With Chronic Hepatitis B', Clinical Gastroenterology and Hepatology, vol. 20, no. 6, pp. 1343-1353.e16. https://doi.org/10.1016/j.cgh.2021.09.001

TY - JOUR

T1 - Impact of HBeAg on Hepatocellular Carcinoma Risk During Oral Antiviral Treatment in Patients With Chronic Hepatitis B

AU - Jang, Heejoon

AU - Yoon, Jun Sik

AU - Park, Soo Young

AU - Lee, Han Ah

AU - Jang, Myoung jin

AU - Kim, Seung Up

AU - Sinn, Dong Hyun

AU - Seo, Yeon Seok

AU - Kim, Hwi Young

AU - Kim, Sung Eun

AU - Jun, Dae Won

AU - Yoon, Eileen L.

AU - Sohn, Joo Hyun

AU - Ahn, Sang Bong

AU - Shim, Jae Jun

AU - Jeong, Soung Won

AU - Cho, Yong Kyun

AU - Kim, Hyoung Su

AU - Nam, Joon Yeul

AU - Lee, Yun Bin

AU - Kim, Yoon Jun

AU - Yoon, Jung Hwan

AU - Zoulim, Fabien

AU - Lampertico, Pietro

AU - Dalekos, George N.

AU - Idilman, Ramazan

AU - Sypsa, Vana

AU - Berg, Thomas

AU - Buti, Maria

AU - Calleja, Jose Luis

AU - Goulis, John

AU - Manolakopoulos, Spilios

AU - Janssen, Harry LA

AU - Papatheodoridis, George V.

AU - Lee, Jeong Hoon

N1 - 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: © 2022 AGA Institute

PY - 2022/6

Y1 - 2022/6

N2 - 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.

AB - 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.

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DO - 10.1016/j.cgh.2021.09.001

M3 - Article

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AN - SCOPUS:85119065401

SN - 1542-3565

VL - 20

SP - 1343-1353.e16

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

IS - 6

ER -

Impact of HBeAg on Hepatocellular Carcinoma Risk During Oral Antiviral Treatment in Patients With Chronic Hepatitis B

Abstract

Bibliographical note

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UN SDGs

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