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Direct-acting antivirals in East Asian hepatitis C patients: real-world experience from the REAL-C Consortium

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Abstract

Background and aims

One-third of the global hepatitis C virus (HCV) burden is found in Asia. Real-world data from diverse East Asian cohorts remain limited. This study addressed the real-world status of direct-acting antiviral (DAA) therapy among patients from East Asia.

Methods

Chronic hepatitis C (CHC) patients from clinical sites in Japan, Taiwan, South Korea, and Hong Kong were recruited in the REAL-C registry, an observational chart review registry. The primary outcome was sustained virologic response (SVR12, HCV RNA PCR < 25 IU/mL 12 week post-therapy).

Results

A total of 6287 CHC patients were enrolled. Compared to other East Asian patients, patients from Japan were older (66.3 vs. 61.5 years, p < 0.0001), had lower body mass indices (22.9 kg/m2 vs. 24.6 kg/m2, p < 0.001), and were more likely to have non-liver malignancy history (12.2% vs. 5.0%, p < 0.001).The overall SVR12 rate was 96.4%, similar to patients both inside and outside Japan (96.6% vs. 96%, p = 0.21). The SVR12 rate ranged from 91.1 to 99.4% except treatment-experienced cirrhotic HCV genotype-1 patients who received daclatasvir/asunaprevir (85.9%) and the treatment-experienced cirrhotic HCV genotype-2 patients treated with sofosbuvir/ribavirin (87%). The overall rate of drug discontinuation was 1.9%, also similar across regions. On multivariate regression analyses, there was no significant association between geographic region and SVR outcomes.

Conclusions

In this large multinational CHC cohort from the East Asia, oral DAAs were highly effective and well tolerated across the region. Policies should encourage treatment for all CHC patients with DAAs in Asia with its heavy burden of HCV.

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Abbreviations

HCV:

Hepatitis C virus

CHC:

Chronic hepatitis C

HCC:

Hepatocellular carcinoma

DAAs:

Direct-acting antivirals

SVR:

Sustained virologic response

GT:

Genotype

ORs:

Odds ratios

CI:

Confidence interval

LDV:

Ledipasvir

SOF:

Sofosbuvir

RBV:

Ribavirin

DCV:

Daclatasvir

ASV:

Asunaprevir

PrOD:

Paritaprevir/ritonavir/ombitasvir/dasabuvir

EBR:

Elbasvir

GZR:

Grazoprevir

GLE:

Glecaprevir

PIB:

Pibrentasvir

VEL:

Velpatasvir

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Acknowledgements

The authors gratefully acknowledge the contributions of the study coordinators and staff from all participating institutions who assisted in the data collection and other logistics for this study.

For the REAL-C Investigators: Sang Bong Ahn: Department of Internal Medicine, Eulji University Seoul Hospital, Seoul, South Korea; Koichi Azuma: Department of Medicine, Kyushu Central Hospital, Fukuoka, Japan; Tzu-Haw Chen: Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; Chia-Yen Dai: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Kazufumi Dohmen: Department of Internal Medicine, Chihaya Hospital, Fukuoka, Japan; Mi Jung Jun: Department of Gastroenterology, Good Gang-An Hospital, Busan, Korea; Jang Han Jung: Department of Internal Medicine, Hallym University Dongtan Sacred Heart Hospital, Hwaseong-si, South 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; 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; Do Seon Song: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea; Hirokazu Takahashi: Liver Center, Saga University Hospital, Saga, Japan; Division of Metabolism and Endocrinology, Saga University Faculty of Medicine, Saga, Japan; Kazuhiro Takahashi: Department of Medicine, Hamanomachi Hospital, Fukuoka, Japan; Pei-Chien Tsai: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Chao-Ming Tseng: Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan; Ming-Lun Yeh: Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Eileen L. Yoon: Department of Internal Medicine, Inje University Sanggye Paik Hospital, Seoul, South Korea—are in alphabetical order.

Funding

This study is supported by an investigator-initiated research grant (IN-US-334-4309) from Gilead Sciences to Stanford University. The authors independently collected data, designed and performed all study analyses, and drafted the manuscript.

Author information

Authors and Affiliations

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

    Chung-Feng Huang, Wan-Long Chuang, Jee-Fu Huang & Ming-Lung Yu

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

    Etsuko Iio & Yasuhito Tanaka

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

    Dae Won Jun

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

    Eiichi Ogawa & Norihiro Furusyo

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

    Hidenori Toyoda, Toshifumi Tada & Satoshi Yasuda

  6. Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan

    Yao-Chun Hsu, Cheng-Hao Tseng, Chi-Ming Tai & Gin-Ho Lo

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

    Hiroaki Haga & Yoshiyuki Ueno

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

    Shinji Iwane & Yuichiro Eguchi

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

    Masaru Enomoto & Akihiro Tamori

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

    Dong Hyun Lee

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

    Grace Wong

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

    Grace Wong

  13. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

    Chen-Hua Liu & Jia-Horng Kao

  14. Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan

    Chen-Hua Liu & Jia-Horng Kao

  15. Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, 750 Welch Road, Suite 210, Palo Alto, CA, 94304, USA

