Journal of the Louisiana State Medical Society
• Histologic evidence of nonsuppurative destruc- tive cholangitis and destruction of interlobular bile ducts The only FDA-approved therapy for PBC is ursode- oxycholic acid (UDCA). 11 Several studies have supported the usefulness of UDCA in slowing the progression of liver failure and improving mortality rates. 15 UDCA is indicated for any patient with PBC and abnormal liver chemistries, regardless of stage. Appropriate dosing of UDCA is para- mount, as studies have shown superior results with a dose of 13-15 mg/kg/day when compared to either a lower or higher dose. 16 Some of the other medications that have been tested as a single agent in the treatment of PBC include chlorambucil, penicillamine, cyclosporine, corticosteroids, azathioprine, mycophenolate mofetil, thalidomide, metho- trexate, malotilate, and colchicine. None of the above-men- tioned medications have been shown to be of benefit, either as single-agent treatments or in combination with UDCA. 11 Treatment of the major symptoms of PBC, including fatigue and pruritis, is also often a focus of management. At this time, there is no recommended therapy for fatigue in PBC. The selective serotonin reuptake inhibitor, fluoxetine, has not shown any improvement of fatigue in the setting of PBC, while modafinil, a medication used for excessive daytime sleepiness, has shown some benefit. 11 Pruritis in PBC is not generally relieved by UDCA. The AASLD recommends that bile acid sequestrants be used as a first-line treatment for pruritis, followed by rifampicin, oral opiate antagonists, or sertraline for refractory cases. 11 Outcomes for liver trans- plantation in patients with PBC are generallymore favorable than transplants for other indications. Transplantation also improves fatigue, pruritis, and bone disease in PBC. 11 Timing of transplantation is key and can be better determined by using one of several prognostic formulas. One of the most widely used, the Mayo model, takes into account several factors, including serum bilirubin level, serum albumin level, age, prothrombin time, and presence or absence of peripheral edema. 17 In combination with the Mayo model, the Model for End-Stage Liver Disease (MELD) is also used to guide timing of liver transplantation. Up to 20%-25% of patients who undergo transplantation for PBC will have recurrent disease in 10 years; however, cyclosporine-based immunosuppression appears to reduce recurrence risk. 18 In conclusion, PBC is a progressive, autoimmune dis- ease of the liver seen primarily in women. It is diagnosed based on a combination of clinical findings and laboratory data, with elevation of alkaline phosphatase and the pres- ence of AMA being the hallmarks. The most consistent symptoms of PBC are fatigue and pruritis. Skin hyper- pigmentation due to melanin deposition may also be seen early in the course, while jaundice is a late presentation. Per the AASLD practice guidelines, the diagnosis is largely based on biochemical evidence of cholestasis, presence of AMA, and liver biopsy. The only FDA-approved medica- tion for treatment of PBC is UDCA, which has been shown to improve survival. Liver transplantation is a definitive treatment with overall favorable outcomes. PBC should be
suspected in any patient with unexplained cholestasis or pruritis. Timely diagnosis and early referral to a specialist is imperative for these patients. REFERENCES 1. Selmi C, Mayo M, Bach N, et.al. Primary Biliary Cirrhosis in Monozygotic and Dizygotic Twins: Genetics, Epigenetics, and Environment. Gastroenterology 2004; 127: 485-492. 2. Kaplan M and Gershwin M. Medical Progress: Primary Biliary Cirrhosis. N Engl J Med 1996; 353; 12: 1261-1273. 3. Boyer J, Shockcor W, andMahl T. The Natural History of Primary Biliary Cirrhosis. Trans Am Clin Climatol Assoc. 1992; 103: 157–163. 4. Jacobson D, Gange S, Rose N, et al. Epidemiology and Estimated Population Burden of Selected Autoimmune Diseases in the United States. Clinical Immunology and Immunopathology 1997; Vol. 84, No. 3, 223-243. 5. Gershwin, M and Mackay, I. The Cause of Primary Biliary Cirrhosis: Convenient and Inconvenient Truths. Hepatology 2008; Vol. 47, No.2. 6. Boonstra K, Beuers U, and Ponsioen C. Epidemiology of Primary Sclerosing Cholangitis and Primary Biliary Cirrhosis: A Systematic Review. Journal of Hepatology 2012; vol. 56, 1181-1188. 7. Prince M, Chetwynd A, Craig W, et al. Asymptomatic Primary Biliary Cirrhosis: Clinical Features, Prognosis, and Symptom Progression in a Large Population Cohort. Gut 2004; 53: 1216. 8. BergasaN, Mehlman J, and Jones E. Pruritis and Fatigue in Primary Biliary Cirrhosis. Clinical Liver Disease. 2003. Vol.7, 879-900. 9. Goldblatt J, James O, and Jones D. Grip Strength and Subjective Fatigue in Patients with Primary Biliary Cirrhosis. JAMA 2001; 285 (17): 2196-7. 10. Newton J, Davidson A, Kerr S, et al. Autonomic Dysfunction in Primary Biliary Cirrhosis Correlates with Fatigue Severity. European Journal of Gastroenterology and Hepatology. 2007; 19: 125-132. 11. Lindor K, GershwinM, Poupon R, et al. Primary Biliary Cirrhosis: AASLD Practice Guidelines. Hepatology. July 2009: 291-304. 12. Blachar A, FederleM, and Brancatelli G. Primary Biliary Cirrhosis: Clinical, Pathologic, and Helical CT Findings in 53 Patients. Radiology 2001; 220: 329-336. 13. Wenzel J, Donohoe A, Ford K, et al. MR Imaging Findings and Description of MR Imaging Periportal Halo Sign. American Journal of Roentgenology. 2001; 176: 885-889. 14. Knowlton J, Taylor A, Reichelderfer M, et al. Imaging of Biliary Tract Inflammation: An Update. American Journal of Roentgenology. 2008; 190: 984-992. 15. Lindor K, TherneauT, JorgensenR, et al. Effects of Ursodeoxycholic Acid on Survival in Patients with Primary Biliary Cirrhosis. Gastroenterology. 1996; 110: 1515-1518. 16. Angulo P, Dickson E, Therneau T, et al. Comparison of Three Doses of Ursodeoxycholic Acid in the Treatment of Primary Biliary Cirrhosis: A Randomized Trial. Journal of Hepatology 1999; 30: 830-835. 17. Weisner R, Porayko M, Dickson R, et al. Selection and Timing of Liver Transplantation in Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis. Hepatology. 1992; vol. 16: 1290-1299. 18. Charatcharoenwitthaya P, Pimentel S, Talwalkar J, et al. Long- term Survival and Impact of Ursodeoxycholic Acid Treatment for Recurrent Primary Biliary Cirrhosis After Liver Transplantation. Liver Transplantation 2007; 13:1236-1245.
132 J La State Med Soc VOL 166 May/June 2014
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