Liver transplantation in primary biliary cholangitis (primary biliary cirrhosis)
- Steven Flamm, MD
Steven Flamm, MD
- Chief, Liver Transplantation Program
- Professor of Medicine
- Feinberg School of Medicine
- Northwestern University
- Fredric D Gordon, MD
Fredric D Gordon, MD
- Associate Professor of Medicine
- Tufts University Medical School
- Raoul Poupon, MD
Raoul Poupon, MD
- Professor of Hepatology and Gastroenterology
- University Pierre et Marie Curie
- UPMC, Sorbonne University, Paris, France
- Section Editor
- Robert S Brown, Jr, MD, MPH
Robert S Brown, Jr, MD, MPH
- Section Editor — Liver Transplantation
- Vice Chair, Transitions of Care, Department of Medicine
- Interim Chief, Division of Gastroenterology and Hepatology
- Weill Cornell Medical College
- Professor of Clinical Medicine, Columbia University College of Physicians & Surgeons
Liver transplantation can be successful in treating end-stage liver disease from primary biliary cholangitis (PBC; previously referred to as primary biliary cirrhosis). The total number of transplants performed for PBC in recent years has declined slightly, possibly reflecting benefits of early treatment . Nevertheless, transplantation remains an important option in patients with progressive disease despite medical therapy. In the United States, the average age of patients undergoing transplantation for PBC is in the range of 53 to 55 years .
This topic will review issues related to patient selection for liver transplantation, the timing of transplantation, and transplantation outcomes in patients with PBC. Other issues related to the pathogenesis, clinical manifestations, diagnosis, and treatment of PBC are discussed elsewhere. (See "Clinical manifestations, diagnosis, and prognosis of primary biliary cholangitis (primary biliary cirrhosis)" and "Overview of the treatment of primary biliary cholangitis (primary biliary cirrhosis)" and "Pathogenesis of primary biliary cholangitis (primary biliary cirrhosis)" and "Trials of ursodeoxycholic acid for the treatment of primary biliary cholangitis (primary biliary cirrhosis)".)
OPTIMAL TIME FOR TRANSPLANTATION
An important issue is to determine the optimal time to perform a liver transplantation. Many groups have developed models that use clinical variables to estimate patient survival. Two types of models have been developed: one based upon initial data on entry into the study, and one that uses both initial and follow-up data. The Mayo model (table 1), which uses data from the initial evaluation, is most widely used, but because of individual patient variation, it does not replace the input of an experienced clinician [2,3]. The Mayo model can predict short- and long-term survival using current laboratory and clinical data. This tool can be used to anticipate liver failure, allowing the clinician to refer the patient for transplantation in a timely manner. Although these models are specific to survival in PBC, because the MELD score is used to prioritize patients for transplantation, it is often used to determine when to refer patients for transplantation (See "Model for End-stage Liver Disease (MELD)".)
In addition to considering the MELD score and Mayo model, we suggest that patients with PBC be referred for transplantation evaluation if one or more of the following is present:
●The plasma bilirubin concentration is greater than 5 mg/dL and is increasing
- Lee J, Belanger A, Doucette JT, et al. Transplantation trends in primary biliary cirrhosis. Clin Gastroenterol Hepatol 2007; 5:1313.
- Wiesner RH, Porayko MK, Dickson ER, et al. Selection and timing of liver transplantation in primary biliary cirrhosis and primary sclerosing cholangitis. Hepatology 1992; 16:1290.
- Markus BH, Dickson ER, Grambsch PM, et al. Efficacy of liver transplantation in patients with primary biliary cirrhosis. N Engl J Med 1989; 320:1709.
- Dickson ER, Grambsch PM, Fleming TR, et al. Prognosis in primary biliary cirrhosis: model for decision making. Hepatology 1989; 10:1.
- Roll J, Boyer JL, 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.
- Klion FM, Fabry TL, Palmer M, Schaffner F. Prediction of survival of patients with primary biliary cirrhosis. Examination of the Mayo Clinic model on a group of patients with known endpoint. Gastroenterology 1992; 102:310.
- Goudie BM, Burt AD, Macfarlane GJ, et al. Risk factors and prognosis in primary biliary cirrhosis. Am J Gastroenterol 1989; 84:713.
- Christensen E, Altman DG, Neuberger J, et al. Updating prognosis in primary biliary cirrhosis using a time-dependent Cox regression model. PBC1 and PBC2 trial groups. Gastroenterology 1993; 105:1865.
