Development and validation of a prognostic score for long‐term transplant‐free survival in autoimmune hepatitis type 1

Abstract Background No prognostic score is currently available for long‐term survival in autoimmune hepatitis (AIH) patients. Objective The aim of this study was to develop and validate such a prognostic score for AIH patients at diagnosis. Methods The prognostic score was developed using uni‐ & multivariate Cox regression in a 4‐center Dutch cohort and validated in an independent 6‐center Belgian cohort. Results In the derivation cohort of 396 patients 19 liver transplantations (LTs) and 51 deaths occurred (median follow‐up 118 months; interquartile range 60–202 months). In multivariate analysis age (hazard ratio [HR] 1.045; p < 0.001), non‐caucasian ethnicity (HR 1.897; p = 0.045), cirrhosis (HR 3.266; p < 0.001) and alanine aminotransferase level (HR 0.725; p = 0.003) were significant independent predictors for mortality or LT (C‐statistic 0.827; 95% CI 0.790–0.864). In the validation cohort of 408 patients death or LT occurred in 78 patients during a median follow‐up of 74 months (interquartile range: 25–142 months). Predicted 5‐year event rate did not differ from observed event rate (high risk group 21.5% vs. 15.7% (95% CI: 6.3%–24.2%); moderate risk group 5.8% versus 4.3% (95% CI: 0.0%–9.1%); low risk group 1.9% versus 5.4% (95% CI: 0.0%–11.4%); C‐statistic 0.744 [95% CI 0.644–0.844]). Conclusions A Dutch‐Belgian prognostic score for long‐term transplant‐free survival in AIH patients at diagnosis was developed and validated.

[1]  B. van Hoek,et al.  Early Predictors of Short‐Term Prognosis in Acute and Acute Severe Autoimmune Hepatitis , 2020, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[2]  M. Manns,et al.  Rapid Response to Treatment of Autoimmune Hepatitis Associated with Remission at 6 and 12 Months. , 2019, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[3]  O. Yokosuka,et al.  Acute Severe Autoimmune Hepatitis: Corticosteroids or Liver Transplantation? , 2019, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[4]  J. Drenth,et al.  Association Between Black Race and Presentation and Liver-Related Outcomes of Patients With Autoimmune Hepatitis. , 2019, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[5]  H. Lee,et al.  Long‐term clinical outcomes in patients with autoimmune hepatitis according to treatment response in Asian country , 2019, Liver international : official journal of the International Association for the Study of the Liver.

[6]  N. Heaton,et al.  Acute Severe Autoimmune Hepatitis: Corticosteroids or Liver Transplantation? , 2019, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[7]  C. Mulder,et al.  Increased Mortality Among Patients With vs Without Cirrhosis and Autoimmune Hepatitis , 2019, Clinical Gastroenterology and Hepatology.

[8]  B. van Hoek,et al.  Role of age in presentation, response to therapy and outcome of autoimmune hepatitis , 2018, Clinical and Translational Gastroenterology.

[9]  G. Heinze,et al.  An unjustified benefit: immortal time bias in the analysis of time‐dependent events , 2018, Transplant international : official journal of the European Society for Organ Transplantation.

[10]  G. D’Amico,et al.  Clinical states of cirrhosis and competing risks. , 2017, Journal of hepatology.

[11]  Junfeng Wang,et al.  A novel prognostic model for transplant-free survival in primary sclerosing cholangitis , 2017, Gut.

[12]  A. Czaja.  Global Disparities and Their Implications in the Occurrence and Outcome of Autoimmune Hepatitis , 2017, Digestive Diseases and Sciences.

[13]  C. Mulder,et al.  Auto immune hepatitis. , 2016, World journal of gastroenterology.

[14]  A. Burroughs,et al.  University of Birmingham Development and Validation of a Scoring System to Predict Outcomes of Patients With Primary Biliary Cirrhosis Receiving Ursodeoxycholic Acid Therapy , 2022 .

