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Renal safety of tenofovir disoproxil fumarate and entecavir in liver transplant patients: a nationwide Korean registry study

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Abstract

Background and aims

Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) have been recommended after liver transplantation to prevent recurrence of hepatitis B virus infection. Despite its proven efficacy, the renal safety of TDF has not been established in liver transplant recipients. We aimed to compare the effects of TDF and ETV on renal function in liver transplant recipients and to evaluate risk factors for renal dysfunction after liver transplantation.

Methods

This is a retrospective, observational multicenter study of data from the Korean Organ Transplantation Registry. We included adults who underwent liver transplantation for hepatitis B virus-related complications from April 2014 to December 2017 and received TDF or ETV post-transplantation. Renal dysfunction was defined as an estimated glomerular filtration rate decline by at least 20% from baseline (1 month post-transplantation). Median duration of follow-up was 29 months (interquartile range 19–42).

Results

A total of 804 liver transplant patients were included. The cumulative probability of renal dysfunction was significantly higher in the TDF group than in the ETV group. Multivariable analysis confirmed that TDF was independently associated with an increased risk of renal dysfunction (hazard ratio = 1.47, 95% confidence interval 1.12–1.92; p = 0.005). Independent risk factors for renal dysfunction included older age, worse baseline renal function, and low body mass index. Overall survival rate was significantly lower in patients with renal dysfunction than in those without.

Conclusions

In this nationwide study, the use of TDF was associated with an increased risk of renal dysfunction, when compared with ETV.

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Availability of data and material

The data that support the findings of this study are available from the corresponding author upon seasonable request.

Abbreviations

BMI:

Body mass index

CI:

Confidence interval

eGFR:

Estimated glomerular filtration rate

ETV:

Entecavir

HBIG:

Hepatitis B immune globulin

HBV:

Hepatitis B virus

HIV:

Human immunodeficiency virus

HR:

Hazard ratio

IQR:

Interquartile range

KOTRY:

Korean Organ Transplantation Registry

LT:

Liver transplantation

MELD:

Model for end-stage liver disease

MELD Na:

Model for end-stage liver disease sodium

MMF:

Mycophenolate mofetil

NAs:

Nucleos(t)ide analogues

TAF:

Tenofovir alafenamide fumarate

TDF:

Tenofovir disoproxil fumarate

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Funding

This research was supported by a fund (#2014-ER6301-00, 2014-ER6301-01, 2014-ER6301-02, 2017-ER6301-00, 2017-ER6301-01) by the Research of Korea Centers for Disease Control and Prevention Agency.

Author information

Authors and Affiliations

  1. Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea

    Juhan Lee, Jae Geun Lee & Myoung Soo Kim

  2. Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

    Shin Hwang

  3. Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea

    Kwang-Woong Lee

  4. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

    Jong Man Kim

  5. Division of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation, Department of Surgery, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Republic of Korea

    Je Ho Ryu

  6. Department of Liver Transplantation and Hepatobiliary Surgery, Ajou University School of Medicine, Suwon, Republic of Korea

    Bong-Wan Kim

  7. Department of Surgery, Catholic University of Daegu College of Medicine, Daegu, Republic of Korea

    Dong Lak Choi

  8. Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    Young Kyoung You

  9. Division of HBP Surgery & Liver Transplantation, Department of Surgery, Korea University College of Medicine, Seoul, Republic of Korea

    Dong-Sik Kim

  10. Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea

    Yang Won Nah

  11. Department of Surgery, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Republic of Korea

    Koo Jeong Kang

  12. Department of Surgery, Seoul National University Bundang Hospital, Seongnam, Republic of Korea

    Jai Young Cho

  13. Department of Surgery, Jeonbuk National University Medical School, Jeonju, Republic of Korea

    Hee Chul Yu

  14. Department of Surgery, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Republic of Korea

    Geun Hong

  15. Department of Surgery, Hanyang University College of Medicine, Seoul, Republic of Korea

    Dongho Choi

  16. Department of Surgery, Konyang University Hospital, Konyang University College of Medicine, Daejeon, Republic of Korea

    Ju Ik Moon

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  1. Juhan Lee
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Contributions

JL, JGL, and MSK involved in study concept and design. JL and MSK drafted the manuscript. All authors interpreted the data and critically revised the manuscript for important intellectual content. All authors approved the final manuscript.

Corresponding author

Correspondence to Myoung Soo Kim.

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Conflict of interest

Juhan Lee, Jae Geun Lee, Shin Hwang, Kwang-Woong Lee, Jong Man Kim, Je Ho Ryu, Bong-Wan Kim, Dong Lak Choi, Young Kyoung You, Dong-Sik Kim, Yang Won Nah, Koo Jeong Kang, Jai Young Cho, Hee Chul Yu, Geun Hong, Dongho Choi, Ju Ik Moon, Myoung Soo Kim declare no conflict of interest.

Ethics approval

The study protocol was approved by the institutional review boards of Severance Hospital (2019-2303-001).

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

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All authors approved the manuscript for publication.

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Lee, J., Lee, J.G., Hwang, S. et al. Renal safety of tenofovir disoproxil fumarate and entecavir in liver transplant patients: a nationwide Korean registry study. Hepatol Int 16, 537–544 (2022). https://doi.org/10.1007/s12072-022-10320-z

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