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Hepatology International

, Volume 13, Issue 5, pp 587–598 | Cite as

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

  • Chung-Feng Huang
  • Etsuko Iio
  • Dae Won Jun
  • Eiichi Ogawa
  • Hidenori Toyoda
  • Yao-Chun Hsu
  • Hiroaki Haga
  • Shinji Iwane
  • Masaru Enomoto
  • Dong Hyun Lee
  • Grace Wong
  • Chen-Hua Liu
  • Toshifumi Tada
  • Wan-Long Chuang
  • Ramsey Cheung
  • Jun Hayashi
  • Cheng-Hao Tseng
  • Satoshi Yasuda
  • Sally Tran
  • Leslie Kam
  • Linda Henry
  • Jae Yoon Jeong
  • Hideyuki Nomura
  • Seung Ha Park
  • Makoto Nakamuta
  • Jee-Fu Huang
  • Chi-Ming Tai
  • Gin-Ho Lo
  • Mei-Hsuan Lee
  • Hwai-I Yang
  • Jia-Horng Kao
  • Akihiro Tamori
  • Yuichiro Eguchi
  • Yoshiyuki Ueno
  • Norihiro Furusyo
  • Yasuhito Tanaka
  • Ming-Lung Yu
  • Mindie H. NguyenEmail author
  • For the REAL-C Investigators
Original Article

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.

Keywords

DAA CHC Korea Taiwan Japan Hong Kong 

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

Notes

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.

Author 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

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.

Compliance with ethical standards

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.

Supplementary material

12072_2019_9974_MOESM1_ESM.docx (81 kb)
Supplementary material 1 (DOCX 78 kb)

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Copyright information

© Asian Pacific Association for the Study of the Liver 2019

Authors and Affiliations

  • Chung-Feng Huang
    • 1
  • Etsuko Iio
    • 2
  • Dae Won Jun
    • 3
  • Eiichi Ogawa
    • 4
  • Hidenori Toyoda
    • 5
  • Yao-Chun Hsu
    • 6
  • Hiroaki Haga
    • 7
  • Shinji Iwane
    • 8
  • Masaru Enomoto
    • 9
  • Dong Hyun Lee
    • 10
  • Grace Wong
    • 11
    • 12
  • Chen-Hua Liu
    • 13
    • 14
  • Toshifumi Tada
    • 5
  • Wan-Long Chuang
    • 1
  • Ramsey Cheung
    • 15
    • 16
  • Jun Hayashi
    • 17
  • Cheng-Hao Tseng
    • 6
  • Satoshi Yasuda
    • 5
  • Sally Tran
    • 15
  • Leslie Kam
    • 15
  • Linda Henry
    • 15
  • Jae Yoon Jeong
    • 18
  • Hideyuki Nomura
    • 19
  • Seung Ha Park
    • 20
  • Makoto Nakamuta
    • 21
  • Jee-Fu Huang
    • 1
  • Chi-Ming Tai
    • 6
  • Gin-Ho Lo
    • 6
  • Mei-Hsuan Lee
    • 22
  • Hwai-I Yang
    • 23
  • Jia-Horng Kao
    • 13
    • 14
  • Akihiro Tamori
    • 9
  • Yuichiro Eguchi
    • 8
  • Yoshiyuki Ueno
    • 7
  • Norihiro Furusyo
    • 4
  • Yasuhito Tanaka
    • 2
  • Ming-Lung Yu
    • 1
  • Mindie H. Nguyen
    • 15
    Email author
  • For the REAL-C Investigators
  1. 1.Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University HospitalKaohsiung Medical UniversityKaohsiungTaiwan
  2. 2.Department of Virology and Liver Unit, Graduate School of Medical SciencesNagoya City UniversityNagoyaJapan
  3. 3.Department of GastroenterologyHanyang UniversitySeoulSouth Korea
  4. 4.Department of General Internal MedicineKyushu University HospitalFukuokaJapan
  5. 5.Department of GastroenterologyOgaki Municipal HospitalOgakiJapan
  6. 6.Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da HospitalI-Shou UniversityKaohsiungTaiwan
  7. 7.Department of Gastroenterology, Faculty of MedicineYamagata UniversityYamagataJapan
  8. 8.Liver CenterSaga University HospitalSagaJapan
  9. 9.Department of HepatologyOsaka City University Graduate School of MedicineOsakaJapan
  10. 10.Department of GastroenterologyGood Gang-An HospitalBusanSouth Korea
  11. 11.Department of Medicine and TherapeuticsThe Chinese University of Hong KongHong KongHong Kong
  12. 12.State Key Laboratory of Digestive DiseaseThe Chinese University of Hong KongHong KongHong Kong
  13. 13.Department of Internal MedicineNational Taiwan University HospitalTaipeiTaiwan
  14. 14.Hepatitis Research CenterNational Taiwan University HospitalTaipeiTaiwan
  15. 15.Division of Gastroenterology and Hepatology, Department of MedicineStanford University Medical CenterPalo AltoUSA
  16. 16.Division of Gastroenterology and HepatologyVeterans Affairs Palo Alto Health Care SystemPalo AltoUSA
  17. 17.Kyushu General Internal Medicine CenterHaradoi HospitalFukuokaJapan
  18. 18.Department of Internal Medicine, Hanyang University College of MedicineGuri HospitalGuriSouth Korea
  19. 19.The Center for Liver DiseaseShin-Kokura HospitalKitakyushuJapan
  20. 20.Department of Internal MedicineInje University Haeundae Paik HospitalBusanSouth Korea
  21. 21.Department of Gastroenterology, Kyushu Medical CenterNational Hospital OrganizationFukuokaJapan
  22. 22.Institute of Clinical MedicineNational Yang-Ming UniversityTaipeiTaiwan
  23. 23.Genomics Research Center, Academia SinicaTaipeiTaiwan

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