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Efficacy of entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide in treatment-naive hepatitis B patients

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Abstract

Background and aims

Antiviral agents for chronic hepatitis B (CHB) reduced the risk of hepatocellular carcinoma (HCC) development. The outcomes of entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) were compared in patients with CHB.

Methods

Between 2017 and 2019, treatment-naïve patients with CHB treated with ETV, TDF, and TAF were recruited from three Korean tertiary institutes. The cumulative incidences of HCC and orthotopic liver transplantation (OLT) or mortality were calculated and compared using Kaplan–Meier analysis before and after trimatch.

Results

Among recruited 2082 patients, 43 patients developed HCC, whereas 66 developed OLT or mortality. Before trimatch, the cumulative incidence of HCC was statistically similar among patients treated with three antiviral agents (p = 0.340). However, the cumulative probability of OLT or mortality development in patients treated with ETV or TDF was significantly higher than that of patients with TAF before trimatch (all p < 0.05). On multivariate analysis, male sex [hazard ratio (HR) 2.990] and older age (HR 1.044) were independently associated with an increased risk of HCC development, whereas higher platelet count (HR 0.993) was independently associated with a decreased risk (all p < 0.05). The type of antiviral agents did not significantly influence the risk of HCC and OLT or mortality development (all p > 0.05). After trimatch, no significant difference in the cumulative probability for HCC and OLT or mortality according to antiviral agents was found (all p > 0.05).

Conclusions

The outcomes of ETV, TDF, and TAF on the risk of HCC and OLT or mortality were statistically similar in treatment-naïve patients with CHB.

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Availability of data and material

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

CHB:

Chronic hepatitis B

HCC:

Hepatocellular carcinoma

ETV:

Entecavir

TDF:

Tenofovir disoproxil fumarate

TAF:

Tenofovir alafenamide

OLT:

Orthotopic liver transplantation

HR:

Hazard ratio

AVT:

Antiviral therapy

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

HBV:

Hepatitis B virus

IQR:

Interquartile range

HBeAg:

Hepatitis B e antigen

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Funding

This study was funded in part by the grant from Bristol-Myers Squibb (Grant number: MB007-026). In addition, this study was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2019R1A2C4070136). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Internal Medicine, Konyang University College of Medicine, Daejeon, Korea

    Hye Yeon Chon

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

    Sang Hoon Ahn & Seung Up Kim

  3. Department of Internal Medicine, Seoul National University College of Medicine, 101, Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea

    Yoon Jun Kim, Jung-Hwan Yoon & Jeong-Hoon Lee

  4. Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea

    Dong Hyun Sinn

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Contributions

Conception: HYC, DHS, J-HL and SUK; study design: HYC, DHS, J-HL and SUK; participation in patient management and data collection: SHA, YJK, J-HY; contribution to the data acquisition: DHS and J-HL; responsibility for writing the paper: HYC, DHS, J-HL and SUK; statistical analysis: SHA, HYC and SUK. All authors reviewed the paper and approved the final version.

Corresponding authors

Correspondence to Jeong-Hoon Lee, Dong Hyun Sinn or Seung Up Kim.

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None to declare

Ethics approval

The study protocol satisfied the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the institutional review boards of all three institutes.

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The requirement for written informed consent was waived because of the retrospective nature of this study.

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The requirement for written informed consent was waived because of the retrospective nature of this study.

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Supplementary Information

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12072_2021_10262_MOESM1_ESM.tif

Supplementary figure 2. Complete virological response (HBV DNA < 20 IU/mL) and biochemical response (ALT ≤ 40 IU/L) according to antiviral therapy. ETV, entecavir; TDF, tenofovir disoproxil fumarate; TAF, tenofovir alafenamide; HBV, hepatitis B virus. (TIF 573 KB)

Supplementary figure 1. Selection of study population (TIF 629 KB)

Supplementary file3 (DOCX 23 KB)

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Chon, H.Y., Ahn, S.H., Kim, Y.J. et al. Efficacy of entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide in treatment-naive hepatitis B patients. Hepatol Int 15, 1328–1336 (2021). https://doi.org/10.1007/s12072-021-10262-y

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