Factors associated with treatment failure of direct-acting antivirals for chronic hepatitis C: A real-world nationwide hepatitis C virus registry programme in Taiwan

Chi-Yi Chen; Chung-Feng Huang; Pin-Nan Cheng; Kuo-Chih Tseng; Ching-Chu Lo; Hsing-Tao Kuo; Yi-Hsiang Huang; Chi-Ming Tai; Cheng-Yuan Peng; Ming-Jong Bair; Chien-Hung Chen; Ming-Lun Yeh; Chih-Lang Lin; Chun-Yen Lin; Pei-Lun Lee; Lee-Won Chong; Chao-Hung Hung; Jee-Fu Huang; Chi-Chieh Yang; Jui-Ting Hu; Chih-Wen Lin; Chun-Ting Chen; Chia-Chi Wang; Wei-Wen Su; Tsai-Yuan Hsieh; Chih-Lin Lin; Wei-Lun Tsai; Tzong-Hsi Lee; Guei-Ying Chen; Szu-Jen Wang; Chun-Chao Chang; Lein-Ray Mo; Sheng-Shun Yang; Wen-Chih Wu; Chia-Sheng Huang; Chou-Kwok Hsiung; Chien-Neng Kao; Pei-Chien Tsai; Chen-Hua Liu; Mei-Hsuan Lee; Chun-Jen Liu; Chia-Yen Dai; Jia-Horng Kao; Wan-Long Chuang; Han-Chieh Lin; Ming-Lung Yu

doi:10.1111/liv.14849

Factors associated with treatment failure of direct-acting antivirals for chronic hepatitis C: A real-world nationwide hepatitis C virus registry programme in Taiwan

Liver Int. 2021 Jun;41(6):1265-1277. doi: 10.1111/liv.14849. Epub 2021 Mar 12.

Authors

Chi-Yi Chen¹, Chung-Feng Huang^{2

3}, Pin-Nan Cheng⁴, Kuo-Chih Tseng^{5

6}, Ching-Chu Lo⁷, Hsing-Tao Kuo⁸, Yi-Hsiang Huang^{9

10}, Chi-Ming Tai^{11

12}, Cheng-Yuan Peng¹³, Ming-Jong Bair^{14

15}, Chien-Hung Chen¹⁶, Ming-Lun Yeh^{3

17}, Chih-Lang Lin¹⁸, Chun-Yen Lin^{19

20}, Pei-Lun Lee²¹, Lee-Won Chong^{22

23}, Chao-Hung Hung^{16

24}, Jee-Fu Huang^{3

25}, Chi-Chieh Yang²⁶, Jui-Ting Hu²⁷, Chih-Wen Lin^{12

28}, Chun-Ting Chen^{29

30}, Chia-Chi Wang³¹, Wei-Wen Su³², Tsai-Yuan Hsieh³⁰, Chih-Lin Lin³³, Wei-Lun Tsai³⁴, Tzong-Hsi Lee³⁵, Guei-Ying Chen³⁶, Szu-Jen Wang³⁷, Chun-Chao Chang^{38

39}, Lein-Ray Mo⁴⁰, Sheng-Shun Yang⁴¹, Wen-Chih Wu⁴², Chia-Sheng Huang⁴³, Chou-Kwok Hsiung⁴⁴, Chien-Neng Kao⁴⁵, Pei-Chien Tsai², Chen-Hua Liu⁴⁶, Mei-Hsuan Lee⁴⁷, Chun-Jen Liu⁴⁶, Chia-Yen Dai^{2

3}, Jia-Horng Kao⁴⁶, Wan-Long Chuang^{2

3}, Han-Chieh Lin^{9

10}, Ming-Lung Yu^{2

3}

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan.
² Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
³ School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁴ Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan.
⁵ Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.
⁶ School of Medicine, Tzuchi University, Hualien, Taiwan.
⁷ Division of Gastroenterology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan.
⁸ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan.
⁹ Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital.
¹⁰ Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
¹¹ Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan.
¹² School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan.
¹³ Center for Digestive Medicine, Department of Internal Medicine, School of Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan.
¹⁴ Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan.
¹⁵ Mackay Medical College, New Taipei City, Taiwan.
¹⁶ Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
¹⁷ Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹⁸ Department of Gastroenterology and Hepatology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.
¹⁹ Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan.
²⁰ Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
²¹ Liouying Division of Gastroenterology and Hepatology, Department of Internal medicine, Chi Mei Medical Center, Tainan, Taiwan.
²² Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
²³ School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
²⁴ Division of Hepatogastroenterology, Department of Internal Medicine, ChiaYi Chang Gung Memorial Hospital, Puzi, Taiwan.
²⁵ Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
²⁶ Department of Gastroenterology, Division of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan.
²⁷ Liver Center, Cathay General Hospital, Taipei, Taiwan.
²⁸ Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, Kaohsiung, Taiwan.
²⁹ Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital Penghu Branch, National Defense Medical Center, Taipei, Taiwan.
³⁰ Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
³¹ School of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan.
³² Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua, Taiwan.
³³ Department of Gastroenterology, Renai branch, Taipei City Hospital, Taipei, Taiwan.
³⁴ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
³⁵ Division of Gastroenterology and Hepatology, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
³⁶ Penghu Hospital, Ministry of Health and Welfare, Taipei, Taiwan.
³⁷ Division of Gastroenterology, Department of Internal Medicine, Yuan's General Hospital, Kaohsiung, Taiwan.
³⁸ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
³⁹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁴⁰ Division of Gastroenterology, Tainan Municipal Hospital, Tainan, Taiwan.
⁴¹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
⁴² Wu Wen-Chih Clinic, Kaohsiung, Taiwan.
⁴³ Yang Ming Hospital, Chiayi, Taiwan.
⁴⁴ Chou Kwok Hsiung Clinic, Penghu, Taiwan.
⁴⁵ National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan.
⁴⁶ Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
⁴⁷ Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Abstract

Background/aims: Direct-acting antivirals (DAAs) are highly effective in treating chronic hepatitis C virus (HCV)-infected patients. The real-world treatment outcome in Taiwanese patients on a nationwide basis is elusive.

Methods: The Taiwan HCV Registry (TACR) programme is a nationwide registry platform including 48 study sites, which is organized and supervised by the Taiwan Association for the Study of the Liver. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA 12 weeks after end-of-treatment).

Results: A total of 13 951 registered patients with SVR12 data available were analysed (mean age, 63.0 years; female, 55.9%; HCV genotype-1 [GT1], 57.9%; cirrhosis, 38.4%; preexisting hepatocellular carcinoma [HCC], 10.6%; and hepatitis B virus coinfection, 7.7%). The overall SVR12 rate was 98.3%, with 98.7%, 98.0%, 98.4% and 97.4% in treatment-naïve noncirrhotic, treatment-naïve cirrhotic, treatment-experienced noncirrhotic and treatment-experienced cirrhotic patients, respectively. The SVR12 rate was > 95% across all subgroups except treatment-experienced cirrhotic patients who received sofosbuvir/ribavirin (88.7%), treatment-naïve noncirrhotic patients (94.8%) and treatment-experienced cirrhotic (94.8%) patients who received daclatasvir/asunaprevir. The most important factor associated with treatment failure was DAA adherence < 60% ( adjusted odds ratio [aOR]/95% confidence interval [CI]: 117.1/52.4-261.3, P < .001), followed by GT3/GT2 (aOR/CI: 5.78/2.25-14.9, P = .0003 and aOR/CI: 1.55/1.05-2.29, P = .03, compared with GT1), active hepatocellular carcinoma (aOR/CI: 4.29/2.57-7.16, P < .001), the use of sofosbuvir/ribavirin (aOR/CI: 2.51/1.67-3.77, P < .001) and daclatasvir/asunaprevir (aOR/CI: 3.29/1.94-5.58, P < .001), decompensated liver cirrhosis (aOR/CI: 2.50/1.20-5.22, P = .02) and high HCV viral loads (aOR/CI: 2.16/1.57-2.97, P < .001).

Conclusions: DAAs are highly effective in treating Taiwanese HCV patients in the real-world setting. Maintaining DAA adherence and selecting highly efficacious regimens are keys to ensure treatment success.

Keywords: CHC; DAA; HCV; Taiwan; real world; registry.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / therapeutic use
Carcinoma, Hepatocellular* / drug therapy
Carcinoma, Hepatocellular* / epidemiology
Drug Therapy, Combination
Female
Hepacivirus / genetics
Hepatitis C* / drug therapy
Hepatitis C, Chronic* / drug therapy
Humans
Liver Neoplasms* / drug therapy
Middle Aged
Registries
Sofosbuvir / therapeutic use
Sustained Virologic Response
Taiwan / epidemiology
Treatment Failure
Treatment Outcome

Substances

Antiviral Agents
Sofosbuvir