Primary sclerosing cholangitis is a chronic cholestatic liver disease characterized by progressive inflammation, fibrosis and multiple strictures of the bile ducts. The etiology and pathogenesis of PSC are not yet clear, but may be related to genetic and immune mechanisms. the extent of PSC may involve both intrahepatic and extrahepatic bile ducts. some patients have typical cholestasis manifestations and histological features of PSC, but normal cholangiograms, which are currently considered to be a variant of PSC, called small bile duct PSC. The course of PSC is chronic and progressive, with most patients developing cholestasis, cholangitis, and eventually end-stage liver disease. 60-80% of patients with PSC have inflammatory bowel disease and about 20% have bile duct cancer. Currently, there is no definitive and effective treatment for PSC, except for liver transplantation. 1, the epidemiological characteristics of PSC Due to the large variability in the clinical manifestations of PSC and the lack of uniform diagnostic criteria, there is no exact incidence and prevalence statistics. The available information is mainly from the United States, Norway and other Western countries, whose studies have shown that the incidence of PSC is 0.9-1.3/100,000 and the prevalence is 8.6-13.6/100,000. About 70% of PSC patients are men, mostly aged 25-45 years, with an average age of onset of about 39 years. There is a lack of epidemiological data on PSC in China. 2, the diagnosis of PSC For the diagnosis of PSC there is a lack of uniform diagnostic criteria. At present, the diagnosis of PSC mainly includes three aspects: 1, biochemical manifestations of typical cholestasis; 2, bile duct imaging (including magnetic resonance cholangiography, endoscopic retrograde cholangiography or percutaneous transhepatic cholangiography) shows characteristic manifestations of PSC such as multifocal stenosis and segmental dilatation; 3, except for secondary factors that can cause sclerosing cholangitis, including long-term bile duct obstruction, infection, IgG4 related sclerosing cholangitis, etc. PSC can be diagnosed as small bile duct PSC when the clinical manifestations, biochemical indexes and histopathological features are consistent with PSC, but the cholangiogram is normal. (1) Clinical manifestations PSC patients have various clinical manifestations, and common symptoms include: malaise, skin pruritus, jaundice, abdominal discomfort, wasting, etc. Among them, intermittent skin pruritus, jaundice with right upper abdominal pain and fever are the most typical manifestations, which are associated with microstones or bile sludge discharge process. PSC patients have no specific signs, jaundice and hepatosplenomegaly are the most common signs. (2) Laboratory tests The most common and typical biochemical abnormality in patients with PSC is elevated serum ALP, usually 3-5 times the normal level, but there are still about 6% of patients with normal ALP, so normal ALP does not exclude PSC. most patients may have 2-3 times elevated serum transaminases. Bilirubin levels are usually fluctuating, and most patients have normal bilirubin at diagnosis. Serum IgG levels are moderately elevated in about 60% of patients. a variety of autoantibodies can be detected in the serum of patients with PSC, including anti-neutrophil cytoplasmic antibodies, anti-nuclear antibodies (ANA), anti-smooth muscle antibodies (SMA), anti-endothelial cell antibodies, and anti-cardiolipin antibodies, but they are generally low-titer positive and have no diagnostic value for PSC. (3) Imaging tests Traditionally, it is believed that endoscopic retrograde cholangiography (ERC) is the gold standard for the diagnosis of PSC. However, ERC is an invasive test and may lead to serious complications, such as injectable pancreatitis and bacterial cholangitis, and repeated multiple operations may also lead to bacterial colonization in the biliary system, which may result in progressive disease deterioration. The literature reports that approximately 10% of PSC patients undergoing ERC are hospitalized for operation-related complications. However, ERC also has the advantage that it can be performed simultaneously with bile duct cancer screening, such as bile duct cytology brushing or biopsy, and with bile duct dilation or stent placement. The literature reports similar complication rates after therapeutic ERC in patients with PSC and patients with other causes of biliary strictures. In contrast, magnetic resonance cholangiography (MRC) has become the imaging method of choice for the diagnosis of PSC because it is non-invasive and has comparable accuracy to ERC, with a diagnostic sensitivity of ≥80% and specificity of ≥87% for PSC. However, there are still some patients with early PSC that cannot be diagnosed by MRC and require ERC to