Insufficient pretransplant induction therapy is associated with diffuse intrahepatic cholangiopathy in ABO-incompatible living donor liver transplantation for acute liver failure.

Abstract

Background: ABO-incompatible liver transplantation (ABOi LT) can now be successfully performed with standard pretransplant induction therapy. For patients with chronic end-stage liver disease (ESLD), ABOi LT can achieve long-term outcomes comparable to those of blood type-compatible (ABOc) LT. Outcomes of patients with acute liver failure (ALF) who undergo urgent transplantation surgery with a limited induction period should be further investigated.

Methods: Between 2004 and 2023, adult patients who underwent living donor liver transplantation (LDLT) at Taipei Veterans General Hospital were enrolled. Based on the chronicity of liver disease and the transplant type, patients were divided into 4 groups for outcome analysis: ALF patients who received ABOi LDLT, ALF patients who received ABOc LDLT, ESLD patients who received ABOi LDLT, and ESLD patients who received ABOc LDLT.

Results: Four instances of diffuse intrahepatic cholangiopathy (DIC) occurred in the ABOi LDLT group (n=3, 27.3% in group 1 and n=1, 2.6% in group 3, p=0.03). In ABOi LDLT patients, rituximab was administered closer to LT in group 1 (5 [3~6] days before LDLT) than that in group 3 (15 [14~22] days before LDLT) (p<0.01). Univariate analysis revealed that ALF, small graft-to-recipient weight ratio (GRWR), low rituximab dose (<210 mg/m 2) and postoperative rebound of isoagglutinin immunoglobulin M (IgM) antibody titers were factors contributing to an increased risk of DIC. Allograft loss eventually occurred in 3 of the 4 patients with DIC. Overall, ABOi LDLT showed inferior long-term outcomes for ALF (5-year patient survival: 62.3%/73.6%/74.1%/76.7% in groups 1/2/3/4, respectively, p=0.25).

Conclusion: ABOi LDLT achieved outcomes comparable to those of ABOc LDLT among ESLD patients but not among ALF patients. DIC results in a high risk of allograft loss; however, the combination of potent immunosuppressive agents and early recognition of antibody rebound and the initiation of salvage treatment may improve long-term outcomes among these patients.