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HCC risk post-SVR with DAAs in East Asians: findings from the REAL-C cohort

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Abstract

Background

Despite HCV cure, patients remain at risk for HCC, but risk factor data for HCC following SVR are limited for Asian patients.

Methods

To address this gap, we analyzed 5814 patients (5646 SVR, 168 non-SVR) from the Real-World Evidence from the Asia Liver Consortium for HCV (REAL-C) who did not have HCC or a history of HCC at baseline (pre-DAA treatment) and did not develop HCC within 6 months of baseline. To assess the effect of SVR on HCC incidence, we used 1:4 propensity score matching [(PSM), age, sex, baseline cirrhosis, and baseline AFP] to balance the SVR and non-SVR groups.

Results

In the PSM cohort (160 non-SVR and 612 SVR), the HCC incidence rate per 100 person years was higher in the non-SVR compared to the SVR group (5.26 vs. 1.94, p < 0.001). Achieving SVR was independently associated with decreased HCC risk (adjusted HR [aHR]: 0.41, p = 0.002). Next, we stratified the SVR cohort of 5646 patients to cirrhotic and noncirrhotic subgroups. Among cirrhotic SVR patients, aged ≥ 60, having an albumin bilirubin grade (ALBI) of 2 or 3 (aHR: 2.5, p < 0.001), and baseline AFP ≥ 10 ng/mL (aHR: 1.6, p = 0.001) were associated with higher HCC risk, while among the non-cirrhotic SVR group, only baseline AFP ≥ 10 ng/mL was significant (aHR: 4.26, p = 0.005).

Conclusions

Achieving SVR decreases HCC risk; however, among East Asians, patients with elevated pretreatment AFP remained at risk. Pretreatment AFP, an easily obtained serum marker, may provide both prognostic and surveillance value for HCC in East Asian patients who obtained SVR.

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Abbreviations

HCV:

Hepatitis C virus

HCC:

Hepatocellular carcinoma

REAL-C:

Real-World Evidence from the Asia Liver Consortium for HCV

DAA:

Direct acting antiviral

ALBI:

Albumin-bilirubin

PSM:

Propensity score matching

AFP:

Alpha-fetoprotein

SVR:

Sustained virologic response

HR:

Hazard ratio

CI:

Confidence interval

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Acknowledgements

The members of the REAL-C Investigators are: Koichi Azuma: Department of Medicine, Kyushu Central Hospital, Fukuoka, Japan; Wan-Long Chuang: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital; Hepatitis Research Center, College of Medicine and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; Chia-Yen Dai: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital; Hepatitis Research Center, College of Medicine and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; Kazufumi Dohmen: Department of Internal Medicine, Chihaya Hospital, Fukuoka, Japan; Jee-Fu Huang: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital; Hepatitis Research Center, College of Medicine and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; Mi Jung Jun: Department of Gastroenterology, Good Gang-An Hospital, Busan, Korea; Eiji Kajiwara: Kajiwara Clinic, Kitakyushu, Japan; Masaki Kato: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Akira Kawano: Department of Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan; Toshimasa Koyanagi: Department of Medicine, Fukuoka City Hospital, Fukuoka, Japan; Mei-Hsuan Lee: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Aritsune Ooho: Department of Hepatology, Steel Memorial Yawata Hospital, Kitakyushu, Japan; Takeaki Satoh: Center for Liver Disease, National Hospital Organization Kokura Medical Center, Kitakyushu, Japan; Shinji Shimoda: Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Kazuhiro Takahashi: Department of Medicine, Hamanomachi Hospital, Fukuoka, Japan; Hwai-I Yang: Genomics Research Center, Academia Sinica, Taipei, Taiwan.

Funding

This study was supported in part by an investigator-initiated research grant to Stanford University by Gilead Sciences and ML Yu wishes to acknowledge partial support for work performed at Kaohsiung Medical University by Kaohsiung Medical University Grant KMUDK109002, Research Center Grant, Cohort Research Center KMU-TC108B07 and Center of Cancer Research KMU-TCA04-3.

Author information

Authors and Affiliations

  1. Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    Yasuhito Tanaka & Etsuko Iio

  2. Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan

    Eiichi Ogawa & Norihiro Furusyo

  3. Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

    Chung-Feng Huang, Ming-Lun Yeh, Pei-Chien Tsai & Ming-Lung Yu

  4. Hepatitis Research Center, College of Medicine and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan

    Chung-Feng Huang, Ming-Lun Yeh, Pei-Chien Tsai & Ming-Lung Yu

  5. Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan

    Hidenori Toyoda & Satoshi Yasuda

  6. Department of Gastroenterology, Hanyang University, Seoul, South Korea

    Dae Won Jun

  7. Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung, Taiwan

    Cheng-Hao Tseng & Yao-Chun Hsu

  8. Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan

    Masaru Enomoto & Akihiro Tamori

  9. Liver Center, Saga University Hospital, Saga, Japan

    Hirokazu Takahashi & Yuichiro Eguchi

  10. Division of Metabolism and Endocrinology, Saga University Faculty of Medicine, Saga, Japan

    Hirokazu Takahashi

  11. Department of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong

    Carla Pui-Mei Lam & Man-Fung Yuen

  12. State Key Laboratory of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong

    Man-Fung Yuen

  13. Department of Gastroenterology, Good Gang-An Hospital, Busan, Korea

    Dong Hyun Lee

  14. Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan

    Hiroaki Haga & Yoshiyuki Ueno

  15. Department of Internal Medicine, Inje University Sanggye Paik Hospital, Seoul, South Korea

    Eileen L. Yoon

  16. Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University College of Medicine, Seoul, South Korea

