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Incidence, Factors, and Patient-Level Data for Spontaneous HBsAg Seroclearance: A Cohort Study of 11,264 Patients
Spontaneous hepatitis B surface antigen (HBsAg) seroclearance, the functional cure of hepatitis B infection, occurs rarely. Prior original studies are limited by insufficient sample size and/or follow-up, and recent meta-analyses are limited by inclusion of only study-level data and lack of adjustme...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494149/ https://www.ncbi.nlm.nih.gov/pubmed/33094953 http://dx.doi.org/10.14309/ctg.0000000000000196 |
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author | Yeo, Yee Hui Tseng, Tai-Chung Hosaka, Tetsuya Cunningham, Chris Fung, James Yan Yue Ho, Hsiu J. Kwak, Min-Sun Trinh, Huy N. Ungtrakul, Teerapat Yu, Ming-Lung Kobayashi, Mariko Le, An K. Henry, Linda Li, Jiayi Zhang, Jian Sriprayoon, Tassanee Jeong, Donghak Tanwandee, Tawesak Gane, Ed Cheung, Ramsey C. Wu, Chun-Ying Lok, Anna S. Lee, Hyo-Suk Suzuki, Fumitaka Yuen, Man-Fung Kao, Jia-Horng Yang, Hwai-I Nguyen, Mindie H. |
author_facet | Yeo, Yee Hui Tseng, Tai-Chung Hosaka, Tetsuya Cunningham, Chris Fung, James Yan Yue Ho, Hsiu J. Kwak, Min-Sun Trinh, Huy N. Ungtrakul, Teerapat Yu, Ming-Lung Kobayashi, Mariko Le, An K. Henry, Linda Li, Jiayi Zhang, Jian Sriprayoon, Tassanee Jeong, Donghak Tanwandee, Tawesak Gane, Ed Cheung, Ramsey C. Wu, Chun-Ying Lok, Anna S. Lee, Hyo-Suk Suzuki, Fumitaka Yuen, Man-Fung Kao, Jia-Horng Yang, Hwai-I Nguyen, Mindie H. |
author_sort | Yeo, Yee Hui |
collection | PubMed |
description | Spontaneous hepatitis B surface antigen (HBsAg) seroclearance, the functional cure of hepatitis B infection, occurs rarely. Prior original studies are limited by insufficient sample size and/or follow-up, and recent meta-analyses are limited by inclusion of only study-level data and lack of adjustment for confounders to investigate HBsAg seroclearance rates in most relevant subgroups. Using a cohort with detailed individual patient data, we estimated spontaneous HBsAg seroclearance rates through patient and virologic characteristics. METHODS: We analyzed 11,264 untreated patients with chronic hepatitis B with serial HBsAg data from 4 North American and 8 Asian Pacific centers, with 1,393 patients with HBsAg seroclearance (≥2 undetectable HBsAg ≥6 months apart) during 106,192 person-years. The annual seroclearance rate with detailed categorization by infection phase, further stratified by hepatitis B e antigen (HBeAg) status, sex, age, and quantitative HBsAg (qHBsAg), was performed. RESULTS: The annual seroclearance rate was 1.31% (95% confidence interval: 1.25–1.38) and over 7% in immune inactive patients aged ≥55 years and with qHBsAg <100 IU/mL. The 5-, 10-, 15-, and 20-year cumulative rates were 4.74%, 10.72%, 18.80%, and 24.79%, respectively. On multivariable analysis, male (adjusted hazard ratio [aHR] = 1.66), older age (41–55 years: aHR = 1.16; >55 years: aHR = 1.21), negative HBeAg (aHR = 6.34), and genotype C (aHR = 1.82) predicted higher seroclearance rates, as did lower hepatitis B virus DNA and lower qHBsAg (P < 0.05 for all), and inactive carrier state. DISCUSSION: The spontaneous annual HBsAg seroclearance rate was 1.31%, but varied from close to zero to about 5% among most chronic hepatitis B subgroups, with older, male, HBeAg-negative, and genotype C patients with lower alanine aminotransferase and hepatitis B virus DNA, and qHBsAg independently associated with higher rates (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/CTG/A367). |
format | Online Article Text |
id | pubmed-7494149 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Wolters Kluwer |
record_format | MEDLINE/PubMed |
