Autoimmune Hepatitis (AIH) Drug Development

What is Autoimmune Hepatitis?

Autoimmune hepatitis (AIH), also known as lupoid hepatitis, is a chronic autoimmune disease first described in 1951 in which the immune system attacks the autogenous liver cells causing progressive inflammation. It is an immune-mediated inflammatory disorder characterized by the increased circulating immunoglobulins or autoantibodies and transaminase.

AIH is generally classified into 2 different types according to the nature of the serum autoantibodies, type 1 AIH characterized by the presence of antinuclear antibody (ANA) and/or anti-smooth muscle antibody (SMA), and type 2 AIH characterized by the positivity for anti-liver kidney microsomal type 1 antibody (anti-LKM-1) and/or for anti-liver cytosol type 1 antibody (anti-LC-1). AIH can occur at any age, in all ethnic groups, and both global children and adults, but predominantly in women. It has been reported that AIH affected 4 to 25 individuals per 100,000 population, of which type 1 AIH dominates, about 80%, and type 2 AIH is mainly diagnosed among children and young adults. The AIH pathogenesis, similar to other autoimmune diseases, was thought to be closely related to abnormal immune tolerance mechanisms, which may be caused by viral infections, medication, genetic and environmental factors.

Pathogenesis of autoimmune hepatitis. Fig.1 Pathogenesis of autoimmune hepatitis. (Sucher, 2019)

Current Diagnosis and Treatment of Autoimmune Hepatitis

To diagnose AIH, other chronic liver diseases should be excluded according to clinical features, such as drug-induced hepatitis, viral hepatitis, alcohol-induced hepatitis, and idiopathic chronic hepatitis. One of the key diagnostic criteria is the detection of elevated autoantibodies (ANA, SMA, anti-LKM-1, and anti-LC-1). The autoantibody tests are more than helpful for AIH diagnosis, also for a specific classification of AIH. The increased serum transaminase level is another indicator of the AIH diagnosis. The liver biopsy is also a useful method to distinguish AIH from other liver diseases.

Currently, the frontline treatment mainly relies on immunosuppressive therapy, in which corticosteroids and azathioprine are usually used as a standard to suppress inflammation, relieve symptoms and liver functions, and avoid relapse. Alternative therapies are recommended when treatment fails or relapses frequently.

  1. Mycofenolate mofetil, a noncompetitive inhibitor of inosine monophosphate dehydrogenase, is currently used as an alternative treatment option for autoimmune hepatitis, which inhibits the proliferation of T cells and B cells by suppressing the purine synthesis;
  2. Cyclosporine and Tacrolimus are calcineurin inhibitors as well as powerful immunosuppressants applied for the treatment of AIH, acting by inhibiting Treg activation and IL-2 production;
  3. Sirolimus and Everolimus, rapamycin (mTOR) inhibitors, have been shown to successfully treat refractory AIH and posttransplant AIH;
  4. Monoclonal antibodies also have been applied for the treatment of refractory AIH.

Additionally, other novel therapeutics, such as microRNAs (miRNAs) therapy and PD-1 antibody, are being investigated for AIH treatment. And an array of useful targets and biomarkers have been identified, which also provides clues for the new drug development for the treatment of AIH.

Treatment strategy in autoimmune hepatitis. Fig.2 Treatment strategy in autoimmune hepatitis. (Lowe, 2018)

Our Featured Autoimmune Hepatitis Drug Development Services

Having been actively exploring effective autoimmune hepatitis treatments for many years, Creative Biolabs has gained significant knowledge and rich experience in autoimmune hepatitis new therapy development. We are now providing novel monoclonal antibody, bispecific antibody, and cell-based therapy development services for the treatment of autoimmune hepatitis, based on the advantages of:

  • Abundant experience and expertise
  • Comprehensively well-constructed technology platforms
  • One-stop services covering from target validation to drug discovery
  • Perfect after-sale service

Please directly contact us for more details.

References

  1. Sucher, E., et al. Autoimmune Hepatitis-Immunologically Triggered Liver Pathogenesis-Diagnostic and Therapeutic Strategies. Journal of Immunology Research. 2019, 2019: 9437043.
  2. Lowe, D., John, S. Autoimmune hepatitis: Appraisal of current treatment guidelines. World Journal of Hepatology. 2018, 10(12): 911-923.

For Research Use Only | Not For Clinical Use



Online Inquiry

Autoimmune Diseases

We are dedicated to advancing and facilitating your drug development against autoimmune diseases

Contact us

USA

  • Location:

  • Call:

  • Fax:

  • Email:

UK

  • Location:

  • Call:

  • Email:

Autoimmune Diseases,Drug Development for
Autoimmune Diseases

Creative Biolabs is a world-leading CRO that is skilled in developing novel therapies,
especially in antibody and cell therapy for autoimmune diseases.

Copyright © 2022 Creative Biolabs. All Rights Reserved.