Sex Differences in Treatment Response to Nucleos(t)ide Therapy in Chronic Hepatitis B: A Multicenter Longitudinal Study

Angela Chau; Ming Lun Yeh; Pei Chien Tsai; Daniel Q. Huang; Sung Eun Kim; Huy Trinh; Eileen L. Yoon; Hyunwoo Oh; Jae Yoon Jeong; Sang Bong Ahn; Jihyun An; Cheng Hao Tseng; Yao Chun Hsu; Soung Won Jeong; Yong Kyun Cho; Jae Jun Shim; Hyoung Su Kim; Takanori Ito; Sebastián Marciano; Keigo Kawashima; Takanori Suzuki; Tsunamasa Watanabe; Akito Nozaki; Toru Ishikawa; Kaori Inoue; Yuichiro Eguchi; Haruki Uojima; Hiroshi Abe; Hirokazu Takahashi; Makoto Chuma; Masatoshi Ishigami; Joseph K. Hoang; Mayumi Maeda; Chung Feng Huang; Adrian Gadano; Chia Yen Dai; Jee Fu Huang; Yasuhito Tanaka; Wan Long Chuang; Seng Gee Lim; Ramsey Cheung; Ming Lung Yu; Dae Won Jun; Mindie H. Nguyen

doi:10.1016/j.cgh.2023.09.002

Sex Differences in Treatment Response to Nucleos(t)ide Therapy in Chronic Hepatitis B: A Multicenter Longitudinal Study

Angela Chau
, Ming Lun Yeh
, Pei Chien Tsai
, Daniel Q. Huang
, Sung Eun Kim
, Huy Trinh
, Eileen L. Yoon
, Hyunwoo Oh
, Jae Yoon Jeong
, Sang Bong Ahn
, Jihyun An
, Cheng Hao Tseng
, Yao Chun Hsu
, Soung Won Jeong
, Yong Kyun Cho
, Jae Jun Shim
, Hyoung Su Kim
, Takanori Ito
, Sebastián Marciano
, Keigo Kawashima

Takanori Suzuki, Tsunamasa Watanabe, Akito Nozaki, Toru Ishikawa, Kaori Inoue, Yuichiro Eguchi, Haruki Uojima, Hiroshi Abe, Hirokazu Takahashi, Makoto Chuma, Masatoshi Ishigami, Joseph K. Hoang, Mayumi Maeda, Chung Feng Huang, Adrian Gadano, Chia Yen Dai, Jee Fu Huang, Yasuhito Tanaka, Wan Long Chuang, Seng Gee Lim, Ramsey Cheung, Ming Lung Yu, Dae Won Jun, Mindie H. Nguyen

Stanford University
Kaohsiung Medical University
National University Hospital
National University of Singapore
Hallym University Sacred Heart Hospital
San Jose Gastroenterology
Hanyang University
Inje University
Eulji University
I-Shou University
Soonchunhyang University
Kangbuk Samsung Hospital
Kyung Hee University
Hallym University
Nagoya University
Hospital Italiano de Buenos Aires
Nagoya City University
St. Marianna University School of Medicine
Yokohama City University
Saiseikai Niigata Hospital
Saga University
Locomedical Eguchi Hospital
Kitasato University
Shinmatsudo Central General Hospital
Kumamoto University
National Sun Yat-sen University

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

8 Scopus citations

Abstract

Background & Aims: It is unclear if there may be sex differences in response to nucleos(t)ide analogs including virologic response (VR), biochemical response (BR), complete response (CR), and hepatocellular carcinoma (HCC) incidence among hepatitis B patients. We compared nucleos(t)ide analog treatment outcomes by sex. Methods: We performed a retrospective cohort study of 3388 treatment-naïve adult hepatitis B patients (1250 female, 2138 male) from the Real-World Evidence from the Global Alliance for the Study of Hepatitis B Virus consortium who initiated therapy with either entecavir or tenofovir from 22 sites (Argentina, Korea, Japan, Taiwan, and the United States). We used propensity-score matching to balance background characteristics of the male and female groups and competing-risks analysis to estimate the incidence and subdistribution hazard ratios (SHRs) of VR, BR, CR, and HCC. Results: Females (vs males) were older (52.0 vs 48.6 y); less likely to be overweight/obese (49.3% vs 65.7%), diabetic (9.9% vs 13.1%), or cirrhotic (27.9% vs 33.0%); and had a lower HBV DNA level (5.9 vs 6.0 log10 IU/mL) and alanine aminotransferase level (91 vs 102 IU/L) (all P < .01). However, after propensity-score matching, relevant background characteristics were balanced between the 2 groups. Females (vs males) had similar 5-year cumulative VR (91.3% vs 90.3%; P = .40) and HCC incidence rates (5.1% vs 4.4%; P = .64), but lower BR (84.0% vs 90.9%; P < .001) and CR (78.8% vs 83.4%; P = .016). Males were more likely to achieve BR (SHR, 1.31; 95% CI, 1.17–1.46; P < .001) and CR (SHR, 1.16; 95% CI, 1.03–1.31; P = .016), but VR and HCC risks were similar. Conclusions: Sex differences exist for treatment outcomes among hepatitis B patients. Male sex was associated with a 16% higher likelihood of clinical remission and a 31% higher likelihood of biochemical response than females, while virologic response and HCC incidence were similar between the 2 groups.