    Ramsey Cheung, Sally Tran, Leslie Kam, Linda Henry & Mindie H. Nguyen

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

    Ramsey Cheung

  17. Kyushu General Internal Medicine Center, Haradoi Hospital, Fukuoka, Japan

    Jun Hayashi

  18. Department of Internal Medicine, Hanyang University College of Medicine, Guri Hospital, Guri, South Korea

    Jae Yoon Jeong

  19. The Center for Liver Disease, Shin-Kokura Hospital, Kitakyushu, Japan

    Hideyuki Nomura

  20. Department of Internal Medicine, Inje University Haeundae Paik Hospital, Busan, South Korea

    Seung Ha Park

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

    Makoto Nakamuta

  22. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan

    Mei-Hsuan Lee

  23. Genomics Research Center, Academia Sinica, Taipei, Taiwan

    Hwai-I Yang

Authors
  1. Chung-Feng Huang
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  2. Etsuko Iio
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  4. Eiichi Ogawa
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  5. Hidenori Toyoda
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  6. Yao-Chun Hsu
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  7. Hiroaki Haga
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  8. Shinji Iwane
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  9. Masaru Enomoto
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  10. Dong Hyun Lee
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  11. Grace Wong
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  12. Chen-Hua Liu
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  13. Toshifumi Tada
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  14. Wan-Long Chuang
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  15. Ramsey Cheung
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  16. Jun Hayashi
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  17. Cheng-Hao Tseng
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  18. Satoshi Yasuda
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  19. Sally Tran
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  20. Leslie Kam
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  21. Linda Henry
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  22. Jae Yoon Jeong
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  23. Hideyuki Nomura
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  24. Seung Ha Park
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  25. Makoto Nakamuta
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  26. Jee-Fu Huang
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  27. Chi-Ming Tai
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  28. Gin-Ho Lo
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  29. Mei-Hsuan Lee
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  30. Hwai-I Yang
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  31. Jia-Horng Kao
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  32. Akihiro Tamori
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  33. Yuichiro Eguchi
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  34. Yoshiyuki Ueno
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  35. Norihiro Furusyo
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  36. Yasuhito Tanaka
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  37. Ming-Lung Yu
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  38. Mindie H. Nguyen
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Consortia

For the REAL-C Investigators

Contributions

Guarantor of the study: NMH. All authors: study design and/or data collection, data analysis and/or interpretation, and critical review and/or revision of the manuscript. Drafting of the manuscript: HCF, TS, KL, HL, CR, MLY, and NMH. Study concept, acquisition of funding, and study supervision: NMH

Corresponding author

Correspondence to Mindie H. Nguyen.

Ethics declarations

Conflict of interest

HT: Speaker for AbbVie and MSD. YCH: Research support from Gilead; advisory board for Gilead; speaker for Abbvie, BMS, Gilead, and Merck Sharp & Dohme. GW: Research support from Gilead; advisory board/consulting for Gilead; speaker for Abbott, Abbvie, BMS, Echosens, Furui, and Gilead. CHL: Research support from Abbvie, Gilead, and MSD; advisory board/consulting for Abbvie, Gilead, and MSD; speaker for Abbvie, Gilead, MSD, and Abbott. WLC: Advisory board for Gilead, Abbvie, MSD, BMS, PharmaEssentia. RC: Research support from Gilead. CYD: Advisory board for Abbvie; speaker for Abbvie, Merck, and Gilead. JHK: Research support from Gilead and BMS; advisory board/consulting for Gilead, Abbvie, BMS, and MSD; speaker for Gilead, Abbvie, MSD, and BMS. YU: Research support from Abbvie, Gilead, and Bayer. NF: Research support from Janssen Pharmaceutical K.K., Bristol-Myers Squibb, Gilead Sciences, Merck Sharp & Dohme, and Abbvie GK; speaker for Bristol-Myers Squibb, Gilead Sciences, Merck Sharp & Dohme, Torii Pharmaceutical Co., Ltd. and Roche Diagnostics K.K. MLY: Research support: Abbvie, BMS, Gilead, Torpedo and Merck; consultant for Abbvie, Abbott, Ascletis, BMS, Gilead, Merck, and PharmaEssentia; speaker for Abbvie, Abbott, Ascletis, BMS, Gilead, and Merck. YT: Research support from Chugai Pharmaceutical, Janssen, and the Japan Agency for Medical Research and Development (AMED); honoraria from Gilead. MHN: Research support from Janssen, Pfizer, Gilead, National Cancer Institute; BK Kee Foundation; advisory board/consulting for Novartis, Gilead, Janssen, Bayer, Eisai, Exact Sciences, Laboratory of Advanced Medicine. All other authors have no relevant conflict of interests to disclose.

Ethical approval

The study was conducted according to the Helsinki Declaration of 1975, as revised in 2008, and was approved by the Institutional Review Board at Stanford University, Stanford, California, USA and participating study centers.

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Huang, CF., Iio, E., Jun, D.W. et al. Direct-acting antivirals in East Asian hepatitis C patients: real-world experience from the REAL-C Consortium. Hepatol Int 13, 587–598 (2019). https://doi.org/10.1007/s12072-019-09974-z

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