Extremely low risk of hepatocellular carcinoma development in patients with chronic hepatitis B in immune-tolerant phase

Han Ah Lee; Hyun Woong Lee; In Hee Kim; Soo Young Park; Dong Hyun Sinn; Jung Hwan Yu; Yeon Seok Seo; Soon Ho Um; Jung Il Lee; Kwan Sik Lee; Chang Hun Lee; Won Young Tak; Young Oh Kweon; Wonseok Kang; Yong Han Paik; Jin Woo Lee; Sang Jun Suh; Young Kul Jung; Beom Kyung Kim; Jun Yong Park; Do Young Kim; Sang Hoon Ahn; Kwang Hyub Han; Hyung Joon Yim; Seung Up Kim

doi:10.1111/apt.15741

Extremely low risk of hepatocellular carcinoma development in patients with chronic hepatitis B in immune-tolerant phase

Han Ah Lee, Hyun Woong Lee, In Hee Kim, Soo Young Park, Dong Hyun Sinn, Jung Hwan Yu, Yeon Seok Seo, Soon Ho Um, Jung Il Lee, Kwan Sik Lee, Chang Hun Lee, Won Young Tak, Young Oh Kweon, Wonseok Kang, Yong Han Paik, Jin Woo Lee, Sang Jun Suh, Young Kul Jung, Beom Kyung Kim, Jun Yong ParkDo Young Kim, Sang Hoon Ahn, Kwang Hyub Han, Hyung Joon Yim, Seung Up Kim

Department of Internal Medicine

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

45 Citations (Scopus)

Abstract

Background: Anti-viral therapy is not indicated for patients with chronic hepatitis B (CHB) in the immune-tolerant phase. Aims: To investigate the cumulative incidence of phase change and hepatocellular carcinoma (HCC) and independent predictors for phase change in patients with CHB in immune-tolerant phase. Methods: In total, 946 patients in immune-tolerant phase, defined as hepatitis B e antigen positivity, HBV-DNA >20 000 IU/mL and alanine aminotransferase (ALT) ≤40 IU/L, between 1989 and 2017 were enrolled from eight institutes. Results: The mean age of study population (429 men and 517 women) was 36.7 years. The mean ALT and HBV-DNA levels were 24.6 IU/L and 8.50 log₁₀ IU/mL, respectively. Of the study population, 476 (50.3%) patients remained in immune-tolerant phase throughout the study period (median: 63.6 months). The cumulative incidence rates of phase change and HCC at 10 years were 70.7% and 1.7%, respectively. Multivariate analyses revealed that HBV-DNA level >10⁷ IU/mL was associated independently with a reduced risk of phase change (hazard ratio [HR] = 0.734, P = 0.008), whereas a high ALT level, above the cut-off recommended in the Korean Association for the Study of the Liver guidelines (34 IU/L for men and 30 IU/L for women), was associated independently with a greater risk of phase change (HR = 1.885, P < 0.001). Conclusions: The criterion of HBV-DNA level > 10⁷ IU/mL may be useful to define immune-tolerant phase. In addition, an extremely low risk of HCC development was observed in patients with CHB in immune-tolerant phase.

Original language	English
Pages (from-to)	196-204
Number of pages	9
Journal	Alimentary Pharmacology and Therapeutics
Volume	52
Issue number	1
DOIs	https://doi.org/10.1111/apt.15741
Publication status	Published - 2020 Jul 1

Bibliographical note

Funding Information:
This study was supported the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2019R1A2C4070136). The funders had no role in study design, data collection and analysis, decision to publish or manuscript preparation.

Funding Information:
: This study was funded in part by National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2019R1A2C4070136). The funders had no role in study design, data collection and analysis, decision to publish or manuscript preparation. Declaration of funding interests

Publisher Copyright:
© 2020 John Wiley & Sons Ltd

All Science Journal Classification (ASJC) codes

Hepatology
Gastroenterology
Pharmacology (medical)

UN SDGs

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

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10.1111/apt.15741

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Lee, H. A., Lee, H. W., Kim, I. H., Park, S. Y., Sinn, D. H., Yu, J. H., Seo, Y. S., Um, S. H., Lee, J. I., Lee, K. S., Lee, C. H., Tak, W. Y., Kweon, Y. O., Kang, W., Paik, Y. H., Lee, J. W., Suh, S. J., Jung, Y. K., Kim, B. K., ... Kim, S. U. (2020). Extremely low risk of hepatocellular carcinoma development in patients with chronic hepatitis B in immune-tolerant phase. Alimentary Pharmacology and Therapeutics, 52(1), 196-204. https://doi.org/10.1111/apt.15741

