Idiopathic Post-Transplantation Hepatitis: Clinicopathologic Features
Nicole Kramer, Tsung-Teh Wu, Charles B Rosen, Taofic Mounajjed. Auckland Hospital, Auckland, New Zealand; Mayo Clinic, Rochester, MN
Background: Idiopathic post-transplantation hepatitis (IPTH) has been described in orthotopic liver transplantation (OLT) recipients with variable reported incidence. The significance of IPTH and its relationship to de novo autoimmune hepatitis (DNAIH) is unclear. The aim of this study is to elucidate these features in our OLT population.
Design: We searched our database for chronic hepatitis following OLT. Patients transplanted for viral hepatitis, autoimmune hepatitis, PBC, or PSC were excluded, resulting in a total pool of 735 patients (1987 to 2008). Histologic features including ISHAK hepatic activity index (mHAI) of the first biopsy with IPTH were recorded. Previous and follow-up biopsies were also reviewed. Relevant clinical and laboratory data were recorded. Patients were scored using the international autoimmune hepatitis Group (IAHG) criteria; scores >15 were diagnostic of DNAIH. Graft loss, mortality, acute cellular rejection (ACR), and end-point fibrosis were compared with an age and OLT date-matched control group of 90 patients.
Results: Seventeen (2.3%) of 735 patients had histologically confirmed IPTH (10 males, 7 females, age: 2-62 years, 5 patients <18 years). Biopsies with IPTH occurred at an average of 850 ± 688 days after OLT. The clinical and histologic follow-up periods averaged 10.6 ± 4.6 and 6.3 ± 4.4 years, respectively. Viral hepatitis serology was negative in all patients except one with positive CMV-IgM. ANA and ASMA were positive in 9 (of 15) and 3 (of 13) patients, respectively. mHAI score averaged A:2.1 B:1.5 C:1.8 D:2.1. Plasma cell percentage averaged 20 ± 17%. Six patients (35%) with DNAIH had significantly higher plasma cell percentage (mean=33%) and lobular necroinflammatory activity (mean mHAI C=2.5) compared to the remaining IPTH patients (p=0.015 and 0.006, respectively). They also tended to have higher mortality (17%), graft loss rate (20%), fibrosis stage (mean=2.3 of 4), and a higher rate of previous ACR episodes (83%). Of all IPTH patients, 13 (76%) had previous episodes of ACR, significantly higher than 47% in the control group, p=0.02. IPTH patients also had significantly higher end-point fibrosis (mean=stage 2) and graft loss rate (13%) compared to the control group (mean stage=0.5 and graft loss rate=1.3%); p=0.0001 and 0.015, respectively. There was no difference in mortality between IPTH patients (12%) and the control group (13%); p=0.9.
Conclusions: IPTH is rare following OLT and is associated with increased fibrosis and graft loss. Association with ACR suggests alloimmune pathogenesis. DNAIH appears to be a more aggressive subset of IPTH.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 146, Tuesday Afternoon