Disease recurrence following Liver Transplantation

Key Points:

• Long term survival following liver transplantation may be threatened by recurrence of the original disease

• Hepatitis B

  • Greater risk in patients with active viral replication pre-transplant

  • Re-activation of Hep B may occur if the donor is Hep B Core antibody +

  • “Fibrosing cholestatic hepatitis” with massive viral replication may occur

  • Strategies to decrease Hep B recurrence or reactivation include:

    • Use of HBIG during anhepatic phase of the transplant, post-op and for 7 days post

    • Use of Lamivudine / 3TC or Adefovir to minimize HBV replication

      • Long term Lamivudine use may be associated with HBV mutation (YMDD)

      • Consider Adefovir if mutations occur

    • Redosing with HBIG either monthly or when the Hep B surface Antibody titer is < 500 IU/L (some centers use <100 IU/L)

    • Most centers use both HBIG and Lamivudine

• Hepatitis C

  • Recurrence of HCV post-OLT is universal

  • 50-90% of patients develop histologic hepatitis

  • High pre-transplant viremia (HCV RNA > 1 x 10⁶ ) prior to OLT may be associated with diminished graft and patient survival post OLT

  • Natural history-progression to cirrhosis post OLT is shortened:

    • Non-transplanted patients- 20% of patients with cirrhosis after 20 years

    • Post-transplant patients- 20% of patients with cirrhosis after 5 years

    • 5 year survival post OLT in patients with recurrent HCV

      • non-cirrhotic- 86%

      • cirrhotic <50%

  • Graft survival/patient survival decreased overall when compared to non HCV infected patients. This is influenced by degree of graft dysfunction, cholestasis, and stage of fibrosis

  • Anti-viral therapy (Interferon with/without Ribavirin) in the early post-transplant period to prevent recurrence has been of limited benefit

  • Ongoing studies will determine the benefit of anti-viral therapy/alternative immunosuppression strategies to improve graft and patient survival:

    • Possible role of long term “maintenance” therapy with PEG-Intron

    • Use of immunosuppression with “anti-fibrotic” properties (Sirolimus) or anti-viral properties (Cellcept)?

    • Minimizing steroids

    • Avoiding monoclonal antibodies (OKT-3) to treat rejection

    • IL-10 ?

    • Peg-Interferon

• Hepatic malignancy

  • Risks include pre-transplant HCC > 5 cm, more than 3 tumors each > 3 cm vascular invasion

  • Pre-transplant strategies undergoing investigation to decrease tumor size and improve post-transplant outcomes include:

    • Chemoembolization

    • Radiofrequency ablation

    • Alcohol ablation

• Biliary malignancy

  • Historically, patients with cholangiocarcinoma have not been transplanted due to poor outcomes

  • Recent evidence (Mayo clinic) using a protocol of external beam radiation and chemotherapy pre-operatively has been associated with significant decrease in tumor recurrence post-op

• Primary sclerosing cholangitis

  • Histologic evidence of PSC recurrence post OLT has been reported in up to 20% of patients

  • Time to recurrence ranges between 1 and 10 years (median 3 years)

  • Outcomes following recurrence are favorable, although a small percentage of patients may develop graft failure

• Primary biliary cirrhosis

  • Various reports have indicated that PBC may be recurrent in 15-20% of patients post OLT

  • Median time to recurrence 5.6 years post-op

  • Although contentious, reports in the literature indicate a higher PBC recurrence in patients treated with Tacrolimus

  • Many transplant centers adopt a policy of continuing patients on Ursodeoxycholic acid post-OLT

• Autoimmune Hepatitis

  • True incidence of recurrence post-OLT not well defined

  • May recur despite adequate immunosuppression

  • May be heralded by increase in ANA titers

  • Potentially prevented by not discontinuing steroids or Cellcept post-OLT