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Master Thesis

Biological, histological and immunological factors predicting the relapse of autoimmune hepatitis in patients undergoing first line (azathioprine) and third line (rituximab) treatment

Abstract : Background: Autoimmune hepatitis is a rare chronic inflammatory disease of the liver with complex pathophysiological mechanisms, and a high rate of recurrence when treatment is stoped: 46% in adults and 80% in children, of which 50% at 3 months, 90% at 28 months, according to AASLD (21-23)). The main documented risk factors are ALT, AST, serum IgG, or the presence of persistent inflammation with periportal plasma cells on liver biopsy prior to discontinuation of treatment. These factors have been studied in patients receiving standard first-line corticosteroid or Azathioprine therapy. Little is known about the immunological markers involved in the mechanism of immune dysfunction that promote the onset and maintenance of liver injury. Using the rationale of studies on other dysimmune diseases (myasthenia gravis and optic neuromyelitis), we will focus on a new marker: the CD27+ memory B lymphocyte level as a predictor of recurrence after stopping treatment. Objective: To explore factors predicting recurrence of autoimmune hepatitis after discontinuation of treatment, in patients undergoing 1st line treatment with IMUREL® (control group) and 3rd line treatment with MABTHERA® (refractory autoimmune hepatitis). Material and Methods: Creation of two monocentric study protocols at the Grenoble University Hospital, including 26 patients out of an initial cohort of 173, after verification of the inclusion and exclusion criteria: HAI FR BIO: retrospective study with as CJP the association between the ALT level (measured in IU/L) before stopping treatment and the risk of HAI recurrence. The study started in July 2020 over 2 months, these results are presented in this paper. HAI FR BIH: prospective study allowing the analysis of the association between the CD27+ memory B lymphocyte rate (measured in % of GB), after stopping treatment every 3 months and the risk of HAI recurrence. This protocol will begin in January 2021 after validation by the Committee for the Protection of Persons. Results HAI-FR-BIO: There was no statistically significant association between the ALT level before discontinuation of treatment and the risk of recurrence of autoimmune hepatitis (p value: 0.148). With regard to secondary endpoints, no statistically significant difference was found between the AST level, the IgG level or the presence of lobular, fragmentary or plasma cell necrosis on liver biopsy and the risk of recurrence of autoimmune hepatitis. Conclusion: Analyses of HAI-FR-BIO did not show a statistically significant association between the ALT rate before treatment discontinuation and the risk of recurrence. The main limiting factor is the small number of subjects included as this is a rare disease with realization of a monocentric study. HAI-FR-BIH is a pilot study that will explore the level of CD27+ memory B lymphocytes never studied in HAI. The analysis of this new biomarker would allow a better understanding of the complex immune pathophysiology of this disease with the goal in a close future of reducing the risk of recurrence of autoimmune hepatitis by standardizing patient follow-up.
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Master Thesis
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https://dumas.ccsd.cnrs.fr/dumas-02968451
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Submitted on : Thursday, October 15, 2020 - 5:05:14 PM
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Sabine Tedjini. Biological, histological and immunological factors predicting the relapse of autoimmune hepatitis in patients undergoing first line (azathioprine) and third line (rituximab) treatment. Human health and pathology. 2020. ⟨dumas-02968451⟩

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