What are the causes of autoimmune hepatitis (AIH)?

From the Guidelines

Autoimmune hepatitis is primarily caused by a dysregulated immune response where the body's immune system attacks its own liver cells, with the exact trigger unknown but several factors contributing to its development, including genetic predisposition, environmental triggers, and hormonal factors, as noted in the most recent guidance from the American Association for the Study of Liver Diseases 1. The causes of autoimmune hepatitis (AIH) are multifactorial and involve a complex interaction between genetic predisposition, environmental triggers, and immunoregulatory networks.

• Genetic predisposition plays a significant role, with certain HLA types (particularly HLA-DR3 and HLA-DR4) increasing susceptibility, as discussed in a study published in Hepatology 1.
• Environmental triggers such as viral infections (hepatitis A, B, C, Epstein-Barr virus), medications (minocycline, nitrofurantoin, hydralazine, methyldopa), and toxins can initiate the autoimmune process in genetically susceptible individuals, as outlined in the 2019 practice guidance and guidelines from the American Association for the Study of Liver Diseases 1.
• Molecular mimicry may occur where viral or bacterial proteins resemble liver cell components, causing the immune system to mistakenly target liver tissue.
• Hormonal factors likely contribute as well, explaining the higher prevalence in women, particularly during childbearing years, as noted in a study published in Gut 1. The disease involves both T-cell mediated damage and autoantibody production, resulting in progressive liver inflammation and potential cirrhosis if left untreated.
• Early diagnosis and immunosuppressive treatment with corticosteroids (prednisone 30-60mg daily initially) and/or azathioprine (50-150mg daily) are essential to prevent liver damage, as recommended in the most recent guidance from the American Association for the Study of Liver Diseases 1.
• The main long-term management goals in AIH are to minimize the risk of disease relapse, the combined end point of death from liver disease or liver transplantation, and side effects of treatment, as discussed in a study published in Gut 1.

From the Research

Causes of Autoimmune Hepatitis (AIH)

The causes of AIH are complex and multifactorial, involving both genetic and environmental factors.

• Genetic predisposition is believed to play a significant role in the development of AIH, with certain genetic risk factors increasing the likelihood of developing the disease 2, 3.
• Specific genetic risk factors associated with AIH include:
  • Human leukocyte antigen (HLA) genes, such as HLA DR3 and HLA DR4 2, 3.
  • Non-HLA genes, which have been identified through genome-wide association studies (GWAS) and candidate gene approaches 3.
• Environmental factors may also contribute to the development of AIH, including:
  • Viral infections, which can trigger autoimmune responses and lead to the development of AIH 2, 4.
  • Chemical influences, such as exposure to certain drugs or toxins, which can induce hepatitis with autoimmune involvement 2.
  • Other autoimmune disorders, which may increase the risk of developing AIH 4.

Genetic Risk Factors

Genetic risk factors for AIH have been identified through various studies, including GWAS and candidate gene approaches.

• These risk factors include:
  • HLA genes, such as HLA DRB103:01 and HLA DRB104:01 in Europeans 3.
  • Non-HLA genes, which have been associated with an increased risk of developing AIH 3.
• The identification of genetic risk factors for AIH may help to explain the phenotypic heterogeneity of the disease and provide biomarkers for drug responses 3.

Environmental Triggers

Environmental triggers, such as viral infections and chemical influences, may also contribute to the development of AIH.

• Viral infections, such as hepatitis A and B, have been shown to trigger autoimmune responses and lead to the development of AIH 2, 4.
• Chemical influences, such as exposure to certain drugs or toxins, can induce hepatitis with autoimmune involvement 2.
• Other autoimmune disorders, such as rheumatoid arthritis and lupus, may also increase the risk of developing AIH 4.