Cholestatic Liver Diseases After Liver Transplant

https://doi.org/10.1016/j.cld.2016.12.011Get rights and content

Section snippets

Key points

  • Cholestatic liver disease (CLD) has become an uncommon indication for liver transplant (LT); in general, CLD has the best posttransplant outcomes compared with other indications for LT.

  • Disease recurrence is common after LT, but only recurrent primary sclerosing cholangitis (rPSC) seems to negatively affect posttransplant survival.

  • Ursodiol (ursodeoxycholic acid [UDCA]) has not been shown to improve posttransplant survival in rPSC or PBC, but UDCA is associated with lower recurrence rates of PBC

Primary sclerosing cholangitis

PSC is a chronic, progressive, immune-mediated CLD characterized by inflammation and fibrosis of intrahepatic and extrahepatic bile ducts, leading to formation of multifocal biliary strictures.1 PSC may lead to biliary cirrhosis with development of portal hypertension and its complications. Approximately 60% to 80% of patients with PSC have concomitant inflammatory bowel disease (IBD), which is predominately ulcerative colitis (UC).2 Patients with PSC are at increased risk of developing

Primary biliary cholangitis

PBC is an immune-mediated chronic CLD characterized by progressive destruction of intrahepatic bile ducts that may progress to biliary cirrhosis. Although the use of UDCA has been shown to improve biochemical indices, delay histologic progression, and improve transplant-free survival, LT is the only effective treatment of end-stage liver disease caused by PBC.

Summary

Although the number of LT performed for PSC and PBC has declined over the years, post-LT survival for CLD remains among the highest of all indications for liver transplant. As such, a growing proportion of patients are living longer and are at risk for developing clinically relevant recurrent disease and other complications related to chronic immunosuppression. Although UDCA has not been shown to affect post-LT survival in rPSC or rPBC, UDCA is associated with lower recurrence rates of PBC

First page preview

First page preview
Click to open first page preview

References (88)

  • M. Carbone et al.

    Liver transplantation in PBC and PSC: indications and disease recurrence

    Clin Res Hepatol Gastroenterol

    (2011)
  • I.W. Graziadei

    Recurrence of nonviral liver diseases after liver transplantation

    Clin Liver Dis

    (2014)
  • D.S. Pardi et al.

    Ursodeoxycholic acid as a chemopreventive agent in patients with ulcerative colitis and primary sclerosing cholangitis

    Gastroenterology

    (2003)
  • A. Shaked et al.

    Incidence and severity of acute cellular rejection in recipients undergoing adult living donor or deceased donor liver transplantation

    Am J Transplant

    (2009)
  • S. Narumi et al.

    Liver transplantation for sclerosing cholangitis

    Hepatology

    (1995)
  • R.C. Verdonk et al.

    Inflammatory bowel disease after liver transplantation: risk factors for recurrence and de novo disease

    Am J Transplant

    (2006)
  • K.K. Jorgensen et al.

    Immunosuppression after liver transplantation for primary sclerosing cholangitis influences activity of inflammatory bowel disease

    Clin Gastroenterol Hepatol

    (2013)
  • C. Trautwein et al.

    Bone density and metabolism in patients with viral hepatitis and cholestatic liver diseases before and after liver transplantation

    Am J Gastroenterol

    (2000)
  • European Association for the Study of the Liver

    EASL clinical practice guidelines: management of cholestatic liver diseases

    J Hepatol

    (2009)
  • P. Angulo et al.

    Comparison of three doses of ursodeoxycholic acid in the treatment of primary biliary cirrhosis: a randomized trial

    J Hepatol

    (1999)
  • M.G. Silveira et al.

    Recurrent primary biliary cirrhosis after liver transplantation

    Am J Transplant

    (2010)
  • M. Carbone et al.

    The effect of liver transplantation on fatigue in patients with primary biliary cirrhosis: a prospective study

    J Hepatol

    (2013)
  • H. Egawa et al.

    Long-term outcomes of living-donor liver transplantation for primary biliary cirrhosis: a Japanese multicenter study

    Am J Transplant

    (2016)
  • J. Dmitrewski et al.

