Features and outcome of AIH patients without elevation of IgG
Johannes Hartl,
Rosa Miquel,
Kalliopi Zachou,
Guan-Wee Wong,
Asma Asghar,
Simon Pape,
Marcial Sebode,
Moritz Peiseler,
Roman Zenouzi,
Hanno Ehlken,
Till Krech,
Christina Weiler-Normann,
Joost P.H. Drenth,
Ye H. Oo,
George Nikolaos Dalekos,
Michael Heneghan,
Christoph Schramm,
Ansgar Wilhelm Lohse
Affiliations
Johannes Hartl
First Department of Internal Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; European Reference Network on Hepatological Diseases; Corresponding author. Address: First Department of Internal Medicine, University Medical Centre Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg. Tel.: +1 929 395 6403.
Rosa Miquel
Institute of Liver Studies, King's College Hospital, London, United Kingdom
Kalliopi Zachou
Institute of Internal Medicine and Hepatology, Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, Larissa, Greece
Guan-Wee Wong
Institute of Liver Studies, King's College Hospital, London, United Kingdom
Asma Asghar
Centre for Liver and Gastroenterology Research, NIHR Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, United Kingdom
Simon Pape
Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, the Netherlands; European Reference Network on Hepatological Diseases
Marcial Sebode
First Department of Internal Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; European Reference Network on Hepatological Diseases
Moritz Peiseler
First Department of Internal Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; European Reference Network on Hepatological Diseases
Roman Zenouzi
First Department of Internal Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; European Reference Network on Hepatological Diseases
Hanno Ehlken
Department of Interdisciplinary Endoscopy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; European Reference Network on Hepatological Diseases
Till Krech
Department of Pathology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany
Christina Weiler-Normann
First Department of Internal Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; Martin Zeitz Centre for Rare Diseases, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; European Reference Network on Hepatological Diseases
Joost P.H. Drenth
Department of Gastroenterology and Hepatology, Radboud University Medical Centre, Nijmegen, the Netherlands; European Reference Network on Hepatological Diseases
Ye H. Oo
Centre for Liver and Gastroenterology Research, NIHR Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, United Kingdom; Liver Transplant and Hepatobiliary Unit, University Hospital of Birmingham NHS Foundation Trust, Birmingham, United Kingdom; Centre for Rare Diseases, Institute of Translational Medicine, University of Birmingham, Birmingham, United Kingdom; European Reference Network on Hepatological Diseases
George Nikolaos Dalekos
Institute of Internal Medicine and Hepatology, Department of Medicine and Research Laboratory of Internal Medicine, University Hospital of Larissa, Larissa, Greece
Michael Heneghan
Institute of Liver Studies, King's College Hospital, London, United Kingdom
Christoph Schramm
First Department of Internal Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; Martin Zeitz Centre for Rare Diseases, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; European Reference Network on Hepatological Diseases
Ansgar Wilhelm Lohse
First Department of Internal Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; Martin Zeitz Centre for Rare Diseases, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; European Reference Network on Hepatological Diseases
Background & Aims: High IgG levels are considered a hallmark of autoimmune hepatitis (AIH). A subgroup of patients with AIH has IgG within the normal range despite evidence of clinical disease activity. The clinical significance of this biomarker has not been explored. Methods: In a European multicentre study we compared biochemical, clinical and histological features from patients with AIH and normal IgG-values at diagnosis to an age- and sex-matched control group of patients with typical AIH presenting with elevated IgG. Data were assessed at diagnosis, after 12 months of therapy and at last follow-up. Results: Out of 1,318 patients with AIH, 130 (10%) had normal IgG at presentation. Histological and biochemical parameters at diagnosis, as well as treatment response, showed no difference between groups. Stable remission off treatment was achieved more commonly in the normal IgG group than in the typical AIH group (24 vs. 8%; p = 0.0012). Patients of the control group not only had higher IgG levels (29.5 ± 5.8 vs. 12.5 ± 3.2 g/L; p <0.0001), but also a higher IgG/IgA ratio (9.3 ± 6.9 vs. 5.4 ± 2.4; p <0.0001) at diagnosis. The IgG/IgA ratio only declined in patients with typical AIH and was no longer different between groups after 12 months (6.3 ± 4.3 vs. 5.5 ± 2.2; p = 0.1), indicating a selective increase of IgG in typical AIH and its suppression by immunosuppression. Autoantibody titres were higher in the typical AIH group, but not when controlled for IgG levels. Conclusions: Compared to AIH with typical biochemical features, patients with normal IgG levels at diagnosis (i) show similar biochemical, serological and histological features and comparable treatment response, (ii) appear to lack the selective elevation of serum IgG levels observed in typical active AIH disease, (iii) may represent a subgroup with a higher chance of successful drug withdrawal. Lay summary: A characteristic feature of autoimmune hepatitis (AIH) is an elevation of immunoglobulin G (IgG), which is therefore used as a major diagnostic criterion, as well as to monitor treatment response. Nevertheless, normal IgG does not preclude the diagnosis of AIH. Therefore, we herein assessed the features of patients with AIH and normal IgG in a large multicentre study. This study demonstrates that about 10% of all patients with AIH have normal IgG; these patients are indistinguishable from other patients with AIH with respect to biochemical markers, liver histology, disease severity and treatment response, but might represent a subgroup with a higher chance of remission after drug withdrawal.
