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Dtsch Med Wochenschr 2016; 141(22): 1640-1646
DOI: 10.1055/s-0042-100041
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© Georg Thieme Verlag KG Stuttgart · New York

Erhöhte Leberwerte

Elevated liver enzymes
Axel Holstege
1   Medizinische Klinik 1, Klinikum Landshut
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Publication Date:
04 November 2016 (online)

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Zusammenfassung

Erhöhte Leberwerte sind ein häufiger klinischer Befund bei symptomatischen und asymptomatischen Patienten, der eine weitere Abklärung erfordert. Das Muster der pathologisch veränderten Leberwerte erlaubt eine erste Einordnung. Bei vorwiegender Erhöhung der Transaminasen liegt eine hepatozelluläre Schädigung vor, hinter der sich eine virale Genese, eine genetisch bedingte Stoffwechselerkrankung oder eine medikamentös-toxische Schädigung verbergen kann. Steht die Erhöhung von Cholestaseenzymen im Vordergrund muss durch eine Sonografie zunächst geklärt werden, ob eine intra- oder extrahepatische Ursache der Cholestase vorliegt. Intrahepatische Cholestasen sind auf eine primär biliäre Cholangitis, primär und sekundär sklerosierende Cholangitiden, Störungen der kanalikulären Transporter oder Arzneimittelschäden zurückzuführen. Extrahepatische Cholestasen beruhen im Wesentlichen auf Galleabfluss-Störungen durch Gallensteine oder Tumoren. Eine dritte Gruppe von Leberwerterhöhungen ist durch einen Anstieg der γ-GT charakterisiert. Hinter diesem dritten Enzymmuster verbergen sich toxisch-nutritive, infiltrative und metabolische Lebererkrankungen. Bei der Beurteilung erhöhter Leberenzyme ist zu beachten, dass es neben vielen extrahepatischen Krankheitsursachen auch physiologische Enzymerhöhungen gibt. Niedrige Leberwerterhöhungen bei asymptomatischen Patienten sollten zunächst im Verlauf kontrolliert werden, da sich bei einem Drittel der Betroffenen gering erhöhte Leberwerte spontan normalisieren.

Abstract

Elevated liver enzymes are a frequent finding in both symptomatic and asymptomatic patients necessitating further evaluation to clarify the underlying disease. Three different patterns of increased liver enzymes can be defined to allow for a more precise and rational further diagnostic approach. A predominant increase in transaminase activities reflects a disturbance of hepatocellular integrity which can be found in patients with viral hepatitis, genetic liver diseases like Wilson`s disease or hemochromatosis, and drug-induced liver diseases. A second pattern is characterized by high serum alkaline phosphatase and γ-glutamyltranspeptidase activities indicating cholestatic liver diseases. The next important diagnostic measure in this group is an ultrasound study discerning intra- from extrahepatic cholestasis. Intrahepatic cholestatic diseases include primary and secondary sclerosing cholangitis, genetic disturbances of canalicular membrane transporters or drug-induced liver dieseases. Extrahepatic cholestasis involves obstruction of the large bile ducts by gall stones or tumors. The third enzym pattern is defined by a predominant rise in γ-glutamyl transpeptidase which is observed in alcoholic or non-alcoholic fatty liver disease and infiltrating liver diseases. A rise in liver enzymes is not necessarily indicative of a primary hepatic origin. Extrahepatic diseases often cause similarly increased serum activities. In addition even higher values can be observed under normal conditions during pregnancy or in adolescens. Lower values in asymptomatic patients should only be controlled since more than 30% of elevated transaminases spontaneously normalize during follow-up.

Schlüsselwörter

Leberkrankheiten - Leberenzyme - Cholestase - Transaminasen - alkalische Phosphatase - g-Glutamyltranspeptidase - Differentialdiagnostik

Keywords

Liver disease - serum enzymes - cholestasis - transaminases - alkaline phosphatase - g-glutamyl transpeptidase - differential diagnosis
 

