Treatment and outcome of autoimmune hepatitis: Audit of 28 UK centres

Abstract

Background With few data regarding treatment and outcome of patients with AIH outside of large centres we present such a study of patients with AIH in 28 UK hospitals of varying size and facilities. Methods Patients with AIH were identified in 14 University and 14 District General hospitals; incident cases during 2007–2015 and prevalent cases, presenting 2000–2015. Treatment and outcomes were analysed. Results In 1267 patients with AIH, followed up for 3.8 (0–15) years, 5‐ and 10‐year death/transplant rates were 7.1 ± 0.8% and 10.1 ± 1.3% (all‐cause) and 4.0 ± 0.6% and 5.9 ± 1% (liver related) respectively. Baseline parameters independently associated with death/transplantation for all causes were: older age, vascular/respiratory co‐morbidity, cirrhosis, decompensation, platelet count, attending transplant centre and for liver related: the last four of these and peak bilirubin. All‐cause and liver‐related death/transplantation was independently associated with: non‐treatment with corticosteroids, non‐treatment with a steroid‐sparing agent (SSA), non‐treatment of asymptomatic or non‐cirrhotic patients and initial dose of Prednisolone >35 mg/0.5 mg/kg/day (all‐cause only), but not with type of steroid (Prednisolone vs. Budesonide) or steroid duration beyond 12 months. Subsequent all‐cause and liver‐death/transplant rates showed independent associations with smaller percentage fall in serum ALT after 1 and 3 months, but not with failure to normalise levels over 12 months. Conclusions We observed higher death/transplant rates in patients with AIH who were untreated with steroids (including asymptomatic or non‐cirrhotic subgroups), those receiving higher Prednisolone doses and those who did not receive an SSA. Similar death/transplant rates were seen in those receiving Prednisolone or Budesonide, those continuing steroids after 12 months and patients attaining normal ALT within 12 months versus not.

Treatment of autoimmune hepatitis: Budesonide does not solve our problems

“…Only in a subpopulation of patients with low baseline transaminases (< 2× ULN), response rates of budesonide were not inferior to prednisone-treated patients. [6] This discrepancy in effectiveness of budesonide between the real-life experience and the initial budesonide study is in line with other reports investigating the use of budesonide in real life, [7,8] and thus seriously challenges the assumed superiority or even just equivalence of budesonide to prednis(ol)one treatment in AIH.…”

“…[12] As inflammation can alter systemic bioavailability of budesonide, this variability might explain the wide variation in response rates reported. [5][6][7][8] High systemic drug levels of budesonide in active liver inflammation may lead to higher systemic effects and may in turn increase the effectiveness of budesonide in induction therapy. However, this calls into question the rationale for applying a drug with a very high first-pass effect in the absence of hepatic inflammation.…”

“…As inflammation can alter systemic bioavailability of budesonide, this variability might explain the wide variation in response rates reported 5–8. High systemic drug levels of budesonide in active liver inflammation may lead to higher systemic effects and may in turn increase the effectiveness of budesonide in induction therapy.…”

Histopathologist and clinician interface in diagnosis and management of autoimmune hepatitis

“…In one cohort study, lower necroinflammatory score was associated with a better long-term outcome 36. However, high baseline serum ALT has been a favourable prognostic marker in some,37 although not in other studies 38…”

The clinical imperative of a complete biochemical response to immunosuppression in autoimmune hepatitis: Close is not good enough!

“…To prove that a CBR to immunosuppression results in significantly improved clinical outcomes in a rare disease like AIH has required over 13 years of work to develop well-curated databases of patients with AIH and an adequate duration of monitoring of sufficient numbers of patients with and without CBRs to ascertain differences in outcomes. The UK Audit of national databases [3] provided the first large-scale evidence that patients with AIH achieving a treatment "response," defined as normalization of ALT, had significantly reduced all-cause mortality and adverse liver-related outcomes over a period of 15 years. Disappointingly, only ~60% of patients with AIH who were treated in the United Kingdom achieved such a response.…”