Improvement of diagnostic tools, increasing disease awareness, and digitised patient registration with facilitation of case-findings, along with improved survival, likely contributed to the rising prevalence rates. The disease has been described worldwide, though North America and Northern Europe have shown the highest incidence and prevalence rates. Whether a true variation in disease prevalence exists among populations of different geographical areas and of different ethnicity or if this is a consequence of a difference in study quality is unknown. PBC is more common in women, with a female:male ratio of at least 9:1. The peak incidence of PBC is in the fifth decade of life. In some areas of the US and UK, the prevalence is estimated to be as high as one in 4,000. This is much more common than in South America or Africa, which may be due to better recognition in the US and UK. First-degree relatives may have as much as a 500 times increase in prevalence, but if this risk is greater in the same-generation relatives or the one that follows is debated. PBC is considered a prime example of the female preponderance in autoimmunity with a female to male ratio of up to 9:1, confirmed by large cohort studies, although some recent data, using administrative registries, suggest an increasing male prevalence. Major defects of sex chromosomes, i.e.
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 diseases 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 biliary cirrhosis, such as other biliary 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.