Abstract
BACKGROUND Centrilobular zonal necrosis (CZN) is advocated as a histological hallmark present in a small number of patients with autoimmune hepatitis (CZN-AIH). Moreover, CZN has been detected in the absence of significant interface hepatitis, one of the most important histological findings of AIH. The concept of CZN-AIH as a distinctive subtype of AIH remains controversial, due to the rarity of CZN-AIH and the ambiguous definition of CZN. To elucidate the clinicopathological and immunogenetic features of CZN-AIH, and to evaluate the significance of co-existent interface hepatitis in CZN-AIH. METHODS A total of 102 biopsy samples of AIH, obtained at The Jikei University Katsushika Medical Center and Jikei University Hospital, were reviewed. The 32 patients whose biopsies showed CZN were selected as the CZN-AIH group and the remaining 70 were grouped as the non-CZN-AIH controls. In the CZN-AIH group, interface hepatitis was histologically present in 37.5% (n=12; mixed-type) and absent in 62.5% (n=20; pure-type). Data on clinical, histopathologic and immunogenetic features were statistically compared between the CZN-AIH group and the non-CZH-AIH controls. Additionally, significance of interface hepatitis in CZN-AIH was determined by comparative analysis of the mixed-type and pure-type subgroups. RESULTS Cases of CZN-AIH were more frequently of acute-onset hepatitis (56.2% vs chronic: 32.9%, P=0.031), lower immunoglobulin G level (P<0.001), lower antinuclear antibodies titer (P<0.001), and lower AIH score (P<0.001). Compared to the non-CZN-AIH cases, the CZN-AIH cases also tended to lack the typical histological characteristics of AIH and of the immunogenetic disproportionate distribution of HLA-DR genotypes in AIH (increased HLA-DR4 and decreased HLA-DR9), and responded more favorably to first-line therapy (P=0.054). For the acute-onset CZN-AIH cases, the clinical and histological features were indistinguishable from the non-acute cases. In contrast, the acute-onset non-CZN-AIH cases were distinguishable from the non-acute cases by lower antinuclear antibodies titer, lower immunoglobulin G level, and less advanced histological stage. The presence of interface hepatitis generally did not influence the morbidity of CZN-AIH, except for comorbid autoimmune diseases, higher gamma-glutamyltranspeptidase level, and increased immunoglobulin M level. CONCLUSION CZN-AIH is clinicopathologically and immunogenetically distinguishable. CZN can characterize a distinct AIH subtype, regardless of onset-pattern or co-existent interface hepatitis.
Acute-onset Autoimmune Hepatitis in a Patient with Selective Immunoglobulin M Deficiency
