Z Gastroenterol 2020; 58(05): 431-438
DOI: 10.1055/a-1135-9306
Originalarbeit

Population-based study of autoimmune hepatitis and primary biliary cholangitis in Germany: rising prevalences based on ICD codes, yet deficits in medical treatment

Populationsbasierte Analyse von autoimmuner Hepatitis und primär biliärer Cholangitis in Deutschland: ansteigende Prävalenzen basierend auf ICD Codes, aber Defizite bei der medikamentösen Therapie
Marcial Sebode
1   I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
2   European Reference Network on Rare Hepatological Diseases (ERN RARE-LIVER).
,
Angela Kloppenburg
3   Techniker Krankenkasse, Hamburg, Germany
,
Annette Aigner
4   Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
5   Institute of Biometry and Clinical Epidemiology, Charité – Universitätsmedizin Berlin, Berlin, Germany
,
Ansgar W. Lohse
1   I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
2   European Reference Network on Rare Hepatological Diseases (ERN RARE-LIVER).
,
Christoph Schramm*
1   I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
2   European Reference Network on Rare Hepatological Diseases (ERN RARE-LIVER).
6   Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
,
Roland Linder*
3   Techniker Krankenkasse, Hamburg, Germany
› Author Affiliations

Abstract

Background Population-based data on the prevalence of and real-life treatment for the autoimmune liver diseases (AILD), primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH), are scarce, and such knowledge may help to improve patient care.

Methods Data of 8.1 million individuals having health insurance with the “Techniker Krankenkasse,” the largest German health insurer, were analyzed with regard to the prevalence of and prescribed medication for AILD in Germany from 2011 until 2014. Patients with viral hepatitis B infection (HBV) and alcoholic liver cirrhosis (ALC) served as control groups. Case definition was based on ICD codes.

Results The prevalences of PBC and AIH were 36.9/100 000 inhabitants (95 % CI: 35.6–38.2) and 23.0/100 000 inhabitants (95 % CI: 22.0–24.0) in 2014, respectively. The prevalences of AILD increased from 2011 to 2014 (for PBC by 31 % and for AIH by 29 %), with the largest increase for male patients with PBC. In contrast, the prevalence of HBV declined while that of ALC remained stable. The analysis of prescribed real-life treatment revealed considerable deviations from standard treatment recommendations. Specifically, in older patients with PBC or AIH, undertreatment was common.

Conclusion The prevalence of PBC and AIH based on ICD codes is increasing in Germany. The analysis of real-life treatment in this large and population-based cohort points to the unmet need to improve the implementation of treatment guidelines for autoimmune liver diseases in the broader medical community.

Zusammenfassung

Hintergrund Es gibt nur wenige populationsbasierte Studien zur Prävalenz und zur „Real-Life“-Therapie der autoimmunen Lebererkrankungen Primär Biliäre Cholangitis (PBC) und Autoimmune Hepatitis (AIH).

Methoden Es wurden 8,1 Millionen Versichertendaten der Techniker Krankenkasse analysiert bezüglich der Prävalenz und rezeptierten Medikation von Patienten mit autoimmunen Lebererkrankungen in Deutschland von 2011 bis 2014. Patienten mit einer Virushepatitis-B-Infektion (HBV) und mit alkoholischer Leberzirrhose (C2 LZX) dienten als Kontrollgruppen. Die Patienten wurden anhand von ICD-Codes identifiziert.

Ergebnisse Die PBC und die AIH weisen in Deutschland im Jahr 2014 eine Prävalenz von 36,9 pro 100 000 Einwohner (95 %-KI: 35,6–38,2) beziehungsweise 23,0 pro 100 000 Einwohner (95 %-KI: 22,0–24,0) auf. Die Prävalenz autoimmuner Lebererkrankungen stieg von 2011 bis 2014 an (für die PBC um 31 % und für die AIH um 29 %), wobei männliche PBC-Patienten den stärksten Anstieg aufwiesen. Die Prävalenz von HBV und C2 LZX nahm ab beziehungsweise blieb stabil. Eine Analyse der „Real-Life“-Therapie der autoimmunen Lebererkrankungen ergab erhebliche Abweichungen von Therapieleitlinien; insbesondere bei älteren AIH- und PBC-Patienten lag eine Untertherapie vor.

Schlussfolgerung Die Prävalenz der PBC und AIH basierend auf ICD-Codes steigt in Deutschland an. Die populationsbasierte Analyse der „Real-Life“-Therapie autoimmuner Lebererkrankungen in Deutschland weist auf Defizite in der breiten medizinischen Versorgung hinsichtlich der Umsetzung von Therapieleitlinien hin.

* Shared senior authorship.




