Treatment of hepatic fibrosis Hepatic fibrosis is a common pathological and histological change in the progression of many chronic liver diseases to cirrhosis, and it is an important part of the prognosis of chronic liver diseases. In the absence of effective etiologic treatment for the primary disease (e.g., chronic hepatitis B, the most common disease in China), slowing or stopping the process of liver fibrosis is an important therapeutic response, but to date, there are no drugs or methods to combat liver fibrosis in a substantive sense for clinical application abroad. For a period of time in the future, the focus of foreign research is still on basic research (cell signaling), with the aim of finding a breakthrough in the elucidation of the formation mechanism of liver fibrosis. At present, modern biomedical anti-fibrotic therapeutic research is focused on a key link in the pathogenesis, and such therapeutic approaches seeking to block a single link are not compatible with the complex pathological mechanism of liver fibrosis; and there are still insurmountable contradictions between the double-edged sword-like effects of relevant cytokines and the systemic distribution and organ specificity of connective tissue. Therefore, the idea of focusing on a key point in the pathogenesis of anti-liver fibrosis therapy is worth considering. Liver fibrosis resulting from the accumulation of extracellular matrix (ECM) during chronic liver injury can be reversed with effective treatment, but once cirrhosis has developed, it is difficult to reverse. The effective treatment of liver fibrosis mainly includes the treatment of the etiology of the primary disease, anti-inflammatory therapy and inhibition of intrahepatic ECM production and promotion of ECM degradation. The results of three-year follow-up of α-interferon therapy for chronic hepatitis C showed that the clinical efficacy (serum HCV-RNA turned negative and liver function returned to normal), efficacy (HCV-RNA did not turn negative but liver function returned to normal) and ineffectiveness of the treatment were proportional to the decrease in serum precollagen type III telopeptide (P-III-P) and collagen 7S. The rate of improvement of liver fibrosis in the effective cases was 70%, while that in the effective and ineffective cases was basically unchanged, and the liver fibrosis in the control group not only did not improve, but also deteriorated in 40% of cases. In chronic viral hepatitis B, liver fibrosis was also reduced to a certain extent in those cases that showed effectiveness after long-term treatment with Herceptin. Cirrhosis caused by hemochromatosis, jejuno-colonic anastomosis, familial intrahepatic cholestasis, and secondary biliary cirrhosis can be reversed after removal of the cause or surgical correction; alcoholic cirrhosis can restore the liver to near normal after up to 10 years of abstinence from alcohol. Patients with liver fibrosis who developed ascites and esophageal varices after four years of continuous administration of the anticancer agent UFT rapidly disappeared after discontinuation of the drug, and serum P-III-P, 7S collagen and hyaluronic acid levels decreased significantly, and ICG excretion tests and esophageal varices improved significantly. It shows that effective etiological treatment can inhibit the progress of liver fibrosis and promote the reversal of liver fibrosis; that is, the effective prevention and treatment of liver fibrosis is firstly for the treatment of the primary disease, and at present, the problem of persistent infection of hepatitis B virus needs to be solved urgently in China. 2, anti-inflammatory treatment. Fibrosis is the body’s self-repair response to tissue damage caused by inflammation, long-term, repeated liver inflammation is the premise of liver fibrosis formation. Inflammatory factors and malfunctioning cytokine production in the inflammatory process are the main factors leading to increased ECM production and decreased degradation. The results of recent studies against liver fibrosis in chronic hepatitis B have shown that the suppression or reduction of liver fibrosis is often synchronized with the improvement of liver tissue inflammation. Glucocorticoids, prostaglandins and Xiao Chai Hu Tang all achieve anti-fibrosis goals by suppressing inflammation. Continuous effective anti-inflammatory treatment and suppression of inflammatory response is one of the therapeutic means to inhibit fibrosis progression. 3.Interference with intrahepatic ECM metabolism, inhibition of ECM production and promotion of ECM degradation. This is the focus of research on anti-fibrosis treatment in a narrow sense. Currently, with the in-depth research on the pathobiology of liver fibrosis, various ideas have been proposed for certain important aspects in the therapeutics. For example, the pathways to inhibit HSC activation include antioxidants, blocking MAPK phosphorylation (MAPK phosphorylation mechanism mediates HSC activation), antibodies or antibodies to neutralize the activating factor PDGF and fibrosis stimulating factor TGFβ1, antagonists against some key enzymes of matrix synthesis, or attempts to increase collagenase activity (inserting MMP1 gene into HSC) with a focus on collagen degradation. . However, these ideas are still at the experimental stage and face some difficult problems: how to solve the organ-specific therapeutic measures for connective tissue, which is spread throughout the body? Single blockade of certain important links may bring unpredictable side effects, etc., in the research ideas deserve our high attention. 4, the advantages of Chinese medicine in the anti-liver fibrosis treatment. After more than 20 years of unremitting efforts, the advantages of Chinese medicine in the treatment of liver fibrosis have been recognized by our colleagues and have become a hot topic in the field of liver disease research in China today. The multiple components of TCM may be the basis of its multi-target, multi-channel and multi-level pharmacological effects. So far, the representative compound formulas reported are Strong Liver Softening Soup (composed of Astragalus, Atractylodes, Poria, Radix et Rhizoma, Radix Angelicae Sinensis, Radix Paeoniae Alba, Salviae Miltiorrhizae, Eugenia, Dampi, Gardenia, Turtle A, Yin Chen, etc.; Han Jing-Huan et al. 1979). Peach kernel extract combined with artificial Cordyceps mycelium; Fu Zheng Hua Yu 319 formula (liver pacification capsule); compound 861 combination (composed of 10 herbs including Astragalus, Salviae, and henbane, Beijing, Wang Bao En, et al.); compound turtle nail soft liver tablet (composed of 11 herbs including turtle nail, red peony, Panax notoginseng and Cordyceps, PLA 302 Hospital). Traditional Chinese medicine, such as rhubarb sting worm pill. The results of the second liver biopsy before and after treatment in patients with chronic hepatitis B liver fibrosis showed that the reversal rate of liver tissue fibrosis stage (reduced by 1 stage or more after medication than before medication) was 52%-58.3%. Significant progress has also been made in the study of the active ingredients of Chinese medicines, such as Hanfanganine and Salvianolic acid B (SA-B). The treatment of patients with chronic hepatitis B liver fibrosis (30 cases in each group) was observed in a randomized double-blind control and double simulation method using γ-IFN as a positive control drug for 6 months. The reversal rate of liver fibrosis stage in SA-B group was 36.67%, and the improvement rate of inflammation grade was 40.0%, while that in γ-IFN group was 30.0% and 36.67%, respectively. The mean serum hyaluronic acid (HA) and collagen type IV (C-IV) levels were significantly lower than those before treatment, and the abnormality rate was also significantly reduced. The baseline values of serum ALT, AST and total bilirubin in the SA-B group were significantly lower than those in cases where fibrosis continued to worsen, and no significant adverse effects of SA-B were observed. In vitro studies showed that SA-B could inhibit the intracellular Smad2 and Smad3 protein expression in hepatic stellate cells (HSC) in the transforming growth factor (TGF)b1 signaling pathway, interfering with the intracellular signaling of HSC by TGFβ1, and thus inhibiting the expression of its effector genes (pre-collagen genes, etc.). The formation and development of liver fibrosis is an extremely complex process, and its pathophysiological changes are mainly manifested by the imbalance of ecological balance of intrahepatic cells and their interstitial matrix and the abnormal metabolism of mediators and ECM. The comprehensive pharmacological effects of multi-pathways, multi-levels and multi-targets may be the anti-hepatic fibrosis characteristics of the multi-component Chinese medicine compound. Our recent studies on the mechanism of action of 319 formula for liver fibrosis can be summarized as follows: 1) inhibition of fibroproliferation stimulating factors, such as lipid peroxidation and TGFβ1 production; 2) inhibition of activation and proliferation of HSC, the main ECM-producing cell in the liver, antagonism of platelet-derived growth factor (PDGF)-bb’s pro-HSC proliferative response, inhibition of ECM production of HSC, type I collagen mRNA and protein expression of HSC; 3) inhibit hepatic Kupffer cell paracrine secretion (PDGF, active TGFβ1 production) and HSC autocrine activation of HSC pathway; 4) anti-liver injury, protect hepatocytes, and promote the transformation of chronically injured hepatocytes to normal function; 5) inhibit activated Kupffer cells and HSC vascular endothelial growth factor ( VEGF production, promoting the reversal of hepatic sinusoidal capillarization in the process of liver fibrosis. From one side, it shows the advantages of Chinese herbal compound in regulating the ecological balance of cells and mesenchyme and related functional genes, which is relevant to the complex pathobiological changes of liver fibrosis. It is worth pointing out that, due to the stability of the primary drug and the complexity of the multiple components of the compound formulation, a lot of detailed and in-depth research is still needed to make its composition clear or quality controllable; to strengthen the basic research to clarify how many points of the multi-target action? Obtain strict and standardized clinical research data, and make unremitting efforts to squeeze into the leading position in this research field in China. In addition, the effective prevention and treatment of liver fibrosis is firstly aimed at the treatment of the primary disease, and at present, the problem of persistent infection of hepatitis B virus needs to be solved urgently in China. In the future, if the combination of effective virus inhibiting drugs and Chinese medicinal preparations is further applied, it is expected that more satisfactory clinical results can be obtained in the anti-liver fibrosis. The chronic liver disease in China is mainly chronic hepatitis B and its resultant cirrhosis, and it is expected that further application of effective antiviral drugs (e.g. Herbstine) in combination with Chinese medicinal preparations can achieve more satisfactory clinical results in anti-fibrosis.