Longitudinal renal changes in chronic hepatitis B patients treated with entecavir versus TDF: a REAL-B study

Lung Yi Mak; Joseph Hoang; Dae Won Jun; Chien Hung Chen; Cheng Yuan Peng; Ming Lun Yeh; Sung Eun Kim; Daniel Q. Huang; Jae Yoon Jeong; Eileen Yoon; Hyunwoo Oh; Pei Chien Tsai; Chung Feng Huang; Sang Bong Ahn; Huy Trinh; Qing Xie; Grace L.H. Wong; Masaru Enomoto; Jae Jun Shim; Dong Hyun Lee; Li Liu; Ritsuzo Kozuka; Yong Kyun Cho; Soung Won Jeong; Hyoung Su Kim; Lindsey Trinh; Allen Dao; Rui Huang; Rex Wan Hin Hui; Vivien Tsui; Sabrina Quek; Htet Htet toe Wai Khine; Eiichi Ogawa; Chia Yen Dai; Jee Fu Huang; Ramsey Cheung; Chao Wu; Wan Long Chuang; Seng Gee Lim; Ming Lung Yu; Man Fung Yuen; Mindie H. Nguyen

doi:10.1007/s12072-021-10271-x

Longitudinal renal changes in chronic hepatitis B patients treated with entecavir versus TDF: a REAL-B study

Lung Yi Mak, Joseph Hoang, Dae Won Jun, Chien Hung Chen, Cheng Yuan Peng, Ming Lun Yeh, Sung Eun Kim, Daniel Q. Huang, Jae Yoon Jeong, Eileen Yoon, Hyunwoo Oh, Pei Chien Tsai, Chung Feng Huang, Sang Bong Ahn, Huy Trinh, Qing Xie, Grace L.H. Wong, Masaru Enomoto, Jae Jun Shim, Dong Hyun LeeLi Liu, Ritsuzo Kozuka, Yong Kyun Cho, Soung Won Jeong, Hyoung Su Kim, Lindsey Trinh, Allen Dao, Rui Huang, Rex Wan Hin Hui, Vivien Tsui, Sabrina Quek, Htet Htet toe Wai Khine, Eiichi Ogawa, Chia Yen Dai, Jee Fu Huang, Ramsey Cheung, Chao Wu, Wan Long Chuang, Seng Gee Lim, Ming Lung Yu, Man Fung Yuen, Mindie H. Nguyen

Internal Medicine

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

2 Citations (Scopus)

Abstract

Background and aims: We aimed to compare the longitudinal changes in estimated glomerular filtration rate (eGFR) in chronic hepatitis B (CHB) patients treated with entecavir (ETV) vs. tenofovir disoproxil fumarate (TDF). Methods: This is a retrospective study of 6189 adult treatment-naïve CHB patients initiated therapy with TDF (n = 2482) or ETV (n = 3707) at 25 international centers using multivariable generalized linear modeling (GLM) to determine mean eGFR (mL/min/1.73 m²) and Kaplan–Meier method to estimate incidence of renal impairment (≥ 1 chronic kidney disease [CKD] stage worsening). We also examined above renal changes in matched ETV and TDF patients (via propensity score matching [PSM] on age, sex, diabetes mellitus [DM], hypertension [HTN], cirrhosis, baseline eGFR, and follow-up duration). Results: In the overall cohort (mean age 49.7 years, 66.2% male), the baseline eGFR was higher for TDF vs. ETV group (75.9 vs. 74.0, p = 0.009). PSM yielded 1871 pairs of ETV or TDF patients with baseline eGFR ≥ 60 and 520 pairs for the eGFR < 60 group. GLM analysis of the overall (unmatched) cohort and PSM cohorts revealed lower adjusted mean eGFRs in TDF (vs. ETV) patients (all p < 0.01) during 10 years of follow-up. Among PSM eGFR ≥ 60 patients, the 5-year cumulative incidences of renal impairment were 42.64% for ETV and 48.03% for TDF (p = 0.0023). In multivariable Cox regression, TDF vs. ETV (adjusted HR 1.26, 95% CI 1.11–1.43) was associated with higher risk of worsening renal function. Conclusion: Over the 10-year study follow-up, compared to ETV, TDF was associated with a lower mean eGFR and higher incidence of renal impairment.

