Yameng Sun1, Jialing Zhou1, Lin Wang1, Xiaoning Wu1, Yongpeng Chen2, Hongxin Piao3, Lungen Lu4, Wei Jiang5, Youqing Xu6, Bo Feng7, Yuemin Nan8, Wen Xie9, Guofeng Chen10, Huanwei Zheng11, Hai Li12, Huiguo Ding13, Hui Liu14, Fudong Lv14, Chen Shao15, Tailing Wang15, Xiaojuan Ou1, Bingqiong Wang1, Shuyan Chen1, Aileen Wee16, Neil D Theise17, Hong You1, Jidong Jia1. 1. Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Beijing, China. 2. Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. 3. Infectious Department, Affiliated Hospital of Yanbian University, Yanji, China. 4. Department of Gastroenterology and Hepatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 5. Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China. 6. Department of Digestive System, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. 7. Hepatology Institute, Peking University People's Hospital, Beijing, China. 8. Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. 9. Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China. 10. Second Liver Cirrhosis Diagnosis and Treatment Center, 302 Military Hospital of China, Beijing, China. 11. Department of Infectious Disease, the Fifth Hospital of Shijiazhuang City, Shijiazhuang, China. 12. Department of Hepatopancreatobiliary and Splenic Medicine, Affiliated Hospital, Logistics University of People's Armed Police Force, Tianjin, China. 13. Department of Gastroenterology and Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing, China. 14. Department of Pathology, Beijing Youan Hospital, Capital Medical University, Beijing, China. 15. Department of Pathology, China-Japan Friendship Hospital, Beijing, China. 16. Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, National University Hospital, Singapore, Singapore. 17. Departments of Pathology and Medicine (Division of Digestive Diseases), Mount Sinai Beth Israel Medical Center, New York, NY.
Abstract
Liver fibrosis is the net result of dynamic changes between fibrogenesis and fibrolysis. Evidence has shown that antiviral therapy can reverse liver fibrosis or even early cirrhosis caused by hepatitis B virus. However, current evaluation systems mainly focus on the severity of, but not the dynamic changes in, fibrosis. Here, we propose a new classification to evaluate the dynamic changes in the quality of fibrosis, namely: predominantly progressive (thick/broad/loose/pale septa with inflammation); predominately regressive (delicate/thin/dense/splitting septa); and indeterminate, which displayed an overall balance between progressive and regressive scarring. Then, we used this classification to evaluate 71 paired liver biopsies of chronic hepatitis B patients before and after entecavir-based therapy for 78 weeks. Progressive, indeterminate, and regressive were observed in 58%, 29%, and 13% of patients before treatment versus in 11%, 11%, and 78% after treatment. Of the 55 patients who showed predominantly regressive changes on posttreatment liver biopsy, 29 cases (53%) had fibrosis improvement of at least one Ishak stage, and, more interestingly, 25 cases (45%) had significant improvement in terms of Laennec substage, collagen percentage area, and liver stiffness despite remaining in the same Ishak stage. CONCLUSION: This new classification highlights the importance of assessing and identifying the dynamic changes in the quality of fibrosis, especially relevant in the era of antiviral therapy.(Hepatology 2017;65:1438-1450).
Liver fibrosis is the net result of dynamic changes between fibrogenesis and fibrolysis. Evidence has shown that antiviral therapy can reverse liver fibrosis or even early cirrhosis caused by hepatitis B virus. However, current evaluation systems mainly focus on the severity of, but not the dynamic changes in, fibrosis. Here, we propose a new classification to evaluate the dynamic changes in the quality of fibrosis, namely: predominantly progressive (thick/broad/loose/pale septa with inflammation); predominately regressive (delicate/thin/dense/splitting septa); and indeterminate, which displayed an overall balance between progressive and regressive scarring. Then, we used this classification to evaluate 71 paired liver biopsies of chronic hepatitis Bpatients before and after entecavir-based therapy for 78 weeks. Progressive, indeterminate, and regressive were observed in 58%, 29%, and 13% of patients before treatment versus in 11%, 11%, and 78% after treatment. Of the 55 patients who showed predominantly regressive changes on posttreatment liver biopsy, 29 cases (53%) had fibrosis improvement of at least one Ishak stage, and, more interestingly, 25 cases (45%) had significant improvement in terms of Laennec substage, collagen percentage area, and liver stiffness despite remaining in the same Ishak stage. CONCLUSION: This new classification highlights the importance of assessing and identifying the dynamic changes in the quality of fibrosis, especially relevant in the era of antiviral therapy.(Hepatology 2017;65:1438-1450).