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Impact of tenofovir alafenamide vs. entecavir on hepatocellular carcinoma risk in patients with chronic hepatitis B

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Abstract

Background and aims

Whether entecavir (ETV) or tenofovir alafenamide (TAF) is better at preventing hepatocellular carcinoma (HCC) development among patients with chronic hepatitis B (CHB) remains unclear. The present study was conducted to explore the ability of these two antivirals to prevent HCC.

Methods

From 2012 to 2019, treatment-naïve CHB patients undergoing ETV or TAF therapy were recruited at three academic teaching hospitals. The TAF group comprised patients starting TAF as first-line antiviral and those switching antivirals from tenofovir disoproxil fumarate to TAF. Patients with decompensated cirrhosis or HCC at enrollment were excluded from the analysis. Cumulative probabilities of HCC were assessed using the Kaplan–Meier method.

Results

In total, 1810 patients (1525 and 285 in ETV and TAF groups, respectively) were recruited. The annual HCC incidence was statistically not different between the ETV and TAF groups (1.67 vs. 1.19 per 100 person-years, respectively) with an adjusted hazard ratio (HR) of 0.681 (p = 0.255), as determined by multivariate analysis. Male, hypertension, liver cirrhosis, FIB-4 index, and albumin were independent prognostic factors for HCC development. Propensity score-matched and inverse probability of treatment weighting analyses yielded similar results, with non-statistically different HCC incidence between the ETV and TAF groups (1.07 vs. 1.19 per 100 person-years (HR = 0.973; p = 0.953) and 1.67 vs. 1.89 per 100 person-years, respectively (HR = 0.949; p = 0.743).

Conclusions

These findings suggest that ETV- and TAF-treated CHB patients have similar risk of developing HCC. Further studies with the larger sample size and longer follow-up are needed to validate these results.

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Abbreviations

HBV:

Hepatitis B virus

CHB:

Chronic hepatitis B

HCC:

Hepatocellular carcinoma

NUC:

Nucleos(t)ide analogue

ETV:

Entecavir

TDF:

Tenofovir disoproxil fumarate

TAF:

Tenofovir alafenamide

HR:

Hazard ratio

PS:

Propensity scores

HBeAg:

Hepatitis B e-antigen

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

IPTW:

Inverse probability of treatment weighting

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Funding

This study was supported by a faculty research grant of Yonsei University College of Medicine for (6-2020-0130).

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Author notes

  1. Hye Won Lee and Young Youn Cho have equally contributed to this work as a co-first author.

  2. Beom Kyung Kim and Soo Young Park have equally contributed to this work as a co-corresponding author.

Authors and Affiliations

  1. Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea

    Hye Won Lee, Jae Seung Lee, Seung Up Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn & Beom Kyung Kim

  2. Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea

    Hye Won Lee, Jae Seung Lee, Seung Up Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn & Beom Kyung Kim

  3. Yonsei Liver Center, Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea

    Hye Won Lee, Hyein Lee, Jae Seung Lee, Seung Up Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn & Beom Kyung Kim

  4. Department of Internal Medicine, Chung Ang University College of Medicine, Seoul, Korea

    Young Youn Cho

  5. Department of Internal Medicine, Kyungpook National University School of Medicine, 130 Dongdeok-ro, Jung-gu, Daegu, 41944, Republic of Korea

    Soo Young Park

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Contributions

HWL, HL, and BKK conducted statistical analyses, and all authors interpreted the findings. HWL, YYC, BKK, and SYP drafted the manuscript. HL, JSL, SUK, JYP, DYK, and SHA critically reviewed the manuscript for key intellectual content. All authors approved the final manuscript. BKK and SYP are the guarantors, and as such, had full access to the data and take responsibility for its integrity and accuracy.

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Correspondence to Beom Kyung Kim or Soo Young Park.

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The study protocol was consistent with the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Institutional Review Board of each participating institution.

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Lee, H.W., Cho, Y.Y., Lee, H. et al. Impact of tenofovir alafenamide vs. entecavir on hepatocellular carcinoma risk in patients with chronic hepatitis B. Hepatol Int 15, 1083–1092 (2021). https://doi.org/10.1007/s12072-021-10234-2

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