Acute onset of autoimmune hepatitis with sinusoidal and central vein endotheliitis, and marked involvement of activated dendritic cells

Abstract

Rationale:Autoimmune hepatitis (AIH) is characterised by interface hepatitis. However, some acute cases exhibit atypical centrilobular necrosis with mild portal inflammation. Detailed histological and ultrastructural analyses of acute AIH are limited.Patient concerns:A 44-year-old female was admitted to our hospital with jaundice, general fatigue and liver dysfunction. Her transaminase levels were elevated, her immunoglobulin G level was 1735 mg/dL and her anti-nuclear titres were ×80.Diagnosis:AIH was diagnosed, and histochemical examination of a liver biopsy showed the presence of atypical histological features of prominent centrilobular necrosis and central vein and hepatic sinusoidal endotheliitis. Electron microscopy showed that dendritic cells (DCs) and lymphocytes were attached to disrupted liver sinusoidal endothelial cells (LSECs) in hepatic sinusoids and that DCs attached to LSECs via pseudopods in the central vein.Interventions and outcomes:The patient was started on 40 mg/day prednisolone to control the hepatic inflammation. Her aspartate and alanine aminotransferase levels started declining after prednisolone was initiated. Three weeks later, these levels had normalised. The dosage of prednisolone was gradually decreased as liver function improved. The patient remains under observation and continues to receive 2.5 mg prednisolone.Lessons:An important marker of acute AIH may be the presence of activated DCs in the hepatic sinusoids and central vein.

Critical roles of conventional dendritic cells in autoimmune hepatitis via autophagy regulation

“…Our data demonstrate an increase in the frequency of mature cDCs in the periphery and liver tissues of AIH, which is paralleled by an increase in ALT. Yokomori H. et al suggested that the presence of activated DCs in the hepatic sinusoids and central vein may be an important marker of AIH by electron microscopy founding 30 . Wang et al demonstrated a detrimental role of cDCs in ConA-induced hepatitis by depletion of cDCs using either CD11c-diphtheria toxin receptor transgenic mice (DTR Tg) mice or anti-CD11c antibody with reduced the severity of liver injury significantly 31 .…”

Vascular endotheliitis associated with infections: Its pathogenetic role and therapeutic implication

“…It is thus considered to be an intimate lymphocyte-endothelial cell interaction universally associated with active hepatic inflammation [22] . Although the pathogenesis of endotheliitis-like changes in chronic hepatitis C is not known so far, endotheliitis-like changes may represent a reaction related to the inflammatory response to hepatitis virus and be attributed to immune-mediated mechanisms taking place in close vicinity, and endothelial cells in small portal veins may be the site of direct immune-mediated damage [26] .…”

“…Histochemical examination of a liver biopsy of patients with autoimmune hepatitis, a form of hepatitis that is characterized by autoantibodies and hypergrammaglobulinemia, also show central vein and hepatic sinusoidal endotheliitis [26] . In this study, it has been suggested that central vein and sinusoidal endothelial cells promote the activation of dendritic cells in autoimmune hepatitis [26] . This endotheliitis is likely to stem from the subendothelial infiltration of dendritic cells and their activation of cytotoxic T cells [27] .…”

“…This endotheliitis is likely to stem from the subendothelial infiltration of dendritic cells and their activation of cytotoxic T cells [27] . Vascular cell adhesion molecule-1 (VCAM-1) expression was evident in hepatic sinusoids and the central vein in autoimmune hepatitis [26] . VCAM-1 plays a major role in inducing changes to the shape and structure of endothelial cells during transendothelial migration of leukocytes [28] .…”

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

“…[9][10][11] However, the validity and value of this novel classification approach remain controversial, due at least in part to the rarity of CZN-AIH and the continuing ambiguity of the definition of CZN in the literature. [8][9][10][11][12][13][14][15][16] In the present study, in order to clarify the significance of CZN-AIH, we first collected a larger number of CZN-AIH cases according to the application of a strict pathological diagnostic criterion for CZN, and the clinicopathological and immunogenetic features were compared to non CZN (control) AIH. The patients who collected this study were added to the previous study population.…”