[1] The reasons for this disparity are unclear, but may involve the expression of sex hormones such as estrogen, which impact immune system response.

[8] Because cirrhosis is a feature only of advanced disease, a change of its name to "primary biliary cholangitis" was proposed by patient advocacy groups in 2014.

Comorbidities that could contribute to or worsen fatigue, such as depression, hypothyroidism, anaemia, obesity, or medication side effects, should be promptly identified and treated.

This, in turn, may lead to a number of symptoms or complications, including: People with PBC may also sometimes have the findings of an associated extrahepatic autoimmune disorder such as thyroid disease or rheumatoid arthritis or Sjögren's syndrome (in up to 80% of cases).

[13] People with PBC may also have been diagnosed with another autoimmune disease, such as a rheumatological, endocrinological, gastrointestinal, pulmonary, or dermatological condition, suggesting shared genetic and immune abnormalities.

[12] Common associations include Sjögren's syndrome, systemic sclerosis, rheumatoid arthritis, lupus, hypothyroidism, and coeliac disease.

In 2009, a Canadian-led group of investigators reported in the New England Journal of Medicine results from the first PBC genome-wide association study.

[16][17] This research revealed parts of the IL12 signaling cascade, particularly IL12A and IL12RB2 polymorphisms, to be important in the aetiology of the disease in addition to the HLA region.

An environmental Gram-negative Alphaproteobacterium — Novosphingobium aromaticivorans[21] has been associated with this disease, with several reports suggesting an aetiological role for this organism.

[25] A failure of immune tolerance against the mitochondrial pyruvate dehydrogenase complex (PDC-E2) is a primary cause, with shedding of the antigen into apoptotic bodies or "apotopes" leading to the anatomic localization.

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.

On microscopic examination of liver biopsy specimens, PBC is characterized by chronic, nonsuppurative inflammation, which surrounds and destroys interlobular and septal bile ducts.

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.

In patients with inadequate response to UDCA, liver biopsy may provide the explanation and could undoubtedly inform risk stratification.

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.

[38] Additional medications are being investigated as potential treatments for PBC, and found to be ineffective as single agents (monotherapy), including: chlorambucil, colchicine, cyclosporine, corticosteroids, azathioprine, malotilate, methotrexate, mycophenolate mofetil, penicillamine, and thalidomide.

[33] Rifampicin may rarely cause drug induced liver injury and should be avoided if serum bilirubin is elevated (greater than 2.5 mg/dL).

Numerous trials and observational studies have demonstrated its efficacy on liver biochemistry, histological progression, and transplant-free survival.

In the absence of cirrhosis, people who experience an improvement of liver enzymes to the normal range on treatment with UDCA have excellent survival, which may be similar to the general population.

Qualitative and quantitative definitions of UDCA-response have been developed, based on changes of bilirubin, transaminases and ALP, after a period of 6 to 24 months of treatment with UDCA at 13–15 mg/kg/day.

This is relevant to identify patients who would be eligible for second-line therapies before waiting for the treatment failure under UDCA, with potential impact on disease course.

Recent large-scale cohort studies highlighted that the lack of UDCA-response after 12 months of therapy and male sex are associated with increased future risk of developing HCC in PBC.

The disease has been described worldwide, though North America and Northern Europe have shown the highest incidence and prevalence rates.

The first report of the disease dates back 1851 by Addison and Gull, who described a clinical picture of progressive jaundice in the absence of mechanical obstruction of the large bile ducts.

Ahrens et al. in 1950 published the first detailed description of 17 patients with this condition, and coined the term "primary biliary cirrhosis".

In 1959, Dame Sheila Sherlock reported a further series of PBC patients and recognised that the disease could be diagnosed in a precirrhotic stage and proposed the term "chronic intrahepatic cholestasis" as more appropriate description of this disease, but this nomenclature failed to gain acceptance, and the term "primary biliary cirrhosis" lasted for decades.

In 2014, to correct the inaccuracy and remove the social stigma of cirrhosis, as well as all the misunderstanding, disadvantages, and discrimination emanating from this misnomer in daily life for patients, international liver associations agreed to rename the disease "primary biliary cholangitis", as it is now known.

[9][10][62] The PBCers Organization is a US-based nonprofit patient support group that was founded by Linie Moore in 1996; it advocates for greater awareness of the disease and new treatments.