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Diagnosing PBC (primary biliary cholangitis)

PBC is easy to diagnose, based on the presence of at least two of the following three criteria:

  • elevated alkaline phosphatase levels;
  • anti-mitochondrial antibodies at a titre ≥ 1/40 or positive for anti-gp210 or anti-sp100;
  • compatible liver histology

However, a liver biopsy is unnecessary in the majority of cases as the first two criteria most frequently coincide.

One special case is overlap syndrome, a combined form of PBC and autoimmune hepatitis (AIH). This diagnosis (with disputed definition and diagnostic criteria) makes up 10% of PBC cases and is found in young women. It is characterised by elevated ALAT and IgG levels and a high HAI score from a biopsy. Combined therapy is recommended.

Focus on antibodies

Anti-mitochondrial antibodies

Identification of anti-mitochondrial antibodies via indirect immunofluorescence (IIF) should be confirmed using dot blot, western blot or ELISA with specific anti-mitochondrial M2 antibody tests. These antibodies are found in 90% to 95% of patients with PBC and their specificity for diagnosis PBC is over 95%.

Anti-nuclear antibodies (ANA) specific to PBC

Anti-nuclear antibodies (ANA) specific to PBC are present in around 25% of cases and up to 50% of cases where anti-mitochondrial antibodies are not present. In IIF of Hep2 cells, two types of fluorescence are characterised: ‘rim-like’ fluorescence (antibodies directed at pores in the nuclear envelope, primarily consisting of anti-gp210 antibodies) and ‘multiple nuclear dot’ fluorescence (antibodies directed at the nuclear dots, primarily consisting of anti-sp100 antibodies). Detection of ANA with these kinds of fluorescence using IIF should be confirmed via screening for the suspected antibodies (anti-gp210 or anti-sp100) using a specific antigen assay technique, usually ELISA. In a context of unexplained chronic cholestasis, the specificity of these antibodies for diagnosis of PBC is over 95%. Anti-gp210 antibodies are more specific than anti-sp100 antibodies, which may be observed in various connective tissue diseases.

In case of suspected PBC and the absence of anti-mitochondrial antibodies and anti-nuclear antibodies in indirect immunofluorescence, screening for anti-mitochondrial antibodies, anti-gp210 and anti-sp100 should be performed using a specific antigen assay technique (dot blot, ELISA). Specific antibodies for PBC (anti-mitochondrial antibodies, anti-gp210, anti-sp100) are sometimes detected outside of any context of chronic elevation of alkaline phosphatase and GTT levels. In this situation, their presence alone is not sufficient to make a diagnosis of PBC. As such, it is recommended to monitor the patients once a year via alkaline phosphatase and GGT assays.

Diagnosing PSC (primary sclerosing cholangitis)

Diagnosis of PSC is based on biological cholestasis associated with symptoms of abdominal pain and asthenia and characteristic appearance on the MRI of the bile duct (multifocal biliary stricture). A liver biopsy is necessary if the condition is limited to small bile ducts (not visible on the imaging).

According to the clinical context, in order to rule out secondary sclerosing cholangitis, an assay of serum IgG4, a complete blood count and HIV serology should be performed to rule out IgG4 cholangitis, eosinophilic cholangitis (in case of severe hypereosinophily) or a (rare) case of AIDS cholangitis, respectively.

Note: The increase in PAL may be absent in the diagnosis. PSC should be considered in any case of chronic abnormalities in liver tests that remains of unknown aetiology following a standard examination.

A combined form of PSC and AIH is found in 10% of cases of PSC: it is characterised by elevated ALAT and IgG levels and a high HAI score from a biopsy. It affects children and young adults and combined therapy is recommended.