The Natural History of PBC: Has It Changed?

ABSTRACT

The prognosis and natural history of primary biliary cirrhosis (PBC) have improved significantly during the last few decades. Patients are diagnosed at earlier stages, are more likely to be asymptomatic at diagnosis, and are more likely to receive medical treatment. The survival of asymptomatic patients is longer than the median survival of symptomatic patients. The natural history of PBC has been assessed in the presence of effective therapy, ursodeoxycholic acid (UDCA). Evidence suggests that UDCA delays histological progression in PBC and decreases the risk of development of esophageal varices. Survival of UDCA-treated patients is better than that of untreated patients and also is better than that predicted by the Mayo model. For patients in early stages of PBC, UDCA treatment may normalize survival. However, patients with stage III and IV PBC do not respond as well to UDCA. Therefore, there is a continued need for additional treatment in patients with advanced disease.

KEYWORDS

Natural history - survival - prognosis - outcomes - primary biliary cirrhosis

REFERENCES

• 1 Prince M I, James O F. The epidemiology of primary biliary cirrhosis.  Clin Liver Dis. 2003;  7 795-819
• 2 MacMahon H E, Tannhauser S J. Xanthomatous biliary cirrhosis (a clinical syndrome).  Ann Intern Med. 1949;  30 121-131
• 3 Ahrens E J, Payne M, Kunkel H et al.. Primary biliary cirrhosis.  Medicine. 1950;  29 299-364
• 4 Sherlock S. Primary biliary cirrhosis (chronic intrahepatic cholestasis).  Gastroenterology. 1959;  31 574-582
• 5 Long R G, Scheurer P J, Sherlock S. Presentation and course of asymptomatic primary biliary cirrhosis.  Gastroenterology. 1977;  72 1204-1207
• 6 Roll J, Boyer J L, Barry D, Klatskin G. The prognostic importance of clinical and histologic features in asymptomatic and symptomatic primary biliary cirrhosis.  N Engl J Med. 1983;  308 1-7
• 7 Balasubramaiam K, Grambsch P M, Wiesner R H et al.. Diminished survival in asymptomatic primary biliary cirrhosis: a prospective study.  Gastroenterology. 1990;  98 1567-1571
• 8 Mahl T C, Shockcor W, Boyer J L. Primary biliary cirrhosis: survival of a large cohort of symptomatic and asymptomatic patients followed for 24 years.  J Hepatol. 1994;  20 707-713
• 9 Pares A, Rodes J. Natural history of primary biliary cirrhosis.  Clin Liver Dis. 2003;  7 779-794
• 10 Springer J, Cauch-Dudek K, O'Rourke K, Wanless I, Heathcote E J. Asymptomatic primary biliary cirrhosis: a study of its natural history and prognosis.  Am J Gastroenterol. 1999;  94 47-53
• 11 Prince M I, Chetwynd A, Craig W L et al.. Asymptomatic primary biliary cirrhosis: clinical features, prognosis, and symptom progression in a large population based cohort.  Gut. 2004;  53 860-870
• 12 Christensen E, Neuberger J, Crowe J et al.. Beneficial effect of azathioprine and prediction of prognosis in primary biliary cirrhosis: final result of an international trial.  Gastroenterology. 1985;  89 1084-1091
• 13 Locke G R, Therneau T M, Ludwig J, Dickson E R, Lindor K D. Time course of histological progression in primary biliary cirrhosis.  Hepatology. 1996;  23 52-56
• 14 Angulo P, Batts K P, Therneau T M et al.. Long-term ursodeoxycholic acid delays histological progression in primary biliary cirrhosis.  Hepatology. 1999;  29 644-647
• 15 Degott C, Zafrani E S, Callard P et al.. Histopathological study of primary biliary cirrhosis and the effect of ursodeoxycholic acid treatment on histology progression.  Hepatology. 1999;  29 1007-1012
• 16 Pares A, Caballeria L, Rodes J et al.. Long-term effects of ursodeoxycholic acid in primary biliary cirrhosis: results of a double-blind controlled multicentric trial.  J Hepatol. 2000;  32 561-566
• 17 Corpechot C, Carrat F, Bonnand A. The effect of ursodeoxycholic acid therapy on liver fibrosis progression in primay biliary cirrhosis.  Hepatology. 2000;  32 1196-1199
• 18 Poupon R E, Lindor K D, Pares A et al.. Combined analysis of the effect of treatment with ursodeoxycholic acid on histologic progression in primary biliary cirrhosis.  J Hepatol. 2003;  39 12-16
• 19 Gores G J, Wiesner R H, Dickson E R et al.. Prospective evaluation of esophageal varices in primary biliary cirrhosis: development, natural history, and influence on survival.  Gastroenterology. 1989;  96 1552-1559
• 20 Takeshita E, Kumagi T, Matsui H et al.. Esophagogastric varices as a prognostic factor for the determination of clinical stage in patients with primary biliary cirrhosis.  J Gastroenterol. 2003;  38 1060-1065
• 21 Lindor K D, Jorgensen R A, Therneau T M et al.. Ursodeoxycholic acid delays the onset of esophageal varices in primary biliary cirrhosis.  Mayo Clin Proc. 1997;  72 1137-1140
• 22 Grambsch P M, Dickson E R, Kaplan M et al.. Extramural cross-validation of the Mayo primary biliary cirrhosis survival model establishes its generalizability.  Hepatology. 1989;  10 846-850
• 23 Poupon R E, Lindor K D, Cauch-Dudek K et al.. Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis.  Gastroenterology. 1997;  113 884-890
• 24 Lindor K D, Therneau T M, Jorgensen R A et al.. Effects of ursodeoxycholic acid on survival in patients with primary biliary cirrhosis.  Gastroenterology. 1996;  110 1515-1518
• 25 Corpechot C, Carrat F, Bahr A et al.. The effect of ursodeoxycholic acid therapy on the natural course of primary biliary cirrhosis.  Gastroenterology. 2005;  128 297-303
• 26 Papatheodoridis G V, Hadziyannis E S, Deutsch M, Hadziyannis S J. Ursodeoxycholic acid for primary biliary cirrhosis: final results of a 12-year, prospective, randomized, controlled trial.  Am J Gastroenterol. 2002;  97 2063-2070
• 27 Combes B, Luketic V A, Peters M G et al.. Prolonged follow-up of patients in the U.S. Multicenter trial of ursodeoxycholic acid for primary biliary cirrhosis.  Am J Gastroenterol. 2004;  99 264-268
• 28 Prince M, Chetwynd A, Newman W et al.. Patient survival and symptom progression in a large geographically based cohort of patients with PBC: Follow up for up to 28 years.  Gastroenterology. 2002;  123 1044-1051
• 29 Goulis J, Leandor G, Burroughs A. Randomised controlled trials of ursodeoxycholic-acid therapy for primary biliary cirrhosis: a meta-analysis.  Lancet. 1999;  354 1053-1060
• 30 Gluud C, Christensen E. Ursodeoxycholic acid for primary biliary cirrhosis (Cochrane Review). In: The Cochrane Library, Issue 1 Oxford, United Kingdom; Update Software 2003
• 31 Leuschner M, Dietrich C F, You T et al.. Characterisation of patients with primary biliary cirrhosis responding to long term ursodeoxycholic acid treatment.  Gut. 2000;  46 121-126
• 32 Van Norstrand M D, Malinchoc M, Lindor K et al.. Quantitative measurement of autoantibodies to recombinant mitochondrial antigens in patients with primary biliary cirrhosis: relationship of levels of autoantibodies to disease progression.  Hepatology. 1997;  25 6-11