Original language	English
Pages (from-to)	48-58
Number of pages	11
Journal	Hepatology International
Volume	16
Issue number	1
DOIs	https://doi.org/10.1007/s12072-021-10271-x
Publication status	Published - Feb 2022

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Hepatology

UN SDGs

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

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10.1007/s12072-021-10271-x

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Mak, L. Y., Hoang, J., Jun, D. W., Chen, C. H., Peng, C. Y., Yeh, M. L., Kim, S. E., Huang, D. Q., Jeong, J. Y., Yoon, E., Oh, H., Tsai, P. C., Huang, C. F., Ahn, S. B., Trinh, H., Xie, Q., Wong, G. L. H., Enomoto, M., Shim, J. J., ... Nguyen, M. H. (2022). Longitudinal renal changes in chronic hepatitis B patients treated with entecavir versus TDF: a REAL-B study. Hepatology International, 16(1), 48-58. https://doi.org/10.1007/s12072-021-10271-x

Mak, LY, Hoang, J, Jun, DW, Chen, CH, Peng, CY, Yeh, ML, Kim, SE, Huang, DQ, Jeong, JY, Yoon, E, Oh, H, Tsai, PC, Huang, CF, Ahn, SB, Trinh, H, Xie, Q, Wong, GLH, Enomoto, M, Shim, JJ, Lee, DH, Liu, L, Kozuka, R, Cho, YK, Jeong, SW, Kim, HS, Trinh, L, Dao, A, Huang, R, Hui, RWH, Tsui, V, Quek, S, Khine, HHTW, Ogawa, E, Dai, CY, Huang, JF, Cheung, R, Wu, C, Chuang, WL, Lim, SG, Yu, ML, Yuen, MF & Nguyen, MH 2022, 'Longitudinal renal changes in chronic hepatitis B patients treated with entecavir versus TDF: a REAL-B study', Hepatology International, vol. 16, no. 1, pp. 48-58. https://doi.org/10.1007/s12072-021-10271-x

@article{8827ad7e0e1443e5ac0ecf61502c2251,

title = "Longitudinal renal changes in chronic hepatitis B patients treated with entecavir versus TDF: a REAL-B study",

abstract = "Background and aims: We aimed to compare the longitudinal changes in estimated glomerular filtration rate (eGFR) in chronic hepatitis B (CHB) patients treated with entecavir (ETV) vs. tenofovir disoproxil fumarate (TDF). Methods: This is a retrospective study of 6189 adult treatment-na{\"i}ve CHB patients initiated therapy with TDF (n = 2482) or ETV (n = 3707) at 25 international centers using multivariable generalized linear modeling (GLM) to determine mean eGFR (mL/min/1.73 m2) and Kaplan–Meier method to estimate incidence of renal impairment (≥ 1 chronic kidney disease [CKD] stage worsening). We also examined above renal changes in matched ETV and TDF patients (via propensity score matching [PSM] on age, sex, diabetes mellitus [DM], hypertension [HTN], cirrhosis, baseline eGFR, and follow-up duration). Results: In the overall cohort (mean age 49.7 years, 66.2% male), the baseline eGFR was higher for TDF vs. ETV group (75.9 vs. 74.0, p = 0.009). PSM yielded 1871 pairs of ETV or TDF patients with baseline eGFR ≥ 60 and 520 pairs for the eGFR < 60 group. GLM analysis of the overall (unmatched) cohort and PSM cohorts revealed lower adjusted mean eGFRs in TDF (vs. ETV) patients (all p < 0.01) during 10 years of follow-up. Among PSM eGFR ≥ 60 patients, the 5-year cumulative incidences of renal impairment were 42.64% for ETV and 48.03% for TDF (p = 0.0023). In multivariable Cox regression, TDF vs. ETV (adjusted HR 1.26, 95% CI 1.11–1.43) was associated with higher risk of worsening renal function. Conclusion: Over the 10-year study follow-up, compared to ETV, TDF was associated with a lower mean eGFR and higher incidence of renal impairment.",

author = "Mak, {Lung Yi} and Joseph Hoang and Jun, {Dae Won} and Chen, {Chien Hung} and Peng, {Cheng Yuan} and Yeh, {Ming Lun} and Kim, {Sung Eun} and Huang, {Daniel Q.} and Jeong, {Jae Yoon} and Eileen Yoon and Hyunwoo Oh and Tsai, {Pei Chien} and Huang, {Chung Feng} and Ahn, {Sang Bong} and Huy Trinh and Qing Xie and Wong, {Grace L.H.} and Masaru Enomoto and Shim, {Jae Jun} and Lee, {Dong Hyun} and Li Liu and Ritsuzo Kozuka and Cho, {Yong Kyun} and Jeong, {Soung Won} and Kim, {Hyoung Su} and Lindsey Trinh and Allen Dao and Rui Huang and Hui, {Rex Wan Hin} and Vivien Tsui and Sabrina Quek and Khine, {Htet Htet toe Wai} and Eiichi Ogawa and Dai, {Chia Yen} and Huang, {Jee Fu} and Ramsey Cheung and Chao Wu and Chuang, {Wan Long} and Lim, {Seng Gee} and Yu, {Ming Lung} and Yuen, {Man Fung} and Nguyen, {Mindie H.}",

note = "Funding Information: CYP: Consulting/ Advisory board member: Abbvie, Bristol Myers Squibb, Gilead Sciences, Roche. DQH: Research grant: Exxon Mobil-NUS Fellowship, NMRC Research Training Fellowship. HT: Research grant: Gilead Sciences, Intercept, Target; Consulting/ advisory board: Gilead Sciences; Speaker fees: Gilead Sciences; Stock ownership: Gilead Sciences. GLHW: Research grant: Gilead Sciences; Consulting/ advisory board: Gilead Sciences, Janssen; Speaker fees: Abbott, Abbvie, Bristol Myers Squibb, Gilead Sciences. DHL: Research grant: Bristol Myers Squibb Korea, Gilead Sciences (Korea), Janssen Korea, Korea Pharma. EO: Speaker fees: Gilead Sciences. CYD: Speaker fees: Abbvie, Merck Sharp and Dohme, Gilead Sciences, Roche, Bristol Myers Squibb. WLC: Consulting: Gilead Sciences, Abbvie, Bristol Myers Squibb, Merck Sharp and Dohme, PharmaEssentia; Speaker fees: Gilead Sciences, Abbvie, Bristol Myers Squibb, Merck Sharp and Dohme, PharmaEssentia. MLY: Research grant: Abbott, Bristol Myers Squibb, Gilead Sciences, Merck Sharp and Dohme; Consulting: Abbvie, Abbott, Ascletis, Bristol Myers Squibb, Gilead Sciences, Merck Sharp and Dohme, Roche; Speaker fees: Abbvie, Abbott, Bristol Myers Squibb, Gilead Sciences, Merck Sharp and Dohme, IPSEN. MFY: Research funding: Assembly Biosciences, Arrowhead Pharmaceuticals, Bristol Myer Squibb, Fujirebio Incorporation, Gilead Sciences, Merck Sharp and Dohme, Springbank Pharmaceuticals, Sysmex Corporation; advisory board member: Abbvie, Arbutus Biopharma, Assembly Biosciences, Bristol Myer Squibb, Dicerna Pharmaceuticals, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, Clear B Therapeutics, Springbank Pharmaceuticals. MHN: Research grant: Gilead, Vir; Consulting/advisory board: Novartis, Spring Bank, Janssen, Gilead, Exact Sciences, Eli Lilly. All other authors have disclosed no personal conflict of interests in regards to the content of this paper. Publisher Copyright: {\textcopyright} 2021, Asian Pacific Association for the Study of the Liver.",

year = "2022",

month = feb,

doi = "10.1007/s12072-021-10271-x",

language = "English",

volume = "16",

pages = "48--58",

journal = "Hepatology International",

issn = "1936-0533",

publisher = "Springer New York",

number = "1",

}

TY - JOUR

T1 - Longitudinal renal changes in chronic hepatitis B patients treated with entecavir versus TDF

T2 - a REAL-B study

AU - Mak, Lung Yi

AU - Hoang, Joseph

AU - Jun, Dae Won

AU - Chen, Chien Hung

AU - Peng, Cheng Yuan

AU - Yeh, Ming Lun

AU - Kim, Sung Eun

AU - Huang, Daniel Q.

