ABSTRACT FINAL ID: 1651
TITLE: Understanding the importance of pro- and anti-inflammatory cytokines in autoimmune hepatitis
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UK-AIH is funded by the NIHR Rare Diseases Translational Research Collaboration
Background and Aims
There have been few therapeutic advances in autoimmune hepatitis (AIH) for decades. The United Kingdom AIH (UK-AIH) Cohort aims to understand the mechanistic basis of risk in AIH and explore novel therapeutic approaches. This pilot study explored the biological differences between patients in biochemical remission and those in whom disease is poorly controlled in order to identify potential treatment targets.
UK-AIH includes a subset of prevalent patients, who have been diagnosed and treated for at least 12 months, divided into “responders” with complete biochemical response (normal ALT and IgG) and “non-responders” (abnormal biochemistry despite treatment or requiring high dose steroids to achieve normal results). Panels of serum cytokines, chemokines, adhesion molecules and angiogenic factors were assessed in responders, non-responders and healthy controls using the MSD Human Biomarker Assays V-PLEX panel.
Results were obtained on 116 patients with AIH (50 responders and 66 non-responders) and 30 healthy controls. Following correction for multiple testing, 9 out of 40 molecules were found to have significant inter-group differences (Kruskal-Wallis p<0.00125; 3/19 cytokine, 2/7 angiogenesis, 2/10 chemokine, 2/4 vascular adhesion molecules). For VEGF-D and IL-15, this principally reflected a difference between AIH and healthy controls unrelated to disease activity. Using a post-hoc analysis of responders vs non-responders, 7 markers were significantly different (after correcting for multiple testing) between responders and non-responders with all except VEGF-C and MDC showing elevation in non-responders.
We have identified important molecular pathways which are associated with incomplete treatment response that represent plausible targets for second-line therapy. Significant TNF-α elevation was seen in incomplete responders and the potential of anti-TNF therapy should be systematically explored in AIH.