In my clinical practice, I often encounter patients with chronic hepatitis who are anxious to come to the hospital because they are worried about liver fibrosis; there are also patients who have been suffering from fatty liver for several years but have never sought medical attention, and have to come to the hospital when they hear about the risk of developing liver fibrosis. On the contrary, there are also patients with liver disease who have liver fibrosis but do not pay attention to it and do not want to treat it with medicine, thinking that cirrhosis is a distant thing and it is not too late to treat it after a few years. As a medical worker who has been engaged in liver fibrosis research for 25 years, I have the obligation to tell the majority of liver disease patients about liver fibrosis, never take liver fibrosis lightly and never ignore the treatment of liver fibrosis. 1.What is liver fibrosis? Liver fibrosis is a liver lesion that accompanies a variety of chronic liver diseases and is not yet considered an independent disease. To understand fibrosis, let’s make a common analogy. If we break the skin somewhere on the surface of our body, there will be a wound and when it grows back, it will leave a scar. This scar is formed by fibrous tissue, and the process of scarring is called fibrosis. If the wound is small and the incision is neat, the defective part is mainly repaired by the original skin tissue proliferation, the scar formed is less and the degree of fibrosis is light; on the contrary, if the wound is large and the incision is not neat, the defective part has to be filled by fibrous tissue, so the scar formed is large and the degree of fibrosis is heavier. The liver fibrosis situation is similar to this scarring process, but the site of scarring is in the liver. If the hepatocytes damaged by inflammation in the liver are removed by the body after necrosis, and the defective area is repaired by proliferating hepatocytes, the degree of liver fibrosis is light or even no fibrosis; if the defective area is filled by proliferating fibrous tissue, the degree of liver fibrosis is heavier; if the fibrous tissue keeps proliferating and invades into the liver tissue, destroying the structure of normal liver tissue, forming many nodules surrounded by fibrous tissue, and the texture of the liver This is cirrhosis. It can be seen that liver fibrosis is a concept of pathological process, and the relationship between liver fibrosis and cirrhosis is a quantitative to qualitative change. The pathologists classify the pathological changes of liver fibrosis into 4 levels, called “stages”, which are indicated by S. S1 indicates the lightest degree of liver fibrosis, while S4 indicates the heaviest degree of liver fibrosis, which has reached the degree of early cirrhosis. 2.What liver diseases are associated with liver fibrosis? Generally speaking, chronic liver diseases are associated with liver fibrosis due to persistent liver damage. Chronic hepatitis B is the most common chronic liver disease in China, and chronic hepatitis C is not uncommon. Both types of hepatitis are caused by hepatitis virus replication, which stimulates the body’s immune system and causes immune lymphocytes to “accidentally” injure liver cells when removing the virus, resulting in inflammation in the liver and inducing fibrous tissue proliferation, leading to liver fibrosis. With the improvement of people’s living standard, the incidence of alcoholic liver disease and non-alcoholic liver disease in China has been increasing. The more serious lesion of these two liver diseases is steatohepatitis. If not actively treated, the damaged liver cells can also stimulate the massive proliferation of fibrous tissue in the liver and develop from liver fibrosis to cirrhosis. Hepatocellular carcinoma is the most aggressive of all liver diseases and is often accompanied by cirrhosis. Other diseases, such as drug-related liver disease, metabolic liver disease, autoimmune liver disease or schistosomiasis, are also associated with liver fibrosis. As each patient’s physical condition and morbidity are different, the degree of fibrosis may not be proportional to the degree of the disease or the length of the disease. 3.What are the consequences of liver fibrosis? First, due to the destruction of liver tissue structure, the intrahepatic blood vessels are distorted by compression, atresia or “short-circuit” anastomosis between arteries and veins, resulting in increased vascular resistance in the portal vein system and portal hypertension, leading to splenomegaly, ascites generation and esophageal varices in the fundus of the stomach, with the potential risk of upper gastrointestinal varices The second is that the blood microcirculation channels between normal liver cells cause circulatory disorders due to the deposition of fibrous tissue components, which affects the blood supply to liver cells, making it difficult to repair the liver cells damaged by inflammation or even aggravate the damage, until the normal functioning liver cells become less and less, finally leading to liver failure. Both hazards are fatal. 4, liver fibrosis need treatment can be cured? Since liver fibrosis causes great and life-threatening harm, it must be treated. Since liver fibrosis is the path to cirrhosis in the end of various chronic liver diseases, anti-fibrosis treatment at this stage can stop or slow down the occurrence of cirrhosis. Even after liver cancer surgery, concomitant cirrhosis needs to be treated by anti-fibrosis. As the late Professor Hans Popper, a founding father of modern hepatology and an authority on hepatology, once noted, “Whoever can prevent or mitigate liver fibrosis will be able to cure most chronic liver diseases.” More than 10 years ago, liver fibrosis was considered irreversible. After years of tireless efforts by researchers to prove that liver fibrosis and even early cirrhosis can be reversed, the study of liver fibrosis has become a popular topic in hepatology. As with the treatment of most diseases, early diagnosis and treatment are important in the treatment of liver fibrosis and help to reduce, reverse or even cure it. For patients with cirrhosis, anti-fibrotic treatment can slow down the rate of disease progression and prolong life. 5.How to diagnose liver fibrosis? The most reliable method to diagnose liver fibrosis is liver aspiration for pathological examination, which is the internationally recognized “gold standard”. Abdominal ultrasound, CT and magnetic resonance imaging (MRI) can detect the