Presumed Cryptogenic Liver Disease in Germany: High Prevalence of Autoantibody-Negative Autoimmune Hepatitis, Low Prevalence of NASH, No Evidence for Occult Viral Etiology

Zusammenfassung

Ziel war es, mögliche Ursachen für vermutete kryptogene Lebererkrankungen zu untersuchen. Methoden: 126 konsekutive Patienten mit vermuteter kryptogener Lebererkrankung, die an eine Universitätsklinik überwiesen worden waren, wurden anhand der klinischen, laborchemischen und histologischen Daten reevaluiert. Ergebnisse: Bei 19 Patienten konnte eine exogen toxische Ursache nachgewiesen werden. Eine nicht alkoholische Steatohepatitis wurde bei 22 Patienten gefunden. Eine virale Ursache konnte bei allen Patienten durch serologische und PCR-basierte Nachweisverfahren für die bekannten Hepatitisviren ebenso wie für die Viren GBV-C und SENV ausgeschlossen werden. Darüber hinaus wurde in Transmissionstudien, bei denen Akutphase-Plasma von Patienten mit hochflorider kryptogener Hepatitis in nicht humanen Primaten inokuliert wurde, kein Hinweis für die Existenz weiterer, bislang unbekannter Viren gefunden. Autoantikörper waren bei allen Patienten negativ. Trotzdem konnte bei 43 Patienten die Diagnose einer definitiven oder wahrscheinlichen seronegativen Autoimmunhepatitis unter Anwendung des Internationalen Autoimmunhepatitis-Scores (IAH-Score) etabliert werden. Nur 42 Patienten verblieben noch mit tatsächlich kryptogener Lebererkrankung (CLD). Im Vergleich zu Patienten mit seronegativer Autoimmunhepatitis waren CLD-Patienten signifikant älter, hatten eine längere Erkrankungsdauer, niedrigere Transaminasen, häufiger ein cholestatisches Enzymmuster, einen niedrigeren Inflammationsgrad in der Leber und sprachen nicht auf eine immunsuppressive Therapie an. Zusammenfassung: Nur bei einem Drittel der Patienten mit initial vermuteter kryptogener Lebererkrankung war diese tatsächlich kryptogenen Ursprungs, während bei einem weiteren Drittel der Patienten durch Verwendung des IAH-Scores eine seronegative Autoimmunhepatitis diagnostiziert wurde, die erfolgreich mit einer immunsuppressiven Therapie behandelt werden konnte.

Abstract

Aim was to investigate possible underlying causes of presumed cryptogenic liver disease. Methods: A cohort of 126 consecutive patients with presumed cryptogenic hepatitis referred to a university hospital were reanalysed with respect to their clinical, laboratory and histological data. Results: In 19 patients there was evidence for an exogenous-toxic liver damage. Diagnosis of non-alcoholic steatohepatitis could be established in 22 patients. Viral origin was excluded in all patients by serological and PCR-based assays for the known hepatitis viruses and the viruses GBV-C and SENV. Furthermore, transmission studies in non-human primates using acute phase plasma of patients with severe cryptogenic hepatitis revealed no episode of transmissible hepatitis, that could give a hint to so far unknown viruses as etiological agent. In all patients negative autoantibodies were recorded. Nevertheless, in 43 patients the diagnosis of definite or probable seronegative autoimmune hepatitis (AIH) could be assumed by the application of the International Autoimmune Hepatitis (IAH)-Score. Only 42 patients still remained with cryptogenic liver disease (CLD). Compared to patients with seronegative AIH patients with CLD were significantly older, had a longer duration of their disease, lower values of transaminases, more frequently a cholestatic liver enzyme pattern, a lower grade of inflammation in the liver and no response to immunosuppressive therapy. Conclusion: Only one third of patients with initially presumed cryptogenic liver disease remained cryptogenic, while another third of patients could be identified as seronegative autoimmune hepatitis by the IAH-Score with obvious benefit from immunosuppressive therapy.

Schlüsselwörter

kryptogene Lebererkrankungen - Autoimmunhepatitis - Internationaler Autoimmunhepatitis-Score, IAH-Score

Key words

cryptogenic liver disease - autoimmune hepatitis - International Autoimmune Hepatitis Score

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