Zytokeratin-18 als Marker zur nichtinvasiven Diagnostik und Prognose akuter und chronischer Lebererkrankungen

Zusammenfassung

Einleitung: Die Leberbiopsie repräsentiert gegenwärtig den Goldstandard zur Beurteilung der Krankheitsaktivität und des Fibrosestadiums bei Lebererkrankungen. Allerdings ist dieses aufwendige und kostenintensive, invasive Verfahren mit möglichen Komplikationen assoziiert. Nichtinvasive Verfahren und Biomarker, die eine unkomplizierte, verlässliche und wiederholbare Beurteilung der Lebererkrankung ermöglichen, sind deshalb wünschenswert. Zytokeratin (CK)-18 ist ein in Hepatozyten exprimiertes Intermediärfilamentprotein, das während der Leberschädigung proteolytisch gespalten wird. Die entstandenen CK-18-Fragmente werden von Hepatozyten freigesetzt und können im Serum nachgewiesen werden.

Methode: Selektive Literaturrecherche in PubMed nach Originalartikeln zum Nachweis von CK-18-Zelltodbiomarkern bei Lebererkrankungen.

Ergebnisse: Die Bestimmung von CK-18-Zelltodbiomarkern im Serum ermöglicht es, frühzeitig Leberschädigung bei akuten und chronischen Lebererkrankungen nachzuweisen. Dies gelingt sogar bei Patienten mit im Normbereich liegenden Transaminasen. Der serologische Nachweis von CK-18-Biomarkern lässt dabei auf die Krankheitsaktivität und das Ausmaß der Leberschädigung schließen. Beispielsweise zeigen Patienten mit nichtalkoholischer Steatohepatitis im Vergleich zu Personen mit einfacher Verfettung höhere Serumwerte für Zelltodbiomarker. Weiterhin sind bei Patienten mit relevanter Fibrose höhere CK-18-Werte im Vergleich zu Patienten mit geringer Leberfibrose zu verzeichnen. Bei akutem Leberversagen können diese Zelltodbiomarker möglicherweise zur Entscheidung bez. der Notwendigkeit einer Lebertransplantation beitragen.

Diskussion: Aufgrund der vielversprechenden Ergebnisse nationaler und internationaler Studien könnten die CK-18-Zelltodbiomarker zukünftig auch Anwendung im klinischen Alltag finden.

Abstract

Introduction: Currently liver biopsy represents the gold standard to assess severity and fibrosis grade in liver diseases. Since this laborious, costly, and invasive procedure is associated with possible complications, non-invasive methods and biomarkers, which allow for an easy, reliable, and repeatable assessment of liver disease are warranted. Cytokeratin (CK) 18 is an intermediary filament protein, expressed in hepatocytes, which is proteolytically cleaved during liver damage. The resultant CK-18 fragments are released by hepatocytes and can be detected in serum.

Methods: A selective literature search in PubMed for original publications about the detection of CK-18 cell death markers in liver diseases was undertaken.

Results: Assessment of CK-18 cell death biomarkers allows for the early detection of liver damage in acute and chronic liver diseases. This is even feasible when transaminases are in the normal ranges. Detection of CK-18 biomarkers can also hint at disease activity and severity. For example, patients with non-alcoholic steatohepatitis exhibit elevated serum cell-death markers compared to those with simple steatosis. Furthermore, in patients with relevant fibrosis higher CK-18 values are found as compared to those with low fibrosis. In acute liver failure, cell death biomarkers may assist decision finding for the necessity of liver transplantation.

Discussion: Due to promising results of various studies, CK-18 cell death markers could be applied in clinical routine soon.

Schlüsselwörter

nichtinvasive Diagnostik - Apoptose - Leberfibrose - Biomarker - Zelltod

Key words

non-invasive diagnostics - apoptosis - liver fibrosis - biomarkers - cell death

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