Posttransplant considerations in autoimmune liver disease: Recurrence of disease and de novo

Abstract

Autoimmune liver diseases (ALDs), including autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), and primary biliary cholangitis (PBC), are an indication for liver transplantation (LT) in 3%-5% of transplants in the United States. 1,2 Not all patients with ALD go on to need LT, but indications for LT can include acute liver failure, decompensated cirrhosis, a Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease score ≥ 15, malignancy, or refractory pruritus (PBC). Transplantation for ALD presents unique considerations given the possibility of recurrent disease and increased incidence of rejection. 3,4 Despite the potential for recurrent disease, outcomes after LT for ALD are similar to other indications. In adult LT recipients, long-term survival for AIH was similar to alcoholic cirrhosis, although worse than PBC and PSC, possibly related to immunosuppression and serious infections. 5 Patients with AIH post-LT were also at an increased risk for graft loss compared with PBC, PSC, and alcoholism, with a graft survival rate of 73.2% at 5 years and 50.9% at 15 years. 5 According to a United Network for Organ Sharing database analysis, patient survival for children transplanted for both AIH and PSC was >90% at 5 years. 6 RECURRENT DISE ASE AFTER TR ANSPL ANTBiochemical, imaging, histological features, and treatment of recurrent ALD are summarized in Table 1.

Evolving challenges with long‐term care of liver transplant recipients

“…The reported incidence of recurrent AIH is 8%-12% within the first year post-transplant and 36%-68% after 5 years. 87 A recent multinational cohort reported 20% recurrence after 5 years, 31% after 10 years, and 49% after 20 years. 88 Risk factors for recurrent AIH include younger age at transplant (<42 years-old), donor and recipient sex mismatch, higher IgG level pre-transplant, 88 longer time from transplant, discontinuation of steroids, type I AIH, HLA-DRB1 3 or 4 positivity as well as pre-transplant tacrolimus 87 or post-transplant Mycophenolate mofetil (MMF) use.…”

“…A recent multinational cohort reported 20% recurrence after 5 years, 31% after 10 years, and 49% after 20 years 88 . Risk factors for recurrent AIH include younger age at transplant (<42 years‐old), donor and recipient sex mismatch, higher IgG level pre‐transplant, 88 longer time from transplant, discontinuation of steroids, type I AIH, HLA‐DRB1 3 or 4 positivity as well as pre‐transplant tacrolimus 87 or post‐transplant Mycophenolate mofetil (MMF) use 88 . Pre‐transplant levels of antinuclear antibody (ANA) and anti‐smooth muscle antibody (ASMA) do not predict AIH recurrence 89 .…”

“…This discrepancy may be due to the deranged metabolic profiles in the pre‐transplant population which may underestimate the ∼25% prevalence of coronary artery disease (CAD) in this group 118 . The incidence of CAD in the pre‐LT population is likely rising given the increasing incidence of MASH as an indication for transplant 87 . Together, these data highlight the need for (1) adequate preoperative coronary disease risk stratification and (2) intensive screening and targeted therapy to modify cardiovascular disease risk factors.…”

“…The reported incidence of recurrent AIH is 8%–12% within the first year post‐transplant and 36%–68% after 5 years 87 . A recent multinational cohort reported 20% recurrence after 5 years, 31% after 10 years, and 49% after 20 years 88 .…”

“…This occurs in 1%-3% of adult transplant recipients in North America 91 with variable timeline and may represent an atypical form of rejection in genetically predisposed individuals. 87 Risk factors include ACR, steroid dependence, HLA DR3 phenotype, and older female donors. 92 Presentation, histology, and treatment are identical to recurrent AIH.…”