Project belongs to the field of traditional Chinese medicine (TCM) internal medicine. Main technical innovation content: This research team has long been engaged in clinical and basic research on the prevention and treatment of chronic hepatitis B (CHB) liver fibrosis with TCM. Relying on the 'Eleventh Five-Year' and 'Twelfth Five-Year' National Science and Technology Major Projects, as well as the 'Eleventh Five-Year' National Science and Technology Support Plan, a staging and syndrome differentiation treatment plan for CHB liver fibrosis patients was established based on the pathological characteristics of the liver and the pathogenesis of TCM. Taking the stage of fibrosis as the main efficacy indicator, it was confirmed that this plan can significantly improve clinical efficacy and preliminarily clarify the mechanism of action of TCM in reversing liver fibrosis. 1) Based on the pathological characteristics of the liver and the pathogenesis of TCM, establish a staging and syndrome differentiation treatment plan for CHB liver fibrosis: Collected 705 cases of CHB patients for liver biopsy pathology examination, among which 49 cases were classified as stage S0 fibrosis ( 6.95%), 188 cases (26.67%) in S1, 308 cases (43.69%) in S2, 137 cases (19.43%) in S3, and 23 cases (3.26%) in S4; among those with liver fibrosis < S2, there were 545 cases (77.31%), with the basic pathogenesis being spleen deficiency and damp-heat; for those with liver fibrosis ≥ S2, there were 160 cases (22.69%), with the basic pathogenesis being yin deficiency and blood stasis. Based on this, a staging and syndrome differentiation treatment plan was established, which primarily uses 'tonifying the spleen, clearing heat, and promoting diuresis' for early stages and 'nourishing yin, activating blood circulation, and soothing the liver' for late stages. 2) The combination of Jianpi Shuizhi decoction with entecavir therapy in patients with CHB liver fibrosis at an early stage can improve HBeAg seroconversion rates and enhance pathological liver fibrosis staging: A total of 400 patients with early CHB liver fibrosis from 12 research centers across the country were collected. After 12 months of treatment with Shenbu Jianpi decoction combined with entecavir, The HBeAg seroconversion rate increased by 11.02% compared to the entecavir monotherapy group (22.83% vs. 11.81%). A total of 112 patients underwent liver biopsy before and after treatment. The proportion of patients with liver fibrosis stage ≥S2 in the treatment group decreased from 63.39% to 41.07%. 3) The treatment of CHB liver fibrosis in the late stage with Yangyin Huoxue Rougan decoction can improve HBeAg seroconversion rate, as well as pathological inflammation and fibrosis scores: Rougan Chongji (an in-house preparation, batch number: Z05100975), which is mainly based on the treatment method of 'Yangyin Huoxue Rougan', was used to treat CHB liver fibrosis in the late stage for 12 months, with a total effective rate of 90.5%, of which the significant response rate was 52.1%; The HBeAg seroconversion rates were 20% respectively, and the liver inflammation activity score decreased from 8.44±4.21 to 7.11±5.03, The degree of fibrosis score decreased from 7.55±5.05 to 5.92±4.21. 4) The mechanism of action of traditional Chinese medicine compound in reversing liver fibrosis mainly includes: ① Inhibiting the secretion of fibrogenic proteins by CD4+ T lymphocytes; ② Suppressing the production of osteopontin and plasminogen activator inhibitor, TGFβ1; ③ Inhibiting the activation and proliferation of hepatic stellate cells (HSC), which are the main cells producing extracellular matrix within the liver, antagonizing HSC autocrine; ④ Inhibiting the expression of cell matrix metalloproteinases and their inhibitors, suppressing the synthesis of type I collagen, type III procollagen, and type IV collagen. Key innovations: 1. Based on the pathological characteristics of the liver and the pathogenesis features of traditional Chinese medicine, a staging and syndrome differentiation treatment plan for CHB liver fibrosis was established; 2. Multicenter, randomized, double-blind, controlled trials have shown that this plan can effectively reverse liver fibrosis. 3. Preliminary clarification of the mechanism of action of traditional Chinese medicine compound in reversing liver fibrosis. Intellectual property and application promotion: This program has been promoted and applied in 9 tertiary-level hospitals nationwide and 5 community health service centers in Pudong New District, and has been verified as a recommended scheme by the key specialty collaboration group of traditional Chinese medicine liver diseases at the National Administration of Traditional Chinese Medicine. It has obtained 1 national invention patent, published 72 academic papers, with a total of 658 citations. It has organized 10 national continuing education classes, training a total of 2000 participants.