Patient selection based on treatment duration and liver biochemistry increases success rates after treatment withdrawal in autoimmune hepatitis

Published:October 18, 2014DOI:

      Background & Aims

      In autoimmune hepatitis (AIH), relapse rates as high as 90% have been reported after treatment withdrawal. We therefore investigated, whether longer duration of treatment and proper patient selection could increase the long-term success rates after treatment withdrawal.


      Following our previously published experience, treatment withdrawal was considered when biochemical remission was maintained under immunosuppressive monotherapy for at least 2 years. Remission was defined as repeatedly normal serum aminotransferase levels as well as normal IgG levels.


      Out of 288 patients with well-defined AIH, 28 patients were included. Median duration of treatment was 48.5 months (range 35–179) and a sustained remission was observed for 45 months (range 24–111). All patients were in remission on immunosuppressive monotherapy for a minimum of 2 years before treatment was withdrawn. Using this strict approach, 15 patients (54%) remained in long-term remission after a median of 28 months follow-up (range 17–57) and 13 patients (46%) required reinstitution of treatment. Higher ALT and IgG levels – although within the normal range in all patients – were associated with the time to relapse. All patients who remained in remission had ALT levels less than half the ULN and IgG levels not higher than 12 g/L at the time of treatment withdrawal.


      Proper patient selection including a sustained complete biochemical remission on immunosuppressive monotherapy for a minimum of 2 years can markedly improve the success rates of treatment withdrawal. The interpretation of aminotransferase and IgG levels within the normal range could aid in predicting the risk of relapse.

      Graphical abstract


      AIH (autoimmune hepatitis), AASLD (American Association of the Study of Liver Diseases), ALT (alanine-aminotransferase), IgG (immunoglobulin G), ANA (antinuclear antibody), SMA (smooth muscle antibody), LKM (liver kidney microsomal antibody), AMA (anti-mitochondrial antibody), SLA/LP (soluble liver antigen/liver-pancreas protein), AST (aspartate aminotransferase), INR (international normalized ratio), ULN (upper limit of normal), mHAI (modified histological activity index)