  • Literatur

  • 1 Holstege A. Überraschende Transaminasenerhöhung. MMW-Fortschr Med 2014; 156: 62-63
    PubMedSearch in Google Scholar
  • 2 Vogt W, Holstege A. Problem: Abklärung mäßig erhöhter Transaminasen und γ-GT. In: Schölmerich J, Bischoff SC, Manns MP, Hrsg. Diagnostik in der Gastroenterologie und Hepatologie. Stuttgart: Thieme; 1997: 151-160
    Search in Google Scholar
  • 3 Von Herbay A, Strohmeyer G. Die erhöhte γ-GT Dtsch Med Wochenschr 1994; 119: 1041-1044
    PubMedSearch in Google Scholar
  • 4 Willson RA, Clayson KJ, Leon S. Unmeasurable serum alkaline phosphatase activity in Wilson’s disease associated with fulminant hepatic failure and hemolysis. Hepatology 1987; 7: 613-615
    CrossrefPubMedSearch in Google Scholar
  • 5 Williams AL, Hoofnagle JH. Ratio of serum aspartate to alanine aminotransferase in chronic hepatitis. Relationship to cirrhosis. Gastroenterology 1988; 95: 734-739
    CrossrefPubMedSearch in Google Scholar
  • 6 Patel K, Bedossa P, Castera L. Diagnosis of liver fibrosis: present and future. Semin Liver Dis 2015; 35: 166-183
    Thieme ConnectPubMedSearch in Google Scholar
  • 7 Triger DR, Wright R. Hyperglobulinaemia in liver disease. Lancet 1973; 1 (7818) 1494-1496
    PubMedSearch in Google Scholar
  • 8 Wedemeyer H, Pischke S, Manns MP. Pathogenesis and treatment of hepatitis E virus Infection. Gastroenterology 2012; 142: 1388-1397
    CrossrefPubMedSearch in Google Scholar
  • 9 Manns MP, Lohse AW, Vergani D. Autoimmune hepatitis--Update 2015. J Hepatol 2015; 62 (1 Suppl) S100-111
    CrossrefPubMedSearch in Google Scholar
  • 10 Bacon BR, Adams PC, Kowdley KV et al. Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology 2011; 54: 328-343
    CrossrefPubMedSearch in Google Scholar
  • 11 Ioannou GN, Dominitz JA, Weiss NS et al. The effect of alcohol consumption on the prevalence of iron overload, iron deficiency, and iron deficiency anemia. Gastroenterology 2004; 126: 1293-1301
    CrossrefPubMedSearch in Google Scholar
  • 12 Bomford A. Genetics of haemochromatosis. Lancet 2002; 360 (9346) 1673-1681
    CrossrefPubMedSearch in Google Scholar
  • 13 Sarigianni M, Liakos A, Vlachaki E et al. Accuracy of magnetic resonance imaging in diagnosis of liver iron overload: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2015; 13: 55-63
    CrossrefPubMedSearch in Google Scholar
  • 14 Roberts EA, Schilsky ML. American Association for the Study of Liver Diseases (AASLD). Diagnosis and treatment of Wilson disease: an update. Hepatology. 2008; 47: 2089-2111
    PubMedSearch in Google Scholar
  • 15 Fontana RJ, Seeff LB, Andrade RJ et al. Standardization of nomenclature and causality assessment in drug-induced liver injury: summary of a clinical research workshop. Hepatology 2010; 52: 730-742
    CrossrefPubMedSearch in Google Scholar
  • 16 Holstege A. Leberschäden durch Medikamente. Kapitel 6.7.2. In: Messmann H, Hrsg. Klinische Gastroenterologie. Stuttgart: Thieme; 2012: 599-605
    Search in Google Scholar
  • 17 Li J, Zhang YL, Chen R et al. Elevated serum liver enzymes in patients with obstructive sleep apnea-hypopnea syndrome. Chin Med J 2015; 128: 2983-2987
    CrossrefPubMedSearch in Google Scholar
  • 18 Kiladjian JJ, Cervantes F, Leebeek FW et al. The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: a report on 241 cases. Blood 2008; 111: 4922-4929
    CrossrefPubMedSearch in Google Scholar
  • 19 McDonald GB, Hinds MS, Fisher LD et al. Veno-occlusive Disease of the Liver and Multiorgan Failure after Bone Marrow Transplantation: A Cohort Study of 355 Patients. Ann Intern Med 1993; 118: 255-267
    CrossrefPubMedSearch in Google Scholar
  • 20 Kechagias S, Ernersson A, Dahlqvist O et al. Fast-food-based hyper-alimentation can induce rapid and profound elevation of serum alanine aminotransferase in healthy subjects. Gut 2008; 57: 649-654
    CrossrefPubMedSearch in Google Scholar
  • 21 Rogal SS, Ukomadu C, Levy BD et al. A Sweet Source of Abdominal Pain. N Engl J Med 2011; 364: 1762-1767
    CrossrefPubMedSearch in Google Scholar
  • 22 Beuers U, Gershwin ME, Gish RG et al. Changing nomenclature for PBC: From ‘cirrhosis’ to ‘cholangitis’. Clin Res Hepatol Gastroenterol 2015; 39: e57-e59
    CrossrefPubMedSearch in Google Scholar
