Clinicopathological study of primary biliary cirrhosis with interface hepatitis compared to autoimmune hepatitis

Kobayashi, Mio; Kakuda, Yuko; Harada, Kenichi; Sato, Yasunori; Sasaki, Motoko; Ikeda, Hiroko; Terada, Mitsuhiro; Mukai, Munenori; Kaneko, Shuichi; Nakanuma, Yasuni

doi:10.3748/wjg.v20.i13.3597

Cited by 26 publications

(10 citation statements)

References 35 publications

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“…ANA is frequently detectable in PBC patients 36. In the liver pathology of PBC, mild to moderate interface hepatitis is not an uncommon feature 37. Thus, the distinctive differentiation between a variant form of PBC (PBC exhibiting active hepatitis) and PBC-AIH overlap syndrome is rather uncertain.…”

Section: Diagnosis and Management Of Atypical Aihmentioning

confidence: 99%

Autoimmune hepatitis: current challenges and future prospects

Aizawa¹,

Hokari²

2017

CEG

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Autoimmune hepatitis (AIH) is a chronic progressive liver disease characterized by high levels of aminotransferases and autoantibodies, hypergammaglobulinemia, and interface hepatitis. AIH affects all races and all ages worldwide, regardless of sex, although a preponderance of females is a constant finding. The etiology of AIH has not been completely elucidated, but immunogenetic background and environmental parameters may contribute to its development. The most important genetic factor is human leukocyte antigens (HLAs), especially HLA-DR, whereas the role of environmental factors is not completely understood. Immunologically, disruption of the immune tolerance to autologous liver antigens may be a trigger of AIH. The diagnosis of classical AIH is fairly easy, though not without pitfalls. In contrast, the diagnosis of atypical AIH poses great challenges. There is confusion as to the definition of the disease entity and its boundaries in the diagnosis of overlap syndrome, drug-induced autoimmune hepatitis, and AIH with concomitant nonalcoholic fatty liver disease (NAFLD) or chronic hepatitis C. Centrilobular zonal necrosis is now included in the histological spectrum of AIH. However, the definition and the significance of AIH presenting with centrilobular zonal necrosis have not been examined extensively. In ~20% of AIH patients who are treated for the first time with standard therapy, remission is not achieved. The development of more effective and better tolerated novel therapies is an urgent need. In this review, we discuss the current challenges and the future prospects in relation to the diagnosis and treatment of AIH, which have been attracting considerable recent attention.

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Section: Diagnosis and Management Of Atypical Aihmentioning

confidence: 99%

Autoimmune hepatitis: current challenges and future prospects

Aizawa¹,

Hokari²

2017

CEG

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“…Differential diagnosis from pure AIH that may show focal non-destructive bile duct injury has been discussed in section 4.2.2. In addition, in early stage disease, histological features of chronic cholestasis, with copper-associated protein deposition and keratin 7 immunoreactivity in periportal hepatocytes will support a diagnosis of AIH-PBC variant/'overlap' [3,58] .…”

Section: Aih In Variant/ 'Overlap' Syndromesmentioning

confidence: 99%

Role of Histopathology in Autoimmune Hepatitis

Tiniakos

Brain

Bury

2015

Dig Dis

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The diagnosis of autoimmune hepatitis (AIH) is based on a combination of biochemical, immunological and histological features and exclusion of other causes of liver disease. Typical histological features include a chronic hepatitis pattern of injury with portal inflammation and interface activity, predominance of plasma cells in the portal infiltrate, emperipolesis, and hepatocellular rosette formation. Centrilobular injury with prominent hepatocellular necrosis and mononuclear inflammation is now recognised in the histological spectrum of AIH and may represent an early stage of the disease. Liver histology plays a major role in clinical diagnostic scoring systems and is important to confirm or support the clinical diagnosis of AIH. This review focuses on the role of histopathology in AIH and highlights the contribution of histological interpretation to the diagnosis of AIH, differential diagnosis from other entities, recognition of concurrent liver disease, and identification of the so-called overlap or variant syndromes, and addresses the importance of liver biopsy in the management and prognosis of patients with AIH.

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“…The pathogenesis of both disease entities is closely linked to T cells, CD4 T cells in particular. Indeed, CD4 T cells are present in the inflamed areas surrounding the bile ducts . Moreover, genome‐wide association studies have identified several major histocompatibility complex class II genes that are associated with an increased risk of developing PBC and PSC .…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, CD4 T cells are present in the inflamed areas surrounding the bile ducts. (27,28) Moreover, genome-wide association studies have identified several major histocompatibility complex class II genes that are associated with an increased risk of developing PBC and PSC. (29)(30)(31) Furthermore, pyruvate dehydrogenase E2 has been identified as an autoantigen, targeted by autoreactive CD4 T cells in patients with PBC.…”

Section: Discussionmentioning

confidence: 99%

Follicular T Helper Cell Signatures in Primary Biliary Cholangitis and Primary Sclerosing Cholangitis

Adam

Zoldan

Hofmann

et al. 2018

Hepatology Communications

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Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are the most common cholestatic liver diseases. While PBC is generally accepted to be an autoimmune disorder characterized by pathognomonic autoantibodies against mitochondrial antigens, the pathogenesis of PSC is less precisely defined; however, some degree of altered immunity toward autoantigens has been suggested. Follicular T helper (Tfh) cells, a distinct clusters of differentiation (CD)4 T‐cell subset specialized in facilitating antibody responses, have been shown to contribute to humoral autoimmunity in various disorders; yet, there is only limited information on possible alterations of Tfh cells in the context of cholestatic liver diseases. Thus, we addressed this important question by analyzing the frequency, activation status, and function of Tfh cells and frequencies of regulatory follicular T helper (Tfr) cells in well‐defined cohorts of patients with PBC and patients with PSC. Interestingly, we observed a significant increase in circulating chemokine (C‐X‐C motif) receptor 5 (CXCR5)+programmed death 1 (PD‐1) +CD4+ Tfh cells in patients with PBC but not in those with PSC. Although the frequency of potentially pathogenic chemokine (C‐C motif) receptor 7 (CCR7)lowCXCR5+PD‐1+CD4+ Tfh cells was increased in both disorders compared to healthy donors, the increase was significantly more pronounced in PBC. Furthermore, in patients with PBC, Tfh cells displayed stronger expression of the activation markers OX40 and inducible costimulator of T cells, correlated with anti‐anti‐mitochondrial antibody M2 and immunoglobulin M titers, and were most significantly increased in patients with cirrhosis. Tfr cell numbers were similarly increased; however, Tfh/Tfr ratios were unaltered in PSC and PBC. These alterations did not correlate with increased secretion of the Tfh signature cytokine interleukin‐21 in sorted CD4 T cells. Conclusion: Significant alterations occur in the Tfh cell compartment in cholestatic liver diseases, suggesting that Tfh cells influence the pathogenesis of PBC and to a lesser extend PSC.

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Clinicopathological study of primary biliary cirrhosis with interface hepatitis compared to autoimmune hepatitis

Abstract: These results suggest that the hepatocellular injuries associated with interface and lobular hepatitis in AIH and PBC with interface hepatitis may not be identical.

Cited by 26 publications

References 35 publications

Autoimmune hepatitis: current challenges and future prospects

Autoimmune hepatitis: current challenges and future prospects

Role of Histopathology in Autoimmune Hepatitis

Follicular T Helper Cell Signatures in Primary Biliary Cholangitis and Primary Sclerosing Cholangitis

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