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Rapid response predicts complete biochemical response and histological remission in autoimmune hepatitis

  • You Li
    Affiliations
    Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai JiaoTong University; Shanghai Institute of Digestive Disease; 145 Middle Shandong Road, Shanghai 200001, China
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  • Xiao Xiao
    Affiliations
    Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai JiaoTong University; Shanghai Institute of Digestive Disease; 145 Middle Shandong Road, Shanghai 200001, China
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  • Qi Miao
    Affiliations
    Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai JiaoTong University; Shanghai Institute of Digestive Disease; 145 Middle Shandong Road, Shanghai 200001, China
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  • Xiong Ma
    Correspondence
    Corresponding author. Address: Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai JiaoTong University; Shanghai Institute of Digestive Disease; 145 Middle Shandong Road, Shanghai 200001, China.
    Affiliations
    Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai JiaoTong University; Shanghai Institute of Digestive Disease; 145 Middle Shandong Road, Shanghai 200001, China
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      Linked Article

      To the Editor:
      We read with great interest the manuscript by Pape et al. entitled “Systematic review of response criteria and endpoints in autoimmune hepatitis by the International Autoimmune Hepatitis Group”. In this paper, the International Autoimmune Hepatitis Group (IAIHG) presents a statement on 5 agreed response criteria and endpoints for autoimmune hepatitis (AIH).
      • Pape S.
      • Snijders R.J.A.L.M.
      • Gevers T.J.G.
      • Chazouilleres O.
      • Dalekos G.N.
      • Hirschfield G.M.
      • et al.
      Systematic review of response criteria and endpoints in autoimmune hepatitis by the International Autoimmune Hepatitis Group.
      Herein, we want to validate the new IAIHG response criteria and endpoints in Chinese patients with AIH. We performed a retrospective analysis of patients with AIH recruited from Renji Hospital, Shanghai Jiao Tong University from 2008 to 2020. Details of this cohort have been previously described.
      • Li Y.
      • Yan L.
      • Wang R.
      • Wang Q.
      • You Z.
      • Li B.
      • et al.
      Serum immunoglobulin G levels predict biochemical and histological remission of autoimmune hepatitis type 1: a single-center experience and literature review.
      Adult patients with AIH and a simplified IAIHG score ≥6 were included, whilst patients with variant syndromes or competing liver diseases were excluded.
      • Hennes E.M.
      • Zeniya M.
      • Czaja A.J.
      • Parés A.
      • Dalekos G.N.
      • Krawitt E.L.
      • et al.
      Simplified criteria for the diagnosis of autoimmune hepatitis.
      ,
      European Association for the Study of the L
      EASL clinical practice guidelines: autoimmune hepatitis.
      A total of 650 patients were eligible for the analysis. The mean age was 50.0 ± 12.7 years and 82.9% were female. Patients were initially treated with prednisolone and the prednisolone dose was gradually tapered after remission. Maintenance therapy consisted of prednisolone and/or azathioprine. Mycophenolate mofetil was required if patients developed unacceptable toxicity from azathioprine. According to Pape et al., non-response was defined as <50% decrease of serum transaminases within 4 weeks after initiation of treatment; complete biochemical response (CBR) was defined as normalization of serum transaminases and immunoglobulin G after no more than 6 months of treatment; insufficient response (IR) was defined as lack of complete biochemical response.
      • Pape S.
      • Snijders R.J.A.L.M.
      • Gevers T.J.G.
      • Chazouilleres O.
      • Dalekos G.N.
      • Hirschfield G.M.
      • et al.
      Systematic review of response criteria and endpoints in autoimmune hepatitis by the International Autoimmune Hepatitis Group.
      Most patients (n = 601; 92.5%) scored as responders within 4 weeks after initiation of treatment (Fig. 1). Responders were less likely to have cirrhosis at baseline compared to non-responders (21.5% vs. 36.7%; p = 0.014). Furthermore, 502 patients (77.2%) achieved CBR within 6 months. These patients were less likely to have cirrhosis at baseline (19.1% vs. 34.5%; p <0.001). Additionally, CBR occurred more frequently in 4-week responders (79.0% vs. 55.1%; p <0.001).
      Figure thumbnail gr1
      Fig. 1Validation of the proposed surrogate endpoints in the Chinese AIH cohort. Statistical comparisons were performed using Fisher’s Exact test or the chi-squared test.
      AIH, autoimmune hepatitis. (This figure appears in color on the web.)
      We further evaluated the prognostic significance of the predefined endpoints (non-response, CBR and IR) in histological remission. Liver biopsies were re-evaluated in 276 patients who had received immunosuppressive therapy for at least 3 years, and histological remission (hepatic activity index <4) was achieved in 189 (68.5%) patients. Among them, 4-week responders were more likely to achieve histological remission than non-responders (70.0% vs. 43.8%; p = 0.028). Though the histological remission rate was higher in the CBR than the IR group, there was no statistical difference between the 2 groups (70.6% vs. 56.1%; p = 0.064). This finding could partly be explained by the limitation of the analysis that most patients with follow-up biopsies had already achieved biochemical remission.
      In conclusion, we agree with Pape et al. that the 3 surrogate endpoints are reproducible and valid in AIH treatment and would be helpful to guide future clinical studies. More importantly, we provide further evidence of the predictive value of these surrogate endpoints in histological remission. Our data are in line with previous studies in which a rapid response to immunosuppressive therapy is a reliable predictor of biochemical and histological remission.
      • Li Y.
      • Yan L.
      • Wang R.
      • Wang Q.
      • You Z.
      • Li B.
      • et al.
      Serum immunoglobulin G levels predict biochemical and histological remission of autoimmune hepatitis type 1: a single-center experience and literature review.
      ,
      • Pape S.
      • Gevers T.J.G.
      • Vrolijk J.M.
      • van Hoek B.
      • Bouma G.
      • van Nieuwkerk C.M.J.
      • et al.
      Rapid response to treatment of autoimmune hepatitis associated with remission at 6 and 12 months.

      Financial support

      The authors received no financial support to produce this manuscript.

      Authors’ contributions

      YL: data analysis and manuscript drafting. XX: clinical diagnosis support and manuscript revision. QM: histological analysis support. XM: study concept and design.

      Conflict of interest

      The authors declare no conflicts of interest that pertain to this work.
      Please refer to the accompanying ICMJE disclosure forms for further details.

      Supplementary data

      The following are the supplementary data to this article:

      References

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        • Hirschfield G.M.
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        Systematic review of response criteria and endpoints in autoimmune hepatitis by the International Autoimmune Hepatitis Group.
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        Serum immunoglobulin G levels predict biochemical and histological remission of autoimmune hepatitis type 1: a single-center experience and literature review.
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