  • 23 Marzorati S, Invernizzi P, Lleo A. Making sense of autoantibodies in cholestatic liver diseases. Clin Liver Dis 2016; 20: 33-46
    CrossrefPubMedSearch in Google Scholar
  • 24 Schwarze C, Terjung B, Lilienweiss P et al. IgA class antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis and autoimmune hepatitis. Clin Exp Immunol 2003; 133: 283-289
    CrossrefPubMedSearch in Google Scholar
  • 25 Holstege A, Zolinski P, Woidy L et al. The patient with unexplained elevated serum liver enzymes. Best Pract Res Clin Gastroenterol 2007; 21: 535-550
    PubMedSearch in Google Scholar
  • 26 Boonstra K, Culver EL, de Buy Wenniger LM et al. Serum immunoglobulin G4 and immunoglobulin G1 for distinguishing immunoglobulin G4-associated cholangitis from primary sclerosing cholangitis. Hepatology 2014; 59: 1954-1963
    CrossrefPubMedSearch in Google Scholar
  • 27 Beuers U, Hubers LM, Doorenspleet M et al. IgG4-Associated Cholangitis - A Mimic of PSC. Dig Dis 2015; 33 (Suppl 2) 176-180
    CrossrefPubMedSearch in Google Scholar
  • 28 Ziol 1 M, Barbu V, Rosmorduc O et al. ABCB4 heterozygous gene mutations associated with fibrosing cholestatic liver disease in adults. Gastroenterology 2008; 135: 131-141
    CrossrefPubMedSearch in Google Scholar
  • 29 Boyer JL. Bile formation and secretion. Compr Physiol 2013; 3: 1035-1078
    PubMedSearch in Google Scholar
  • 30 Jangouk P, Hashash JG. An unusual cause of painless jaundice. Renal cell carcinoma (Stauffer syndrome). Gastroenterology 2014; 146: 913 1138
    PubMedSearch in Google Scholar
  • 31 Lammert F, Neubrand MW, Bittner R et al. S3-Leitlinie der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten und der Deutschen Gesellschaft für Viszeralchirurgie zur Diagnostik und Behandlung von Gallensteinen. Z Gastroenterol 2007; 45: 971-1001
    Thieme ConnectPubMedSearch in Google Scholar
  • 32 Zimmer V, Lammert F. Acute bacterial cholangitis. Viszeralmedizin 2015; 31: 166-172
    CrossrefPubMedSearch in Google Scholar
  • 33 Burt AD, Lackner C, Tiniakos DG. Diagnosis and Assessment of NAFLD: Definitions and Histopathological Classification. Semin Liver Dis 2015; 35: 207-220
    Thieme ConnectPubMedSearch in Google Scholar
  • 34 Tannapfel A, Denk H, Dienes HP et al. Histopathologische Diagnose der nicht alkoholischen und alkoholischen Fettlebererkrankung. Z Gastroenterol 2010; 48: 486-498
    Thieme ConnectPubMedSearch in Google Scholar
  • 35 Musso G, Gambino R, Cassader M et al. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med. 2011; 43: 617-649
    CrossrefPubMedSearch in Google Scholar
  • 36 Petta S, Maida M, Macaluso FS et al. The severity of steatosis influences liver stiffness measurement in patients with nonalcoholic fatty liver disease. Hepatology 2015; 62: 1101-1110
    CrossrefPubMedSearch in Google Scholar
  • 37 Tapper EB, Castera L, Afdhal NH. FibroScan (vibration-controlled transient elastography): where does it stand in the United States practice. Clin Gastroenterol Hepatol 2015; 13: 27-36
    CrossrefPubMedSearch in Google Scholar
  • 38 Holstege A. Leberschäden durch Alkohol. Kapitel 6.7.1. In: Messmann H, Hrsg. Klinische Gastroenterologie. Stuttgart: Thieme; 2012: 594-599
    Search in Google Scholar
  • 39 Alte D, Luedemann J, Rose HJ et al. Laboratory markers carbohydrate-deficient transferrin, gamma-glutamyltransferase, and mean corpuscular volume are not useful as screening tools for high-risk drinking in the general population: results from the Study of Health in Pomerania (SHIP). Alcohol Clin Exp Res. 2004; 28: 931-940
    CrossrefPubMedSearch in Google Scholar
  • 40 Strobel D, Bernatik T, Blank W et al. Diagnostic accuracy of CEUS in the differential diagnosis of small (≤ 20 mm) and subcentimetric (≤ 10 mm) focal liver lesions in comparison with histology. Results of the DEGUM multicenter trial. Ultraschall Med. 2011; 32: 593-597
    PubMedSearch in Google Scholar
  • 41 Lazo M, Selvin E, Clark JM. Brief communication: clinical implications of short-term variability in liver function test results. Ann Intern Med 2008; 148: 348-352
    CrossrefPubMedSearch in Google Scholar
  • 42 Pratt DS, Kaplan MM. Evaluation of Abnormal Liver-Enzyme Results in Asymptomatic Patients. N Engl J Med 2000; 342: 1266-1271
    CrossrefPubMedSearch in Google Scholar