more severe forms of liver fibrosis. The four so-called serological indicators of liver fibrosis: hyaluronic acid (HA), laminin (LM, also called LN), precollagen type III (P-III-P) and collagen type IV (IV-C), do not exactly correspond to the “gold standard” in liver fibrosis, and the relationship between elevated HA and liver fibrosis is probably more plausible among the four. The relationship between elevated HA and liver fibrosis is relatively more plausible. Since it is not easy for patients in China to undergo invasive liver puncture, the diagnosis of liver fibrosis is currently based on a combination of medical history, ultrasound and HA indicators, which is often not an early diagnosis. It is recommended that the majority of patients change their mindset and undergo liver puncture pathology as early as possible, as foreign patients do. Nowadays, the instruments for percutaneous liver puncture are advanced and quite safe. If the puncture is performed under laparoscopy, it is more intuitive and safer. 6.How to treat liver fibrosis? There is no safe and effective western medicine for the treatment of liver fibrosis. Chinese and Western liver disease researchers in China have diligently tapped into the treasures of Chinese medicine in the past 20 years, and developed some effective herbal compound preparations for the prevention and treatment of liver fibrosis, reflecting the advantages of Chinese medicine in anti-liver fibrosis. Our “Fuzheng Huayu Capsules” developed by the Institute of Liver Diseases of Shanghai University of Traditional Chinese Medicine, which has been a national basic medical insurance and work injury insurance drug since 2004, has a clear effect on reversing liver fibrosis. The drug is safe and has no significant side effects. The new dosage form of the drug, Fu Zheng Hua Yu Tablets, has been approved by the U.S. Food and Drug Administration and is in phase II clinical trials for the treatment of chronic hepatitis C in the United States. Anti-fibrotic therapy is the basic treatment for liver cirrhosis. Even if cirrhosis is accompanied by esophageal varices, it can still be treated with “Fu Zheng Hua Yu”. Our latest clinical study showed that patients with cirrhosis with esophageal varices who took “Fuzheng Huayu capsule” within 2 years did not increase the risk of upper gastrointestinal bleeding, but reduced the incidence of upper gastrointestinal bleeding, and some patients’ mildly varicose esophageal veins were no longer varicose. This result is related to the improvement of intrahepatic microcirculation through anti-fibrosis of “Fu Zheng Hua Yu Capsules”, thus reducing portal hypertension. 7.What is the relationship between etiological treatment and anti-fibrotic treatment? Hepatitis B and C viruses, alcohol, certain drugs or auto-antibodies, schistosomes, etc. are common causes of liver fibrosis formation. If these causes are removed at the beginning of liver disease, the fire of liver fibrosis will not burn. However, when liver disease enters the chronic stage, the fire of liver fibrosis will burn automatically, because the cells DD hepatic stellate cells, which play a key role in the formation of liver fibrosis, once activated by the causes, can continuously activate themselves, just like becoming automatic burning “firewood” that is not easy to extinguish, will continue to produce fibrous material and gradually increase the degree of fibrosis. The degree of fibrosis will gradually increase. At this time, the above mentioned causes are like “oil”, and the fire is helped by oil, the “fire” of liver fibrosis will burn more and more vigorously. Etiological treatment (e.g. antiviral, alcohol cessation, discontinuing liver-damaging drugs, suppressing autoantibodies, killing schistosomes, etc.) is the best way to stop the fire, while the anti-fibrotic treatment is the best way to get rid of the fuel at the bottom. The mechanism is that etiological treatment can reduce inflammation in the liver, reduce hepatocyte damage, and thus reduce the activation of hepatic stellate cells; while anti-fibrotic treatment can improve liver blood microcirculation by reducing intrahepatic fibrous tissue, thus allowing liver cells to receive more blood nutrients, and also allowing more and better contact with hepatocytes for the antiviral drug components absorbed in the blood to exert their drug effects. Single cause treatment is equivalent to not pouring oil on the fire, but the fire is still burning, so after the cause of the disease is removed, patients with chronic liver disease generally still need anti-fibrotic treatment. If the cause of the disease cannot be eliminated, then simple anti-fibrotic treatment will not put out the “fire”, but it can reduce the “fire”, although it will not achieve the desired effect, but it is better than doing nothing in front of the fire, allowing the fire to spread and doing nothing. The anti-fibrotic treatment at this time is not likely to reverse liver fibrosis, but it is possible to slow down the progress of liver fibrosis or stop its development. Patients with normal hepatitis B “minor tri-positive” liver function are generally not recommended for antiviral therapy because of the poor efficacy. However, being unsuitable for antiviral therapy is not the same as not being treated. It is often found that this group of patients can progress to cirrhosis after several years, because the pathological changes of inflammation and fibrosis in their liver have existed for a long time and have been progressing, and because the patients are unwilling to undergo pathological examination by liver aspiration, the doctors do not know the actual situation of liver lesions in these patients. We recommend that patients with hepatitis B “minor triple-positive”, if the liver transaminase activity is within the normal range but close to the upper limit of the normal value, it is best to have a liver puncture pathology examination to clarify whether there is inflammation and fibrosis in the liver, so that timely and targeted treatment can be provided. If the patient really does not want to undergo liver puncture, it is recommended not to refuse liver-protective and anti-fibrotic treatment. Although the history of human war on liver fibrosis is not long, significant progress has been made. With the deeper understanding of the mechanism of liver fibrosis, there will be more effective anti-liver fibrosis Chinese and Western drugs and biological drugs from the laboratory to the clinic. The goal of defeating liver fibrosis will be achieved.