Natural history and management of refractory autoimmune hepatitis.
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ABSTRACT:
SUBMITTER: Whitehead B
PROVIDER: S-EPMC9549313 | biostudies-literature | 2022 Oct
REPOSITORIES: biostudies-literature
Publications
Natural history and management of refractory autoimmune hepatitis.
Whitehead Bridget B Kriegermeier Alyssa A
Clinical liver disease 20220722 4
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Project description:Background & aimsAutoimmune hepatitis (AIH) is a disease of unknown aetiology with a favourable response to immunosuppression. However, in the clinic, it appears that <50% of patients achieve complete response on standard treatment. Serum B cell-activating factor (BAFF) levels are elevated in patients with AIH and are likely to contribute to disease pathogenesis. Given that belimumab, a BAFF inhibitor, has been shown to be effective in other autoimmune diseases, we investigated its use as a third-line add-on treatment option in patients with advanced AIH who did not respond to conventional treatment.MethodsHerein, we report for the first time two patients, a 27-year-old female and a 58-year-old male, both with AIH-related compensated cirrhosis at diagnosis, who were refractory to standard immunosuppressive therapies and received add-on third-line therapy with belimumab.ResultsBoth patients achieved a complete response and remained in remission while receiving low-dose corticosteroids. No adverse events related to belimumab and/or disease decompensation were observed.ConclusionsThese preliminary findings indicate belimumab as a promising treatment option for patients with AIH and refractory and advanced liver-related fibrosis.Lay summaryA small proportion of patients with autoimmune hepatitis (AIH) are refractory to standard treatments; these patients bear the highest probability of developing decompensated cirrhosis and hepatocellular carcinoma because third-line treatment options are not well established. In this case study, we showed that third-line add-on therapy with belimumab, a B cell-activating factor inhibitor, could be an alternative and promising treatment option in patients with advanced AIH who did not respond to conventional treatment.
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Project description:BackgroundThe most common cause of primary adrenal failure (Addison's disease) in the Western world is autoimmunity characterized by autoantibodies against the steroidogenic enzyme 21-hydroxylase (CYP21A2, 21OH). Detection of 21OH-autoantibodies is currently used for aetiological diagnosis, but how levels of 21OH-autoantibodies vary over time is not known.SettingSamples from the national Norwegian Addison's Registry and Biobank established in 1996 (n = 711). Multi-parameter modelling of the course of 21OH-autoantibody indices over time.Results21OH-autoantibody positivity is remarkably stable, and >90% of the patients are still positive 30 years after diagnosis. Even though the antibody levels decline with disease duration, it is only rarely that this downturn reaches negativity. 21OH-autoantibody indices are affected by age at diagnosis, sex, type of Addison's disease (isolated vs autoimmune polyendocrine syndrome type I or II) and HLA genotype.Conclusion21OH-autoantibodies are reliable and robust markers for autoimmune Addison's disease, linked to HLA risk genotype. However, a negative test in patients with long disease duration does not exclude autoimmune aetiology.
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