171G.Y. Wu et al. (eds.), Atlas of Dermatological Manifestations of Gastrointestinal Disease, DOI 10.1007/978-1-4614-6191-3_65, © Springer Science+Business Media New York 2013

Primary biliary cirrhosis (PBC) is an autoimmune disease characterized by destruction of the small bile ducts in the liver. This ultimately leads to cholestasis followed by fi brosis and cirrhosis. There is a 9:1 female to male ratio, with preva-lence as high as one in 4,000 [ 1 ] .

The gastrointestinal (GI) symptoms include [ 1– 3 ] : There are four stages of disease clinically: (1) preclinical • (only increased antimitochondrial antibody); (2) asymptom-atic (increased alkaline phosphatase and gamma glutamyl-transpeptidase); (3) symptomatic; (4) liver insuf fi ciency Fifty percent–60% of patients present without symptoms, • with most developing symptoms over 2–4 years, although some may remain asymptomatic for up to 20 years; it is unclear why there is a difference in progression and how to predict those who will progress rapidly Common symptoms include fatigue (65–80%), pruritus • (20–70%), anicteric cholestasis, hyperlipidemia (usually with high-density lipoprotein [HDL] > low-density lipopro-tein [LDL] and not requiring therapy), abdominal pain (par-ticularly right upper quadrant pain; etiology often unknown, occasionally secondary to gallstone disease, rarely due to hepatocellular carcinoma, jaundice, hepatomegaly) Jaundice usually occurs prior to hepatic decompensation • with ascites, encephalopathy, coagulopathy

The clinical signs and fi ndings are [ 1– 3 ] : Twenty percent of patients have more severe disease in • the presence of an autoimmune hepatitis picture Five percent–10% of patients have a premature ductopenic • variant with rapid onset of ductopenia leading to severe icteric cholestasis and cirrhosis within 5 years Portal hypertension is often due to presinusoidal presence • of nodular regenerative hyperplasia, not cirrhosis; variceal

hemorrhage can occur but is often not an indication for immediate transplant Disease associations include lichen planus, scleroderma, • CREST (calcinosis; Raynaud syndrome; esophageal dys-motility; sclerodactyly; telangiectasia), systemic lupus erythematosus, Sjögren syndrome, Raynaud syndrome, autoimmune thyroid disease, celiac disease, ulcerative colitis, pulmonary fi brosis, glomerulonephritis, sarcoido-sis, recurrent tubular acidosis, recurrent urinary tract infection, rheumatoid arthritis, periostitis Decreased survival is associated with jaundice, irreversible • bile duct loss, cirrhosis, other autoimmune diseases

The pathogenesis appears to involve autoimmune abnor-malities [ 1– 4 ] :

A genetic component is suggested as the disease in more • common in Northern Europeans, more common in those with relatives with disease (one sixth have an affected relative), 63% concordance in monozygotic twins, and more common in women (10:1 female:male ratio) Most commonly accepted hypothesis is that the disease • represents molecular mimicry immune response due to bacteria (Escherichia coli, Novosplingobium aromaticiv-orans), tobacco use, viruses, and chemicals Immune targets appear to be a family of 2-oxo-acid dehy-• drogenase complexes with in fi ltrating autoreactive T-cells reactive against these proteins Intense immune response against biliary epithelial cells • appears caused by the way bile duct cells handle these proteins versus the way other cells modify them

The pathology seen in liver biopsies can show [ 3, 4 ] : Four stages of the disease (may all be present in same sample, • disease staged by most advanced stage present in the sample)

Stage I: localization of in fl ammation in the portal triads – Stage II: decreased number of bile ducts, in fl ammation –extends into surrounding parenchyma Stage III: fi brous septa link adjacent portal triads – Stage IV: end-stage liver disease, frank cirrhosis with –regenerative nodules

The diagnosis is made based on [ 1– 4 ] :

Primary Biliary Cirrhosis: Gastrointestinal Features

Liam Zakko

65

L. Zakko (*) Yale Department of Internal Medicine , Yale New Haven Hospital , New Haven , CT , USA

Yale Primary Care Clinic , 789 Howard Avenue , New Haven , CT 06519-1304 , USA e-mail: liam.zakko@yale.edu

172 L. Zakko

Three criteria for PBC diagnosis: if all three criteria are • positive, the diagnosis is de fi nite; if two criteria are posi-tive, the diagnosis is probable

Detectable antimitochondrial antibodies – Elevated liver enzymes (alkaline phosphate most com- –mon) for 6 months Histologic fi ndings in the liver compatible with the –disease ( see Fig. 65.1 )

The differential diagnosis of primary biliary cirrhosis should include [ 1– 4 ] :

Nonalcoholic liver disease • Primary sclerosing cholangitis • Lymphoma • Cystic fi brosis • Drug-induced liver injury • Thyrotoxicosis •

There is no cure but symptomatic treatment involves [ 1– 4 ] : Ursodeoxycholic acid (UDCA) is fi rst-line therapy with • 25–30% complete response, 20% with no progression his-tologically if treatment started in stage I and II disease Budesonide can be used with UDCA to improve histol-• ogy and biochemical tests, but has no effect on survival Colchicine: use if there is an incomplete response to • UCDA Methotrexate: use if there is an incomplete response to • UCDA and colchicine Liver transplant: de fi nitive treatment, 92% survival at • 1 year, 85% survival at 5 years; however, does not change antibody status and recurrent at 3 years is 15% and at 10 years is 30%

References

1. Bhandari BM, Bayat H, Rothstein KD. Primary biliary cirrhosis. Gastroenterol Clin North Am. 2011;40:373–86.

2. Crosignani A, Battezzati PM, Invernizzi P, et al. Clinical features and management of primary biliary cirrhosis. World J Gastroenterol. 2008;14:3313–27.

3. Heathcote J. The clinical expression of primary biliary cirrhosis. Semin Liver Dis. 1997;17:23–33.

4. Kaplan MM, Gershwin ME. Primary biliary cirrhosis. N Engl J Med. 2005;353:1261–73.

Fig. 65.1 A photomicrograph of a liver specimen from a patient with primary biliary cirrhosis showing a dense mononuclear in fi ltrate surround-ing and damaged bile ducts. Hematoxylin and eosin stain, low power