A 46-year-old woman with a diagnosis of cirrhosis was hospitalized and eventually died due to liver failure as her condition was advanced. The patient had been treated in several hospitals for quite a long time before hospitalization, and various viral hepatitis markers were negative, and there were no toxic, genetic and metabolic causes that could lead to chronic liver disease. Because of the unclear diagnosis, a number of Chinese and Western drugs were used without therapeutic effect. This hospitalization, after various laboratory tests, led to a clear diagnosis of autoimmune liver disease – primary biliary cirrhosis. Autoimmune liver disease is a kind of unexplained liver parenchymal damage disease closely related to autoimmune reaction. Autoimmune liver disease occurs worldwide, but there is a clear racial predisposition and genetic background. The prevalence is higher among Western Caucasians and used to be thought to be lower among Oriental peoples in Asia; in recent years, the incidence of autoimmune liver disease has been found to be increasing among Asians. Only isolated cases were reported in China before 1980, but now hundreds of cases have been reported in one hospital or region. The increase in incidence may be due to an increase in the actual number of cases, or it may be related to the increased awareness and alertness of clinicians to autoimmune liver disease and improvements in diagnostic methods. Autoimmune liver diseases mainly include autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, and overlapping syndromes between any two of these three diseases. Prevalence in adolescents and women Autoimmune hepatitis is mainly seen in adolescents, the majority of whom are 10 to 30 years old, with a peak incidence at 10 to 20 years of age and another peak age in menopausal women. The disease is more common in women, with a male to female ratio of 1:4-8. About 70% of patients have an insidious onset and gradually develop signs and symptoms of autoimmune liver disease. These signs and symptoms resemble those of chronic liver disease, such as loss of appetite, fatigue, weight loss, and amenorrhea. About 30% of patients have a sudden onset of the disease with clinical manifestations and laboratory findings similar to those of acute viral hepatitis, but negative for various viral hepatitis markers. After the acute phase, the patient’s symptoms and signs can last for several months and gradually develop into autoimmune hepatitis. In addition to the usual symptoms of hepatitis, patients have signs such as jaundice and liver enlargement. Serum bilirubin is usually elevated, but jaundice is absent in about 20% of patients. The liver enlargement is usually progressive, with right upper abdominal pressure pain, and rapidly progresses to cirrhosis. At this time, patients often have spider nevi and visible liver palms on the face, neck, and buttocks. Patients often have skin bruising, nosebleeds and bleeding gums. About 30% of patients already have cirrhosis at the time of diagnosis, and more than 40% have at least one concurrent immune disease such as thyroid disease and joint disease. Diagnosis by specific antibodies The diagnosis of autoimmune hepatitis must exclude viral, drug, alcoholic and hereditary liver diseases. Abnormal liver function and one or more autoantibodies such as antinuclear and anti-smooth muscle antibodies can be detected in the serum. Antibody titers often fluctuate during the course of the disease, and the level of antibody titers does not reliably reflect the severity of the disease. Most of these diagnostic antibodies are not disease-specific or organ-specific. Anti-soluble liver antigen/hepatic-pancreatic antigen is a specific antibody for autoimmune hepatitis, not seen in other liver diseases, and is a particularly valuable diagnostic marker for autoimmune hepatitis. Serum antinuclear and anti-smooth muscle antibodies may be negative in 20-30% of patients, and correct diagnosis often requires histopathological examination of the liver. Glucocorticoid therapy is effective Treatment of autoimmune hepatitis: Several trials have confirmed the efficacy of glucocorticoids in the treatment of autoimmune hepatitis. Prednisone alone or low-dose prednisone in combination with azathioprine resulted in symptomatic remission, improved laboratory abnormalities and histologic changes, and improved survival in severe patients. 65% of patients achieved clinical, biochemical, and histologic remission within 18 months and 80% within 3 years. 20-year survival was 80%. In contrast, 50% of patients with the same severity die within 3 years without treatment, and the 10-year mortality rate is as high as 90%. Autoimmune hepatitis is better treated than other immune-mediated or viral liver diseases, with 50% to 86% of cases that go into remission relapsing after drug withdrawal. 3% of patients experience treatment-related adverse effects that necessitate premature discontinuation. 9% of patients deteriorate despite standard therapy. 13% of patients improve but do not achieve a satisfactory level of disease (partial remission). The success of treatment depends on proper case selection, selection of an appropriate treatment regimen, treatment to the end point, and appropriate management of the unsatisfactory prognosis. Diagnosis of primary biliary cirrhosis Primary biliary cirrhosis is more common in women, with only 10% of cases in men. The age of onset is 20 to 90 years, with a mean age of onset of 50 years, and no cases in children have been reported. The progression of primary biliary cirrhosis is often unaware, and 48% to 60% of patients may have no clinical symptoms. These asymptomatic patients are sometimes diagnosed with primary biliary cirrhosis before the onset of symptoms, and such patients often present with elevated serum alkaline phosphatase and positive anti-smooth muscle antibodies. The most common clinical symptoms in patients are fatigue, lethargy and itching of the skin without jaundice. Jaundice may not appear throughout the course of the disease, but most appear 6 months to 2 years after the onset of pruritus, and about 1/4 of patients present with both jaundice and pruritus. The severity of pruritus does not necessarily correlate with the course of the disease and can occur early in the disease or at any stage of the disease. Physical examination may reveal a darker complexion and scratchy skin. The liver is often enlarged and hard, and there may be an enlarged spleen. In 80% of patients, various autoimmune diseases may be combined. Patients may present with syndromic manifestations such as dry mouth, dry eyes, arthritis, and thyroiditis. The disease should be considered in women over middle age with unexplained weakness, pruritus, hepatomegaly and/or splenomegaly, and elevated serum alkaline phosphatase and immunoglobulin M. Positive serum anti-mitochondrial antibodies are the most prominent immunological indicator of abnormalities in this disease. High titers of antimitochondrial antibodies may precede the abnormal clinical, biochemical and histological manifestations of primary biliary cirrhosis. Anti-mitochondrial antibodies are classified into nine subtypes, M1 to M9, of which M2 is specific for primary biliary cirrhosis. Ursodeoxycholic acid is the only drug approved for the treatment of primary biliary cirrhosis in the United States. Most advocate 13-15 mg per kg body weight per day and should be used for a long time or even for life. Diagnosis of primary sclerosing cholangitis Primary sclerosing cholangitis occurs mostly in Caucasians, more in men than in women, with a male to female ratio of 2:1. 40% of patients with primary sclerosing cholangitis are asymptomatic. Symptoms include malaise, itchy skin and jaundice. Half of the physical examinations have hepatomegaly and splenomegaly, jaundice and skin pigmentation. There is a more rapidly progressive course in patients with symptomatic primary sclerosing cholangitis. Studies have shown that 41% of patients with primary sclerosing cholangitis with 6-25 years of follow-up develop liver failure, with a mean period survival of 11.9 years. Laboratory tests: elevated serum alkaline phosphatase is the main feature of the disease, usually elevated about 3-fold; elevated serum bilirubin levels are variable and fluctuate, but rarely exceed 170 μmol/L. Anti-neutrophil plasma antibodies are often positive, with a positive rate of 60% to 80%. Retrograde cholangiopancreatography and bile duct magnetic resonance imaging are most diagnostic for this disease. The aim of treatment is to slow down the progression of the disease and cholestatic complications, and liver transplantation is the only effective treatment.