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Incidence and Predictors of HBsAg
Seroclearance in 10,614 Untreated Patients
on Long-Term Follow-up: A Collaborative Study
from North America and Asia Pacific
Yee Hui Yeo1, Hsiu J. Ho2, Hwai-I Yang3, Tai-Chung Tseng4,
Huy N. Trinh5, Young Min Park6, Tetsuya Hosaka7, Min-Sun
Kwak8, James Fung9, Teerapat Ungtrakul10, Ming-Lung Yu11,
Jiayi Li12, Jian Zhang13, An K. Le1, Tassanee Sriprayoon14,
Tawesak Tanwandee15, Man-Fung Yuen16, Hyo-Suk Lee8,
Fumitaka Suzuki7, Mariko Kobayashi17, Jia-Horng Kao4,
Chun-Ying Wu18 and Mindie H. Nguyen1, (1)Division of
Gastroenterology and Hepatology, Stanford University Medical
Center, (2)Division of Translational Research, Taipei Veterans
General Hospital, (3)Genomics Research Center, Academia
Sinica, (4)Department of Internal Medicine, Division of
Gastroenterology and Hepatology, National Taiwan University
Hospital, Taipei, Taiwan, (5)San Jose Gastroenterology, (6)
Department of Internal Medicine, and Biomedical Research
Center, Bundang Jesaeng General Hospital, (7)Hepatology,
Toranomon Hospital, (8)Department of Internal Medicine and
Liver Research Institute, Seoul National University Hospital, (9)
Medicine, Queen Mary Hospital, (10)Faculty of Medicine and
Public Health, HRH Princess Chulabhorn College of Medical
Science, (11)Internal Medicine, Kaohsiung Medical University
Hospital, Kaohsiung Medical University, (12)Palo Alto Medical
Foundation, Mountain View Division, (13)Chinese Hospital,
(14)Department of Medicine, Siriraj Hospital, (15)Internal
Medicine, Mahidol University, (16)Medicine, Queen Mary
Hospital, Hong Kong, (17)Research Institute for Hepatology,
Toranomon Hospital, (18)Taipei Veterans General Hospital
Background: Spontaneous HBsAg seroclearance is the
functional cure of hepatitis B virus and is associated with a
better prognosis. However, the reported rates of seroclearance
have been limited by small sample size. In this study, we
combined data from nine cohorts to investigate the incidence
and determinants of HBsAg seroclearance. Methods: Data
were obtained from nine cohorts in North America (one
cohort, n= 1,635) and Asia (eight cohorts, n=8979) totalling
10,614 CHB patients who never received treatment for
hepatitis B infection. Serial laboratory data were collected
to determine HBsAg seroclearance, defined as having
two undetectable HBsAg results six months apart. Annual,
and cumulative incidence rates of HBsAg seroclearance
were estimated. Subgroup analyses and multivariable Cox
proportional hazard regression were performed to assess the
determinants of HBsAg seroclearance. Results: A total of
1,273 spontaneous incident HBsAg seroclearance occurred
during 95,886 person years of follow-up. The pooled annual
seroclearance rate was 1.33% (95% CI: 1.26-1.40), while 5-,
10-, 15-, and 20-year cumulative incidence rate were 5.01%,
11.36%, 19.44%, and 25.49%, respectively. After adjusting for
sex, age, baseline HBeAg status, cirrhosis at baseline, ALT
level, clinical setting, and ethnicity, the hazard of spontaneous
HBsAg seroclearance during follow-up was significantly
higher in males (HR=1.17, 95%CI: 1.04-1.33 vs. female), older
age group (age≥55: HR=1.79, 95%CI: 1.49-2.15; age 45-54:
HR=1.52, 95%CI: 1.28-1.80; age 35-44: HR=1.25, 95%CI:
1.06-1.48 vs. age≤35), higher baseline ALT level (HR=1.01,
95%CI: 1.00-1.01 for every 10 unit increase) and lower in
those with baseline HBeAg (+) (HR=0.25, 95%CI: 0.19-
0.32 vs. HBeAg[-]), higher HBV DNA level (>20,000IU/mL:
HR=0.35, 95%CI: 0.28-0.43; 2,000-20,000IU/mL: HR=0.43,
95%CI: 0.36-0.52 vs. HBV DNA<2,000IU/mL),and higher
quantitative HBsAg (qHBsAg) level (>1,000IU/mL: HR=0.21,
95%CI: 0.18-0.25 vs qHBsAg≤1000IU/mL). Subgroup analysis
showed that patients with genotype C had higher likelihood of
achieving HBsAg seroclearance than those with genotype B.
Conclusion: The spontaneous annual HBsAg seroclearance
rate in hepatitis B patients is 1.33%, with approximately 25%
of patients achieving seroclearance after 20 years of followup.
Being male, older, and HBeAg-negative and having
higher ALT, lower HBV DNA level, and lower qHBsAg level
were associated with a higher likelihood of attaining HBsAg
seroclearance.