@article{73a8144c24d045cba58c6d7d0d4ff9be,

title = "Extremely low risk of hepatocellular carcinoma development in patients with chronic hepatitis B in immune-tolerant phase",

abstract = "Background: Anti-viral therapy is not indicated for patients with chronic hepatitis B (CHB) in the immune-tolerant phase. Aims: To investigate the cumulative incidence of phase change and hepatocellular carcinoma (HCC) and independent predictors for phase change in patients with CHB in immune-tolerant phase. Methods: In total, 946 patients in immune-tolerant phase, defined as hepatitis B e antigen positivity, HBV-DNA >20 000 IU/mL and alanine aminotransferase (ALT) ≤40 IU/L, between 1989 and 2017 were enrolled from eight institutes. Results: The mean age of study population (429 men and 517 women) was 36.7 years. The mean ALT and HBV-DNA levels were 24.6 IU/L and 8.50 log10 IU/mL, respectively. Of the study population, 476 (50.3%) patients remained in immune-tolerant phase throughout the study period (median: 63.6 months). The cumulative incidence rates of phase change and HCC at 10 years were 70.7% and 1.7%, respectively. Multivariate analyses revealed that HBV-DNA level >107 IU/mL was associated independently with a reduced risk of phase change (hazard ratio [HR] = 0.734, P = 0.008), whereas a high ALT level, above the cut-off recommended in the Korean Association for the Study of the Liver guidelines (34 IU/L for men and 30 IU/L for women), was associated independently with a greater risk of phase change (HR = 1.885, P < 0.001). Conclusions: The criterion of HBV-DNA level > 107 IU/mL may be useful to define immune-tolerant phase. In addition, an extremely low risk of HCC development was observed in patients with CHB in immune-tolerant phase.",

author = "Lee, {Han Ah} and Lee, {Hyun Woong} and Kim, {In Hee} and Park, {Soo Young} and Sinn, {Dong Hyun} and Yu, {Jung Hwan} and Seo, {Yeon Seok} and Um, {Soon Ho} and Lee, {Jung Il} and Lee, {Kwan Sik} and Lee, {Chang Hun} and Tak, {Won Young} and Kweon, {Young Oh} and Wonseok Kang and Paik, {Yong Han} and Lee, {Jin Woo} and Suh, {Sang Jun} and Jung, {Young Kul} and Kim, {Beom Kyung} and Park, {Jun Yong} and Kim, {Do Young} and Ahn, {Sang Hoon} and Han, {Kwang Hyub} and Yim, {Hyung Joon} and Kim, {Seung Up}",

note = "Funding Information: This study was supported the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2019R1A2C4070136). The funders had no role in study design, data collection and analysis, decision to publish or manuscript preparation. Funding Information: : This study was funded in part by National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2019R1A2C4070136). The funders had no role in study design, data collection and analysis, decision to publish or manuscript preparation. Declaration of funding interests Publisher Copyright: {\textcopyright} 2020 John Wiley & Sons Ltd",

year = "2020",

month = jul,

day = "1",

doi = "10.1111/apt.15741",

language = "English",

volume = "52",

pages = "196--204",

journal = "Alimentary Pharmacology and Therapeutics",

issn = "0269-2813",

publisher = "Wiley-Blackwell",

number = "1",

}

Lee, HA, Lee, HW, Kim, IH, Park, SY, Sinn, DH, Yu, JH, Seo, YS, Um, SH, Lee, JI, Lee, KS, Lee, CH, Tak, WY, Kweon, YO, Kang, W, Paik, YH, Lee, JW, Suh, SJ, Jung, YK, Kim, BK, Park, JY , Kim, DY , Ahn, SH , Han, KH, Yim, HJ & Kim, SU 2020, 'Extremely low risk of hepatocellular carcinoma development in patients with chronic hepatitis B in immune-tolerant phase', Alimentary Pharmacology and Therapeutics, vol. 52, no. 1, pp. 196-204. https://doi.org/10.1111/apt.15741

TY - JOUR

T1 - Extremely low risk of hepatocellular carcinoma development in patients with chronic hepatitis B in immune-tolerant phase

