Liver fibrosis is mainly characterized by excessive proliferation and abnormal deposition of extracellular matrix (ECM) in liver tissues, which is common in most chronic liver diseases caused by hepatophilic viruses, alcohol, drugs, schistosomiasis, metabolic abnormalities and autoimmune injuries, and is a kind of hepatic reparative response to chronic injuries, which can lead to hepatic hypoplasia and portal hypertension, and ultimately form liver cirrhosis or hepatocellular carcinoma. Therefore, effective treatment of liver fibrosis is essential to improve the prognosis of chronic liver disease and reduce the mortality rate. First, for chronic hepatitis liver fibrosis, etiological treatment is necessary, and anti-hepatic fibrosis treatment is also necessary Inflammation and fibrosis are two important pathological features of various chronic liver diseases, and it has been clarified that liver fibrosis and early cirrhosis are reversible. For example, Chang et al. used ETV to treat chronic hepatitis B for 7 years, 293 patients were enrolled, 57 patients completed 2 valid liver biopsies before and after treatment, resulting in 96% improvement in liver inflammation and 88% improvement in hepatic fibrosis.Marcellin et al. used tenofovir to treat chronic hepatitis B for 5 years, showing that of the 585 patients enrolled in the program, 489 completed 240 weeks of treatment, 348 completed 2 liver biopsies before and after treatment, 176 completed 2 liver biopsies before and after treatment, and 176 completed 2 liver biopsies before and after treatment. Of the 585 patients enrolled, 489 patients completed 240 weeks of treatment, 348 patients completed 2 pre- and post-treatment liver biopsies, and 176 patients (51%) had reduced or reversed liver fibrosis (Ishak score); of these patients, 71 (74%) of the 96 patients who had cirrhosis (Ishak score of 5 or more) at the time of enrollment achieved reversal of liver fibrosis. The above studies suggest that effective suppression of hepatitis B virus replication can reduce or reverse liver fibrosis. However, there are still some problems in the above studies: (1) The enrollment of more studies with hepatic fibrosis as the object of observation and fewer studies with cirrhosis as the object of observation. (2) Lack of parallel control. (3) The evaluation indexes are single and lack of clinical outcome indexes, such as the incidence of hepatic decompensation. (4) There were more cases at enrollment, but the number of cases with a second liver biopsy was small, and the actual pathology of those patients who did not complete the regimen is unknown. In addition, despite a favorable virologic response to anti-HBV or anti-HCV therapy, inflammation and fibrosis remain in the liver tissue of some patients and can continue to activate hepatic stellate cells (HSCs), promoting further development of fibrosis. Patients who are ineffective on antiviral therapy are more likely to develop hepatic fibrosis. In clinical practice, we also increasingly find that although patients have good virologic and biochemical responses to antiviral drugs, they still end up with liver fibrosis or cirrhosis. Therefore, chronic viral hepatitis has a “backward shift” phenomenon, i.e., the number of patients with chronic active hepatitis is decreasing while the number of patients with cirrhosis is increasing. The reason is that HBV is not cleared but inhibited, and HBVDNA and cccDNA still exist in liver tissue. Or even if HCV is cleared, there are many complex reasons such as body immunity, HSCs self-activation, liver tissue microenvironmental changes, etc., which can promote the continued progression of liver fibrosis. Therefore, for chronic viral hepatitis, antiviral is necessary, and treatment against liver fibrosis is also necessary. For chronic liver diseases that lack specific etiological treatment, such as non-alcoholic fatty liver disease, it is even more important to pay attention to anti-hepatic fibrosis treatment. Second, the progress of clinical treatment of anti-hepatic fibrosis by combining traditional Chinese and western medicines In the 1990s, Brenner et al. proposed the ideal drug for anti-hepatic fibrosis “three principles”: specific effect on the liver; specific regulation of the metabolism of collagen and other components of the extracellular matrix; and no obvious toxicity. However, there is still a lack of anti-hepatic fibrosis biological or chemical drugs that meet these principles. Chinese medicine against liver fibrosis has gone through three stages: empirical summarization, experimental exploration and evidence-based medical research. Before the 1970s, it was the period of empirical summary, for example, Prof. Wang Yurun believed that the pathogenesis of liver cirrhosis was “obstruction of liver channels, blood stasis and qi stagnation”, and the basic method of treatment was to activate blood circulation and remove blood stasis, and move qi to open up the channels; Guan Yubo believed that qi deficiency and blood stagnation were the basis of early cirrhosis, and the products that strengthened the spleen and benefited the qi, benefited the kidneys, softened the liver, and activated the blood to open up the channels were used more often, and so on. The 1970s to 1990s was the period of experimental research. More experimental studies were carried out on the anti-hepatic fibrosis of traditional Chinese medicines, representative studies include Strong Liver Soft and Firm Soup, Salvia divinorum, peach kernel and its extracts, licorice sweeteners, etc. After the 1990s, clinical trials were carried out. After the 1990s, clinical trials and studies on the mechanism of action were carried out, highlighting the therapeutic advantages of Chinese medicine against liver fibrosis, as reflected in: (1) The emergence of new drugs or empirical formulas of Chinese medicine against liver fibrosis. Fuzheng Huayu Capsule (Tablet) is one of the representatives, which is composed of Cordyceps sinensis mycelium, Salvia miltiorrhiza, peach kernel, pine huang and gibberellic acid, and is a multicenter, randomized, double-blind, parallel-controlled treatment for chronic hepatitis B patients for 6 months, with liver histopathology as the main index of therapeutic efficacy. 216 patients, 93 patients with liver biopsy before and after the treatment for two times (50 cases in the group of Fuzheng Huayu Formula, and 43 cases in the control group), and the results show that Fuzheng Huayu Formula The results showed that the fibrosis reversal rate of Fuzheng Huayuquan reached 52% after treatment, which was significantly better than that of the control group (23%). Recently, it was found that Fuzheng Huayu capsule also had a better effect on the liver histology of hepatitis B cirrhosis. And the newly completed U.S. phase II clinical trial of Fuzheng Huayu Tablet against chronic hepatitis C liver fibrosis, the results confirmed the safety, tolerability and good effect trend of the product. Compound 861 Combination is composed of 10 traditional Chinese medicines such as Salvia miltiorrhiza, Astragalus membranaceus, Pericarpium Citri Reticulatae, Fragrant Forsythia, and Chickweed Vinegar, etc. It is used in multi-center observation of therapeutic effects on patients with chronic hepatitis B and early cirrhosis, 52 cases in the treatment group, 50 cases in the placebo group, and the results of liver histopathology confirm that the formula is effective in chronic hepatitis B liver fibrosis and early cirrhosis. (2) Formation of consensus on TCM evidence of liver fibrosis. After literature research, expert consultation and discussion, the Liver Disease Committee of the Chinese Society of Integrative Medicine formed the “Guidelines for the Diagnosis and Treatment of Liver Fibrosis in Integrative Medicine” in 2006, which concluded that the basic pathogenesis of hepatic fibrosis is “deficiency in the body, blood stasis”, with deficiency in the body being manifested by deficiency in qi and yin, and stasis in blood being manifested by blood stasis obstructing the collaterals. Of course, at different stages of hepatic fibrosis and in different patients, there are different signs and symptoms, mainly including liver and gallbladder dampness and heat, liver depression and spleen deficiency, and liver and kidney yin deficiency. However, on this basis, combined with the patient’s major syndromes, we should also add Yin Chen Artemisia Tang (liver and gallbladder damp-heat syndrome), Free and Easy Dispersion (liver-depression and spleen deficiency syndrome), or Consistent Decoction (liver and kidney yin deficiency syndrome), etc., respectively. The above consensus has effectively promoted the standardized development of TCM treatment of liver fibrosis over the past 7 years. (3) Preliminary establishment of a new strategy for the treatment of chronic hepatitis B with the combined application of anti-HBV and anti-hepatic fibrosis traditional Chinese medicine. In recent years, a large number of comprehensive therapeutic researches have been carried out in China for the two key links of HBV replication and fibrosis. The results of two systematic evaluations show that the serum hepatic fibrosis markers (HA, LN, P-III-P, IV-C) of Fuzheng Huayu Capsules combined with nucleoside analogues in the treatment of hepatitis B liver fibrosis are better than those of single antiviral therapy. Another systematic evaluation showed that compound turtle shell soft liver tablets combined with adefovir for the treatment of hepatitis B liver fibrosis showed better improvement in serum liver fibrosis markers than adefovir monotherapy group. Liu Jinxu et al. also observed the efficacy of IFNa-2b combined with Fuzheng Huayu capsule in the treatment of chronic hepatitis B. They found that the combination regimen was superior to that of IFNa-2b alone in terms of improvement of liver function and fibrosis markers. It shows that the combination of antiviral and antifibrosis can improve the clinical efficacy of chronic hepatitis B. Third, the development direction of Chinese medicine anti-hepatic fibrosis research Improvement of clinical efficacy is the fundamental purpose of therapeutic research, the current Chinese medicine anti-hepatic fibrosis research still exists in the design of the design is not rigorous, the evaluation indexes are not perfect, the mechanism of action of the combination of Chinese and Western medicines is not clear and so on, need to be optimized in the design of the program, improve the evaluation method, the development of new Chinese medicine and so on, in order to improve the therapeutic level. (1) Strengthen the clinical evaluation research, refine the design, and optimize the treatment plan. Although liver fibrosis is a common pathological feature of various chronic liver diseases, liver fibrosis caused by different etiologies still has its own characteristics in terms of specific pathological patterns and pathological mechanisms, for example, HBV liver fibrosis is dominated by the activation of the TGF-b/Smad2 signaling pathway, while HCV and schistosomiasis liver fibrosis may be dominated by the IL-13/Stat/ERK signaling pathway, which is manifested as different types of evidence in traditional Chinese medicine. The Chinese medicine manifests different types of evidence; moreover, liver fibrosis is a dynamic developmental process, which clinically manifests in different disease stages. Therefore, the combined application of etiologic treatment and anti-hepatic fibrosis herbal intervention should be designed in detail. Different etiologies lead to different interventions, e.g. nucleoside (acid) analogs or interferon for hepatitis B liver fibrosis, interferon and its direct antiviral drugs (Telaprevir, Boceprevir, etc.) for hepatitis C liver fibrosis, and immunosuppressant drugs for autoimmune hepatitis. Anti-hepatic fibrosis herbal medicines should be different for different types of TCM evidence. In the way of joint use, such as hepatitis B virus is difficult to clear, for hepatitis B liver fibrosis at the beginning that is the combination of the two; and hepatitis C virus can now be cleared, for hepatitis C liver fibrosis can be cleared HCV, and then anti-hepatic fibrosis Chinese medicine sequential treatment, and so on. (2) Strengthen the observation of clinical outcome. Hepatic fibrosis as a pathological form, the current common evaluation methods include liver biopsy, serum biochemistry, liver tissue hardness, etc., all of which have the problems of specificity and sensitivity. While the main clinical outcome of liver fibrosis is decompensated cirrhosis or hepatocellular carcinoma, both of which are easy to determine. Therefore, prolonging the observation time and using the incidence of end-stage cirrhosis or hepatocellular carcinoma as the endpoint indicator for efficacy evaluation can better evaluate the long-term benefits of anti-hepatic fibrosis treatment for patients with chronic liver disease, so as to establish a scientific and reliable clinical treatment program. (3) Improve the evaluation method of liver fibrosis. First, improve the pathologic evaluation. At present, the pathological analysis of collagen deposition in liver biopsy tissue has drawbacks such as “sampling error, reflecting static results, and subjective differences among pathologists”. The detection of α-smooth muscle actin (α-SMA) or platelet-derived growth factor receptor can be added to evaluate the activity of liver fibrosis. In addition, for the judgment of the degree of fibrosis, in addition to Ishak or Metavir staging, image scanning and quantitative analysis of the whole tissue section can be adopted to overcome the differences between the adjudicators and improve the reliability. Secondly, the determination of hepatic venous pressure gradient (HVPG), a functional indicator of hepatic fibrosis, should be actively carried out. HVPG is closely related to the fibrotic area and the number of nodules in liver histopathology, which not only directly reflects the portal pressure, but also serves as a functional indicator of hepatic fibrosis. In addition, the genetic background and risk factors of liver fibrosis should be emphasized. Individual differences often exist in the rate of development of liver fibrosis caused by the same etiology, therefore, in the selection of observation subjects, not only the etiological classification and pathological staging, but also the genetic background such as single nucleotide polymorphisms and risk factors should be taken into account, so as to make the baseline more balanced and consistent. (4) Research and development of innovative Chinese medicines based on the clinical experience and key pathological aspects of liver fibrosis in TCM. Over the past half century, Chinese medicine has accumulated rich clinical experience in anti-hepatic fibrosis, based on the advantages of the source of these experiences, based on the key pathological aspects of liver fibrosis, the combination of medicinal chemistry and pharmacology, screening, discovery of effective components, research and development of a new generation of Chinese medicine ingredients with superior efficacy, reliable quality control, clear mechanism of the compound product, will be the important research of Chinese medicine anti-hepatic fibrosis drug research in the future. The research of Chinese medicine anti-hepatic fibrosis drugs will be an important direction in the future. Chinese medicine believes that “prescription and evidence correspond to each other”, first of all, we can compare the efficacy of similar efficacy formulas in empirical prescriptions to find out the effective Chinese medicine compounds for specific symptoms or pathology models. Further, effective formulas can be further developed through optimization of formula compounding, compounding of effective components/ingredients of single-flavored tablets, efficacy evaluation and quality control. The improvement and application of technologies such as modern chemical extraction and separation and high-throughput and high-connotation bioactivity detection have made the discovery of complex active ingredients and their action characteristics of traditional Chinese medicine formulas possible. However, how to optimize the combination of active ingredients originated from different Chinese medicines with different characteristics so that they can exert greater effects is an important scientific issue to be explored. We conducted a preliminary study on the effector components and their combinations of Fuzheng Huayuquan, firstly, chemically characterizing the serum absorption components of the formula after oral administration, clarifying its pharmacokinetic pattern in an animal model of hepatic fibrosis, and then, taking the key signaling molecules of hepatic fibrosis as the target, we conducted computerized virtual screening of the active ingredients, and combined a variety of cellular and holistic model evaluations, and found that a variety of components were directed at hepatocellular injury, Finally, the active ingredients were recombined by the quantitative compounding technique of traditional Chinese medicine components, and then evaluated by in vitro cellular experiments, and several candidate ingredients were initially found to be compounded, laying the foundation for the subsequent research. At present, more experimental studies on anti-hepatic fibrosis drugs have been reported, but few new clinical drugs have been transformed. One of the main reasons is that there is a big difference between animal models and human hepatic fibrosis disease pathogenesis, which makes there is a gap between animal experiments and clinical efficacy, so it is especially important to strengthen and improve the evaluation of preclinical efficacy, and in addition to the evaluation of multiple models, the observation time window should also be diversified, so that not only the efficacy of the drug during the modeling period, but also the efficacy of the model establishment period, which is more important. In addition to the evaluation of multiple models, the observation time window should also be diversified, not only to observe the drug effect during the modeling period, but also to observe the drug effect after the modeling and stopping of drug dyeing. In addition to the pathological morphology of collagen deposition in liver tissue and the quantification of collagen biochemistry, it is also necessary to combine the activation of HSCs, neovascularization, and other pro-fibrotic indexes for a comprehensive evaluation. Through these efforts, it is expected to invent a new generation of anti-hepatic fibrosis herbal products from traditional Chinese medicine with better efficacy and quality than traditional ones.