1.General introduction There are many causes of liver diseases, including infections, drugs, poisoning, alcohol, tumors, metabolic and autoimmune damage, etc. Among them, Autoimmune Liver Diseases (ALD) is a group of liver diseases related to autoimmune damage, although the etiology and pathogenesis are not fully understood, but in patients with these diseases, different degrees of autoimmune phenomena are observed. Although the etiology and pathogenesis are not fully understood, various degrees of autoimmune phenomena have been observed in patients with these diseases. Autoimmune liver damage is commonly referred to as a disruption of the body’s immune system that damages the liver. It is characterized by liver damage accompanied by elevated serum immunoglobulins and the presence of multiple autoantibodies in the blood. As the most important parenchymal organ responsible for metabolism, the liver is mainly composed of hepatic parenchymal cells, blood vessels and bile ducts, etc. Autoimmune liver diseases can be divided into two categories, autoimmune hepatitis (AIH), which is characterized by inflammatory necrosis of hepatocytes, and autoimmune cholangiopathy, which is characterized by inflammatory damage to the biliary system of the liver, the latter including the common clinical primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), etc. The prevalence of autoimmune liver diseases varies, with autoimmune hepatitis accounting for about 20% of all chronic hepatitis in Western Europe and North America, and the prevalence of primary biliary cirrhosis and primary sclerosing cholangitis being 10-20 per 100,000 and 2-7 per 100,000, respectively. In China, there is a lack of statistical data from large samples of studies, but with the advancement of experimental diagnostic techniques, more and more patients with autoimmune liver disease are being diagnosed and are receiving more and more attention from clinicians. Similar to viral hepatitis, autoimmune liver disease, if not diagnosed and treated in time, can progress slowly to develop into serious conditions such as cirrhosis. 2. What are the difficulties in diagnosing autoimmune liver disease? What are the conditions that need to be thought of as having the possibility of autoimmune liver disease? Autoimmune phenomenon is the characteristic of autoimmune liver disease. Autoimmune liver damage occurs insidiously and progresses slowly, often without symptoms in the early stage, but about 20% of patients start with acute hepatitis and develop symptoms similar to those of acute viral hepatitis. Extrahepatic autoimmune symptoms, such as skin and joint damage similar to those common in other rheumatic diseases, are not obvious. In practice, many patients are found to have abnormal liver enzymes during physical examinations and are then diagnosed in detail, as not all hospitals are equipped to carry out autoantibody monitoring and liver biopsy pathology, resulting in many patients not being diagnosed early and clearly; secondly, there are many causes of liver diseases, and the incidence of autoimmune liver disease is relatively low. The incidence of autoimmune liver disease is relatively low, and some patients may have multiple causes of liver damage at the same time. In the case of autoimmune hepatitis, the diagnosis is mainly made through a combination of clinical manifestations and laboratory tests, and the exclusion method, which means that infections, drugs, alcohol and metabolic etiologies should be excluded one by one, combined with autoantibody testing and pathological examination of liver biopsy, and then a specific scoring system. Therefore, the early diagnosis of autoimmune liver disease is still difficult and not widely appreciated. For patients found to have liver damage (mainly abnormal liver enzymes), which cannot be explained by common causative factors such as viral infections, drugs, alcohol, etc., and the following conditions should be considered for this type of disease, and promptly cooperate with professional doctors for in-depth examination and early definitive diagnosis. If, in addition to hepatitis symptoms such as weakness, nausea and vomiting, autoimmune damage such as arthralgia, muscle pain and skin rash occurs, AIH should be considered; if abnormal liver enzymes are found along with abnormally elevated globulin, autoimmune liver disease should also be considered; a few patients with autoimmune hepatitis also have other autoimmune diseases, such as autoimmune thyroiditis, dermatomyositis, rheumatoid arthritis and dry syndrome For those who have autoimmune diseases in their family, they should also pay attention to screening for such diseases during routine physical examinations. 