Inequity of care provision and outcome disparity in autoimmune hepatitis in the United Kingdom

Dyson, Jessica; Wong, Lin Lee; Bigirumurame, Theophile; Hirschfield, Gideon; Kendrick, Stuart; Oo, Ye Htun; Lohse, Ansgar W.; Heneghan, Michael A.; Jones, David

doi:10.1111/apt.14968

Cited by 39 publications

(49 citation statements)

References 44 publications

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“…The strengths of this study are its multicentre, real‐world design and cohort size, as it is the second largest study to date to report on the outcomes of second‐line therapies in AIH patients. Real‐world studies such as this and the recent study by Dyson et al from the UK, provide important insights into the management of AIH across a wide spectrum of hospitals, and in particular the treatment options and results when standard therapy fails; a point highlighted in a recent editorial by Hupa‐Breier et al While most AIH subjects tolerate first‐line treatment well, and achieve remission, for the 20% who do not, it is important to better understand the factors that influence the effectiveness of second‐line therapies in order to optimise treatment choice and facilitate patient counselling and expectations. Our study has shown that only 60% of patients receiving MMF as second‐line therapy achieve complete remission, highlighting the importance of identifying the best candidates and looking at possible other agents such as calcineurin inhibitors where necessary.…”

Section: Discussionmentioning

confidence: 94%

Beneficial response to mycophenolate mofetil by patients with autoimmune hepatitis who have failed standard therapy, is predicted by older age and lower immunoglobulin G and INR levels

Nicoll

Roberts

Lim

et al. 2019

Aliment Pharmacol Ther

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Summary Background Mycophenolate mofetil is a commonly used salvage therapy for patients with autoimmune hepatitis (AIH). Aim To evaluate the predictors of response to mycophenolate rescue therapy to facilitate clinical decision making. Methods We performed a retrospective observational cohort study of AIH patients managed in 17 major Australian liver centres who received mycophenolate after an inadequate response or intolerance to corticosteroids with/without thiopurine(s). Baseline demographic, clinical and laboratory variables were compared between responders and nonresponders. A multivariable logistic regression model was developed using forward selection to identify independent predictors of treatment response. Results A total of 105 patients received mycophenolate rescue therapy of whom 63 (60%) achieved biochemical remission. On univariable analysis, older age (P = 0.003), INR < 1.1 (P = 0.02), and lower immunoglobulin gamma (IgG; P < 0.002) levels were associated with treatment response, while no association was found with cirrhosis status (P = 0.07) or treatment indication (P = 0.63). On multivariable analysis, lower pre‐treatment serum IgG level (P = 0.01), higher age at commencing mycophenolate (P = 0.01) and higher INR (P = 0.03) were the only significant independent predictors. An IgG level <17 g/L had a positive and negative predictive value for response of 71% and 60% respectively, while age ≥54 years when commencing mycophenolate had a positive and negative predictive value for response of 80% and 59% respectively. Conclusion Mycophenolate remains an excellent treatment option for patients with AIH refractory to or intolerant of standard therapy with those most likely to benefit being older and/or having lower pre‐treatment IgG levels.

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Section: Discussionmentioning

confidence: 94%

Beneficial response to mycophenolate mofetil by patients with autoimmune hepatitis who have failed standard therapy, is predicted by older age and lower immunoglobulin G and INR levels

Nicoll

Roberts

Lim

et al. 2019

Aliment Pharmacol Ther

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“…Short‐term side effects of steroids are well recognised. In a multicentre study by the UK‐AIH consortium, 55% patients were taking “long‐term” corticosteroids (at least 12 months after diagnosis of AIH) . Long‐term consequences of steroid therapy are not well documented in patients with AIH…”

Section: Review Criteriamentioning

confidence: 99%

“…[11][12][13][14] Notwithstanding this high initial remission rate, long-term management of AIH remains suboptimal. Despite treatment, de novo cirrhosis develops in 18 (median (range))% patients [15][16][17][18][19][20][21][22][23] and also premature death with standardised mortality ratios of 2.0-4.0. 1,15,24,25 In part, this is because AIH frequently relapses after stopping treatment and sometimes despite continuing treatment.…”

Section: Introductionmentioning

confidence: 99%

Stopping immunosuppressive treatment in autoimmune hepatitis (AIH): Is it justified (and in whom and when)?

Harrison

Gleeson

2019

Liver International

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Background Initial treatment of autoimmune hepatitis (AIH) with prednisolone ± azathioprine is based on randomised controlled trials. Many patients receive long‐term immunosuppressive treatment to prevent disease relapse; this strategy has a weaker evidence base. Aim To consider whether immunosuppressive treatment (IST) withdrawal in AIH is justified and to develop a rationale for patient selection. Methods We reviewed published papers between 1972 and 2018, which addressed the outcomes of IST withdrawal and/or complications of IST in AIH. Results (1) AIH relapse rates after withdrawal of IST vary between 25% and 100%. There is heterogeneity in these studies regarding relapse definition, IST duration prior to withdrawal and criteria for biochemical and histological remission prior to withdrawal. (2) Factors associated with relapse following IST withdrawal include: (a) absence of an identifiable initial disease trigger, (b) presence of other autoimmune diseases, (c) longer time to biochemical remission and (d) elevated serum transaminases on treatment withdrawal. Reports of associations between relapse and age, IST duration and failure of histological remission have been inconsistent. (3) Continued IST reduces risk of AIH relapse over at least 5 years. However, there is no evidence that routine (as opposed to selective) long‐term IST improves disease outcome. (4) Patients with AIH have an increased risk of extrahepatic cancer, notably non‐melanoma skin cancer, to which long‐term IST may contribute. Long‐term corticosteroid therapy is associated with weight gain, low‐trauma fractures, diabetes and possibly vascular disease. Conclusions While further studies are needed, evidence supports a strategy of IST withdrawal in some patients with AIH who have achieved remission.

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“…However, management of AIH differs significantly even among expert centers . Therefore, the study by Dyson et al, published in a recent issue is an important contribution to gain further insight into real‐world management of AIH in particular since the study provides data not only from large academic centers . Interestingly, the reported remission rates in this study are lower than those reported in several publications.…”

mentioning

confidence: 51%

Editorial: “real world data” of AIH—time to connect!

Hupa-Breier

Taubert

Jaeckel

et al. 2018

Aliment Pharmacol Ther

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Inequity of care provision and outcome disparity in autoimmune hepatitis in the United Kingdom

Cited by 39 publications

References 44 publications

Beneficial response to mycophenolate mofetil by patients with autoimmune hepatitis who have failed standard therapy, is predicted by older age and lower immunoglobulin G and INR levels

Beneficial response to mycophenolate mofetil by patients with autoimmune hepatitis who have failed standard therapy, is predicted by older age and lower immunoglobulin G and INR levels

Stopping immunosuppressive treatment in autoimmune hepatitis (AIH): Is it justified (and in whom and when)?

Editorial: “real world data” of AIH—time to connect!

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