    Recurrence of primary biliary cirrhosis in the liver allograft: the effect of immunosuppression

    J Hepatol

    (1996)
  • A. Bosch 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)
  • D.A. Jacob et al.

    Liver transplantation for primary biliary cirrhosis: influence of primary immunosuppression on survival

    Transplant Proc

    (2005)
  • N. Harimoto et al.

    Chronic immune-mediated reaction syndrome as the cause of late graft mortality in living-donor liver transplantation for primary biliary cirrhosis

    Transplant Proc

    (2014)
  • M. Carbone et al.

    Autoimmune liver disease, autoimmunity and liver transplantation

    J Hepatol

    (2014)
  • R. Chapman et al.

    Diagnosis and management of primary sclerosing cholangitis

    Hepatology

    (2010)
  • K. Burak et al.

    Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis

    Am J Gastroenterol

    (2004)
  • P. Milkiewicz et al.

    Liver transplantation in chronic cholestatic conditions

    Front Biosci (Landmark Ed)

    (2012)
  • United Network for Organ Sharing (UNOS). Available at: https://www.unos.org/. Accessed August 31,...
  • B. Fosby et al.

    Liver transplantation in the Nordic countries - an intention to treat and post-transplant analysis from the Nordic Liver Transplant Registry 1982-2013

    Scand J Gastroenterol

    (2015)
  • D.S. Goldberg et al.

    Current trends in living donor liver transplantation for primary sclerosing cholangitis

    Transplantation

    (2011)
  • Y. Futagawa et al.

    An analysis of the OPTN/UNOS liver transplant registry

    Clin Transpl

    (2004)
  • A.K. Singal et al.

    Evolving frequency and outcomes of liver transplantation based on etiology of liver disease

    Transplantation

    (2013)
  • D.S. Goldberg et al.

    Superior survival using living donors and donor-recipient matching using a novel living donor risk index

    Hepatology

    (2014)
  • I.W. Graziadei et al.

    Recurrence of primary sclerosing cholangitis following liver transplantation

    Hepatology

    (1999)
  • M. Dave et al.

    Primary sclerosing cholangitis: meta-analysis of diagnostic performance of MR cholangiopancreatography

    Radiology

    (2010)
  • R. Sheng et al.

    Cholangiographic features of biliary strictures after liver transplantation for primary sclerosing cholangitis: evidence of recurrent disease

    AJR Am J Roentgenol

    (1996)
  • B. Fosby et al.

    Recurrence and rejection in liver transplantation for primary sclerosing cholangitis

    World J Gastroenterol

    (2012)
  • E. Alabraba et al.

    A re-evaluation of the risk factors for the recurrence of primary sclerosing cholangitis in liver allografts

    Liver Transpl

    (2009)
  • J.A. Goss et al.

    Orthotopic liver transplantation for primary sclerosing cholangitis. A 12-year single center experience

    Ann Surg

    (1997)
  • D.R. Jeyarajah et al.

    Recurrent primary sclerosing cholangitis after orthotopic liver transplantation: is chronic rejection part of the disease process?

    Transplantation

    (1998)
  • Cited by (12)

    • Patient and Graft Survival: Biliary Complications after Liver Transplantation

      2018, Journal of the American College of Surgeons
      Citation Excerpt :

      Graziadei and colleagues11 demonstrated a post-LT biliary stricture rate of 43% (16% anastomotic, 27% nonanastomotic) in PSC patients after a mean follow-up of 55 months. Similarly, Polanco and colleagues12 reported biliary strictures in 37% of PSC and 43% of PBC patients, respectively, after LT. In our experience, a BC rate of 35% (31 of 88) in this group of patients is similar to these and other reports. Many of these complications (especially strictures) are a reflection of disease recurrence, which can be as high as 60% in PSC patients after 5 years of LT and 40% in PBC patients after 10 years.13

    View all citing articles on Scopus

    Disclosure: The authors have nothing to disclose.

    View full text