Tenofovir alafenamide and tenofovir disoproxil fumarate reduce incidence of hepatocellular carcinoma in patients with chronic hepatitis B

Young Suk Lim; Henry L.Y. Chan; Sang Hoon Ahn; Wai Kay Seto; Qin Ning; Kosh Agarwal; Harry L.A. Janssen; Calvin Q. Pan; Wan Long Chuang; Namiki Izumi; Scott Fung; Shalimar; Maurizia Brunetto; Aric Josun Hui; Ting Tsung Chang; Seng Gee Lim; Frida Abramov; John F. Flaherty; Hongyuan Wang; Leland J. Yee; Jia Horng Kao; Edward Gane; Jinlin Hou; Maria Buti

doi:10.1016/j.jhepr.2023.100847

Tenofovir alafenamide and tenofovir disoproxil fumarate reduce incidence of hepatocellular carcinoma in patients with chronic hepatitis B

Young Suk Lim^*
, Henry L.Y. Chan
, Sang Hoon Ahn
, Wai Kay Seto
, Qin Ning
, Kosh Agarwal
, Harry L.A. Janssen
, Calvin Q. Pan
, Wan Long Chuang
, Namiki Izumi
, Scott Fung
, Shalimar
, Maurizia Brunetto
, Aric Josun Hui
, Ting Tsung Chang
, Seng Gee Lim
, Frida Abramov
, John F. Flaherty
, Hongyuan Wang
, Leland J. Yee

Jia Horng Kao, Edward Gane, Jinlin Hou, Maria Buti

^*Corresponding author for this work

Gastroenterology & Hepatology

University of Ulsan
Chinese University of Hong Kong
Yonsei University
The University of Hong Kong
Huazhong University of Science and Technology
King’s College Hospital
New York University School of Medicine
Kaohsiung Medical University
Japanese Red Cross Musashino Hospital
University of Toronto
All India Institute of Medical Sciences, New Delhi
University of Pisa
Alice Ho Miu Ling Nethersole Hospital
National Cheng Kung University
National University Hospital (Singapore)
Gilead Sciences, Inc.
National Taiwan University
Auckland Clinical Studies
Nanfang Hospital
Hospital Vall d'Hebron & ARADyAL research network
Centro de Investigación Biomédica en Red (CIBER)
Toronto Western Hospital

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

25 Citations (Scopus)

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Abstract

Background & Aims:

Antiviral therapy may attenuate the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We aimed to explore how tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) affect HCC risk in patients with CHB.

Methods:

The REACH-B, aMAP, and mPAGE-B models were utilized to assess HCC risk in patients with CHB from two global randomized-controlled trials evaluating the impact of TAF vs. TDF treatment. Standard incidence ratios (SIRs) were calculated using data from the REACH-B model as a ratio of observed HCC cases in the TAF- or TDF-treated patients vs. predicted HCC cases for untreated historical controls. Proportions of treated patients shifting aMAP and mPAGE-B risk categories between baseline and Week 240 were calculated.

Results:

Of the 1,632 patients (TAF, n = 1,093; TDF, n = 539) followed for up to 300 weeks, 22 HCC cases developed. Those receiving TAF had an SIR that was lower compared to the SIR of individuals receiving TDF: 0.32 (p <0.001) vs. 0.56 (p = 0.06). In the general study population, individuals without cirrhosis at baseline had an SIR that was lower compared to the SIR of individuals with cirrhosis at baseline: 0.37 (p <0.001) vs. 0.58 (p = 0.15). Of the patients at low risk of HCC at baseline, the majority (97%) remained low risk by mPAGE-B and aMAP scoring at Week 240. Among those at medium or high risk at baseline, substantial portions shifted to a lower risk category by Week 240 (mPAGE-B: 22% and 42%; aMAP: 39% and 63%, respectively).

Conclusions:

This evaluation provides evidence that treatment with TAF or TDF can reduce HCC risk in patients with CHB, particularly in patients without cirrhosis.

Impact and implications:

Despite the substantial impact of HCC on long-term outcomes of patients with CHB, the differential risk of HCC development among those receiving treatment with TAF vs. TDF has not been well elucidated. Using three validated risk prediction models, we found that TAF is at least as effective as TDF in reducing HCC risk in patients with CHB. While TDF is well-studied in the context of HCC risk reduction, our novel findings underscore the effectiveness of TAF as a treatment option for patients with CHB.

Clinical trial numbers:

NCT01940341; NCT02836249; NCT01940471; NCT02836236.

Original language	English
Article number	100847
Journal	JHEP Reports
Volume	5
Issue number	10
DOIs	https://doi.org/10.1016/j.jhepr.2023.100847
Publication status	Published - Oct 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s)

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

SDG 3 Good Health and Well-being

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Tenofovir alafenamide and tenofovir disoproxil fumarate reduce incidence of hepatocellular carcinoma in patients with chronic hepatitis BFinal published version, 951 KBLicence: CC BY-NC-ND

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Lim, Y. S., Chan, H. L. Y., Ahn, S. H., Seto, W. K., Ning, Q., Agarwal, K., Janssen, H. L. A., Pan, C. Q., Chuang, W. L., Izumi, N., Fung, S., Shalimar, Brunetto, M., Hui, A. J., Chang, T. T., Lim, S. G., Abramov, F., Flaherty, J. F., Wang, H., ... Buti, M. (2023). Tenofovir alafenamide and tenofovir disoproxil fumarate reduce incidence of hepatocellular carcinoma in patients with chronic hepatitis B. JHEP Reports, 5(10), Article 100847. https://doi.org/10.1016/j.jhepr.2023.100847

@article{6168a17354bd4e3dab23cb7b6b696dec,

title = "Tenofovir alafenamide and tenofovir disoproxil fumarate reduce incidence of hepatocellular carcinoma in patients with chronic hepatitis B",

abstract = "Background \& Aims: Antiviral therapy may attenuate the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We aimed to explore how tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) affect HCC risk in patients with CHB. Methods: The REACH-B, aMAP, and mPAGE-B models were utilized to assess HCC risk in patients with CHB from two global randomized-controlled trials evaluating the impact of TAF vs. TDF treatment. Standard incidence ratios (SIRs) were calculated using data from the REACH-B model as a ratio of observed HCC cases in the TAF- or TDF-treated patients vs. predicted HCC cases for untreated historical controls. Proportions of treated patients shifting aMAP and mPAGE-B risk categories between baseline and Week 240 were calculated. Results: Of the 1,632 patients (TAF, n = 1,093; TDF, n = 539) followed for up to 300 weeks, 22 HCC cases developed. Those receiving TAF had an SIR that was lower compared to the SIR of individuals receiving TDF: 0.32 (p <0.001) vs. 0.56 (p = 0.06). In the general study population, individuals without cirrhosis at baseline had an SIR that was lower compared to the SIR of individuals with cirrhosis at baseline: 0.37 (p <0.001) vs. 0.58 (p = 0.15). Of the patients at low risk of HCC at baseline, the majority (97\%) remained low risk by mPAGE-B and aMAP scoring at Week 240. Among those at medium or high risk at baseline, substantial portions shifted to a lower risk category by Week 240 (mPAGE-B: 22\% and 42\%; aMAP: 39\% and 63\%, respectively). Conclusions: This evaluation provides evidence that treatment with TAF or TDF can reduce HCC risk in patients with CHB, particularly in patients without cirrhosis. Impact and implications: Despite the substantial impact of HCC on long-term outcomes of patients with CHB, the differential risk of HCC development among those receiving treatment with TAF vs. TDF has not been well elucidated. Using three validated risk prediction models, we found that TAF is at least as effective as TDF in reducing HCC risk in patients with CHB. While TDF is well-studied in the context of HCC risk reduction, our novel findings underscore the effectiveness of TAF as a treatment option for patients with CHB. Clinical trial numbers: NCT01940341; NCT02836249; NCT01940471; NCT02836236.",

author = "Lim, \{Young Suk\} and Chan, \{Henry L.Y.\} and Ahn, \{Sang Hoon\} and Seto, \{Wai Kay\} and Qin Ning and Kosh Agarwal and Janssen, \{Harry L.A.\} and Pan, \{Calvin Q.\} and Chuang, \{Wan Long\} and Namiki Izumi and Scott Fung and Shalimar and Maurizia Brunetto and Hui, \{Aric Josun\} and Chang, \{Ting Tsung\} and Lim, \{Seng Gee\} and Frida Abramov and Flaherty, \{John F.\} and Hongyuan Wang and Yee, \{Leland J.\} and Kao, \{Jia Horng\} and Edward Gane and Jinlin Hou and Maria Buti",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

month = oct,

doi = "10.1016/j.jhepr.2023.100847",

language = "English",

volume = "5",

journal = "JHEP Reports",

issn = "2589-5559",

publisher = "Elsevier",

number = "10",

}

Lim, YS, Chan, HLY, Ahn, SH, Seto, WK, Ning, Q, Agarwal, K, Janssen, HLA, Pan, CQ, Chuang, WL, Izumi, N, Fung, S, Shalimar, Brunetto, M, Hui, AJ, Chang, TT, Lim, SG, Abramov, F, Flaherty, JF, Wang, H, Yee, LJ, Kao, JH, Gane, E, Hou, J & Buti, M 2023, 'Tenofovir alafenamide and tenofovir disoproxil fumarate reduce incidence of hepatocellular carcinoma in patients with chronic hepatitis B', JHEP Reports, vol. 5, no. 10, 100847. https://doi.org/10.1016/j.jhepr.2023.100847

TY - JOUR

T1 - Tenofovir alafenamide and tenofovir disoproxil fumarate reduce incidence of hepatocellular carcinoma in patients with chronic hepatitis B

AU - Lim, Young Suk

AU - Chan, Henry L.Y.

AU - Ahn, Sang Hoon

AU - Seto, Wai Kay

AU - Ning, Qin

AU - Agarwal, Kosh

AU - Janssen, Harry L.A.

AU - Pan, Calvin Q.

AU - Chuang, Wan Long

AU - Izumi, Namiki

AU - Fung, Scott

AU - Shalimar,

AU - Brunetto, Maurizia

AU - Hui, Aric Josun

AU - Chang, Ting Tsung

AU - Lim, Seng Gee

AU - Abramov, Frida

AU - Flaherty, John F.

AU - Wang, Hongyuan

AU - Yee, Leland J.

