Aspects of Longer-Term Management in Autoimmune Hepatitis

Abstract Introduction: Autoimmune hepatitis (AIH) is a chronic, immune-mediated liver disease which, untreated, can lead to cirrhosis and death. Treatment usually includes a steroid (usually Prednisolone, sometimes Budesonide) with a steroid-sparing agent such as Azathioprine. The aims of treatment are to obtain remission whilst minimising treatment-related side effects. There are many unanswered questions regarding the longer-term management. Aims: Analyse a large single-centre cohort of AIH patients to address: a) whether there is a role for immunosuppression withdrawal b) the role of metabolite monitoring to optimise Azathioprine dosing, c) the role of Fibroscan, a non-invasive method of fibrosis assessment to monitor fibrosis, d) the impact of AIH on bone health (osteoporosis and fracture risk), e) and f) the long-term outcomes of patients with AIH – is AIH a lifelong disease? Results: a) Although not standard practice, on retrospective analysis, 26 patients had immunosuppression withdrawn after at least 2 years’ treatment. Six of the 26 (23%) patients had relapses whilst off treatment over 1.29(0.5-9.6) (median (range)) years after stopping IST. Importantly, there were no liver-related deaths in this group. b) After increasing the AZA dose to 2mg/kg and measuring metabolites, 15 patients subsequently needed dose reduction (raising metabolites and side-effects). However, therapeutic 6-TGN levels were obtained 322((123-482) (median(range)) with AZA dosing 1.3 (0.59-2.14) mg/kg (median(range)). Rates of histological remission were no higher than standard dosing of 1mg/kg AZA. c) In a small pilot study, Fibroscan proved effective at detecting significant fibrosis using a cut-off of 11kPa, sensitivity was 83%, specificity 90% and AUROC 0.9. d) Bone health was reviewed in this proactively managed group of steroid-treated patients. Bone mineral density (BMD) remained similar to an age/gender-matched population (Z score 0.1). Total fracture rate was not obviously different from comparable data in the general population. Patient age and hip bone mineral density predicted fracture risk. e) Despite treatment, AIH patients have inferior liver-related survival (SMR 1.59(1.28-1.90), counting transplant as liver-related death. Considering a cohort of 330 patients with complete data capture between 1987-2016, all-cause and liver-related death/transplant rates: 24% (all cause) and 11% (liver) after 10 years and 51% and 21% respectively after 20 years. Five out of 65 patients in the third and fourth decade of follow-up relapsed and five developed de novo cirrhosis. Relapse rate per decade was not significantly different in patients followed up in the second twenty years, compared with patients followed from diagnosis (0.71 relapses/decade compared with 0.93 relapses/decade P = 0.23). Conclusion: AIH is a life-long disease, whereby patients continue to suffer relapses and progression to cirrhosis on treatment. In future, treatment regimes are likely to evolve to minimise dose and duration of treatment. Long-term management in a specialist care setting is important to ensure remission is obtained and retained, whilst mitigating drug side-effects and optimising quality of life.