- Liermann Garcia RF, Evangelista Garcia C, McMaster P, Neuberger J. Transplantation for primary biliary cirrhosis: retrospective analysis of 400 patients in a single center. Hepatology 2001; 33:22.
- Rowe IA, Webb K, Gunson BK, et al. The impact of disease recurrence on graft survival following liver transplantation: a single centre experience. Transpl Int 2008; 21:459.
- Carbone M, Bufton S, Monaco A, et al. The effect of liver transplantation on fatigue in patients with primary biliary cirrhosis: a prospective study. J Hepatol 2013; 59:490.
- Pells G, Mells GF, Carbone M, et al. The impact of liver transplantation on the phenotype of primary biliary cirrhosis patients in the UK-PBC cohort. J Hepatol 2013; 59:67.
- Abu-Elamgd K, Demetris J, Rakela J, et al. Transplantation for primary biliary cirrhosis: Recurrence and outcome in 421 patients (abstract). Hepatology 1997; 26:176A.
- Polson RJ, Portmann B, Neuberger J, et al. Evidence for disease recurrence after liver transplantation for primary biliary cirrhosis. Clinical and histologic follow-up studies. Gastroenterology 1989; 97:715.
- Balan V, Batts KP, Porayko MK, et al. Histological evidence for recurrence of primary biliary cirrhosis after liver transplantation. Hepatology 1993; 18:1392.
- Esquivel CO, Van Thiel DH, Demetris AJ, et al. Transplantation for primary biliary cirrhosis. Gastroenterology 1988; 94:1207.
- Tzakis AG, Carcassonne C, Todo S, et al. Liver transplantation for primary biliary cirrhosis. Semin Liver Dis 1989; 9:144.
- Haagsma EB, Manns M, Klein R, et al. Subtypes of antimitochondrial antibodies in primary biliary cirrhosis before and after orthotopic liver transplantation. Hepatology 1987; 7:129.
- Charatcharoenwitthaya P, Pimentel S, Talwalkar JA, et al. Long-term survival and impact of ursodeoxycholic acid treatment for recurrent primary biliary cirrhosis after liver transplantation. Liver Transpl 2007; 13:1236.
- Neuberger J, Gunson B, Hubscher S, Nightingale P. Immunosuppression affects the rate of recurrent primary biliary cirrhosis after liver transplantation. Liver Transpl 2004; 10:488.
- Bosch A, Dumortier J, Maucort-Boulch D, et al. Preventive administration of UDCA after liver transplantation for primary biliary cirrhosis is associated with a lower risk of disease recurrence. J Hepatol 2015; 63:1449.
- Wong PY, Portmann B, O'Grady JG, et al. Recurrence of primary biliary cirrhosis after liver transplantation following FK506-based immunosuppression. J Hepatol 1993; 17:284.
- Montano-Loza AJ, Wasilenko S, Bintner J, Mason AL. Cyclosporine A protects against primary biliary cirrhosis recurrence after liver transplantation. Am J Transplant 2010; 10:852.
- Hubscher SG, Elias E, Buckels JA, et al. Primary biliary cirrhosis. Histological evidence of disease recurrence after liver transplantation. J Hepatol 1993; 18:173.
- Neuberger J. Recurrent primary biliary cirrhosis. Liver Transpl 2003; 9:539.
- Slapak GI, Saxena R, Portmann B, et al. Graft and systemic disease in long-term survivors of liver transplantation. Hepatology 1997; 25:195.
- Luettig B, Boeker KH, Schoessler W, et al. The antinuclear autoantibodies Sp100 and gp210 persist after orthotopic liver transplantation in patients with primary biliary cirrhosis. J Hepatol 1998; 28:824.
- Dubel L, Farges O, Bismuth H, et al. Kinetics of anti-M2 antibodies after liver transplantation for primary biliary cirrhosis. J Hepatol 1995; 23:674.
- Personal communication from Marshall Kaplan, MD. He observed that five of six patients treated with ursodeoxycholic acid and colchicine developed normal serum transaminase and bilirubin levels and became asymptomatic.
- OPTIMAL TIME FOR TRANSPLANTATION
- Models based upon initial data
- Models based upon initial and follow-up data
- OUTCOME AFTER LIVER TRANSPLANTATION
- Effect of transplantation on symptoms
- Recurrence of PBC in the transplanted liver
- - Rate of recurrence
- - Clinical significance
- - Risk factors
- - Prevention
- - Diagnosis
- - Treatment
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS