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

JHEP Rep. 2023 Jul 13;5(10):100847. doi: 10.1016/j.jhepr.2023.100847. eCollection 2023 Oct.

Authors

Young-Suk Lim¹, Henry L Y Chan², Sang Hoon Ahn³, Wai Kay Seto⁴, Qin Ning⁵, Kosh Agarwal⁶, Harry L A Janssen^{7

8}, Calvin Q Pan⁹, Wan Long Chuang¹⁰, Namiki Izumi¹¹, Scott Fung¹², Shalimar¹³, Maurizia Brunetto¹⁴, Aric Josun Hui¹⁵, Ting-Tsung Chang¹⁶, Seng Gee Lim¹⁷, Frida Abramov¹⁸, John F Flaherty¹⁸, Hongyuan Wang¹⁸, Leland J Yee¹⁸, Jia-Horng Kao¹⁹, Edward Gane²⁰, Jinlin Hou²¹, Maria Buti^{22

23}

Affiliations

¹ Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
² The Chinese University of Hong Kong, Hong Kong.
³ Yonsei University College of Medicine, Seoul, Republic of Korea.
⁴ University of Hong Kong, Hong Kong.
⁵ Tongji Hospital, Tongji Medical College, Wuhan, China.
⁶ Institute of Liver Studies, Kings College Hospital, United Kingdom.
⁷ Toronto Western Hospital, Toronto, ON, Canada.
⁸ Division of Gastroenterology & Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands.
⁹ NYU Langone Health, NYU Grossman School of Medicine, New York, NY, USA.
¹⁰ Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹¹ Musashino Red Cross Hospital, Tokyo, Japan.
¹² Department of Medicine, University of Toronto, Toronto, Canada.
¹³ All India Institute of Medical Sciences, New Delhi, Delhi, India.
¹⁴ University Hospital of Pisa, Pisa, Italy.
¹⁵ Alice Ho Miu Ling Nethersole Hospital, Hong Kong.
¹⁶ National Cheng Kung University Medical College, Tainan, Taiwan.
¹⁷ National University Hospital, Singapore.
¹⁸ Gilead Sciences, Foster City, CA, USA.
¹⁹ National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan.
²⁰ Auckland Clinical Studies, Auckland, New Zealand.
²¹ Nanfang Hospital of Southern Medical University, Guangzhou, China.
²² Hospital Universitario Vall d'Hebron, Barcelona, Spain.
²³ CIBEREHD del Instituto Carlos III., Barcelona, Spain.

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.

Keywords: REACH-B; aMAP; antiviral therapy; incidence; mPAGE-B.

Associated data

ClinicalTrials.gov/NCT01940471
ClinicalTrials.gov/NCT02836249
ClinicalTrials.gov/NCT01940341
ClinicalTrials.gov/NCT02836236