Original language	English
Pages (from-to)	572-580.e5
Journal	Clinical Gastroenterology and Hepatology
Volume	22
Issue number	3
DOIs	https://doi.org/10.1016/j.cgh.2023.09.002
State	Published - Mar 2024
Externally published	Yes

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Antiviral Therapy
Biochemical Response
Complete Response
Virologic Response

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10.1016/j.cgh.2023.09.002

Cite this

Chau, A., Yeh, M. L., Tsai, P. C., Huang, D. Q., Kim, S. E., Trinh, H., Yoon, E. L., Oh, H., Jeong, J. Y., Ahn, S. B., An, J., Tseng, C. H., Hsu, Y. C., Jeong, S. W., Cho, Y. K., Shim, J. J., Kim, H. S., Ito, T., Marciano, S., ... Nguyen, M. H. (2024). Sex Differences in Treatment Response to Nucleos(t)ide Therapy in Chronic Hepatitis B: A Multicenter Longitudinal Study. Clinical Gastroenterology and Hepatology, 22(3), 572-580.e5. https://doi.org/10.1016/j.cgh.2023.09.002

@article{b1a74e0e8d654c2295a7dd5d9ad40ec1,

title = "Sex Differences in Treatment Response to Nucleos(t)ide Therapy in Chronic Hepatitis B: A Multicenter Longitudinal Study",

abstract = "Background \& Aims: It is unclear if there may be sex differences in response to nucleos(t)ide analogs including virologic response (VR), biochemical response (BR), complete response (CR), and hepatocellular carcinoma (HCC) incidence among hepatitis B patients. We compared nucleos(t)ide analog treatment outcomes by sex. Methods: We performed a retrospective cohort study of 3388 treatment-na{\"i}ve adult hepatitis B patients (1250 female, 2138 male) from the Real-World Evidence from the Global Alliance for the Study of Hepatitis B Virus consortium who initiated therapy with either entecavir or tenofovir from 22 sites (Argentina, Korea, Japan, Taiwan, and the United States). We used propensity-score matching to balance background characteristics of the male and female groups and competing-risks analysis to estimate the incidence and subdistribution hazard ratios (SHRs) of VR, BR, CR, and HCC. Results: Females (vs males) were older (52.0 vs 48.6 y); less likely to be overweight/obese (49.3\% vs 65.7\%), diabetic (9.9\% vs 13.1\%), or cirrhotic (27.9\% vs 33.0\%); and had a lower HBV DNA level (5.9 vs 6.0 log10 IU/mL) and alanine aminotransferase level (91 vs 102 IU/L) (all P < .01). However, after propensity-score matching, relevant background characteristics were balanced between the 2 groups. Females (vs males) had similar 5-year cumulative VR (91.3\% vs 90.3\%; P = .40) and HCC incidence rates (5.1\% vs 4.4\%; P = .64), but lower BR (84.0\% vs 90.9\%; P < .001) and CR (78.8\% vs 83.4\%; P = .016). Males were more likely to achieve BR (SHR, 1.31; 95\% CI, 1.17–1.46; P < .001) and CR (SHR, 1.16; 95\% CI, 1.03–1.31; P = .016), but VR and HCC risks were similar. Conclusions: Sex differences exist for treatment outcomes among hepatitis B patients. Male sex was associated with a 16\% higher likelihood of clinical remission and a 31\% higher likelihood of biochemical response than females, while virologic response and HCC incidence were similar between the 2 groups.",

keywords = "Antiviral Therapy, Biochemical Response, Complete Response, Virologic Response",

