Most patients are currently diagnosed when asymptomatic, having been referred to the hepatologist for abnormal liver function tests (mostly raised GGT or alkaline phosphatase) performed for annual screening blood tests. Other frequent scenarios include screening of patients with nonliver autoimmune diseases, e.g. rheumatoid arthritis, or investigation of elevated cholesterol, evaluation of itch or unresolved cholestasis post partum. Diagnosing PBC is generally straightforward. The basis for a definite diagnosis are: * Abnormalities in liver enzyme tests are usually present and elevated gamma-glutamyl transferase and alkaline phosphatase are found in early disease. Elevations in bilirubin occur in advanced disease. * Antimitochondrial antibodies are the characteristic serological marker for PBC, being found in 90-95% of patients and only 1% of controls. PBC patients have AMA against pyruvate dehydrogenase complex (PDC-E2), an enzyme complex that is found in the mitochondria. Those people who are AMA negative but with disease similar to PBC have been found to have AMAs when more sensitive detection methods are employed. * Other auto-antibodies may be present: :: Antinuclear antibody measurements are not diagnostic for PBC because they are not specific, but may have a role in prognosis. :: Anti-glycoprotein-210 antibodies, and to a lesser degree anti-p62 antibodies, correlate with the disease's progression toward end-stage liver failure. Anti-gp210 antibodies are found in 47% of PBC patients. ::Anti-centromere antibodies often correlate with developing portal hypertension. ::Anti-np62 and anti-sp100 are also found in association with PBC. * Abdominal ultrasound, magnetic resonance cholangiopancreatography or a CT scan is usually performed to rule out blockage to the bile ducts. This may be needed if a condition causing secondary<unk>  cirrhosis, such as other<unk>  duct disease or gallstones, needs to be excluded. A liver biopsy may help, and if uncertainty remains as in some patients, an endoscopic retrograde cholangiopancreatography, an endoscopic investigation of the bile duct, may be performed. Given the high specificity of serological markers, liver biopsy is not necessary for the diagnosis of PBC; however, it is still necessary when PBC-specific antibodies are absent, or when co-existent autoimmune hepatitis or nonalcoholic steatohepatitis is suspected. Liver biopsy can be useful to stage the disease for fibrosis and ductopenia. Finally, it may also be appropriate in the presence of other extrahepatic comorbidities. Image:Primary<unk>  cirrhosis low mag.Low-magnification micrograph of PBC, H&E stain Image:Primary<unk>  cirrhosis intermed mag.Intermediate-magnification micrograph of PBC showing bile duct inflammation and periductal granulomas, liver biopsy, H&E stain File:ANA NUCLEAR DOT AND AMA.Immunofluorescence staining pattern of sp100 antibodies (nuclear dots) and antimitochondrial antibodies Liver biopsy On microscopic examination of liver biopsy specimens, PBC is characterized by chronic, nonsuppurative inflammation, which surrounds and destroys interlobular and septal bile ducts. These histopathologic findings in<unk>  include: * Inflammation of the bile ducts, characterized by intraepithelial lymphocytes * Periductal epithelioid granulomas. * Proliferation of bile ductules * Fibrosis (scarring) The Ludwig and Scheuer scoring systems have historically been used to stratify four stages of PBC, with stage 4 indicating the presence of cirrhosis. In the new system of Nakanuma, the stage of disease is based on fibrosis, bile duct loss, and features of cholestasis, i.e. deposition of orcein-positive granules, whereas the grade of necroinflammatory activity is based on cholangitis and interface hepatitis. The accumulation of orcein-positive granules occurs evenly across the PBC liver, which means that staging using the Nakanuma system is more reliable regarding sampling variability. Liver biopsy for the diagnosis and staging of PBC lost favour after the evidence of a patchy distribution of the duct lesions and fibrosis across the organ. The widespread availability of noninvasive measures of fibrosis means that liver biopsy for staging of PBC is somewhat obsolete. Liver biopsy does, however, remain useful in certain settings. The main indications are to confirm the diagnosis of PBC when PBC-specific antibodies are absent and confirm a diagnosis of PBC with AIH features (i.e. overlap PBC-AIH). Liver biopsy is also useful to assess the relative contribution of each liver injury when a comorbid liver disease is present, such as non-alcoholic steatohepatitis. In patients with inadequate response to UDCA, liver biopsy may provide the explanation and could undoubtedly inform risk stratification. For example, it may identify a previously unsuspected variant syndrome, steatohepatitis, or interface hepatitis of moderate or greater severity. It is also useful in AMA and ANA-specific antibody negative cholestatic patients to indicate an alternative process, e.g. sarcoidosis, small duct PSC, adult idiopathic ductopenia.
Primary biliary cholangitis
Autoimmune hepatitis
Secondary sclerosing cholangitis
Primary sclerosing cholangitis
Ischemic hepatitis
Alcoholic hepatitis
Hepatolithiasis
Biliary pseudolithiasis