Publication History

Received: 16 November 2019

Accepted: 05 March 2020

Article published online:
11 May 2020

© Georg Thieme Verlag KG
Stuttgart · New York

 
  • References

  • 1 Jepsen P, Grønbæk L, Vilstrup H. Worldwide incidence of autoimmune liver disease. Dig Dis 2015; 33: 2-12
  • 2 European Association for the Study of the Liver. EASL clinical practice guidelines. The diagnosis and management of patients with primary biliary cholangitis. J Hepatol 2017; 67: 145-172
  • 3 Carbone M, Mells GF, Pells G. et al. Sex and age are determinants of the clinical notype of primary biliary cirrhosis and response to ursodeoxycholic acid. Gastroenterology 2013; 144: 560-569
  • 4 Lleo A, Jepsen P, Morenghi E. et al. Evolving trends in female to male incidence and male mortality of primary biliary cholangitis. Sci Rep 2016; 6: 25906
  • 5 European Association for the Study of the Liver. EASL clinical practice guidelines: management of cholestatic liver diseases. J Hepatol 2009; 51: 237-267
  • 6 Corpechot C, Carrat F, Bonnand AM. et al. The effect of ursodeoxycholic acid therapy on liver fibrosis progression in primary biliary cirrhosis. Hepatology 2000; 32: 1196-1199
  • 7 Corpechot C, Carrat F, Bahr A. et al. The effect of ursodeoxycholic acid therapy on the natural course of primary biliary cirrhosis. Gastroenterology 2005; 128: 297-303
  • 8 European Association for the Study of the Liver. EASL clinical practice guidelines: autoimmune hepatitis. J Hepatol 2015; 63: 971-1004
  • 9 Grønbæk L, Vilstrup H, Jepsen P. Autoimmune hepatitis in Denmark: incidence, prevalence, prognosis, and causes of death. A nationwide registry-based cohort study. J Hepatol 2014; 60: 612-617
  • 10 Van Gerven NM, Verwer BJ, Witte BI. et al. Relapse is almost universal after withdrawal of immunosuppressive medication in patients with autoimmune hepatitis in remission. J Hepatol 2013; 58: 141-147
  • 11 Manns MP, Woynarowski M, Kreisel W. et al. Budesonide induces remission more effectively than prednisone in a controlled trial of patients with autoimmune hepatitis. Gastroenterology 2010; 139: 1198-1206
  • 12 Deutsche Gesellschaft Fur Gastroenterologie, V.-U.S., Deutsche Gesellschaft Fur Innere, et al. Practice guideline autoimmune liver diseases; AWMF-Reg. No. 021-27. Z Gastroenterol 2017; 55: 1135-1226
  • 13 Boonstra K, Beuers U, Ponsioen CY. Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: a systematic review. J Hepatol 2012; 56: 1181-1188
  • 14 Boonstra K, Kunst AE, Stadhouders PH. et al. Rising incidence and prevalence of primary biliary cirrhosis: a large population-based study. Liver Int 2014; 34: e31-e38
  • 15 Kim KA, Ki M, Choi HY. et al. Population-based epidemiology of primary biliary cirrhosis in South Korea. Aliment Pharmacol Ther 2016; 43: 154-162
  • 16 Van Gerven NM, Verwer BJ, Witte BI. et al. Epidemiology and clinical characteristics of autoimmune hepatitis in the Netherlands. Scand J Gastroenterol 2014; 49: 1245-1254
  • 17 Clopper CJ, Pearson ES. The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika 1934; 26: 404-413
  • 18 R Core Team. R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2017 http://www.R-project.org/
  • 19 Dorai-Raj U. Binom: binomial confidence intervals for several parameterizations. R package version 1.1-1. 2014 https://CRAN.R-project.org/package=binom
  • 20 Swart E, Bitzer EM, Gothe H. et al. A consensus German reporting standard for secondary data analyses, version 2 (STROSA-STandardisierte BerichtsROutine für SekundärdatenAnalysen). Gesundheitswesen 2016; 78: e145-e160
  • 21 Swart E, Gothe H, Geyer S. et al. Good practice of secondary data analysis (GPS): guidelines and recommendations. Gesundheitswesen 2015; 77: 120-126
  • 22 Schulz M, Wandrey M, Hering R. et al. Prävalenz seltener Erkrankungen in der ambulanten Versorgung in Deutschland im Zeitraum 2008 bis 2011. Zentralinstitut für die kassenärztliche Versorgung in Deutschland (Zi), Versorgungsatlas-Bericht Nr. 15/13. Berlin: 2015 http://www.versorgungsatlas.de/themen/alle-analysen-nach-datum-sortiert/?tab=6&uid=63
  • 23 Guthoff-Hagen S. PBC 2015—Epidemiologische Auswertungen. 2016
  • 24 Gordon V, Adhikary R, Appleby V. et al. Diagnosis, presentation and initial severity of autoimmune hepatitis (AIH) in patients attending 28 hospitals in the UK. Liver Int 2018; 38: 1686-1695
  • 25 Lu M, Zhou Y, Haller IV. et al. Increasing prevalence of primary biliary cholangitis and reduced mortality with treatment. Clin Gastroenterol Hepatol 2018; 16: 1342-1350
  • 26 Lu M, Li J, Haller IV. et al. Factors associated with prevalence and treatment of primary biliary cholangitis in United States Health Systems. Clin Gastroenterol Hepatol 2018; 16: 1333-1341
  • 27 Boberg KM, Chapman RW, Hirschfield GM. et al. International Autoimmune Hepatitis Group. Overlap syndromes: The International Autoimmune Hepatitis Group (IAIHG) position statement on a controversial issue. J Hepatol 2011; 54: 374-385
  • 28 Janik MK, Wunsch E, Raszeja-Wyszomirska J. et al. Autoimmune hepatitis exerts a profound, negative effect on health-related quality of life: a prospective, single-centre study. Liver Int 2019; 39: 215-221
  • 29 Wong LL, Fisher HF, Stocken DD. et al. The impact of autoimmune hepatitis and its treatment on health utility. Hepatology 2018; 68: 1487-1497
  • 30 Schramm C, Kanzler S, zum Büschenfelde KH. et al. Autoimmune hepatitis in the elderly. Am J Gastroenterol 2001; 96: 1587-1591
  • 31 Al-Chalabi T, Boccato S, Portmann BC. et al. Autoimmune hepatitis (AIH) in the elderly: a systematic retrospective analysis of a large group of consecutive patients with definite AIH followed at a tertiary referral centre. J Hepatol 2006; 45: 575-583
  • 32 Dyson JK, Wong LL, Bigirumurame T. et al. Inequity of care provision and outcome disparity in autoimmune hepatitis in the United Kingdom. Aliment Pharmacol Ther 2018; 48: 951-960