    Sang Bong Ahn

  17. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong

    Grace Wong

  18. State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, Hong Kong

    Grace Wong

  19. Department of Gastroenterology, Kyushu Medical Center, National Hospital Organization, Fukuoka, Japan

    Makoto Nakamuta

  20. Department of Internal Medicine, Haradoi Hospital, Fukuoka, Japan

    Hideyuki Nomura

  21. Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, South Korea

    Jang Han Jung

  22. Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea

    Do Seon Song

  23. Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, 780 Welch Road, Palo Alto, CA, 94304, USA

    Hansen Dang, Mayumi Maeda, Linda Henry, Ramsey Cheung & Mindie H. Nguyen

  24. Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA

    Ramsey Cheung

  25. Kyushu General Internal Medicine, Haradoi Hospital, Fukuoka, Japan

    Jun Hayashi

Authors
  1. Yasuhito Tanaka
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  2. Eiichi Ogawa
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  3. Chung-Feng Huang
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  4. Hidenori Toyoda
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  5. Dae Won Jun
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  6. Cheng-Hao Tseng
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  7. Yao-Chun Hsu
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  8. Masaru Enomoto
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  9. Hirokazu Takahashi
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  10. Norihiro Furusyo
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  11. Ming-Lun Yeh
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  12. Etsuko Iio
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  13. Satoshi Yasuda
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  14. Carla Pui-Mei Lam
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  15. Dong Hyun Lee
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  16. Hiroaki Haga
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  18. Sang Bong Ahn
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  19. Grace Wong
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  20. Makoto Nakamuta
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  21. Hideyuki Nomura
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  22. Pei-Chien Tsai
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  23. Jang Han Jung
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  30. Yoshiyuki Ueno
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  31. Yuichiro Eguchi
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  33. Ming-Lung Yu
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  34. Jun Hayashi
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  35. Mindie H. Nguyen
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Consortia

For the REAL-C Investigators

  • Koichi Azuma
  • , Wan-Long Chuang
  • , Chia-Yen Dai
  • , Kazufumi Dohmen
  • , Jee-Fu Huang
  • , Mi Jung Jun
  • , Eiji Kajiwara
  • , Masaki Kato
  • , Akira Kawano
  • , Toshimasa Koyanagi
  • , Mei-Hsuan Lee
  • , Aritsune Ooho
  • , Takeaki Satoh
  • , Shinji Shimoda
  • , Kazuhiro Takahashi
  •  & Hwai-I. Yang

Contributions

Study concept and study supervision: MHN. Study design: MHN, YT. Data analysis: HD, MHN. Drafting of the manuscript: MHN, LH, HD, YT, RC. Data collection, data interpretation, critical review/revision of the manuscript: all authors.

Corresponding author

Correspondence to Mindie H. Nguyen.

Ethics declarations

Conflict of interest

YT: Research support: Janssen, Gilead, Speaker: Gilead. CFH: Speaker: AbbVie, BMS, Gilead, Merck. YCH: Research support: Gilead, Consultation: Gilead, Speaker: AbbVie, Bristol-Myers Squibb and Gilead. ME: Speaker: AbbVie. DHL: Research support: Gilead Sciences Korea, Korea Pharma. GW: Research support: Gilead, Consultation: Gilead, Speaker: Abbott, AbbVie, BMS, Echosens, Furui, Gilead, Janssen and Roche, Research grant: Gilead. MFY: Consultation: AbbVie, Arbutus Biopharma, Assembly Biosciences, Bristol Myer Squibb, Dicerna Pharmaceuticals, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, Clear B Therapeutics, Springbank Pharmaceutical. YU: Research support: Gilead, AbbVie, Governmental funding for research: AMED. YE: Speaker: Gilead. MLY: Research support: Abbott, BMS, Gilead and Merck, Consultant and/or an advisory board: Abbvie, Abbott, Ascletis, BMS, Gilead and Merck, Speaker: Abbvie, Abbott, BMS, Gilead, Merck, and IPSEN. WLC: Consultation: Gilead, AbbVie, BMS, MSD, PharmaEssentia, Speaker: Gilead, AbbVie, BMS, MSD, PharmaEssentia. CYD: Consultation: Abbvie, Speaker: AbbVie, Merck, BMS, and Gilead. MHL: Research support: The Ministry of Science and Technology, Taipei, Taiwan (105-2628-B010-003-MY4, 107-2314-B-010-004-MY2 and 107-2918-I-010-004), Consultation: Gilead. MHN: Research support: Enanta, Gilead, Pfizer, B.K. Kee Foundation, National Cancer Institute. Consultant and/or an advisory board: Novartis, Bayer, Eisai, Intercept, Gilead, Janssen, Laboratory of Advanced Medicine, Exact Sciences, and Intercept. All other authors have nothing to disclose.

Statement of ethics

The study was conducted in accordance with the ethics principles of the Declaration of Helsinki in 1975, as revised in 2008, and was approved by the Institutional Review Board of Stanford University, Stanford, California, USA and at each participating study center.

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The members of the REAL-C Investigators are listed in “Acknowledgements”.

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Tanaka, Y., Ogawa, E., Huang, CF. et al. HCC risk post-SVR with DAAs in East Asians: findings from the REAL-C cohort. Hepatol Int 14, 1023–1033 (2020). https://doi.org/10.1007/s12072-020-10105-2

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  • DOI: https://doi.org/10.1007/s12072-020-10105-2

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