Immunoglobulin G4 (IgG4)‐related autoimmune hepatitis and IgG4‐hepatopathy: A histopathological and clinical perspective

Abstract

Immunoglobulin G4 (IgG4)‐related disease (IgG4‐RD) is a chronic inflammatory disease that simultaneously or consecutively involves multiple organs of the body. It is characterized by elevated serum IgG4 levels and massive infiltration of IgG4+ plasma cells in the damaged tissues. IgG4‐related autoimmune hepatitis (IgG4‐AIH) and IgG4‐hepatopathy are relatively new entities that have been proposed as a phenotype of IgG4‐RD in the liver. Immunoglobulin G4‐AIH is defined as a disorder with serological, histopathological, and clinical features of both IgG4‐RD and AIH, simultaneously satisfying the diagnostic criteria of both classical AIH and IgG4‐RD. Although there are several case reports and studies of IgG4‐AIH among the published works, no consensus regarding the histopathological characteristics of IgG4‐AIH has been established, and its clinical implications remain obscure. Immunoglobulin G4‐hepatopathy is defined as a comorbidity of IgG4‐RD in the liver, and patients not meeting the diagnostic criteria of classical AIH could be diagnosed with IgG4‐hepatopathy. Numerous issues regarding these diseases, especially their epidemiology, histopathological and clinical characteristics, and treatment response to corticosteroids, remain unsolved, and need to be determined to establish the disease concepts of IgG4‐AIH and IgG4‐hepathopathy.

Immunoglobulin G4-related Hepatopathy after COVID-19 Vaccination

“…The findings did not meet the criteria for IgG4-related autoimmune hepatitis proposed by Uemura and Nakanuma et al (3,4) or the criteria for IgG4-related sclerosing cholangitis on imaging (5). Therefore, IgG4-related hepatopathy was diagnosed.…”

“…IgG4-related disease has become a well-established disease entity that features high serum IgG4 levels, IgG4positive plasma cell proliferation and characteristic fibrosis in two or more organs (1,2). Regarding liver involvement, the following disease concepts have been proposed: IgG4related sclerosing cholangitis, IgG4-related autoimmune hepatitis (AIH) and IgG4-related hepatopathy (3,4).…”

Autoimmune liver diseases in systemic rheumatic diseases

“…Infiltrating IgG4-positive plasma cells can be observed in the AIH liver, suggesting involvement of IgG4 in its pathogenesis[ 180 ]. Nevertheless, the disease concept of IgG4-AIH remains to be established[ 181 ].…”

Immune-Mediated Inner Ear Disease Associated with Type 1 Autoimmune Hepatitis: A Challenging Coexistence

“…IgG4-RD is a multi-organ immune-mediated disease that imitates various malignant, infectious, and inflammatory disorders. 29 , 30 Hepatic involvement 49 and particularly laboratory features of cholestasis 28 as well as SNHL could be indicative of IgG4-RD. Since pancreato-hepatobiliary disease is the potential clinical phenotype 30 for this patient, then morphological changes of affected organs would be expected to be found.…”

“…It is also remarkable that the liver biopsy did not reveal typical histologic findings of IgG4-associated AIH, or IgG4-related sclerosing cholangitis such as storiform fibrosis, obliterative phlebitis, significant accumulation of plasmacytes in the liver, lymphoplasmacytic infiltrates surrounding the bile ducts, or tissue eosinophilia. 29 , 49 On the other hand, SNHL is a rare manifestation of IgG4-RD 29 where pachymeningitis, mass forming lesions or erosions of the temporal bone are frequently described 31 ; yet, such imaging findings were not found at the patient. The absence of other organ involvement, such as IgG4-related dacryoadenitis/sialadenitis, retroperitoneal fibrosis, or renal lesions that may coexist in about 26% of patients with IgG4-related sclerosing cholangitis 28 also makes the disease unlikely.…”