AU - Kao, Jia Horng

AU - Gane, Edward

AU - Hou, Jinlin

AU - Buti, Maria

PY - 2023/10

Y1 - 2023/10

N2 - Background & Aims: Antiviral therapy may attenuate the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We aimed to explore how tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) affect HCC risk in patients with CHB. Methods: The REACH-B, aMAP, and mPAGE-B models were utilized to assess HCC risk in patients with CHB from two global randomized-controlled trials evaluating the impact of TAF vs. TDF treatment. Standard incidence ratios (SIRs) were calculated using data from the REACH-B model as a ratio of observed HCC cases in the TAF- or TDF-treated patients vs. predicted HCC cases for untreated historical controls. Proportions of treated patients shifting aMAP and mPAGE-B risk categories between baseline and Week 240 were calculated. Results: Of the 1,632 patients (TAF, n = 1,093; TDF, n = 539) followed for up to 300 weeks, 22 HCC cases developed. Those receiving TAF had an SIR that was lower compared to the SIR of individuals receiving TDF: 0.32 (p <0.001) vs. 0.56 (p = 0.06). In the general study population, individuals without cirrhosis at baseline had an SIR that was lower compared to the SIR of individuals with cirrhosis at baseline: 0.37 (p <0.001) vs. 0.58 (p = 0.15). Of the patients at low risk of HCC at baseline, the majority (97%) remained low risk by mPAGE-B and aMAP scoring at Week 240. Among those at medium or high risk at baseline, substantial portions shifted to a lower risk category by Week 240 (mPAGE-B: 22% and 42%; aMAP: 39% and 63%, respectively). Conclusions: This evaluation provides evidence that treatment with TAF or TDF can reduce HCC risk in patients with CHB, particularly in patients without cirrhosis. Impact and implications: Despite the substantial impact of HCC on long-term outcomes of patients with CHB, the differential risk of HCC development among those receiving treatment with TAF vs. TDF has not been well elucidated. Using three validated risk prediction models, we found that TAF is at least as effective as TDF in reducing HCC risk in patients with CHB. While TDF is well-studied in the context of HCC risk reduction, our novel findings underscore the effectiveness of TAF as a treatment option for patients with CHB. Clinical trial numbers: NCT01940341; NCT02836249; NCT01940471; NCT02836236.

AB - Background & Aims: Antiviral therapy may attenuate the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We aimed to explore how tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) affect HCC risk in patients with CHB. Methods: The REACH-B, aMAP, and mPAGE-B models were utilized to assess HCC risk in patients with CHB from two global randomized-controlled trials evaluating the impact of TAF vs. TDF treatment. Standard incidence ratios (SIRs) were calculated using data from the REACH-B model as a ratio of observed HCC cases in the TAF- or TDF-treated patients vs. predicted HCC cases for untreated historical controls. Proportions of treated patients shifting aMAP and mPAGE-B risk categories between baseline and Week 240 were calculated. Results: Of the 1,632 patients (TAF, n = 1,093; TDF, n = 539) followed for up to 300 weeks, 22 HCC cases developed. Those receiving TAF had an SIR that was lower compared to the SIR of individuals receiving TDF: 0.32 (p <0.001) vs. 0.56 (p = 0.06). In the general study population, individuals without cirrhosis at baseline had an SIR that was lower compared to the SIR of individuals with cirrhosis at baseline: 0.37 (p <0.001) vs. 0.58 (p = 0.15). Of the patients at low risk of HCC at baseline, the majority (97%) remained low risk by mPAGE-B and aMAP scoring at Week 240. Among those at medium or high risk at baseline, substantial portions shifted to a lower risk category by Week 240 (mPAGE-B: 22% and 42%; aMAP: 39% and 63%, respectively). Conclusions: This evaluation provides evidence that treatment with TAF or TDF can reduce HCC risk in patients with CHB, particularly in patients without cirrhosis. Impact and implications: Despite the substantial impact of HCC on long-term outcomes of patients with CHB, the differential risk of HCC development among those receiving treatment with TAF vs. TDF has not been well elucidated. Using three validated risk prediction models, we found that TAF is at least as effective as TDF in reducing HCC risk in patients with CHB. While TDF is well-studied in the context of HCC risk reduction, our novel findings underscore the effectiveness of TAF as a treatment option for patients with CHB. Clinical trial numbers: NCT01940341; NCT02836249; NCT01940471; NCT02836236.

UR - https://www.scopus.com/pages/publications/85172927447

U2 - 10.1016/j.jhepr.2023.100847

DO - 10.1016/j.jhepr.2023.100847

M3 - Article

C2 - 37771546

AN - SCOPUS:85172927447

SN - 2589-5559

VL - 5

JO - JHEP Reports

JF - JHEP Reports

IS - 10

M1 - 100847

ER -

Tenofovir alafenamide and tenofovir disoproxil fumarate reduce incidence of hepatocellular carcinoma in patients with chronic hepatitis B

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