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Chapter 51. Primary Biliary Cirrhosis

Daniel S. Pratt, MD

  • Most patients with primary biliary cirrhosis (PBC) are asymptomatic at the time of diagnosis but eventually develop symptoms, including fatigue and pruritus.
  • Consider PBC in any patient in whom liver enzymes are elevated in a cholestatic pattern; an isolated elevated alkaline phosphatase level always requires further evaluation.
  • Antimitochondrial antibodies have 95% sensitivity for PBC and are central to the diagnosis.

Primary biliary cirrhosis (PBC) is a classical autoimmune disease. Although it is predominantly a disease of middle-aged woman, with a median age of diagnosis of approximately 50 years, 5–10% of patients are men, and the reported age range is 22–93 years. It is reported throughout the world, but with varying geographic incidence and prevalence; the highest reported incidence and prevalence is in northern Europe. Studies have suggested the incidence and prevalence are increasing worldwide. Antimitochondrial autoantibodies (AMAs) are found in 95% of patients with PBC. The targets of the autoantibodies are members of the family of the 2-oxo-acid dehydrogenase complexes, most particularly the E2 subunits of the pyruvate dehydrogenase complex (PDC-E2). The immunologic injury is marked by a T-cell–mediated destruction of the intrahepatic bile ducts. The only proven therapy for PBC is ursodeoxycholic acid (UDCA). Despite early diagnosis and treatment, most patients have an inexorable disease progression leading ultimately to cirrhosis and end-stage liver disease.

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Kaplan MM, Gershwin ME. Primary biliary cirrhosis. N Engl J Med. 2005;353:1261–1273.   [PubMed: 16177252]
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Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ. Primary biliary cirrhosis. Hepatology. 2010;50:291–306.   [PubMed: 19554543]

Figure 51–1

Figure 51–1.
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Pathogenesis and natural history of primary biliary cirrhosis (PBC). It is believed that genetically susceptible patients if exposed to specific environmental triggers may develop autoimmunity through molecular mimicry, with the primary target of the resultant antimitochondrial antibodies being pyruvate dehydrogenase E2 complex (PDC-E2). Through an as yet undetermined process this leads to a persistent T-cell–mediated destruction of the intrahepatic bile ducts. Untreated, this destructive process eventually destroys a critical percentage of bile ducts and secondary injury from retained bile salts ensues. Injury progresses to biliary cirrhosis and eventually to decompensated liver disease. ALP, alkaline phosphatase; AMA, antimitochondrial antibody; GGT, γ-glutamyl transferase; LFTs, liver function tests.

Genetic Factors

There have been several studies indicating the role of genetics in determining the susceptibility to PBC. Particularly important observations include the following:

  1. First-degree relatives of patients with PBC have a 4–6% prevalence of disease.

  2. PBC has the highest reported concordance rate (62.5%) in monozygotic twins of any autoimmune disease.

  3. The prevalence of AMAs in first-degree relatives of patients with PBC was 13.1% compared with 1% of controls.

A number of candidate genes have been implicated in PBC including CTLA4 and IL12A.

Environmental Factors

As with other autoimmune ...

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