Centrilobular zonal necrosis is a unique subtype of autoimmune hepatitis: A cohort study

Centrilobular zonal necrosis (CZN) is described as a histological feature present in a small number of autoimmune hepatitis (CZN-AIH) patients. CZN may be detected in the absence of significant interface hepatitis, which is the most important histological finding of AIH. The clinical and histopathological spectra of CZN-AIH were not homogeneous, and 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 clinical and immunogenetic features of CZN-AIH, a total of 102 biopsy samples of AIH, obtained at The Jikei University Katsushika Medical Center and Jikei University Hospital from 2000 to 2018, 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 (control AIH). Data on clinical, histopathologic, and immunogenetic features were statistically compared between the CZN-AIH and the control AIH group. Additionally, the impact of the onset pattern (acute or chronic) and coexistent significant interface hepatitis in CZN-AIH was determined.

In CZN-AIH, the frequency of acute-onset cases was significantly higher than that in control AIH (56.2% vs 32.9%; P < .05), and the number of cases with moderate-to-severe interface hepatitis in liver histology was significantly lower (37.5% vs 87.1%; P < .001). Compared to the control AIH, cases of CZN-AIH had lower immunoglobulin G level (P < .001), lower antinuclear antibodies titer (P < .001), and lower AIH score (P < .001). The immunogenetic disproportionate distribution of HLA-DR phenotypes in control AIH (increased HLA-DR4 and decreased HLA-DR9) was not found in CZN-AIH. Moreover, CZN-AIH was less frequently relapsed (P < .05). For the acute-onset CZN-AIH cases, the clinical features were hardly indistinguishable from the chronic CZN-AIH cases. Similarly, the existence of interface hepatitis did not influence on the pathophysiology of CZN-AIH. Moreover, the acute-onset CZN-AIH cases is clinically distinguishable from acute-onset control AIH.

CZN can characterize as a distinct AIH subtype, regardless of onset-pattern or coexistence of significant interface hepatitis. To further strengthen this hypothesis, collection of more CZN-AIH cases is needed.