confirm the diagnosis. The typical imaging presentation of PSC is bile duct “bead-like” changes, i.e. multiple, short segmental, circumferential bile duct stenoses with normal or mildly dilated interstitial bile ducts. Patients with progressive disease may show long stenoses and cystic or diverticular dilatation of the bile ducts. When the intrahepatic bile ducts are extensively involved, they may show “twig-like” changes, which are not easily distinguished from diffuse intrahepatic bile duct reduction due to cirrhosis of any cause. Approximately 75% of patients with PSC have both intrahepatic and extrahepatic bile duct involvement, while 15-20% have only intrahepatic bile duct lesions and only a very small number of patients have lesions limited to the extrahepatic bile ducts. Some patients may also have lesions of the gallbladder, cystic duct and pancreatic duct. Abdominal CT lacks specificity for the diagnosis of PSC, but it can show thickening and enhancement of the bile duct wall, cystic dilatation of the intrahepatic bile ducts, splenomegaly, ascites, lymph node enlargement, varices, and intrahepatic and bile duct occupying lesions, which can help in the staging and differential diagnosis of disease. The diagnostic value of the newly emerged CT bile duct imaging technique for PSC has not yet been reported in the literature. (4) Histological examination The typical liver pathology of PSC patients is onion skin-like bile duct fibrosis, but the acquisition rate of percutaneous liver puncture biopsy is only about 10%, and these manifestations can also be seen in secondary sclerosing cholangitis. The results of a retrospective study including 138 patients with PSC showed that liver aspiration biopsy did not provide additional diagnostic information when the diagnosis was confirmed by cholangiography in patients with PSC. Therefore, further liver aspiration biopsy is not required in patients with abnormal findings on bile duct imaging. However, when the clinical features are highly suspicious for small bile duct PSC or overlap syndrome, liver biopsy can help in the diagnosis and differential diagnosis. 3, PSC treatment Except for liver transplantation, there is no specific treatment for PSC, and the existing treatment mainly focuses on the complications of PSC, such as recurrent bacterial cholangitis, jaundice, bile duct cancer, liver failure, etc. Treatment methods include drug therapy, endoscopic intervention, surgical treatment and symptomatic support therapy. The most commonly used drug is ursodeoxycholic acid (UDCA), but studies have shown that although it can improve serum liver function test indicators, it cannot improve symptoms, much less the prognosis of PSC. It also increases the risk of death and liver transplantation when applied at high doses (28-30 mg/kg/d). Therefore, UDCA is not recommended in the treatment of PSC in the guidelines for the diagnosis and management of PSC developed by the American Association for the Study of Liver Diseases in 2010. As for glucocorticoids and immunosuppressants, there is no evidence of their definite therapeutic effect on PSC. However, they can be considered when PSC-AIH overlap or when PSC is combined with AIP. The main goal of endoscopic intervention is to relieve the symptoms of biliary obstruction in patients with PSC. Common methods include Oddi’s sphincter dissection, probe or balloon dilation, and stent placement. Although there is still a lack of clinical randomized controlled studies to assess the effectiveness of endoscopic interventions, several retrospective studies have shown that endoscopic interventions improve clinical symptoms and prolong survival in patients with PSC. Therefore, it is recommended that endoscopic intervention be considered first for severe strictures located in the common bile duct or hepatic duct, and that bile duct cell brushing or biopsy be performed during the procedure to exclude bile duct cancer; however, for diffuse stricture lesions located in the intrahepatic bile duct, endoscopic intervention not only does not benefit, but may also lead to serious complications such as ERCP-related cholangitis. Liver transplantation is currently the most effective treatment for PSC and is the only feasible treatment for the end stage of PSC. Clinical symptoms such as skin pruritus can be rapidly resolved in patients after surgery. The 5-year survival rate of PSC patients after liver transplantation can reach 83-88%, but 20-25% of patients still relapse within 5-10 years after surgery. Indications for liver transplantation in PSC patients, in addition to end-stage chronic liver disease, include intractable pruritus, recurrent bacterial cholangitis and cholangiocarcinoma. However, its use in clinical practice is limited due to the limited availability and high cost of transplanted livers.