Primary Biliary Cirrhosis (PBC)
PBC is a chronic disease that is most likely to afflict women older than 30 years. Its etiology is poorly understood, but it shares many features with other diseases characterized as autoimmune. Prominent among these are the presence of autoantibodies and the tendency to be associated with other autoimmune diseases, including thyroid disease, Sjögren syndrome, Raynaud syndrome, and occasionally CREST syndrome.
A regular feature is the presence of antimitochondrial antibodies (AMAs). Th-1 class CD4+ T cells predominate in the inflammatory reaction. Metabolic bone disease, especially osteoporosis, is common.
PBC requires 10 to 20 years to display its natural evolution. Among asymptomatic patients, only 50% develop symptomatic disease over 10 years of observation.
The extrahepatic manifestations of PBC require attention and occasionally may overshadow the hepatic disease. Some features can be traced to the malabsorption of fat-soluble vitamins, although most patients with PBC have normal serum levels of vitamin A, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, prothrombin, and vitamin E levels.
Premature osteoporosis and, occasionally in late-stage disease, osteomalacia may be seen. Bone pain, compression spine fractures, and other pathological bone fractures may be the consequence of PBC-related osteoporosis and occur in up to 20% of affected persons. Malabsorption of vitamin D is one cause. Hepatic biotransformation to 1,25-dihydroxy vitamin D appears to be intact in PBC patients. Despite normal absorption and biotransformation, bone biopsies in PBC show decreased osteoblastic and increased osteoclastic activity. Replacement with calcium and vitamin D may have little effect on rapid bone loss in PBC patients and alternative therapies such as bisphosphonate are often required.