Extrahepatic Malignancy Among Patients With Chronic Hepatitis C After Antiviral Therapy: A Real-World Nationwide Study on Taiwanese Chronic Hepatitis C Cohort (T-COACH)

Chung-Feng Huang¹, Hsueh-Chou Lai², Chi-Yi Chen³, Kuo-Chih Tseng⁴, Hsing-Tao Kuo⁵, Chao-Hung Hung⁶, Jing-Houng Wang⁷, Jyh-Jou Chen⁸, Pei-Lun Lee⁸, Rong-Nan Chien⁹, Chi-Chieh Yang¹⁰, Gin-Ho Lo¹¹, Chi-Ming Tai¹¹, Chih-Wen Lin¹¹, Jia-Horng Kao^{12

13}, Chun-Jen Liu^{12

13}, Chen-Hua Liu^{12

13}, Sheng-Lei Yan¹⁴, Ming-Jong Bair¹⁵, Chun-Yen Lin⁹, Wei-Wen Su¹⁶, Cheng-Hsin Chu¹⁷, Chih-Jen Chen¹⁷, Shui-Yi Tung⁶, Ching-Chu Lo¹⁸, Pin-Nan Cheng¹⁹, Yen-Cheng Chiu¹⁹, Chia-Chi Wang²⁰, Jin-Shiung Cheng²¹, Wei-Lun Tsai²¹, Han-Chieh Lin²², Yi-Hsiang Huang^{22

23}, Ming-Lun Yeh¹, Jee-Fu Huang¹, Chia-Yen Dai¹, Wan-Long Chuang¹, Pei-Chien Tsai¹, Cheng-Yuan Peng², Ming-Lung Yu¹

Affiliations

¹ Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
² Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, School of Medicine, China Medical University, Taichung, Taiwan.
³ Department of Internal Medicine, Chiayi Christian Hospital, Chiayi, Taiwan.
⁴ Department of Gastroenterology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan.
⁵ Division of Hepato-gastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan.
⁶ Division of Hepatogastroenterology, Department of Internal Medicine, ChiaYi Chang Gung Memorial Hospital, Chiayi, Taiwan.
⁷ Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
⁸ Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Liouying, Tainan.
⁹ Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
¹⁰ Division of Gastroenterology, Department of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan.
¹¹ Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan.
¹² Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
¹³ Division of Gastroenterology and Hepatology, the National Taiwan University Hospital, Taipei, Taiwan.
¹⁴ Division of Gastroenterology, Department of Internal Medicine, Chang Bing Show-Chwan Memorial Hospital, Changhua City, Taiwan.
¹⁵ Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung City, Taiwan.
¹⁶ Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan.
¹⁷ Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan.
¹⁸ Department of Internal Medicine, St. Martin De Porres Hospital, Daya, Chiayi, Taiwan.
¹⁹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
²⁰ Division of Gastroenterology, Department of Internal Medicine, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, New Taipei City, Taiwan.
²¹ Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
²² Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
²³ Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.

PMID: 32221162
DOI: 10.14309/ajg.0000000000000606

Extrahepatic Malignancy Among Patients With Chronic Hepatitis C After Antiviral Therapy: A Real-World Nationwide Study on Taiwanese Chronic Hepatitis C Cohort (T-COACH)

Chung-Feng Huang et al. Am J Gastroenterol. 2020 Aug.

. 2020 Aug;115(8):1226-1235.

doi: 10.14309/ajg.0000000000000606.

Authors

Affiliations

¹ Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
² Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, School of Medicine, China Medical University, Taichung, Taiwan.
³ Department of Internal Medicine, Chiayi Christian Hospital, Chiayi, Taiwan.
⁴ Department of Gastroenterology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi, Taiwan.
⁵ Division of Hepato-gastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan.
⁶ Division of Hepatogastroenterology, Department of Internal Medicine, ChiaYi Chang Gung Memorial Hospital, Chiayi, Taiwan.
⁷ Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
⁸ Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Liouying, Tainan.
⁹ Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
¹⁰ Division of Gastroenterology, Department of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan.
¹¹ Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan.
¹² Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
¹³ Division of Gastroenterology and Hepatology, the National Taiwan University Hospital, Taipei, Taiwan.
¹⁴ Division of Gastroenterology, Department of Internal Medicine, Chang Bing Show-Chwan Memorial Hospital, Changhua City, Taiwan.
¹⁵ Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung City, Taiwan.
¹⁶ Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan.
¹⁷ Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan.
¹⁸ Department of Internal Medicine, St. Martin De Porres Hospital, Daya, Chiayi, Taiwan.
¹⁹ Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
²⁰ Division of Gastroenterology, Department of Internal Medicine, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, New Taipei City, Taiwan.
²¹ Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
²² Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
²³ Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.

PMID: 32221162
DOI: 10.14309/ajg.0000000000000606

Abstract

Introduction: Chronic hepatitis C virus (HCV) infection is associated with nonhepatocellular carcinoma malignancies. We aimed to evaluate whether achieving a sustained virological response (SVR, defined as HCV RNA seronegativity throughout posttreatment 24-week follow-up) could reduce the risk of non-hepatocellular carcinoma malignancy in a real-world nationwide Taiwanese Chronic Hepatitis C Cohort (T-COACH).

Methods: A total of 10,714 patients with chronic hepatitis C who had received interferon-based therapy (8,186 SVR and 2,528 non-SVR) enrolled in T-COACH and were linked to the National Cancer Registry database for the development of 12 extrahepatic malignancies, including those with potential associations with HCV and with the top-ranking incidence in Taiwan, over a median follow-up period was 3.79 years (range, 0-16.44 years).

Results: During the 44,354 person-years of follow-up, 324 (3.02%) patients developed extrahepatic malignancies, without a difference between patients with and without SVR (annual incidence: 0.69% vs 0.87%, respectively). Compared with patients with SVR, patients without SVR had a significantly higher risk of gastric cancer (0.10% vs 0.03% per person-year, P = 0.004) and non-Hodgkin lymphoma (NHL) (0.08% vs 0.03% per person-year, respectively, P = 0.03). When considering death as a competing risk, non-SVR was independently associated with gastric cancer (hazard ratio [HR]/95% confidence intervals [CIs]: 3.29/1.37-7.93, P = 0.008). When patients were stratified by age, the effect of SVR in reducing gastric cancer (HR/CI: 0.30/0.11-0.83) and NHL (HR/CI: 0.28/0.09-0.85) was noted only in patients aged <65 years but not those aged >65 years.

Discussion: HCV eradication reduced the risk of gastric cancer and NHL, in particular among younger patients, indicating that patients with chronic hepatitis C should be treated as early as possible.

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References

1. Huang CF, Yeh ML, Tsai PC, et al. Baseline gamma-glutamyl transferase levels strongly correlate with hepatocellular carcinoma development in non-cirrhotic patients with successful hepatitis C virus eradication. J Hepatol 2014;61:67–74.
1. Huang JF, Yu ML, Dai CY, et al. Reappraisal of the characteristics of glucose abnormalities in patients with chronic hepatitis C infection. Am J Gastroenterol 2008;103:1933–40.
1. Younossi ZM, Henry L, P Ong J, et al. Systematic review with meta-analysis: Extrahepatic manifestations in chronic hepatitis C virus-infected patients in East Asia. Aliment Pharmacol Ther 2019;49:644–53.
1. Cacoub P, Desbois AC, Comarmond C, et al. Impact of sustained virological response on the extrahepatic manifestations of chronic hepatitis C: A meta-analysis. Gut 2018;67:2025–34.
1. Huang JF, Dai CY, Yu ML, et al. Pegylated interferon plus ribavirin therapy improves pancreatic beta-cell function in chronic hepatitis C patients. Liver Int 2011;31:1155–62.

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Extrahepatic Malignancy Among Patients With Chronic Hepatitis C After Antiviral Therapy: A Real-World Nationwide Study on Taiwanese Chronic Hepatitis C Cohort (T-COACH)

Affiliations

Extrahepatic Malignancy Among Patients With Chronic Hepatitis C After Antiviral Therapy: A Real-World Nationwide Study on Taiwanese Chronic Hepatitis C Cohort (T-COACH)

Authors

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Abstract

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Medical