Well-controlled autoimmune hepatitis treatment withdrawal may be safely accomplished without liver-biopsy guidance

Guirguis, John; Alonso, Yilien; López, Rocío; Carey, William D.

doi:10.1093/gastro/goy020

Cited by 9 publications

(10 citation statements)

References 14 publications

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“…(384) In adult patients with and without prewithdrawal liver biopsy, the frequency of relapse (30% versus 21%, P = 0.57) was similar after treatment for at least 2 years, during which serum AST and ALT levels had been normal or near-normal. (389) Of 28 treated patients with AIH who were in biochemical remission for at least 2 years before withdrawal, 15 (54%) remained in biochemical remission after treatment withdrawal during a median follow-up of 28 months Abbreviations: no pred, no predniso(lo)ne; pred, predniso(ol)ne.…”

Section: Putative Predictors Of Treatment Responsementioning

confidence: 99%

“…(390) The principal predisposing factors for relapse are the duration and completeness of inactive disease prior to treatment withdrawal. (385,389) Various other factors have been proposed, including psychological stress, (323) concurrent autoimmune disease, (244) treatment with multiple agents, (244) increased serum ALT and IgG levels at drug withdrawal, (106,338,385) portal plasma cells in the liver tissue prewithdrawal, (106,388) delayed biochemical remission, (396) and prednisolone monotherapy. (397) Patients who relapse almost invariably respond to retreatment with the original regimen.…”

Section: Relapsementioning

confidence: 99%

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Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases

et al. 2020

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US children, 9%-12% (14-16) UK children, 38% (13) Age at presentation Peripubertal and adults Usually under 14 years (153) Mode of presentation Chronic symptoms common Acute onset (~40%) Ascites or GI bleeding rare Acute liver failure possible (555,556) Asymptomatic in 25%-34% Relapse frequent (108) Acute in 25%-75% Acute severe in 2%-6% Laboratory features Hypergammaglobulinemia IgA levels may be reduced (153) Autoantibodies ANA Anti-LKM1 SMA, anti-actin [Anti-LC1, Anti-LKM3] SLA Concurrent immune diseases Autoimmune thyroiditis Autoimmune thyroiditis Rheumatic diseases Diabetes mellitus IBD Vitiligo Autoimmune overlap with PSC (ASC in children) Common in children Rare Atypical pANCA-positive Atypical pANCA-negative Overlap with PBC Seen in adults (not children) Not reported Cirrhosis at presentation Adults, 28%-33% (especially elderly) Rare Children, ≤33% Remission after drug withdrawal Possible Rare, usually need long-term immunosuppression Abbreviations: GI, gastrointestinal; IgA, serum immunoglobulin A. *Removed from marketplace. Abbreviation: anti-PD-L1, antibody to programmed death protein ligand 1. taBle 6. Features of Drug-Induced aIH-like Injury and aIH Clinical Features Drug Induced AIH-Like Injury AIH Gender Mainly women (187) Female predominance, but men also affected (2,384,467) Acute onset Majority (>60%) (231) <20% (2,136) Hypersensitivity (fever, rash, eosinophilia) Up to 30% (231,232,613) Unusual (2,384,467) Temporal relationship with drug Positive (231-234) Negative (2,56,188) HLA DRB1*03:01 or DRB1*04:01 association None (236) Common (29) Concurrent autoimmune diseases Unusual (187) Present in 14%-44% (129,149-152) Cirrhosis at presentation Rare (187) 28%-33% (9,104-107) Management Stop offending drug ± glucocorticoids (187,231,232) Glucocorticoids with AZA (2,384,467) Relapse after drug withdrawal Rare (187) 60%-87% (243,244) Progression to cirrhosis Rare (187) 7%-40% (105) Survival without transplantation 90%-100% (187,232) 10-year survival, 89%-91% (105,451

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Section: Putative Predictors Of Treatment Responsementioning

confidence: 99%

Section: Relapsementioning

confidence: 99%

Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases

et al. 2020

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“…Finally, duration of treatment and follow‐up after IST withdrawal have varied. It is therefore unsurprising that the reported relapse rates range from 25% to 100% (Table ).…”

Section: Review Criteriamentioning

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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“…The duration of remission and alanine aminotransferase (ALT) and immunoglobulin G (IgG) levels before IST withdrawal are risk factors for relapse. 4,5 On the other hand, relapse sometimes occurs during IST. In Japan, most patients with AIH receive low-dose corticosteroid treatment after remission.…”

Section: Introductionmentioning

confidence: 99%

“…Repeated relapses affect the development of cirrhosis 2 and the patient's prognosis 3 ; therefore, risk factors for relapse have been evaluated in numerous studies. The duration of remission and alanine aminotransferase (ALT) and immunoglobulin G (IgG) levels before IST withdrawal are risk factors for relapse 4,5 . On the other hand, relapse sometimes occurs during IST.…”

Section: Introductionmentioning

confidence: 99%

Risk factors for relapse of autoimmune hepatitis in Japan: A nationwide survey

Takahashi

Ohira

Abe

et al. 2022

Hepatology Research

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Aim Some autoimmune hepatitis (AIH) patients experience relapse during their clinical course, and some risk factors for relapse have been identified previously using a relatively small sample size. The aim of the present study was to identify the risk factors for relapse in recently diagnosed AIH patients using a nationwide survey in Japan. Methods The nationwide survey performed in Japan in 2018 of AIH patients diagnosed between 2014 and 2017 was re‐evaluated. A total of 614 patients who received corticosteroids were enrolled in the present study. Associations between relapse and patients' characteristics at diagnosis were evaluated using logistic regression analysis. Results Relapse was identified in 143 (23.3%) patients after remission. At the time of diagnosis of the disease, there were significant differences in the γ‐glutamyl transpeptidase (γ‐GTP) level, prevalence of liver cirrhosis, and degree of liver fibrosis. Multivariable logistic regression analysis showed that γ‐GTP elevation and liver cirrhosis were significantly associated with relapse. Conclusion The γ‐GTP level at diagnosis could help identify AIH patients at higher risk of relapse.

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Well-controlled autoimmune hepatitis treatment withdrawal may be safely accomplished without liver-biopsy guidance

Cited by 9 publications

References 14 publications

Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases

Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases

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

Risk factors for relapse of autoimmune hepatitis in Japan: A nationwide survey

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