3.What are the common autoimmune liver diseases? Common clinical autoimmune liver diseases include: autoimmune hepatitis (AIH) primary biliary cirrhosis (PBC) primary sclerosing cholangitis (PSC), as well as having both AIN and PBC or PSC or other autoimmune diseases, called overlap syndrome. (1) Autoimmune hepatitis (AIH) Patient Liu, a 40-year-old female, was found to have elevated alanine aminotransferase (ALT) on physical examination for three consecutive years, and in the past six months, she came from a feeling of weakness, poor appetite, occasional generalized joint pain, and irregular menstruation. There was no history of special medication or alcohol consumption. After admission, liver function was investigated, alanine aminotransferase (ALT) 231 IU/L, aspartate aminotransferase (AST) 156 IU/L, globulin 43 g/L, albumin 39 g/L, hepatitis A, B, C, D and E virus serum markers were negative, serum immunoglobulin assay IgG 22 g/L. Ultrasound examination of the liver showed hepatic echogenicity with thickened and enhanced light spots. The spleen was normal in size. While viral hepatitis, drug-related hepatitis and fatty liver diseases were excluded, anti-nuclear antibody (ANA) 1:1000 was positive, anti-smooth muscle antibody was positive, and anti-liver and kidney microsomal antibody was positive. Further pathological examination of liver biopsy showed that the structure of liver lobules was still intact, hepatocytes were seen to have punctate necrosis, some hepatocytes showed rosette-like changes, lymphocytic infiltration in the confluent area, and fibrous tissue hyperplasia. The diagnosis of autoimmune hepatitis was confirmed and he was treated with prednisone 30 mg/day, which was gradually and slowly reduced, and the liver function returned to normal after three months. Autoimmune hepatitis is more common in women, with a male to female ratio of 4:1, and occurs mostly during menopause, accounting for 10%-15% of chronic liver disease in the United States, and no statistics are available in China, but with the promotion of relevant laboratory tests, more and more patients are being diagnosed. Some studies have found the existence of susceptibility genes for histocompatibility complex (MHC), suggesting that the disease has a certain genetic background. Most patients have no obvious clinical symptoms in the early stage, often chronic and progressive, with gastrointestinal symptoms such as nausea and weakness when the liver damage is severe, some patients will have skin and joint symptoms, and very few patients have acute attacks. In practice, most patients are found to have elevated ALT during physical examination, and further examination will reveal elevated blood gammaglobulin, mainly elevated IgG levels. 80% of patients are positive for some autoantibodies, mainly anti-nuclear and anti-smooth muscle antibodies, a few patients are positive for anti-liver and kidney microsomal antibodies, other autoantibodies that can be positive are anti-SLA/LP antibodies, neutrophil Other autoantibodies that may be positive include anti-SLA/LP antibodies, neutrophil cytoplasmic antibodies (P-ANCA), and hepatocyte-specific cytoplasmic antibodies (LC1). Liver biopsy will reveal characteristic interfacial hepatitis changes, rosette-like changes in hepatocytes, bridging necrosis in severe cases, and progression to cirrhosis. For the diagnosis of this disease, we must first exclude liver disease caused by viruses, drugs, alcohol and other factors, and combine with positive autoantibodies and pathological changes on liver biopsy to make a comprehensive score before we can determine the diagnosis. Autoimmune hepatitis can develop into cirrhosis if the diagnosis and treatment are delayed for a long time, so early diagnosis and treatment are emphasized. If it progresses to cirrhosis, the outcome and prognosis are poor, and if it progresses to severe liver failure, liver transplantation needs to be considered. For patients with autoimmune hepatitis, attention should be paid to maintaining a good state of mind, exercising moderately, avoiding strain and staying up late, avoiding alcohol, and eating greasy, spicy and stimulating foods. In recent years, some drug-induced autoimmune hepatitis has been observed, called drug-induced autoimmune hepatitis, for which special attention should be paid to avoid drug abuse, especially some health products of unknown composition should also be used with caution. (2) Primary biliary cirrhosis (PBC) Patient Li, a 52-year-old female, was admitted to the hospital with yellow eyes and urine with itchy skin for more than 3 months, and was