The PBC Foundation is the only UK organisation exclusively dedicated to providing support and information to those affected by PBC
Biochemistry & Haematology
PBC is a cholestatic liver disease in which there is disproportionate elevation of the ALP and GGT. There may be moderate elevation of the ALT or AST but very high transaminases should raise suspicion of PBC/AIH overlap. In patients with cirrhosis and splenomegaly, the platelet count may be reduced owing to splenic sequestration. In patients with end-stage liver disease (ESLD), the total and direct bilirubin may be elevated, and the PT may be prolonged. Patients with ESLD may also have hyponatraemia and elevated creatinine.
More than 90% of PBC patients have anti-mitochondrial antibodies (AMA) with specificity for PDC-E2. The combination of detectable AMA and elevated ALP (or GGT) is diagnostic for the disease. Antinuclear antibodies (ANA) are also found in PBC, including anti-centromere, anti-sp100 antibodies and anti-gp210 antibodies. Anti-centromere antibodies are also found in scleroderma, whereas sp100 and gp210 antibodies are specific to PBC. In PBC, different ANAs are risk markers for different clinical outcomes. Specifically, the presence of anti-gp210 antibodies seems to be a risk marker for progression to liver failure. On the other hand, the presence of ACA seems to be a risk marker for development of portal hypertension. A positive test for anti-SMA should raise suspicion of PBC/AIH overlap. PBC is also characterised by disproportionate elevated of the serum IgM. In PBC/AIH overlap syndrome, there may also be marked elevation of the serum IgG.
The characteristic histological lesion in PBC is non-suppurative destructive cholangitis, in which the bile duct is surrounded by an intense lymphocytic or granulomatous infiltrate and the biliary epithelium is infiltrated by individual lymphocytes. Other features include portal granulomas, interface hepatitis, ductular proliferation and cholate-stasis. Progressive destruction of bile ducts leads to ductopenia. Progressive fibrosis eventually leads to biliary cirrhosis.
Liver biopsy is recommended in the following scenarios:
- To confirm the diagnosis of PBC in AMA-negative cases;
- Where there is a suspicion of PBC/AIH overlap syndrome (e.g. patients with elevated markedly elevated transaminases, markedly elevated IgG and positive anti-SMA). In patients with PBC/AIH overlap, the liver biopsy may reveal infiltrates rich in plasma cells; marked interface hepatitis, and lobular hepatitis.
Liver biopsy may also be useful in UDCA non-responders, to look for a potential explanation for non-response and to guide further treatment, for example PBC/AIH overlap or co-existent non-alcoholic fatty liver disease.
Histological staging of PBC liver biopsies is currently out of vogue. However, biopsy to stage disease may inform management and should not be completely discounted. Several staging systems have been proposed, all of which are highly comparable. One example is the Scheuer staging system, consisting of four stages:
- Stage 1: chronic non-suppurative destructive cholangitis;
- Stage 2: ductular proliferation;
- Stage 3: scarring short of cirrhosis;
- Stage 4: nodular cirrhosis.
Newer grading and staging systems are currently under evaluation.