Jiyoon Park1, An K Le2, Tai-Chung Tseng3, Ming-Lun Yeh4, Dae Won Jun5, Huy Trinh6, Grace L H Wong7, Chien-Hung Chen8, Cheng-Yuan Peng9, Sung Eun Kim10, Hyunwoo Oh11, Min-Sun Kwak11, Ka Shing Cheung12, Hidenori Toyoda13, Yao-Chun Hsu14, Jae Yoon Jeong15, Eileen L Yoon5, Teerapat Ungtrakul16, Jian Zhang17, Qing Xie18, Sang Bong Ahn19, Masaru Enomoto20, Jae-Jun Shim21, Chris Cunningham22, Soung Won Jeong23, Yong Kyun Cho24, Eiichi Ogawa25, Rui Huang26, Dong-Hyun Lee27, Hirokazu Takahashi28, Pei-Chien Tsai4, Chung-Feng Huang4, Chia-Yen Dai4, Cheng-Hao Tseng14, Satoshi Yasuda13, Ritsuzo Kozuka20, Jiayi Li29, Christopher Wong30, Clifford C Wong31, Changqing Zhao32, Joseph Hoang2, Yuichiro Eguchi28, Chao Wu26, Yasuhito Tanaka33, Ed Gane34, Tawesak Tanwandee35, Ramsey Cheung2, Man-Fung Yuen12, Hyo-Suk Lee11, Ming-Lung Yu4, Jia-Horng Kao3, Hwai-I Yang36, Mindie H Nguyen37. 1. Department of Medicine, Santa Clara Valley Medical Center, Santa Clara, California; Division of Gastroenterology and Hepatology, Stanford University Medical Center, California. 2. Division of Gastroenterology and Hepatology, Stanford University Medical Center, California. 3. Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. 4. Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan. 5. Department of Gastroenterology, Hanyang University College of Medicine, Seoul, Republic of Korea. 6. San Jose Gastroenterology, San Jose, California. 7. Department of Medicine and Therapeutics, the Chinese University of Hong Kong, Hong Kong SAR, China. 8. Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. 9. Department of Gastroenterology, China Medical University Hospital, Taichung, Taiwan. 10. Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea. 11. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. 12. Department of Medicine, the University of Hong Kong, Hong Kong SAR, China. 13. Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan. 14. Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan. 15. Department of Internal Medicine, National Medical Center, Seoul, Republic of Korea. 16. Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand. 17. Chinese Hospital, San Francisco, California. 18. Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 19. Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University College of Medicine, Seoul, Republic of Korea. 20. Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan. 21. Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul, Republic of Korea. 22. Research Centre for Maori Health and Development, Massey University, Wellington, New Zealand. 23. Department of Internal Medicine, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea. 24. Department of Internal Medicine, Sungkyunkwan University, Seoul, Republic of Korea. 25. Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan. 26. Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China. 27. Department of Gastroenterology, Good Gang-An Hospital, Busan, Republic of Korea. 28. Department of Internal Medicine, Saga University Hospital, Saga, Japan. 29. Palo Alto Medical Foundation, Mountain View Division, Mountain View, California. 30. Wong Clinics, San Francisco, California. 31. Wong Clinics, San Francisco, California; Department of Cirrhosis, Institute of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. 32. Department of Cirrhosis, Institute of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China. 33. Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan. 34. New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand. 35. Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. 36. Genomics Research Center, Academia Sinica, Taipei, Taiwan. 37. Division of Gastroenterology and Hepatology, Stanford University Medical Center, California; Department of Epidemiology and Population Health, Stanford University, Stanford, California. Electronic address: mindiehn@stanford.edu.
Abstract
BACKGROUND & AIMS: Antiviral treatment criteria are based on disease progression risk, and hepatocellular carcinoma (HCC) surveillance recommendations for patients with chronic hepatitis B (CHB) without cirrhosis is based on an annual incidence threshold of 0.2%. However, accurate and precise disease progression estimate data are limited. Thus, we aimed to determine rates of cirrhosis and HCC development stratified by age, sex, treatment status, and disease activity based on the 2018 American Association for the Study of Liver Diseases and 2017 European Association for the Study of the Liver guidelines. METHODS: We analyzed 18,338 patients (8914 treated, 9424 untreated) from 6 centers from the United States and 27 centers from Asia-Pacific countries. The Kaplan-Meier method was used to estimate annual progression rates to cirrhosis or HCC in person-years. RESULTS: The cohort was 63% male, with a mean age of 46.19 years, with baseline cirrhosis of 14.3% and median follow up of 9.60 years. By American Association for the Study of Liver Diseases criteria, depending on age, sex, and disease activity, annual incidence rates ranged from 0.07% to 3.94% for cirrhosis, from 0.04% to 2.19% for HCC in patients without cirrhosis, and from 0.40% to 8.83% for HCC in patients with cirrhosis. Several subgroups of patients without cirrhosis including males younger than 40 years of age and females younger than 50 years of age had annual HCC risk near or exceeding 0.2%. Similar results were found using European Association for the Study of the Liver criteria. CONCLUSION: There is great variability in CHB disease progression rates even among "lower-risk" populations. Future CHB modeling studies, public health planning, and HCC surveillance recommendation should be based on more precise disease progression rates based on sex, age, and disease activity, plus treatment status.
BACKGROUND & AIMS: Antiviral treatment criteria are based on disease progression risk, and hepatocellular carcinoma (HCC) surveillance recommendations for patients with chronic hepatitis B (CHB) without cirrhosis is based on an annual incidence threshold of 0.2%. However, accurate and precise disease progression estimate data are limited. Thus, we aimed to determine rates of cirrhosis and HCC development stratified by age, sex, treatment status, and disease activity based on the 2018 American Association for the Study of Liver Diseases and 2017 European Association for the Study of the Liver guidelines. METHODS: We analyzed 18,338 patients (8914 treated, 9424 untreated) from 6 centers from the United States and 27 centers from Asia-Pacific countries. The Kaplan-Meier method was used to estimate annual progression rates to cirrhosis or HCC in person-years. RESULTS: The cohort was 63% male, with a mean age of 46.19 years, with baseline cirrhosis of 14.3% and median follow up of 9.60 years. By American Association for the Study of Liver Diseases criteria, depending on age, sex, and disease activity, annual incidence rates ranged from 0.07% to 3.94% for cirrhosis, from 0.04% to 2.19% for HCC in patients without cirrhosis, and from 0.40% to 8.83% for HCC in patients with cirrhosis. Several subgroups of patients without cirrhosis including males younger than 40 years of age and females younger than 50 years of age had annual HCC risk near or exceeding 0.2%. Similar results were found using European Association for the Study of the Liver criteria. CONCLUSION: There is great variability in CHB disease progression rates even among "lower-risk" populations. Future CHB modeling studies, public health planning, and HCC surveillance recommendation should be based on more precise disease progression rates based on sex, age, and disease activity, plus treatment status.