AU - Lee, Han Ah

AU - Lee, Hyun Woong

AU - Kim, In Hee

AU - Park, Soo Young

AU - Sinn, Dong Hyun

AU - Yu, Jung Hwan

AU - Seo, Yeon Seok

AU - Um, Soon Ho

AU - Lee, Jung Il

AU - Lee, Kwan Sik

AU - Lee, Chang Hun

AU - Tak, Won Young

AU - Kweon, Young Oh

AU - Kang, Wonseok

AU - Paik, Yong Han

AU - Lee, Jin Woo

AU - Suh, Sang Jun

AU - Jung, Young Kul

AU - Kim, Beom Kyung

AU - Park, Jun Yong

AU - Kim, Do Young

AU - Ahn, Sang Hoon

AU - Han, Kwang Hyub

AU - Yim, Hyung Joon

AU - Kim, Seung Up

N1 - Funding Information: This study was supported the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2019R1A2C4070136). The funders had no role in study design, data collection and analysis, decision to publish or manuscript preparation. Funding Information: : This study was funded in part by National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2019R1A2C4070136). The funders had no role in study design, data collection and analysis, decision to publish or manuscript preparation. Declaration of funding interests Publisher Copyright: © 2020 John Wiley & Sons Ltd

PY - 2020/7/1

Y1 - 2020/7/1

N2 - Background: Anti-viral therapy is not indicated for patients with chronic hepatitis B (CHB) in the immune-tolerant phase. Aims: To investigate the cumulative incidence of phase change and hepatocellular carcinoma (HCC) and independent predictors for phase change in patients with CHB in immune-tolerant phase. Methods: In total, 946 patients in immune-tolerant phase, defined as hepatitis B e antigen positivity, HBV-DNA >20 000 IU/mL and alanine aminotransferase (ALT) ≤40 IU/L, between 1989 and 2017 were enrolled from eight institutes. Results: The mean age of study population (429 men and 517 women) was 36.7 years. The mean ALT and HBV-DNA levels were 24.6 IU/L and 8.50 log10 IU/mL, respectively. Of the study population, 476 (50.3%) patients remained in immune-tolerant phase throughout the study period (median: 63.6 months). The cumulative incidence rates of phase change and HCC at 10 years were 70.7% and 1.7%, respectively. Multivariate analyses revealed that HBV-DNA level >107 IU/mL was associated independently with a reduced risk of phase change (hazard ratio [HR] = 0.734, P = 0.008), whereas a high ALT level, above the cut-off recommended in the Korean Association for the Study of the Liver guidelines (34 IU/L for men and 30 IU/L for women), was associated independently with a greater risk of phase change (HR = 1.885, P < 0.001). Conclusions: The criterion of HBV-DNA level > 107 IU/mL may be useful to define immune-tolerant phase. In addition, an extremely low risk of HCC development was observed in patients with CHB in immune-tolerant phase.

AB - Background: Anti-viral therapy is not indicated for patients with chronic hepatitis B (CHB) in the immune-tolerant phase. Aims: To investigate the cumulative incidence of phase change and hepatocellular carcinoma (HCC) and independent predictors for phase change in patients with CHB in immune-tolerant phase. Methods: In total, 946 patients in immune-tolerant phase, defined as hepatitis B e antigen positivity, HBV-DNA >20 000 IU/mL and alanine aminotransferase (ALT) ≤40 IU/L, between 1989 and 2017 were enrolled from eight institutes. Results: The mean age of study population (429 men and 517 women) was 36.7 years. The mean ALT and HBV-DNA levels were 24.6 IU/L and 8.50 log10 IU/mL, respectively. Of the study population, 476 (50.3%) patients remained in immune-tolerant phase throughout the study period (median: 63.6 months). The cumulative incidence rates of phase change and HCC at 10 years were 70.7% and 1.7%, respectively. Multivariate analyses revealed that HBV-DNA level >107 IU/mL was associated independently with a reduced risk of phase change (hazard ratio [HR] = 0.734, P = 0.008), whereas a high ALT level, above the cut-off recommended in the Korean Association for the Study of the Liver guidelines (34 IU/L for men and 30 IU/L for women), was associated independently with a greater risk of phase change (HR = 1.885, P < 0.001). Conclusions: The criterion of HBV-DNA level > 107 IU/mL may be useful to define immune-tolerant phase. In addition, an extremely low risk of HCC development was observed in patients with CHB in immune-tolerant phase.

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U2 - 10.1111/apt.15741

DO - 10.1111/apt.15741

M3 - Article

C2 - 32452564

AN - SCOPUS:85085643041

SN - 0269-2813

VL - 52

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EP - 204

JO - Alimentary Pharmacology and Therapeutics

JF - Alimentary Pharmacology and Therapeutics

IS - 1

ER -

Extremely low risk of hepatocellular carcinoma development in patients with chronic hepatitis B in immune-tolerant phase

Abstract

Bibliographical note

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UN SDGs

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