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Direct-Acting Antivirals Improve Treatment Outcomes in Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma Treated with Transarterial Chemoembolization: A Nationwide, Multi-center, Retrospective Cohort Study

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Abstract

Background and Aims

The influence of direct-acting antivirals (DAAs) on chronic hepatitis C (CHC)-related hepatocellular carcinoma (HCC) remains controversial. We investigated the effect of eradicating CHC using DAAs on treatment outcomes in patients with CHC-related HCC treated with transarterial chemoembolization (TACE).

Methods

This nationwide, multi-center, retrospective study recruited patients with CHC-related HCC treated with TACE as the first-line anti-cancer treatment, and who achieved a sustained virological response (SVR) using DAAs (DAA group) between 2006 and 2017. Patients achieving an SVR following interferon-based treatment (IFN group) and those without treatment (control group) were also recruited for comparison.

Results

A total of 425 patients were eligible for the study. Of these, 356 (83.8%), 26 (6.1%), and 43 (10.1%) were allocated to the control, IFN, and DAA groups, respectively. A multivariate analysis showed that liver cirrhosis, segmental portal vein thrombosis, and larger maximal tumor size independently predicted an increased risk of progression (all p < 0.05), whereas, the DAA group (vs. IFN and control groups) independently predicted a reduced risk of progression (hazard ratio (HR) = 0.630, 95% confidence interval 0.411–0.966, p = 0.034). The cumulative incidence rate of HCC progression in the DAA group was significantly lower than that in the IFN and control groups (p = 0.033, log-rank test). In addition, the DAA group (vs. IFN and control groups) was independently associated with a reduced risk of mortality (p = 0.042).

Conclusions

DAA treatment provided significantly prolonged progression-free survival in patients with CHC-related HCC treated with TACE compared to that in patients administered IFN or no treatment.

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Abbreviations

DAA:

Direct-acting antiviral

CHC:

Chronic hepatitis C

HCC:

Hepatocellular carcinoma

TACE:

Transarterial chemoembolization

SVR:

Sustained virological response

IFN:

Interferon-based treatment

HCV:

Hepatitis C virus

HR:

Hazard ratio

AFP:

Alpha-fetoprotein

DCP:

Des-gamma-carboxy-prothrombin

mRECIST:

The modified response evaluation criteria in solid tumors

CR:

Complete response

PR:

Partial response

SD:

Stable disease

AVT:

Antiviral treatment

AST:

Aspartate aminotransferase

ALT:

Alanine aminotransferase

BCLC:

Barcelona Clinic Liver Cancer

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Funding

This study was supported by the 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 the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Author notes

  1. Dong Hyun Sinn and Seung Up Kim have contributed equally to this work.

Authors and Affiliations

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

    Hye Kyung Hyun, Chan Sik An, Hyung Jin Rhee, Hyun Woong Lee, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han & Seung Up Kim

  2. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea

    Eun Ju Cho, Jeong-Hoon Lee, Su Jong Yu, Yoon Jun Kim & Jung-Hwan Yoon

  3. Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

    Soo Young Park, Won Young Tak & Young Oh Kweon

  4. Department of Internal Medicine, Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea

    Young Mi Hong, Ki Tae Yoon & Mong Cho

  5. Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea

    Soon Sun Kim & Jae Youn Cheong

  6. Department of Internal Medicine, College of Medicine, Ewha Woman University, Seoul, Republic of Korea

    Hwi Young Kim

  7. Departments of Internal Medicine, Inje University College of Medicine, Busan, Republic of Korea

    Nae-Yun Heo & Seung Ha Park

  8. Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Republic of Korea

    Jung Gil Park

  9. Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea

    Dong Hyun Sinn & Wonseok Kang

  10. Department of Internal Medicine, Soonchunhyang University Hospital Seoul, Soonchunhyang University College of Medicine, Seoul, Republic of Korea

    Song Won Jeong

  11. Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    Myeong Jun Song

  12. Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea

    Hana Park & Danbi Lee

  13. Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea

    Yong Sun Lee

  14. Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea

    Sung Bum Cho

Authors
  1. Hye Kyung Hyun
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Consortia

The Korean TACE Study Group

Contributions

Conception and design were contributed by Hye Kyung Hyun, Eun Ju Cho, Dong Hyun Sinn, and Seung Up Kim. Development of methodology was contributed by Hye Kyung Hyun, Eun Ju Cho, Dong Hyun Sinn, and Seung Up Kim. Acquisition, analysis and interpretation of data were contributed by Hye Kyung Hyun, Eun Ju Cho, Soo Young Park, Young Mi Hong, Soon Sun Kim, Hwi Young Kim, Nae-Yun Heo, Jung Gil Park, Dong Hyun Sinn, Wonseok Kang, Song Won Jeong, Myeong Jun Song, Hana Park, Danbi Lee, Yong Sun Lee, Sung Bum Cho, Chan Sik An, Hyung Jin Rhee, Hyun Woong Lee, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han, Jeong-Hoon Lee, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon, Won Young Tak, Young Oh Kweon, Ki Tae Yoon, Mong Cho, Jae Youn Cheong, Seung Ha Park, Seung Up Kim. Writing, review, and/or revision of the manuscript was contributed by Hye Kyung Hyun, Eun Ju Cho, Dong Hyun Sinn, and Seung Up Kim. Administrative, technical, or material support was contributed by Hye Kyung Hyun, Eun Ju Cho, Dong Hyun Sinn, and Seung Up Kim. Study supervision was contributed by Dong Hyun Sinn and Seung Up Kim.

Corresponding author

Correspondence to Seung Up Kim.

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Hyun, H.K., Cho, E.J., Park, S.Y. et al. Direct-Acting Antivirals Improve Treatment Outcomes in Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma Treated with Transarterial Chemoembolization: A Nationwide, Multi-center, Retrospective Cohort Study. Dig Dis Sci 66, 2427–2438 (2021). https://doi.org/10.1007/s10620-020-06533-7

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