Treatment of jaundice in Chinese medicine for chronic severe hepatitis

  Chronic severe hepatitis is a type of disease that leads to liver failure based on chronic liver disease, which is difficult to treat and has a morbidity and mortality rate of more than 70%. In recent years, the combined treatment of Chinese and Western medicine has reduced the death rate of chronic severe hepatitis to about 60%, but the modern medical mechanism of its effect is not clear. Our center is the vice leader of the “11th Five-Year Plan” TCM key specialty-hepatitis group of the State Administration of Traditional Chinese Medicine, and the key laboratory of heavy hepatitis in Hunan Province, and we have done a lot of research on the TCM treatment and mechanism of chronic heavy hepatitis. Now, from the perspective of specific cellular immunology, we will elaborate on the mechanism of TCM jaundice treatment for chronic heavy hepatitis and briefly introduce the research conducted by our center in this field.  It is known that the immune system-mediated liver damage is the primary pathogenesis of chronic severe hepatitis, and the immune damage caused by HBV is dominated by cellular immunity and supplemented by humoral immunity. The main immune cells involved in the cellular immune process include: dendritic cells (DC) and Kupffer cells (Kupffer), cytotoxic T lymphocytes (CTL), natural killer (NK) cells/natural killer T lymphocytes (NKT) cells, etc. And the immune status and cytokine expression vary in different stages of chronic severe hepatitis: 1.1 Early stage of chronic severe hepatitis, the body’s cellular function is hyper-immune, and inflammatory factors are over-released. The liver is dominated by immune damage of CTL, NK and other cytokines, and a large number of cellular inflammatory factors are activated. The number of CD4+ and CD8+ T lymphocytes expressed in the liver increases significantly, and cellular inflammatory factors such as tumor necrosis factor α (TNFα), scrambler (IFN)α, IFN-γ, interleukin (IL)-6, IL-1, etc. are significantly increased, when hepatocytes have not yet developed large sheets of necrosis and are in the disease progression stage. As endotoxin-tumor necrosis factor activates waterfall-like inflammatory factors and continues to activate, leading to inflammatory response syndrome (SIRS), which in turn is causally related to hepatocyte necrosis, aggravating liver injury and continuing disease progression. If the hyper-immune response, which is the initiating factor of liver failure, can be suppressed and the excessive release of inflammatory factors can be inhibited, the disease can be effectively controlled.  1.2 Immunosuppression of cellular function and enhanced expression of anti-inflammatory cytokines in the middle and late stages of liver failure Due to the persistent SIRS, IL-4, IL-10 and other anti-inflammatory cytokines increase compensatingly, causing the compensatory anti-inflammatory response syndrome (CARS) of the body, which results in extensive immunosuppression and puts the body in an “immune paralysis state The result is widespread immunosuppression, leaving the body in a state of “immune paralysis”. This is characterized by apoptosis of a large number of activated CD4+ T cells within a short period of time, a decrease in peripheral blood CD4+ and CD8+ lymphocyte counts, “depletion” of lymphocytes in liver tissues, decreased expression of HLA-DR molecules on the surface of mononuclear macrophages, and decreased antigen-presentation ability. Based on this mechanism, the direction of treatment at this stage is to positively regulate the body’s immunity, restore the activity and antigen-presenting ability of monocytes, regulate the number and distribution of peripheral blood T cells, and reduce the expression of anti-inflammatory cytokines.  2, Chinese medicine jaundice treatment (Yang Huang – Yin Huang) exists in two different stages of immune status (immune enhancement – suppression) 2.1 Chinese medicine jaundice treatment exists in two different stages of immune status of the theoretical basis of Chinese medicine chronic heavy hepatitis belongs to the category of Chinese medicine “jaundice”, divided into Yang Huang and Yin Huang two types of treatment. In the Yuan Dynasty, the system of differentiation and treatment of yin and yang yellowness was systematized and inherited to this day. The treatment of Yang Huang and Yin Huang is based on “clearing heat and relieving dampness” and “warming yang and strengthening the spleen” respectively, with Yin Chen Artemisia Tang (Gan Lu Disinfectant Dan) and Yin Chen Artemisia with Tang as the representative formula. As early as the Jin dynasty Cheng Wuji found: “…… began to get Yang evidence, to cold treatment, cold and excessive, change Yang for Yin also. Jaundice at the beginning, more with the gradual increase of evil, but the pathological characteristics of the right qi does not decline, for Yang Huang is a real evidence; Yang Huang day long, the evil qi (moisture, heat, stasis, poison) gradually consume the right qi, or vegetative deficiency of the right qi, damage to the spleen Yang, wet from the cold, it is transformed into Yin Huang, mostly deficiency, and mixed with deficiency, so Yin Huang is mostly a symptom of liver disease in the late stage.  