spelling | pubmed-74941492020-09-24 Incidence, Factors, and Patient-Level Data for Spontaneous HBsAg Seroclearance: A Cohort Study of 11,264 Patients Yeo, Yee Hui Tseng, Tai-Chung Hosaka, Tetsuya Cunningham, Chris Fung, James Yan Yue Ho, Hsiu J. Kwak, Min-Sun Trinh, Huy N. Ungtrakul, Teerapat Yu, Ming-Lung Kobayashi, Mariko Le, An K. Henry, Linda Li, Jiayi Zhang, Jian Sriprayoon, Tassanee Jeong, Donghak Tanwandee, Tawesak Gane, Ed Cheung, Ramsey C. Wu, Chun-Ying Lok, Anna S. Lee, Hyo-Suk Suzuki, Fumitaka Yuen, Man-Fung Kao, Jia-Horng Yang, Hwai-I Nguyen, Mindie H. Clin Transl Gastroenterol Article Spontaneous hepatitis B surface antigen (HBsAg) seroclearance, the functional cure of hepatitis B infection, occurs rarely. Prior original studies are limited by insufficient sample size and/or follow-up, and recent meta-analyses are limited by inclusion of only study-level data and lack of adjustment for confounders to investigate HBsAg seroclearance rates in most relevant subgroups. Using a cohort with detailed individual patient data, we estimated spontaneous HBsAg seroclearance rates through patient and virologic characteristics. METHODS: We analyzed 11,264 untreated patients with chronic hepatitis B with serial HBsAg data from 4 North American and 8 Asian Pacific centers, with 1,393 patients with HBsAg seroclearance (≥2 undetectable HBsAg ≥6 months apart) during 106,192 person-years. The annual seroclearance rate with detailed categorization by infection phase, further stratified by hepatitis B e antigen (HBeAg) status, sex, age, and quantitative HBsAg (qHBsAg), was performed. RESULTS: The annual seroclearance rate was 1.31% (95% confidence interval: 1.25–1.38) and over 7% in immune inactive patients aged ≥55 years and with qHBsAg <100 IU/mL. The 5-, 10-, 15-, and 20-year cumulative rates were 4.74%, 10.72%, 18.80%, and 24.79%, respectively. On multivariable analysis, male (adjusted hazard ratio [aHR] = 1.66), older age (41–55 years: aHR = 1.16; >55 years: aHR = 1.21), negative HBeAg (aHR = 6.34), and genotype C (aHR = 1.82) predicted higher seroclearance rates, as did lower hepatitis B virus DNA and lower qHBsAg (P < 0.05 for all), and inactive carrier state. DISCUSSION: The spontaneous annual HBsAg seroclearance rate was 1.31%, but varied from close to zero to about 5% among most chronic hepatitis B subgroups, with older, male, HBeAg-negative, and genotype C patients with lower alanine aminotransferase and hepatitis B virus DNA, and qHBsAg independently associated with higher rates (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/CTG/A367). Wolters Kluwer 2020-09-15 /pmc/articles/PMC7494149/ /pubmed/33094953 http://dx.doi.org/10.14309/ctg.0000000000000196 Text en © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY) (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Article Yeo, Yee Hui Tseng, Tai-Chung Hosaka, Tetsuya Cunningham, Chris Fung, James Yan Yue Ho, Hsiu J. Kwak, Min-Sun Trinh, Huy N. Ungtrakul, Teerapat Yu, Ming-Lung Kobayashi, Mariko Le, An K. Henry, Linda Li, Jiayi Zhang, Jian Sriprayoon, Tassanee Jeong, Donghak Tanwandee, Tawesak Gane, Ed Cheung, Ramsey C. Wu, Chun-Ying Lok, Anna S. Lee, Hyo-Suk Suzuki, Fumitaka Yuen, Man-Fung Kao, Jia-Horng Yang, Hwai-I Nguyen, Mindie H. Incidence, Factors, and Patient-Level Data for Spontaneous HBsAg Seroclearance: A Cohort Study of 11,264 Patients |
title | Incidence, Factors, and Patient-Level Data for Spontaneous HBsAg Seroclearance: A Cohort Study of 11,264 Patients |
title_full | Incidence, Factors, and Patient-Level Data for Spontaneous HBsAg Seroclearance: A Cohort Study of 11,264 Patients |
title_fullStr | Incidence, Factors, and Patient-Level Data for Spontaneous HBsAg Seroclearance: A Cohort Study of 11,264 Patients |
title_full_unstemmed | Incidence, Factors, and Patient-Level Data for Spontaneous HBsAg Seroclearance: A Cohort Study of 11,264 Patients |
title_short | Incidence, Factors, and Patient-Level Data for Spontaneous HBsAg Seroclearance: A Cohort Study of 11,264 Patients |
title_sort | incidence, factors, and patient-level data for spontaneous hbsag seroclearance: a cohort study of 11,264 patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494149/ https://www.ncbi.nlm.nih.gov/pubmed/33094953 http://dx.doi.org/10.14309/ctg.0000000000000196 |
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