[15]  M. Manns,et al.  Prediction of short‐ and long‐term outcome in patients with autoimmune hepatitis , 2015, Hepatology.

[16]  A. Zhernakova,et al.  HLA-DRB1*03:01 and HLA-DRB1*04:01 modify the presentation and outcome in autoimmune hepatitis type-1 , 2015, Genes and Immunity.

[17]  J. Drenth.  EASL Clinical Practice Guidelines: Autoimmune hepatitis. , 2015, Journal of hepatology.

[18]  M. Tzardi,et al.  Clinical outcomes of compensated and decompensated cirrhosis: A long term study. , 2014, World journal of hepatology.

[19]  C. Stedman,et al.  Predictors of poor outcome in patients w ith autoimmune hepatitis: A population‐based study , 2013, Hepatology.

[20]  M. Abe,et al.  Long‐term outcome of Japanese patients with type 1 autoimmune hepatitis , 2012, Hepatology.

[21]  Masahiro Ito,et al.  Hepatocellular carcinoma and survival in patients with autoimmune hepatitis (Japanese National Hospital Organization‐autoimmune hepatitis prospective study) , 2012, Liver international : official journal of the International Association for the Study of the Liver.

[22]  R. Gish,et al.  The Impact of Race/Ethnicity on the Clinical Epidemiology of Autoimmune Hepatitis , 2012, Journal of clinical gastroenterology.

[23]  E. Fassio,et al.  Effect of cirrhosis at baseline on the outcome of type 1 autoimmune hepatitis. , 2012, Annals of hepatology.

[24]  M. Campbell,et al.  Long-term outcomes of patients with autoimmune hepatitis managed at a nontransplant center. , 2011, Gastroenterology.

[25]  A. Bergquist,et al.  Characteristics and long-term outcome of patients with autoimmune hepatitis related to the initial treatment response , 2010, Scandinavian journal of gastroenterology.

[26]  B. Portmann,et al.  Effects of serum aspartate aminotransferase levels in patients with autoimmune hepatitis influence disease course and outcome. , 2008, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[27]  M. Torbenson,et al.  The impact of ethnicity on the natural history of autoimmune hepatitis , 2007, Hepatology.

[28]  A. Floreani,et al.  Type I autoimmune hepatitis: clinical course and outcome in an Italian multicentre study. , 2006, Alimentary pharmacology & therapeutics.

[29]  T. Arenovich,et al.  Autoimmune hepatitis: Effect of symptoms and cirrhosis on natural history and outcome , 2005, Hepatology.

[30]  S. Verma,et al.  Factors Predicting Relapse and Poor Outcome in Type I Autoimmune Hepatitis: Role of Cirrhosis Development, Patterns of Transaminases During Remission and Plasma Cell Activity in the Liver Biopsy , 2004, American Journal of Gastroenterology.

[31]  P. Donaldson,et al.  Genetic effects on susceptibility, clinical expression, and treatment outcome of type 1 autoimmune hepatitis. , 2002, Clinics in liver disease.

[32]  G. Gerken,et al.  Long-term management and prognosis of autoimmune hepatitis (AIH): a single center experience. , 2001, Zeitschrift fur Gastroenterologie.

[33]  M. Manns,et al.  International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. , 1999, Journal of hepatology.

[34]  T. Therneau,et al.  Prognosis of histological cirrhosis in type 1 autoimmune hepatitis. , 1996, Gastroenterology.

[35]  R. Wiesner,et al.  Prognostic features and role of liver transplantation in severe corticosteroid‐treated autoimmune chronic active hepatitis , 1992, Hepatology.

[36]  R. Stern,et al.  Controlled trial of prednisone and azathioprine in active chronic hepatitis. , 1973, Lancet.

[37]  L. Elveback,et al.  Clinical, biochemical, and histological remission of severe chronic active liver disease: a controlled study of treatments and early prognosis. , 1972, Gastroenterology.

[38]  S. Sherlock,et al.  Controlled prospective trial of corticosteroid therapy in active chronic hepatitis. , 1971, The Quarterly journal of medicine.