author = "Angela Chau and Yeh, \{Ming Lun\} and Tsai, \{Pei Chien\} and Huang, \{Daniel Q.\} and Kim, \{Sung Eun\} and Huy Trinh and Yoon, \{Eileen L.\} and Hyunwoo Oh and Jeong, \{Jae Yoon\} and Ahn, \{Sang Bong\} and Jihyun An and Tseng, \{Cheng Hao\} and Hsu, \{Yao Chun\} and Jeong, \{Soung Won\} and Cho, \{Yong Kyun\} and Shim, \{Jae Jun\} and Kim, \{Hyoung Su\} and Takanori Ito and Sebasti{\'a}n Marciano and Keigo Kawashima and Takanori Suzuki and Tsunamasa Watanabe and Akito Nozaki and Toru Ishikawa and Kaori Inoue and Yuichiro Eguchi and Haruki Uojima and Hiroshi Abe and Hirokazu Takahashi and Makoto Chuma and Masatoshi Ishigami and Hoang, \{Joseph K.\} and Mayumi Maeda and Huang, \{Chung Feng\} and Adrian Gadano and Dai, \{Chia Yen\} and Huang, \{Jee Fu\} and Yasuhito Tanaka and Chuang, \{Wan Long\} and Lim, \{Seng Gee\} and Ramsey Cheung and Yu, \{Ming Lung\} and Jun, \{Dae Won\} and Nguyen, \{Mindie H.\}",

note = "Publisher Copyright: {\textcopyright} 2024 AGA Institute",

year = "2024",

month = mar,

doi = "10.1016/j.cgh.2023.09.002",

language = "English",

volume = "22",

pages = "572--580.e5",

journal = "Clinical Gastroenterology and Hepatology",

issn = "1542-3565",

publisher = "W.B. Saunders",

number = "3",

}

Chau, A, Yeh, ML, Tsai, PC, Huang, DQ, Kim, SE, Trinh, H, Yoon, EL, Oh, H, Jeong, JY, Ahn, SB, An, J, Tseng, CH, Hsu, YC, Jeong, SW, Cho, YK, Shim, JJ, Kim, HS, Ito, T, Marciano, S, Kawashima, K, Suzuki, T, Watanabe, T, Nozaki, A, Ishikawa, T, Inoue, K, Eguchi, Y, Uojima, H, Abe, H, Takahashi, H, Chuma, M, Ishigami, M, Hoang, JK, Maeda, M, Huang, CF, Gadano, A, Dai, CY, Huang, JF, Tanaka, Y, Chuang, WL, Lim, SG, Cheung, R, Yu, ML, Jun, DW & Nguyen, MH 2024, 'Sex Differences in Treatment Response to Nucleos(t)ide Therapy in Chronic Hepatitis B: A Multicenter Longitudinal Study', Clinical Gastroenterology and Hepatology, vol. 22, no. 3, pp. 572-580.e5. https://doi.org/10.1016/j.cgh.2023.09.002

TY - JOUR

T1 - Sex Differences in Treatment Response to Nucleos(t)ide Therapy in Chronic Hepatitis B

T2 - A Multicenter Longitudinal Study

AU - Chau, Angela

AU - Yeh, Ming Lun

AU - Tsai, Pei Chien

AU - Huang, Daniel Q.

AU - Kim, Sung Eun

AU - Trinh, Huy

AU - Yoon, Eileen L.

AU - Oh, Hyunwoo

AU - Jeong, Jae Yoon

AU - Ahn, Sang Bong

AU - An, Jihyun

AU - Tseng, Cheng Hao

AU - Hsu, Yao Chun

AU - Jeong, Soung Won

AU - Cho, Yong Kyun

AU - Shim, Jae Jun

AU - Kim, Hyoung Su

AU - Ito, Takanori

AU - Marciano, Sebastián

AU - Kawashima, Keigo

AU - Suzuki, Takanori

AU - Watanabe, Tsunamasa

AU - Nozaki, Akito

AU - Ishikawa, Toru

AU - Inoue, Kaori

AU - Eguchi, Yuichiro

AU - Uojima, Haruki

AU - Abe, Hiroshi

AU - Takahashi, Hirokazu

AU - Chuma, Makoto

AU - Ishigami, Masatoshi

AU - Hoang, Joseph K.

AU - Maeda, Mayumi

AU - Huang, Chung Feng

AU - Gadano, Adrian

AU - Dai, Chia Yen

AU - Huang, Jee Fu

AU - Tanaka, Yasuhito

AU - Chuang, Wan Long

AU - Lim, Seng Gee

AU - Cheung, Ramsey

AU - Yu, Ming Lung

AU - Jun, Dae Won

AU - Nguyen, Mindie H.

PY - 2024/3

Y1 - 2024/3

N2 - Background & Aims: It is unclear if there may be sex differences in response to nucleos(t)ide analogs including virologic response (VR), biochemical response (BR), complete response (CR), and hepatocellular carcinoma (HCC) incidence among hepatitis B patients. We compared nucleos(t)ide analog treatment outcomes by sex. Methods: We performed a retrospective cohort study of 3388 treatment-naïve adult hepatitis B patients (1250 female, 2138 male) from the Real-World Evidence from the Global Alliance for the Study of Hepatitis B Virus consortium who initiated therapy with either entecavir or tenofovir from 22 sites (Argentina, Korea, Japan, Taiwan, and the United States). We used propensity-score matching to balance background characteristics of the male and female groups and competing-risks analysis to estimate the incidence and subdistribution hazard ratios (SHRs) of VR, BR, CR, and HCC. Results: Females (vs males) were older (52.0 vs 48.6 y); less likely to be overweight/obese (49.3% vs 65.7%), diabetic (9.9% vs 13.1%), or cirrhotic (27.9% vs 33.0%); and had a lower HBV DNA level (5.9 vs 6.0 log10 IU/mL) and alanine aminotransferase level (91 vs 102 IU/L) (all P < .01). However, after propensity-score matching, relevant background characteristics were balanced between the 2 groups. Females (vs males) had similar 5-year cumulative VR (91.3% vs 90.3%; P = .40) and HCC incidence rates (5.1% vs 4.4%; P = .64), but lower BR (84.0% vs 90.9%; P < .001) and CR (78.8% vs 83.4%; P = .016). Males were more likely to achieve BR (SHR, 1.31; 95% CI, 1.17–1.46; P < .001) and CR (SHR, 1.16; 95% CI, 1.03–1.31; P = .016), but VR and HCC risks were similar. Conclusions: Sex differences exist for treatment outcomes among hepatitis B patients. Male sex was associated with a 16% higher likelihood of clinical remission and a 31% higher likelihood of biochemical response than females, while virologic response and HCC incidence were similar between the 2 groups.

AB - Background & Aims: It is unclear if there may be sex differences in response to nucleos(t)ide analogs including virologic response (VR), biochemical response (BR), complete response (CR), and hepatocellular carcinoma (HCC) incidence among hepatitis B patients. We compared nucleos(t)ide analog treatment outcomes by sex. Methods: We performed a retrospective cohort study of 3388 treatment-naïve adult hepatitis B patients (1250 female, 2138 male) from the Real-World Evidence from the Global Alliance for the Study of Hepatitis B Virus consortium who initiated therapy with either entecavir or tenofovir from 22 sites (Argentina, Korea, Japan, Taiwan, and the United States). We used propensity-score matching to balance background characteristics of the male and female groups and competing-risks analysis to estimate the incidence and subdistribution hazard ratios (SHRs) of VR, BR, CR, and HCC. Results: Females (vs males) were older (52.0 vs 48.6 y); less likely to be overweight/obese (49.3% vs 65.7%), diabetic (9.9% vs 13.1%), or cirrhotic (27.9% vs 33.0%); and had a lower HBV DNA level (5.9 vs 6.0 log10 IU/mL) and alanine aminotransferase level (91 vs 102 IU/L) (all P < .01). However, after propensity-score matching, relevant background characteristics were balanced between the 2 groups. Females (vs males) had similar 5-year cumulative VR (91.3% vs 90.3%; P = .40) and HCC incidence rates (5.1% vs 4.4%; P = .64), but lower BR (84.0% vs 90.9%; P < .001) and CR (78.8% vs 83.4%; P = .016). Males were more likely to achieve BR (SHR, 1.31; 95% CI, 1.17–1.46; P < .001) and CR (SHR, 1.16; 95% CI, 1.03–1.31; P = .016), but VR and HCC risks were similar. Conclusions: Sex differences exist for treatment outcomes among hepatitis B patients. Male sex was associated with a 16% higher likelihood of clinical remission and a 31% higher likelihood of biochemical response than females, while virologic response and HCC incidence were similar between the 2 groups.

KW - Antiviral Therapy

KW - Biochemical Response

KW - Complete Response

KW - Virologic Response

UR - https://www.scopus.com/pages/publications/85175712353

U2 - 10.1016/j.cgh.2023.09.002

DO - 10.1016/j.cgh.2023.09.002

M3 - Article

C2 - 37734582

AN - SCOPUS:85175712353

SN - 1542-3565

VL - 22

SP - 572-580.e5

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

IS - 3

ER -

Sex Differences in Treatment Response to Nucleos(t)ide Therapy in Chronic Hepatitis B: A Multicenter Longitudinal Study

Abstract

UN SDGs

Keywords

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