Non-alcoholic fatty liver disease (NAFLD) potentiates autoimmune hepatitis in the CYP2D6 mouse model

Müller, P; Messmer, Marie C.; Bayer, Monika; Pfeilschifter, Josef; Hintermann, Edith; Christen, Urs

doi:10.1016/j.jaut.2016.02.007

Cited by 34 publications

(25 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This finding suggests that the simultaneous presence of AIH and NASH may confer an increased risk of progressive liver disease and death. This hypothesis is supported by the finding from a mouse model that preexisting NAFLD potentiates the severity of AIH 52. In patients with NAFLD/NASH, a high prevalence of ANA and ASMA has been noted 53.…”

Section: Diagnosis and Management Of Atypical Aihmentioning

confidence: 75%

Autoimmune hepatitis: current challenges and future prospects

Aizawa¹,

Hokari²

2017

CEG

View full text Add to dashboard Cite

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.

show abstract

Section: Diagnosis and Management Of Atypical Aihmentioning

confidence: 75%

Autoimmune hepatitis: current challenges and future prospects

Aizawa¹,

Hokari²

2017

CEG

View full text Add to dashboard Cite

show abstract

“…The prevalence, and impact on outcome and treatment response, of NAFLD or NASH in confirmed AIH patients is largely unknown. There is evidence that obesity worsens the course (and treatment response) of other autoimmune diseases and pre‐existing NAFLDseems to potentiate the severity of AIH in the cytochrome P450 2D6 mouse model . To date, there is only one small retrospective study indicating that patients with concurrent AIH and NASH(but not simple steatosis) are more likely to present with advanced disease with adverse clinical outcomes and decreased survival …”

Section: Pathogenesismentioning

confidence: 99%

Review article: unanswered clinical and research questions in autoimmune hepatitis‐conclusions of the International Autoimmune Hepatitis Group Research Workshop

Dyson

Martin²,

Dalekos³

et al. 2019

Aliment Pharmacol Ther

View full text Add to dashboard Cite

Background: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that results in substantial morbidity and mortality with many unanswered clinical and research questions. Improved understanding of disease pathogenesis, including the extra-hepatic manifestations of AIH, may allow targeted treatments with greater efficacy and fewer associated adverse events. Aim:To identify the spectrum of unanswered clinical and research questions facing care providers in the management of patients with autoimmune hepatitis (AIH). Methods:The International Autoimmune Hepatitis Group initiated a series of research workshops to start to address these questions. Key issues were discussed in small group sessions with collation of all discussions to be summarised in this manuscript.Results: Key issues were identified as: the need for better understanding of disease pathogenesis, standardisation of the methods and assays used to evaluate autoantibodies in AIH, refinement of the histopathological criteria for "typical" or "compatible" AIH, focus on the interaction with non-alcohol related fatty liver disease, how to treat acute severe AIH, better assessment of quality of life in adults and paediatrics, standardising use of standard, third-line and experimental therapies in AIH and search for biomarkers early in the disease course that predict outcome. Conclusion:This workshop has outlined the key unanswered clinical and research questions to help to define the research agenda in AIH.

show abstract

“…Thus, similar to alcoholic liver disease and its influence on autoimmunity [56], there is neither firm proof that NAFLD or NASH induce or at least promote autoimmune liver disease nor that they influence the severity of disease. However, it has been demonstrated that pre-existing NAFLD leads to an increased frequency of liver autoantigen-specific T cells and a higher severity of AIH in the mouse [57]. Drugs are known to induce acute and/or chronic liver injury and may cause autoimmune-mediated hepatitis with similar manifestations as AIH.…”

Section: Mechanistic Insight From Clinical Observationsmentioning

confidence: 99%

Immunopathogenic Mechanisms of Autoimmune Hepatitis: How Much Do We Know from Animal Models?

Christen

Hintermann

2016

IJMS

Self Cite

View full text Add to dashboard Cite

Autoimmune hepatitis (AIH) is characterized by a progressive destruction of the liver parenchyma and a chronic fibrosis. The current treatment of autoimmune hepatitis is still largely dependent on the administration of corticosteroids and cytostatic drugs. For a long time the development of novel therapeutic strategies has been hampered by a lack of understanding the basic immunopathogenic mechanisms of AIH and the absence of valid animal models. However, in the past decade, knowledge from clinical observations in AIH patients and the development of innovative animal models have led to a situation where critical factors driving the disease have been identified and alternative treatments are being evaluated. Here we will review the insight on the immunopathogenesis of AIH as gained from clinical observation and from animal models.

show abstract

Non-alcoholic fatty liver disease (NAFLD) potentiates autoimmune hepatitis in the CYP2D6 mouse model

Cited by 34 publications

References 34 publications

Autoimmune hepatitis: current challenges and future prospects

Autoimmune hepatitis: current challenges and future prospects

Review article: unanswered clinical and research questions in autoimmune hepatitis‐conclusions of the International Autoimmune Hepatitis Group Research Workshop

Immunopathogenic Mechanisms of Autoimmune Hepatitis: How Much Do We Know from Animal Models?

Contact Info

Product

Resources

About