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        • Krawitt E.L.
        Autoimmune hepatitis.
        N Engl J Med. 2006; 354: 54
        • Lohse A.W.
        • Mieli-Vergani G.
        Autoimmune hepatitis.
        J Hepatol. 2011; 55: 171-182
        • Heneghan M.A.
        • Yeoman A.D.
        • Verma S.
        • Smith A.D.
        • Longhi M.S.
        Autoimmune hepatitis.
        Lancet. 2013; 382: 1433-1444
        • Manns M.P.
        • Czaja A.J.
        • Gorha J.D.
        • Krawitt E.L.
        • Mieli-Vergani G.
        • Vergani D.
        • et al.
        Diagnosis and management of autoimmune hepatitis.
        Hepatology. 2010; 51: 2193-2213
        • Gleeson D.
        • Heneghan M.A.
        British Society of Gastroenterology (BSG) guidelines for management of autoimmune hepatitis.
        Gut. 2011; 60: 1611-1629
        • Roberts S.K.
        • Therneau T.M.
        • Czaja A.J.
        Prognosis of histological cirrhosis in type 1 autoimmune hepatitis.
        Gastroenterology. 1996; 110: 848
        • Hoeroldt B.
        • McFarlane E.
        • Dube A.
        • Basumani P.
        • Karajeh M.
        • Campell M.J.
        • et al.
        Long-term outcomes of patients with autoimmune hepatitis managed at a nontransplant center.
        Gastroenterology. 2011; 140: 1980-1989
        • van Gerven N.M.
        • Verwer B.J.
        • Witte B.I.
        • Hoek B.V.
        • Coenraad M.J.
        • van Erpecum K.J.
        • et al.
        Relapse is almost universal after withdrawal of immunosuppressive medication in patients with autoimmune hepatitis in remission.
        J Hepatol. 2013; 58: 141-147
        • Soloway R.D.
        • Summerskill W.H.
        • Baggenstoss A.H.
        • Geall M.G.
        • Gitnick G.L.
        • Elveback I.R.
        • et al.
        Clinical, biochemical, and histological remission of severe chronic active liver disease: a controlled study of treatments and early prognosis.
        Gastroenterology. 1972; 63: 820-833
        • Czaja A.J.
        • Ammon H.V.
        • Summerskill W.H.
        Clinical features and prognosis of severe chronic active liver diseases (CALD) after corticosteroid-induced remission.
        Gastroenterology. 1980; 78: 518-523
        • Hegarty J.E.
        • Aria Nouri
        • Kayhan T.
        • Portmann B.
        • Eddleston A.L.
        • Williams R.
        Relapse following treatment withdrawal in patients with autoimmune chronic active hepatitis.
        Hepatology. 1983; 5: 685-689
        • Czaja A.J.
        • Ludwig J.
        • Baggenstoss A.H.
        • Wolf A.
        Corticosteroid-treated chronic active hepatitis in remission: uncertain prognosis of chronic persistent hepatitis.
        N Engl J Med. 1981; 304: 5-9
        • Kanzler S.
        • Gerken G.
        • Löhr H.
        • Galle P.R.
        • Meyer zum Büschenfelde K.H.
        • Lohse A.W.
        Duration of immunosuppressive therapy in autoimmune hepatitis.
        J Hepatol. 2001; 34: 354
        • Montano-Loza A.J.
        • Carpenter H.A.
        • Czaja A.J.
        Improving the end point of corticosteroid therapy in type 1 autoimmune hepatitis to reduce the frequency of relapse.
        Am J Gastroenterol. 2007; 102: 1005-1012
        • Lüth S.
        • Herkel J.
        • Kanzler S.
        • Frenzel C.
        • Galle P.R.
        • Dienes H.P.
        • et al.
        Serologic markers compared with liver biopsy for monitoring disease activity in autoimmune hepatitis.
        J Clin Gastroenterol. 2008; 42: 926-930
        • 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.
        Hepatology. 2008; 48: 169-176
        • Weiler-Normann C.
        • Lohse A.W.
        Autoimmune hepatitis: a life-long disease.
        J Hepatol. 2013; 58: 5-7
        • Montano-Loza A.
        • Carpenter H.
        • Czaja A.
        Consequences of treatment withdrawal in type 1 autoimmune hepatitis.
        Liver Int. 2007; 27: 507-515
        • Muratori L.
        • Muratori P.
        • Lanzoni G.
        • Ferri S.
        • Lenzi M.
        Application of the 2010 American Association for the study of liver diseases criteria of remission to a cohort of Italian patients with autoimmune hepatitis.
        Hepatology. 2010; 52: 1857
        • Prati D.
        • Taioli E.
        • Zanella A.
        • Della Torre E.
        • Butelli S.
        • Del Vecchio E.
        • et al.
        Updated definitions of healthy ranges for serum alanine aminotransferase levels.
        Ann Intern Med. 2002; 137: 1-10
        • Verma S.
        • Gunuwan B.
        • Mendler M.
        • Govindrajan S.
        • Redeker A.
        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.
        Am J Gastroenterol. 2004; 99: 1510-1516
        • Czaja A.J.
        • Wolf A.M.
        • Baggenstoss A.H.
        Laboratory assessment of severe chronic active liver disease during and after corticosteroid therapy: correlation of serum transaminase and gamma globulin levels with histologic features.
        Gastroenterology. 1998; 80: 687-692
        • Czaja A.J.
        • Carpenter H.A.
        Histological features associated with relapse after corticosteroid withdrawal in type 1 autoimmune hepatitis.
        Liver Int. 2003; 23: 116
        • Czaja A.J.
        Review article: the management of autoimmune hepatitis beyond consensus guidelines.
        Aliment Pharmacol Ther. 2013; 38: 343-364
        • Czaja A.J.
        Late relapse of type 1 autoimmune hepatitis after corticosteroid withdrawal.
        Dig Dis Sci. 2010; 55: 1761-1769