Disclosures:
Tai-Chung Tseng – Abbott: Grant/Research Support
Huy N. Trinh – gilead: Advisory Committee or Review Panel; gilead: Consulting;
Gilead, Intercept: Grant/Research Support
James Fung – Novartis: Grant/Research Support
Ming-Lung Yu – Abbvie, Abbott, Ascletis, BMS, Gilead, J&J, Merck,
Pharmaessential.: Advisory Committee or Review Panel; Abbvie, Abbott,
Ascletis, BMS, Gilead, J&J, Merck, Novartis, Pharmaessential and Roche.:
Speaking and Teaching; BMS, Gilead, and Merck: Grant/Research Support
Man-Fung Yuen – Abbvie: Advisory Committee or Review Panel; Arrowhead:
Grant/Research Support; Bristol Myers Squibb: Grant/Research Support;
Gilead: Advisory Committee or Review Panel; Fujerubio: Speaking and
Teaching; Roche: Advisory Committee or Review Panel; MSD: Advisory
Committee or Review Panel
Mindie H. Nguyen – Norvatis: Advisory Committee or Review Panel; Spring
Bank: Advisory Committee or Review Panel; Gilead: Advisory Committee or
Review Panel; B K Kee Foundation: Grant/Research Support; Gilead: Grant/
Research Support; Janssen: Advisory Committee or Review Panel; Eisai:
Advisory Committee or Review Panel; Exact Science: Grant/Research Support;
The following people have nothing to disclose: Yee Hui Yeo, Hsiu J. Ho, Hwai-I
Yang, Young Min Park, Tetsuya Hosaka, Min-Sun Kwak, Teerapat Ungtrakul,
Jiayi Li, Jian Zhang, An K. Le, Tassanee Sriprayoon, Tawesak Tanwandee, Hyo-
Suk Lee, Fumitaka Suzuki, Mariko Kobayashi, Jia-Horng Kao, Chun-Ying Wu作者: StephenW 时间: 2018-10-7 18:52
Incidence and Predictors of HBsAg Seroclearance in 10,614
Untreated Patients on Long-Term Follow-up:
A Collaborative Study from North America and Asia Pacific Yee Hui Yeo1, Hsiu J. Ho2, Hwai-I Yang3, Tai-Chung Tseng4, Huy N. Trinh5, Young Min Park6, Tetsuya Hosaka7, Min-Sun Kwak8, James Fung9, Teerapat Ungtrakul10, Ming-Lung Yu11, Jiayi Li12, Jian Zhang13, An K. Le1, Tassanee Sriprayoon14, Tawesak Tanwandee15, Man-Fung Yuen16, Hyo-Suk Lee8, Fumitaka Suzuki7, Mariko Kobayashi17, Jia-Horng Kao4, Chun-Ying Wu18 and Mindie H. Nguyen1, (1)Division of Gastroenterology and Hepatology, Stanford University Medical Center, (2)Division of Translational Research, Taipei Veterans General Hospital, (3)Genomics Research Center, Academia Sinica, (4)Department of Internal Medicine, Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan, (5)San Jose Gastroenterology, (6) Department of Internal Medicine, and Biomedical Research Center, Bundang Jesaeng General Hospital, (7)Hepatology, Toranomon Hospital, (8)Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, (9) Medicine, Queen Mary Hospital, (10)Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, (11)Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, (12)Palo Alto Medical Foundation, Mountain View Division, (13)Chinese Hospital, (14)Department of Medicine, Siriraj Hospital, (15)Internal Medicine, Mahidol University, (16)Medicine, Queen Mary Hospital, Hong Kong, (17)Research Institute for Hepatology, Toranomon Hospital, (18)Taipei Veterans General Hospital
Background:
Spontaneous HBsAg seroclearance is the functional cure of hepatitis B virus and is associated with a better prognosis. However, the reported rates of seroclearance have been limited by small sample size. In this study, we combined data from nine cohorts to investigate the incidence and determinants of HBsAg seroclearance.
Methods:
Data were obtained from nine cohorts in North America (one cohort, n= 1,635) and Asia (eight cohorts, n=8979) totalling 10,614 CHB patients who never received treatment for hepatitis B infection. Serial laboratory data were collected to determine HBsAg seroclearance, defined as having two undetectable HBsAg results six months apart. Annual, and cumulative incidence rates of HBsAg seroclearance were estimated. Subgroup analyses and multivariable Cox proportional hazard regression were performed to assess the determinants of HBsAg seroclearance.
