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Title: Understanding the Clinical Impact of Autoimmune Hepatitis
Authors: Wong, Lin Lee
Issue Date: 2022
Publisher: Newcastle University
Abstract: Background: Autoimmune hepatitis (AIH) is a heterogenous, chronic inflammatory liver disease that remains a challenge in diagnosis and management. Failure to achieve biochemical remission has serious consequences (cirrhosis, liver failure and death). Existing immunosuppressive treatments (mainly prednisolone and azathioprine) are usually lifelong and some patients develop intolerable side effects. There is a pervading perception amongst clinicians that AIH is easy to treat and the treatments are effective. There is a gap between clinician perception, clinical data and viewpoints of patients. Aims and Methods: To explore the mechanistic evidence behind three domains of unmet need in AIH (inadequate response to therapy, effective therapy with undesirable side-effects and quality of life) using the national UK-AIH multicentre cohort. Clinical indices and quality of life (QOL) information were analysed. A novel thiopurine metabolite (deoxythioguanosine in DNA of leukocytes, dtG DNA) as a potential biomarker for treatment optimisation was explored in a subgroup of 57 patients, divided by treatment response. Findings: In a cohort of approximately 1000 patients, 29 different treatment regimens were reported and biochemical remission rate was 59%. Remission rates were significantly higher in transplant centres compared to non-transplant centres. 55% remain on corticosteroids. There was no significant correlation in the leukocyte metabolite (dtG DNA) levels with disease response or azathioprine dose which suggests that this biomarker is not clinically useful. There was evidence of QOL impairment compared to the general population with corticosteroid use being strongly associated with decreased QOL, independent of remission status. Conclusions: This demonstrates suboptimal areas of care for patients with AIH with variable treatment regimens, suboptimal remission rates, high use of corticosteroids and poor QOL. This highlights the need for better corticosteroid-free therapy approaches and emphasizes the need for continued future efforts in improving treatment approaches for AIH (which encompasses better therapies combined with focus on improving QOL).
Description: Ph. D. Thesis.
Appears in Collections:Institute of Cellular Medicine

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