Histologic and Clinical Outcomes of Patients Developing Post-Liver Transplant Plasma Cell-Rich Rejection

Am J Clin Pathol. 2023 Jul 5;160(1):49-57. doi: 10.1093/ajcp/aqad004.


Objectives: Plasma cell-rich rejection (PCCR), also known as "plasma cell hepatitis" or "de novo autoimmune hepatitis," is a cause of allograft dysfunction occurring post-liver transplantation (LT). Patients often develop allograft failure and may require repeat LT. PCRR may fall within the spectrum of different histologies associated with antibody-mediated rejection (AMR), which is associated with donor-specific antibodies (DSAs) and positive complement component C4 (C4d) immunostaining. We sought to analyze the histologic and clinical outcomes of patients having biopsy-proven PCRR as well as to examine its C4d staining and DSA profiles.

Methods: We identified patients having PCRR between 2000 and 2020 using the electronic pathology database at our institution. We included patients who underwent at least one follow-up liver biopsy after establishing the PCRR diagnosis to assess future histologic progression and outcomes. Mean fluorescence intensity for at least one single DSA of 2,000 or higher was considered positive. Histologic diagnosis of PCRR was independently made by an experienced liver pathologist.

Results: A total of 35 patients were included in the study. Hepatitis C virus was the most common etiology for LT (59.5%). Mean ± SD age at LT was 49.0 ± 12.7 years. Forty percent of patients developed PCRR within 2 years of LT. Most patients (68.5%) had negative outcomes, with progression from PCRR to cirrhosis or chronic ductopenic rejection (CDR). Patients who had hepatitis C virus were more likely to develop cirrhosis rather than CDR following the PCRR diagnosis (P = .01). Twenty-three (65.7%) patients had at least one prior episode of T-cell-mediated rejection before being diagnosed with PCRR. DSAs were positive in 16 of 19 patients assessed, and C4d immunostaining was positive in 9 of 10 patients.

Conclusions: Development of PCRR negatively affects liver allograft outcomes and patient survival after LT. The presence of DSA and C4d in PCRR patients supports it to be within the histologic spectrum of AMR.

Keywords: Cirrhosis; De novo autoimmune hepatitis; Liver biopsy; Plasma cell hepatitis; Plasma cell–rich rejection.

MeSH terms

  • Adult
  • Biopsy
  • Complement C4b
  • Fibrosis
  • Graft Rejection
  • Humans
  • Isoantibodies
  • Liver Cirrhosis / pathology
  • Liver Diseases*
  • Liver Transplantation* / adverse effects
  • Middle Aged
  • Peptide Fragments
  • Plasma Cells / pathology


  • Isoantibodies
  • Complement C4b
  • Peptide Fragments