Results:
A total of 1,273 spontaneous incident HBsAg seroclearance occurred during 95,886 person years of follow-up. The pooled annual seroclearance rate was 1.33% (95% CI: 1.26-1.40), while 5-, 10-, 15-, and 20-year cumulative incidence rate were 5.01%, 11.36%, 19.44%, and 25.49%, respectively. After adjusting for sex, age, baseline HBeAg status, cirrhosis at baseline, ALT level, clinical setting, and ethnicity, the hazard of spontaneous HBsAg seroclearance during follow-up was significantly higher in males (HR=1.17, 95%CI: 1.04-1.33 vs. female), older age group (age≥55: HR=1.79, 95%CI: 1.49-2.15; age 45-54: HR=1.52, 95%CI: 1.28-1.80; age 35-44: HR=1.25, 95%CI: 1.06-1.48 vs. age≤35), higher baseline ALT level (HR=1.01, 95%CI: 1.00-1.01 for every 10 unit increase) and lower in those with baseline HBeAg (+) (HR=0.25, 95%CI: 0.19- 0.32 vs. HBeAg[-]), higher HBV DNA level (>20,000IU/mL: HR=0.35, 95%CI: 0.28-0.43; 2,000-20,000IU/mL: HR=0.43, 95%CI: 0.36-0.52 vs. HBV DNA<2,000IU/mL),and higher quantitative HBsAg (qHBsAg) level (>1,000IU/mL: HR=0.21, 95%CI: 0.18-0.25 vs qHBsAg≤1000IU/mL). Subgroup analysis showed that patients with genotype C had higher likelihood of achieving HBsAg seroclearance than those with genotype B.
Conclusion:
The spontaneous annual HBsAg seroclearance rate in hepatitis B patients is 1.33%, with approximately 25% of patients achieving seroclearance after 20 years of followup. Being male, older, and HBeAg-negative and having higher ALT, lower HBV DNA level, and lower qHBsAg level were associated with a higher likelihood of attaining HBsAg seroclearance.
Disclosures:
Tai-Chung Tseng – Abbott: Grant/Research Support Huy N. Trinh – gilead: Advisory Committee or Review Panel; gilead: Consulting; Gilead, Intercept: Grant/Research Support James Fung – Novartis: Grant/Research Support Ming-Lung Yu – Abbvie, Abbott, Ascletis, BMS, Gilead, J&J, Merck, Pharmaessential.: Advisory Committee or Review Panel; Abbvie, Abbott, Ascletis, BMS, Gilead, J&J, Merck, Novartis, Pharmaessential and Roche.: Speaking and Teaching; BMS, Gilead, and Merck: Grant/Research Support Man-Fung Yuen – Abbvie: Advisory Committee or Review Panel; Arrowhead: Grant/Research Support; Bristol Myers Squibb: Grant/Research Support; Gilead: Advisory Committee or Review Panel; Fujerubio: Speaking and Teaching; Roche: Advisory Committee or Review Panel; MSD: Advisory Committee or Review Panel Mindie H. Nguyen – Norvatis: Advisory Committee or Review Panel; Spring Bank: Advisory Committee or Review Panel; Gilead: Advisory Committee or Review Panel; B K Kee Foundation: Grant/Research Support; Gilead: Grant/ Research Support; Janssen: Advisory Committee or Review Panel; Eisai: Advisory Committee or Review Panel; Exact Science: Grant/Research Support; The following people have nothing to disclose: Yee Hui Yeo, Hsiu J. Ho, Hwai-I Yang, Young Min Park, Tetsuya Hosaka, Min-Sun Kwak, Teerapat Ungtrakul, Jiayi Li, Jian Zhang, An K. Le, Tassanee Sriprayoon, Tawesak Tanwandee, Hyo- Suk Lee, Fumitaka Suzuki, Mariko Kobayashi, Jia-Horng Kao, Chun-Ying Wu作者: antiHBVren 时间: 2018-10-8 16:08
10,614例HBsAg血清清除的发生率和预测因子
未经治疗的患者进行长期随访：
来自北美和亚太地区的合作研究Yee Hui Yeo，Hsiu J. Ho2，Hwai-I Yang3，Tai-Chung Tseng4，Huy N. Trinh5，Young Min Park6，Tetsuya Hosaka7，Min-Sun Kwak8，James Fung9，Teerapat Ungtrakul10 ，Ming-Lung Yu11，Jiayi Li12，Jian Zhang13，An K. Le1，Tassanee Sriprayoon14，Tawesak Tanwandee15，Man-Fung Yuen16，Hyo-Suk Lee8，Fumitaka Suzuki7，Mariko Kobayashi17，Jia-Horng Kao4，Chun-Ying Wu18和Mindie H. Nguyen，（1）斯坦福大学医学中心消化内科和肝病学系，（2）台北退伍军人总医院转化研究部，（3）中国科学院基因组学研究中心，（4）内科，科室台湾台北国立台湾大学医院消化内科，（5）圣何塞消化内科，（6）盆唐耶赛总医院内科，生物医学研究中心，（7）虎之门医院肝病学，（8）内科和肝脏研究所tute，首尔国立大学医院，（9）医学，玛丽医院，（10）医学和公共卫生学院，Chulabhorn公主医学院，（11）高雄医科大学附属高雄医科大学内科，（11） 12）帕洛阿尔托医学基金会，山景科，（13）中国医院，（14）医学系，Siriraj医院，（15）Mahidol大学内科，（16）医学，香港玛丽医院，（17） ）虎之门医院肝病研究所，（18）台北退伍军人总医院