found to have “yellow tumors” in the inner canthus of the eyelids bilaterally, moderate yellow sclera, scratch marks on the skin of the chest and back, and an enlarged left lobe of the liver. The liver function tests showed total bilirubin 60umol/L, direct bilirubin 56umol/L, alkaline phosphatase 467IU/L, g glutamyl transpeptidase 740IU/L, globulin 39g/L, cholesterol 6.2g/L. The patient was admitted to the hospital to exclude viral, drug, alcohol and other liver damage, inflammation of the biliary system, tumors and other diseases. The diagnosis of primary biliary cirrhosis was clearly made with positive serum anti-mitochondrial antibody and positive anti-mitochondrial antibody M2 typing. The patient was treated with ursodeoxycholic acid and glycyrrhetinic acid preparations, and the jaundice subsided after six months, and the condition improved. The histopathological features of the liver are non-suppurative granulomatous inflammatory destruction of small bile ducts and capillary bile ducts, with an incidence of 10-12 per 100,000, more than 70% being female, mostly during menopause, and some patients coexisting with other immune diseases such as rheumatoid arthritis and dry syndrome. At the beginning of the disease, patients mostly seek medical attention only when symptoms such as jaundice and itchy skin appear, so a considerable number of patients are found to have progressed to cirrhosis, and this stage is often characterized by intrahepatic cholestasis and hyperlipidemia. In recent years, with the popularity of health checkups, many patients have found elevated g glutamyl transpeptidase, alkaline phosphatase and globulin during physical examinations, which led to early diagnosis by in-depth examination of autoantibodies, while the patients had not progressed to cirrhosis at that time; therefore, many scholars suggest a name change for this disease to avoid misleading patients. A positive mitochondrial antibody (AMA) among autoantibodies is the characteristic of this disease, and the relevance of this antibody is greater in M2 type. a significant proportion of people who screen positive for AMA can develop this disease after several years of observation, so screening for AMA can help us to identify those who may develop this disease as early as possible, so as to improve the prognosis by early treatment. The current treatment for this disease is mainly ursodeoxycholic acid (UDCA), which has good efficacy in improving symptoms and alleviating disease progression. The application of corticosteroids is controversial, and the pros and cons should be weighed when applying them. Patients with PBC should abstain from alcohol, including all types of alcoholic beverages. The diet should be low in salt, fat, starch and high protein, with attention to vitamin D, E and K. Avoid spicy, greasy, cold and hard foods; avoid liver-damaging foods, drugs and health care products of unknown composition, as well as adjusting the mentality, exercising moderately and avoiding strain. Autoimmune hepatitis is mainly a manifestation of liver parenchymal cell damage, while primary biliary cirrhosis is mainly a manifestation of bile duct system damage, but it should be noted that about 10% of patients have both, which we call overlap syndrome. (3) Primary sclerosing cholangitis (PSC) But mostly seen in men, accounting for more than 70%, its clinical manifestations are similar to PBC, the incidence is low, most patients can be accompanied by ulcerative colitis, the pathology is mainly bold duct sclerosing inflammation, about 80% of patients have positive autoantibodies in blood pANCA, while AMA negative, in addition to the need to combine with cholangioscopy or retrograde cholangiopancreatography (ERCP) examination The diagnosis should be confirmed, and the treatment and precautions are the same as those for PBC. In conclusion, the etiology and pathogenesis of autoimmune liver disease are not fully understood. The current tendency is to believe that it is induced by poor lifestyle habits, exertion, viral infection, drugs and other factors in a certain genetic background. Due to the hidden clinical manifestations at the beginning of the disease, the symptoms are similar to viral hepatitis, and the diagnosis relies heavily on laboratory tests, which have not yet attracted widespread attention, the disease often progresses insidiously, resulting in the development of cirrhosis and even severe liver failure. For this reason, if liver damage is detected during physical examination, it is important to cooperate with a specialist for further investigation, and to have relevant autoantibodies measured and, if necessary, liver biopsy.