2.2 Cellular immunological mechanism of different immune status in the treatment of jaundice in TCM There are few reports on the study of yin and yang yellowness in chronic heavy hepatitis based on specific cellular immunological mechanism, in clinical practice, we found that the TCM pattern of chronic heavy hepatitis is a gradual evolution from yang yellowness to yin yellowness. At the same time, many scholars have confirmed that: Yang Huang is in the early stage of the disease, the condition is urgent, the body is hyper-immune and the inflammatory response of liver cells is obvious; Yin Huang patients are in the late stage of jaundice, immune dysfunction and low immune function, but the mechanism and substance are not completely clear. Based on the theoretical basis of Chinese medicine that “dampness is transformed from heat to yang yellowness and dampness is transformed from cold to yin yellowness”, it may be a breakthrough to study the substance of yin yellowness and yang yellowness.  2.2.1 Damp-heat evidence of hyperactive cellular immunity and overreaction of inflammatory factors, “clearing heat and dampness” method can inhibit the immune response and expression of inflammatory cytokines Recent studies have found that “damp-heat evidence” in Chinese medicine is closely related to immunity. Patients with “damp-heat syndrome” have an imbalance in the ratio of T-lymphocyte subsets, especially a significant decrease in CD8+ suppressor T-cells and an increase in CD4+/CD8+ ratio, suggesting the enhancement of immune function in patients with “damp-heat syndrome”; at the same time, it was found that At the same time, it was found that TNFα, IFNα, IL-6 and other cellular inflammatory factors were significantly increased in patients with “damp-heat evidence”. The method of “clearing heat and dampness” can significantly reduce the number of CD4+ cell expression of helper T cells, lower the body’s immune response and reduce the immune damage of the liver; at the same time, it can suspend the transcription of NF-κBp, the central mediator of inflammatory response, and reduce the expression of TNFα, IL-6 and other cellular inflammatory factors, thus inhibiting the inflammatory response.  2.2.2 Cellular immune function is suppressed in the evidence of spleen-kidney yang deficiency, and the method of “warming the Yang and strengthening the spleen” can enhance cellular immune function and reduce the expression of anti-inflammatory cytokines. The study found that the peripheral blood T-lymphocyte subpopulation of patients with chronic hepatitis B also had abnormalities [21], and the CD4+ and CD4+/CD8+ ratios decreased significantly, suggesting that the immune function of patients with spleen-kidney yang deficiency was significantly lower. CD8+ ratio, increase the secretion level of IFN-γ and IL-2, and decrease the expression number of CD8+ cells, thus improving the cellular immune function of the body. It was also found that the method of “warming the Yang and strengthening the spleen” can reduce the expression of anti-inflammatory cytokines IL-4 and IL-10, thus regulating the balance of “anti-inflammatory cytokines/anti-inflammatory cytokines” and preventing the occurrence of CARS.  3.The current research work of our center in this field Dendritic cells (DC) are the strongest antigen presenting cells (APC) in the body and play a key role in the specific immune response in liver failure. With DC function test as the entry point, our center has conducted in-depth research on the pathogenesis of chronic viral hepatitis and its severe disease, and the mechanism of Chinese medicine intervention from the perspective of specific cellular immunology. At present, we have mastered the techniques of culture and detection of dendritic cells, and we have also found that patients with liver depression and spleen deficiency and those with liver-biliary damp-heat symptoms both exhibit peripheral blood DC phenotype deficiency and function downregulation under different states of HBV chronic infection, but patients with liver-biliary damp-heat symptoms have relatively higher cellular immune function. The peripheral blood DC function was significantly lower in patients with chronic type B severe hepatitis with yin-yang evidence than in patients with yang-yang evidence. By tonifying the kidney and strengthening the spleen method can promote the maturation of peripheral blood DC function in patients with different immune status of HBV chronic infection. The above research work has laid the foundation for the application of specific cellular immunology to elaborate the mechanism of TCM jaundice treatment in chronic heavy hepatitis, and we will further strengthen our research on DC function in patients with different evidence of chronic heavy hepatitis in TCM in the future.