Sekundäre Ursachen der Fettleber – Neues zur Pathogenese, rationalen Diagnostik und Therapie

 

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Sekundäre Ursachen der Fettleber sollten erkannt werden, da für diese oftmals Therapieoptionen bestehen. Sekundäre Ursachen einer Fettleber umfassen eine Hepatitis-C-Virusinfektion (HCV-Infektion), endokrinologische Erkrankungen, ernährungs- und darmassoziierte Erkrankungen sowie genetische Leber- und Stoffwechselerkrankungen. Medikamente können ebenfalls eine Fettleber hervorrufen. Die primäre Fettleber ist durch das Auftreten einer Steatosis hepatis ohne relevanten Alkoholkonsum oder andere Ursachen einer sekundären Fettleber definiert. Sie tritt gehäuft bei Patienten mit metabolischem Syndrom auf (hepatische Manifestation des metabolischen Syndroms).

Basisdiagnostik umfasst die Abklärung eines metabolischen Syndroms sowie den Ausschluss eines relevanten Alkoholkonsums.

Weiterführende Diagnostik erfolgt als Stufendiagnostik, bei der zunächst eine HCV-Infektion und Hypothyreose abgeklärt und Steatose-induzierende Medikamente abgefragt werden. Im nächsten Schritt sollten diagnostische Tests für Morbus Wilson, Hämochromatose, Zöliakie sowie Fettstoffwechselstörungen erfolgen. Eine erweiterte endokrinologische Abklärung sollte erwogen und bei weiterhin unklarer Ursache eine Leberbiopsie angestrebt werden.

Häufige genetische Polymorphismen bei Fettlebererkrankung wurden in verschiedenen Genen wie PNPLA3, TM6SF2 und MBOAT7 identifiziert und begünstigen die Entwicklung und Progression einer Fettlebererkrankung bei unterschiedlichen Ätiologien wie metabolischem Syndrom, alkoholischer Lebererkrankung und HCV-Infektion. Dabei wirken diese Varianten additiv.

Therapie bei sekundären Fettlebererkrankungen kann ein Fortschreiten der Fettlebererkrankung verhindern. Für eine Reihe sekundärer Ursachen existieren zielgerichtete Therapien.

Abstract

Secondary causes of fatty liver disease are important to recognize since specific therapy options are available for some of these causes. Common causes of secondary fatty liver disease comprise hepatitis C virus infection (HCV), endocrinological diseases, nutritional and intestinal diseases as well as genetic liver and metabolic diseases. Certain drugs may also predispose to the development of fatty liver disease. Primary fatty liver disease, also known as non-alcoholic fatty liver disease (NAFLD) is defined by the presence of steatosis hepatis without relevant alcohol consumption or other causes of secondary fatty liver disease. NAFLD occurs more frequently in patients with metabolic syndrome and thus can be seen as the hepatic manifestation of the metabolic syndrome.

Therefore, presence of features of the metabolic syndrome should be assessed in all patients with fatty liver disease. Furthermore, alcohol consumption should be determined to rule out alcoholic liver disease (ASH). Further diagnostic work up for secondary causes of fatty liver disease should include screening for HCV infection, for hypothyroidism and for drugs associated with steatosis development. In a next step screening for Wilson’s disease, hemochromatosis, celiac disease and lipid metabolism disorders should be performed. An extended endocrinological workup and a liver biopsy should be considered if the etiology of fatty liver disease remains unclear.

Common genetic polymorphisms have been identified in several genes, such as PNPLA3, TM6SF2 and MBOAT7, which may promote the development and the progression of fatty liver disease irrespective of the underlying etiology (e. g. metabolic syndrome, ASH or HCV). The risk variants in these genes have additive effects on steatosis development and diseases progression towards fibrosis and cirrhosis. The diagnosis of secondary causes of fatty liver disease may allow for therapeutic intervention and prevent disease progression. Accordingly, secondary causes of fatty liver disease should be considered during the diagnostic workup of NAFLD patients.

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