Infiltrative (sinusoidal) and hepatitic patterns of injury in acute cellular rejection in liver allograft with clinical implications

Abstract

Acute cellular rejection post liver transplant occurs most commonly but not exclusively in the first year. In this study, we report two patterns: sinusoidal infiltrative and hepatitic, which are not considered in the Banff system. We describe their presentation, response to Solu-Medrol, and compare these to the typical moderate-severe acute cellular rejection. Patients transplanted from 2007 to 2012 at University Health Network, who had biopsyproven rejection in the first year, were studied. Baseline transaminases and bilirubin, time of acute cellular rejection, follow-up, and treatment responses were analyzed. A total of 407 biopsies were received, of which 77 had diagnosis of acute cellular rejection with rejection activity index 5 or above; 49 from viral hepatitis patients were excluded. Twenty-eight were included; 15/28 (54%) had typical acute cellular rejection (tACR) using Banff criteria. Six (21%) had hepatitic acute cellular rejection overlapping with typical features of acute cellular rejection; seven (25%) had infiltrative acute cellular rejection (iACR) overlapping with typical features. The iACR occurred later than the tACR (124 versus 50 days; P = 0.032) and had a higher rise in baseline aspartate aminotransferase (ΔAST) compared with tACR (289 U/l versus 109 U/l; P = 0.046). Only one out of seven patients with iACR (14 versus 40% in tACR) failed Solu-Medrol boluses and required thymoglobulin. Patients with hepatitic acute cellular rejection (hACR) had similar ΔAST (P = 0.12) but higher bilirubinemia than typical acute cellular rejection (tACR) (160 μmol/l versus 35 mol/l; P = 0.039) and required thymoglobulin in four out of six (67% versus 40%) instances. Patients with iACR had higher ΔAST than tACR but better Solu-Medrol response compared with both tACR and hACR. hACR is different from plasma cell-rich late-occurring cellular rejection in its pattern but similar in its poor Solu-Medrol response.

Evidence for Alloimmune Sinusoidal Injury in De Novo Nodular Regenerative Hyperplasia After Liver Transplantation

“…The late lymphocyte recruitment argues that it did not cause NRH. We ruled out the potential confounding factors such as recurrent disease, adverse drug reactions, and severe TCMR [ 19 , 20 ]. We did not identify sinusoidal microthrombi in any case of NRH with or without infiltrate, although we would postulate that these have occurred previously at a time when a biopsy was not taken or that they were so subtle that they were not detected by standard staining [ 21 ].…”

Poorly formed hepatic granulomas: a rare manifestation of acute T cell‐mediated rejection

“…3 Non-classical variants of TCMR have also been described, including the central perivenulitis variant, sinusoidal infiltrative variant and plasma-cell rich hepatitis variant. 3 A more rarely described entity includes the hepatic granulomatous variant. 1,2 The hepatic granulomatous variant was first described by Ferrell et al in a multicentric study evaluating granulomas in allograft livers.…”

“…The diagnostic features of TCMR are mixed predominantly lymphocytic portal inflammation, lymphocytic bile duct damage and endotheliitis, involving the portal and central veins 3 . Non‐classical variants of TCMR have also been described, including the central perivenulitis variant, sinusoidal infiltrative variant and plasma‐cell rich hepatitis variant 3 . A more rarely described entity includes the hepatic granulomatous variant 1,2 …”

Sinusoid endotheliitis as a histological parameter for diagnosing acute liver allograft rejection

“…Sinusoidal lymphocyte infiltration has been recognized as a common histological finding in the liver in experimental and clinical graft- vs -host disease[ 7 , 8 ]. Previous studies have demonstrated that infiltration of lymphocytes in the sinusoidal space, and particularly adherence of lymphocytes to the endothelium are associated with various liver diseases[ 16 - 18 ]. In reality, it is often difficult to determine whether sinusoidal lymphocytes are attached to the endothelium or simply the result of tangential cuts.…”