AU - Jeong, Jae Yoon

AU - Yoon, Eileen

AU - Oh, Hyunwoo

AU - Tsai, Pei Chien

AU - Huang, Chung Feng

AU - Ahn, Sang Bong

AU - Trinh, Huy

AU - Xie, Qing

AU - Wong, Grace L.H.

AU - Enomoto, Masaru

AU - Shim, Jae Jun

AU - Lee, Dong Hyun

AU - Liu, Li

AU - Kozuka, Ritsuzo

AU - Cho, Yong Kyun

AU - Jeong, Soung Won

AU - Kim, Hyoung Su

AU - Trinh, Lindsey

AU - Dao, Allen

AU - Huang, Rui

AU - Hui, Rex Wan Hin

AU - Tsui, Vivien

AU - Quek, Sabrina

AU - Khine, Htet Htet toe Wai

AU - Ogawa, Eiichi

AU - Dai, Chia Yen

AU - Huang, Jee Fu

AU - Cheung, Ramsey

AU - Wu, Chao

AU - Chuang, Wan Long

AU - Lim, Seng Gee

AU - Yu, Ming Lung

AU - Yuen, Man Fung

AU - Nguyen, Mindie H.

N1 - Funding Information: CYP: Consulting/ Advisory board member: Abbvie, Bristol Myers Squibb, Gilead Sciences, Roche. DQH: Research grant: Exxon Mobil-NUS Fellowship, NMRC Research Training Fellowship. HT: Research grant: Gilead Sciences, Intercept, Target; Consulting/ advisory board: Gilead Sciences; Speaker fees: Gilead Sciences; Stock ownership: Gilead Sciences. GLHW: Research grant: Gilead Sciences; Consulting/ advisory board: Gilead Sciences, Janssen; Speaker fees: Abbott, Abbvie, Bristol Myers Squibb, Gilead Sciences. DHL: Research grant: Bristol Myers Squibb Korea, Gilead Sciences (Korea), Janssen Korea, Korea Pharma. EO: Speaker fees: Gilead Sciences. CYD: Speaker fees: Abbvie, Merck Sharp and Dohme, Gilead Sciences, Roche, Bristol Myers Squibb. WLC: Consulting: Gilead Sciences, Abbvie, Bristol Myers Squibb, Merck Sharp and Dohme, PharmaEssentia; Speaker fees: Gilead Sciences, Abbvie, Bristol Myers Squibb, Merck Sharp and Dohme, PharmaEssentia. MLY: Research grant: Abbott, Bristol Myers Squibb, Gilead Sciences, Merck Sharp and Dohme; Consulting: Abbvie, Abbott, Ascletis, Bristol Myers Squibb, Gilead Sciences, Merck Sharp and Dohme, Roche; Speaker fees: Abbvie, Abbott, Bristol Myers Squibb, Gilead Sciences, Merck Sharp and Dohme, IPSEN. MFY: Research funding: Assembly Biosciences, Arrowhead Pharmaceuticals, Bristol Myer Squibb, Fujirebio Incorporation, Gilead Sciences, Merck Sharp and Dohme, Springbank Pharmaceuticals, Sysmex Corporation; advisory board member: Abbvie, Arbutus Biopharma, Assembly Biosciences, Bristol Myer Squibb, Dicerna Pharmaceuticals, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, Clear B Therapeutics, Springbank Pharmaceuticals. MHN: Research grant: Gilead, Vir; Consulting/advisory board: Novartis, Spring Bank, Janssen, Gilead, Exact Sciences, Eli Lilly. All other authors have disclosed no personal conflict of interests in regards to the content of this paper. Publisher Copyright: © 2021, Asian Pacific Association for the Study of the Liver.

PY - 2022/2

Y1 - 2022/2

N2 - Background and aims: We aimed to compare the longitudinal changes in estimated glomerular filtration rate (eGFR) in chronic hepatitis B (CHB) patients treated with entecavir (ETV) vs. tenofovir disoproxil fumarate (TDF). Methods: This is a retrospective study of 6189 adult treatment-naïve CHB patients initiated therapy with TDF (n = 2482) or ETV (n = 3707) at 25 international centers using multivariable generalized linear modeling (GLM) to determine mean eGFR (mL/min/1.73 m2) and Kaplan–Meier method to estimate incidence of renal impairment (≥ 1 chronic kidney disease [CKD] stage worsening). We also examined above renal changes in matched ETV and TDF patients (via propensity score matching [PSM] on age, sex, diabetes mellitus [DM], hypertension [HTN], cirrhosis, baseline eGFR, and follow-up duration). Results: In the overall cohort (mean age 49.7 years, 66.2% male), the baseline eGFR was higher for TDF vs. ETV group (75.9 vs. 74.0, p = 0.009). PSM yielded 1871 pairs of ETV or TDF patients with baseline eGFR ≥ 60 and 520 pairs for the eGFR < 60 group. GLM analysis of the overall (unmatched) cohort and PSM cohorts revealed lower adjusted mean eGFRs in TDF (vs. ETV) patients (all p < 0.01) during 10 years of follow-up. Among PSM eGFR ≥ 60 patients, the 5-year cumulative incidences of renal impairment were 42.64% for ETV and 48.03% for TDF (p = 0.0023). In multivariable Cox regression, TDF vs. ETV (adjusted HR 1.26, 95% CI 1.11–1.43) was associated with higher risk of worsening renal function. Conclusion: Over the 10-year study follow-up, compared to ETV, TDF was associated with a lower mean eGFR and higher incidence of renal impairment.

AB - Background and aims: We aimed to compare the longitudinal changes in estimated glomerular filtration rate (eGFR) in chronic hepatitis B (CHB) patients treated with entecavir (ETV) vs. tenofovir disoproxil fumarate (TDF). Methods: This is a retrospective study of 6189 adult treatment-naïve CHB patients initiated therapy with TDF (n = 2482) or ETV (n = 3707) at 25 international centers using multivariable generalized linear modeling (GLM) to determine mean eGFR (mL/min/1.73 m2) and Kaplan–Meier method to estimate incidence of renal impairment (≥ 1 chronic kidney disease [CKD] stage worsening). We also examined above renal changes in matched ETV and TDF patients (via propensity score matching [PSM] on age, sex, diabetes mellitus [DM], hypertension [HTN], cirrhosis, baseline eGFR, and follow-up duration). Results: In the overall cohort (mean age 49.7 years, 66.2% male), the baseline eGFR was higher for TDF vs. ETV group (75.9 vs. 74.0, p = 0.009). PSM yielded 1871 pairs of ETV or TDF patients with baseline eGFR ≥ 60 and 520 pairs for the eGFR < 60 group. GLM analysis of the overall (unmatched) cohort and PSM cohorts revealed lower adjusted mean eGFRs in TDF (vs. ETV) patients (all p < 0.01) during 10 years of follow-up. Among PSM eGFR ≥ 60 patients, the 5-year cumulative incidences of renal impairment were 42.64% for ETV and 48.03% for TDF (p = 0.0023). In multivariable Cox regression, TDF vs. ETV (adjusted HR 1.26, 95% CI 1.11–1.43) was associated with higher risk of worsening renal function. Conclusion: Over the 10-year study follow-up, compared to ETV, TDF was associated with a lower mean eGFR and higher incidence of renal impairment.

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JO - Hepatology International

JF - Hepatology International

SN - 1936-0533

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ER -

Longitudinal renal changes in chronic hepatitis B patients treated with entecavir versus TDF: a REAL-B study

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