Laura Harrison1,2, Dermot Gleeson1. 1. Liver Unit, Northern General Hospital, Sheffield Teaching Hospital's NHS Foundation Trust, Sheffield, UK. 2. Department of Infection, Immunity and Cardiovascular Disease, The University of Sheffield, Medical School, Sheffield, UK.
Abstract
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.
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.
Authors: Nwe Ni Than; James Hodson; Daniel Schmidt-Martin; Richard Taubert; Rebecca E Wawman; Meemee Botter; Nishant Gautam; Kilian Bock; Rebecca Jones; Gautham D Appanna; Andrew Godkin; Aldo J Montano-Loza; Frank Lammert; Christoph Schramm; Michael P Manns; Mark Swain; Kelly W Burak; David H Adams; Gideon M Hirschfield; Ye Htun Oo Journal: JHEP Rep Date: 2019-11-05