The diagnosis of PBC needs to be considered when there are signs of cholestasis [elevated alkaline phosphatase (ALP) and gamma-glutamyl transaminase (GGT)] on liver function tests and extrahepatic cholestasis (mechanical biliary obstruction) has been excluded. 2009 AASLD recommended criteria for the diagnosis of PBC are. (1) the presence of biochemical evidence of cholestasis, mainly elevated ALP; (2) positive anti-mitochondrial antibody (AMA); and (3) histological evidence of nonsuppurative destructive cholangitis as well as interlobular bile duct destruction. If AMA is positive, liver aspiration biopsy is not necessary for the diagnosis of PBC, but it can help to clarify the activity and stage of the disease. Meng Fanping, Department of Hepatology, PLA 302 Hospital It should be noted that positive AMA is not only seen in PBC, but also in AIH, idiopathic thrombocytopenic purpura, systemic sclerosis, lymphoma, etc. Therefore, it is necessary to combine with biochemical indexes to further clarify the diagnosis. It is controversial whether AMA positive patients without clinical and biochemical manifestations of cholestasis will progress to PBC, and close follow-up is needed for these patients. For AMA negative patients, anti-nuclear antibody subclasses with high specificity for PBC, such as anti-sp100, anti-gp210, anti-p62, anti-sp140, etc., can be detected; if still negative, liver histological examination is required. Usually PBC can have mild transaminase elevation, but if ALT > 5ULN, IgG > 2ULN or anti-smooth muscle antibody is positive, the possibility of PBC-AIH overlap syndrome needs to be considered and liver histology should be performed to clarify the diagnosis as soon as possible. Most PBC patients have a good biochemical response to UDCA, and those with a good early biochemical response have the potential to improve long-term prognosis; however, more large-scale clinical trials are needed to confirm alternative treatment for patients with a poor UDCA response. Treatment: UDCA is the only effective drug Currently, ursodeoxycholic acid (UDCA) remains the only effective drug approved for the treatment of PBC, and the recommended dose of UDCA for the treatment of PBC in both the AASLD and EASL guidelines is 13-15 mg/(kg?d) orally for a long period of time. Previous studies have shown that UDCA can improve biochemical and immunological parameters [including reduction of serum transaminases, ALP, bilirubin and serum immunoglobulin (IgM)] in PBC patients, but it is controversial whether it can delay histological progression and reduce mortality and liver transplantation rates. In a recent prospective, multicenter, cohort study from the Netherlands, 225 PBC patients with normal baseline serum bilirubin and albumin levels treated with UDCA 13-15 mg/(kg?d) for 1.1-17.3 years resulted in significant biochemical improvements within 1-3 years of treatment, and biochemical responses persisted until 15 years after treatment; as treatment duration increased, serum As the treatment time increased, the serum bilirubin level gradually increased and albumin level gradually decreased, but the fluctuation range was small and the average value was still within the normal range. Recent studies have shown that the early biochemical response to UDCA treatment (1 year) is important in predicting long-term efficacy and survival. Current criteria for evaluating good biochemical response include “Paris criteria” and “Barcelona criteria”, the former referring to a total serum bilirubin level ≤ 17.1 μmol/L (1 mg/dl), AST ≤ 2 ULN, and ALP ≤ 3 ULN at one year after UDCA treatment. 2ULN, ALP≤3ULN; the latter refers to the decrease of serum ALP by 40% or to normal. Regardless of which criteria are applied, those with a good early response have a better long-term prognosis. The EASL guidelines suggest that UDCA combined with budesonide (6-9 mg/d) may be given to patients without cirrhosis (histological stage 1 to 3); American authors also believe that the benefits of immunosuppressive therapy in PBC patients with poor UDCA response outweigh the risks. Recently, Rabahi et al. applied the triple combination of UDCA, budesonide, and mortification to treat 15 non-cirrhotic PBC patients with poor UDCA response, and showed that six patients had complete normalization of biochemical parameters and seven had partial biochemical response, as well as significant improvement of histological inflammatory activity and fibrosis. In addition, methotrexate and fibrate lipid-lowering drugs have been tried for the treatment of patients with poor UDCA response.