Editing Primary biliary cholangitis (section)

==Diagnosis==
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 function tests|liver enzyme test]]s are usually present and elevated [[gamma-glutamyl transferase]] and [[alkaline phosphatase]]  are found in early disease.<ref name="pmid=19554543"/>  Elevations in [[bilirubin]] occur in advanced disease.
* [[Antimitochondrial antibody|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]].<ref name="pmid=19554543"/> 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.<ref name="pmid15062200"/>
* Other [[autoantibody|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.{{cn|date=March 2025}}
:: [[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.<ref name="pmid7504063">{{cite journal | vauthors = Nickowitz RE, Worman HJ | title = Autoantibodies From Patients With Primary Biliary Cirrhosis Recognize a Restricted Region Within the Cytoplasmic Tail of Nuclear Pore Membrane Glycoprotein Gp210 | journal = The Journal of Experimental Medicine | volume = 178 | issue = 6 | pages = 2237–2242 | date = December 1993 | pmid = 7504063 | pmc = 2191303 | doi = 10.1084/jem.178.6.2237 }}</ref><ref name="pmid17621358">{{cite journal | vauthors = Bauer A, Habior A | title = Measurement of gp210 autoantibodies in sera of patients with primary biliary cirrhosis | journal = Journal of Clinical Laboratory Analysis | volume = 21 | issue = 4 | pages = 227–231 | year = 2007 | pmid = 17621358 | pmc = 6648998 | doi = 10.1002/jcla.20170 }}</ref>
::[[Anti-centromere antibodies]] often correlate with developing portal hypertension.<ref name="pmid17187436">{{cite journal | vauthors = Nakamura M, Kondo H, Mori T, Komori A, Matsuyama M, Ito M, Takii Y, Koyabu M, Yokoyama T, Migita K, Daikoku M, Abiru S, Yatsuhashi H, Takezaki E, Masaki N, Sugi K, Honda K, Adachi H, Nishi H, Watanabe Y, Nakamura Y, Shimada M, Komatsu T, Saito A, Saoshiro T, Harada H, Sodeyama T, Hayashi S, Masumoto A, Sando T, Yamamoto T, Sakai H, Kobayashi M, Muro T, Koga M, Shums Z, Norman GL, Ishibashi H | display-authors = 6 | title = Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis | journal = Hepatology | volume = 45 | issue = 1 | pages = 118–127 | date = January 2007 | pmid = 17187436 | doi = 10.1002/hep.21472 | s2cid = 19225707 | doi-access = free }}</ref>
::Anti-np62<ref name="pmid11303304">{{cite journal | vauthors = Nesher G, Margalit R, Ashkenazi YJ | title = Anti-nuclear envelope antibodies: Clinical associations | journal = Seminars in Arthritis and Rheumatism | volume = 30 | issue = 5 | pages = 313–320 | date = April 2001 | pmid = 11303304 | doi = 10.1053/sarh.2001.20266 }}</ref> and anti-sp100 are also found in association with PBC.
* Abdominal [[medical ultrasonography|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 [[endoscopy|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.
<gallery mode="packed" widths="360px" heights="220">
Image:Primary biliary cirrhosis low mag.jpg|Low-magnification [[micrograph]] of PBC, [[H&E stain]]
Image:Primary biliary cirrhosis intermed mag.jpg|Intermediate-magnification micrograph of PBC showing bile duct inflammation and periductal [[granuloma]]s, liver biopsy, H&E stain
File:ANA NUCLEAR DOT AND AMA.jpg|[[Immunofluorescence]] staining pattern of [[sp100 nuclear antigen|sp100]] antibodies (nuclear dots) and antimitochondrial antibodies
</gallery>

===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 primary biliary cholangitis include:<ref name=pmid10976014>{{cite journal | vauthors = Nakanuma Y, Tsuneyama K, Sasaki M, Harada K | title = Destruction of bile ducts in primary biliary cirrhosis | journal = Baillière's Best Practice & Research. Clinical Gastroenterology | volume = 14 | issue = 4 | pages = 549–570 | date = August 2000 | pmid = 10976014 | doi = 10.1053/bega.2000.0103 }}</ref>
* Inflammation of the bile ducts, characterized by intraepithelial [[lymphocyte]]s
* Periductal [[Epithelioid cell|epithelioid]] [[granuloma]]s.
* 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.