Non-Alcoholic Steatohepatitis Occurs in Celiac Disease and is Associated with Cellular Stress

Abstract

Background and Aims: Liver and gut not only share alimentary but also immunological features. Major histocompatibility complex class I-related chains A and B (MIC A/B) function as indicators for cellular stress. These so called stress-induced ligands are suggested to play an important role in the progression of non-alcoholic fatty liver disease (NAFLD) and are a prominent feature of celiac disease (CD).

Patients and Methods: In the present study, 24 patients with celiac disease and 20 patients with non-alcoholic steatohepatitis (NASH) were included. Liver enzymes, serum cell death markers (M30, M65), MIC B and expression of adiponectin were determined.

Results: Mean patient age was 42 years (18 − 69) for CD and 49 years (33 − 68) for the NASH group. ALT and AST values were lower in CD compared to NASH patients. While serum cell death markers were higher in NASH, the predominant type of cell death in CD was apoptosis. Also, expression of MIC B was significantly up-regulated in CD patients as compared to NASH patients. Adiponectin values were significantly lower in NASH compared to CD patients.

Conclusion: Stress-induced ligands and apoptosis are induced in CD. Prospective studies need to determine the exact role of cellular stress and apoptosis in the gut-liver axis and the clinical implications to screen for NAFLD in CD patients.

Zusammenfassung

Hintergrund: Leber und Darm weisen simultane alimentäre und immunologische Funktionen auf. Die Histokompatibilitätskomplex-Klasse I Kette A und B (MIC A/B) fungieren als Indikator für zellulären Stress. Es wird angenommen, dass diese sog. stressinduzierten Liganden, die ein bekanntes Charakteristikum der Zöliakie sind, auch eine wichtige Rolle in der Progression der nicht alkoholischen Fettlebererkrankung (NAFLD) spielen.

Methodik: In dieser Analyse wurden 24 Zöliakie-Patienten mit 20 Patienten einer nicht alkoholischen Steatohepatitis (NASH) hinsichtlich ihrer Leberenzyme, Zelltodmarkern (M30, M65), MIC B und der Expression von Adiponektin verglichen.

Ergebnisse: Das mittlere Alter der Zöliakie-Patienten betrug 42 Jahre (18 − 69), das der NASH-Patienten lag bei 49 Jahren (33 − 68). Patienten mit Zöliakie wiesen im Vergleich zu NASH-Patienten sowohl höhere Leberenzyme als auch vermehrte Apoptosemarker (Verhältnis Apoptose/Nekrose) auf. Gleichzeitig war die Expression von MIC B in Patienten mit Zöliakie im Vergleich zu NASH-Patienten signifikant erhöht. Patienten mit NASH hatten darüber hinaus signifikant niedrigere Adiponektin-Werte als Zöliakie-Patienten.

Schlussfolgerung: Stressinduzierte Liganden und Apoptose-induzierter Zelltod sind bei Patienten mit Zöliakie aktiviert. Weitere prospektive Studien, welche die Beziehung zwischen Leber und Darm näher untersuchen, sind notwendig, um zu klären, wann Zöliakie-Patienten für das Vorliegen einer NAFLD untersucht werden sollten.

Schlüsselwörter

Sprue - Leber - Darm - MIC A/B - NAFLD

Key words

celiac disease - liver - gut - MIC A/B - NAFLD

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