Der Gastroenterologe

, 4:557 | Cite as

Diagnostik bei erhöhten Leberwerten

CME Weiterbildung · Zertifizierte Fortbildung

Zusammenfassung

Erhöhte Transaminasen, γ-Glutamyl-Transferase (GGT) oder alkalische Phosphatase (AP) werden häufig im Rahmen von Routineuntersuchungen gefunden. Bei Persistenz der Transaminasenerhöhung ist an das Vorliegen infektiöser, exogen-toxischer, toxisch-allergischer, immunpathologischer bzw. autoimmuner, vaskulärer und endogen-metabolischer Prozesse zu denken. Leberenzymerhöhungen finden sich auch bei einer Reihe primär extrahepatischer, systemischer Erkrankungen (hepatische Begleitreaktionen). In diesen Situationen ist oft die klinische Symptomatik wegweisend für die Diagnosestellung.

Die rationale Diagnostik sollte insbesondere im Hinblick auf die zu erwartenden therapeutischen Konsequenzen sowie auf die Dringlichkeit der Diagnosestellung als Stufendiagnostik erfolgen. In der Mehrzahl der Fälle kann allein mittels Anamnese (Symptome, Medikamente, metabolisches Syndrom, Alkoholabusus?) und Labordiagnostik (biochemische, serologische und molekulargenetische Parameter) sowie der Abdomensonographie eine ätiologische Zuordnung erfolgen. Bereits die Konstellation der Transaminasen wie Alaninaminotransferase (ALT) und Aspartataminotransferase (AST) sowie der Cholestaseparameter (GGT-, AP-Erhöhung) erlaubt oft schon eine erste diagnostische Weichenstellung. In bestimmten Situationen kann auch eine Intervention (z. B. Weglassen von Noxen bei Verdacht auf toxische Hepatopathie oder Gewichtsreduktion bei Verdacht auf nichtalkoholische Fettlebererkrankung) für die Diagnosestellung hilfreich sein. In unklaren Fällen stellt die Leberbiopsie weiterhin ein wichtiges diagnostisches Instrument dar.

Schlüsselwörter

Transaminasen Stufendiagnostik Serologie Molekulare Diagnostik Leberbiopsie 

Diagnostics for increased liver parameters

Abstract

Increased levels of transaminases, GGT or alkaline phosphatase (AP) are often found during routine investigations. If increased transaminase levels persist, the presence of infectious, exogen toxic, toxic allergic, immunopathologic or autoimmune, vascular and metabolic processes should be considered. Raised hepatic enzyme levels are also present in a number of primary extrahepatic systemic diseases. In this situation the clinical symptoms are often indicative for the diagnosis.

The rational diagnostic procedure should be carried out in stages particularly with respect to the expected therapeutic consequences as well as the urgency of the diagnosis (rapid progression of the disease?). In the majority of cases an etiologic classification can only be made by means of the patient’s history (symptoms, medication, metabolic syndrome, alcohol abuse?) and laboratory test results (biochemical, serological and molecular genetic parameters) as well as an abdominal ultrasound examination. The constellation of transaminases (ALT, AST) and cholestasis parameters (increased GGT and AP) even often allows an initial diagnostic indication. In certain situations an intervention, such as omitting noxa when there is a suspicion of toxic hepatopathy or weight reduction by suspected non-alcoholic fatty liver disease, can also be useful for the diagnosis. In unclear cases a liver biopsy represents a further important diagnostic instrument.

Keywords

Transaminases Stepwise diagnostics Serology Molecular diagnostics Liver biopsy 

Literatur

  1. 1.
    Lim YS, Kim WR (2008) The global impact of hepatic fibrosis and end-stage liver disease. Clin Liver Dis 12: 733–746CrossRefPubMedGoogle Scholar
  2. 2.
    Pratt DS, Kaplan MM (2000) Evaluation of abnormal liver-enzyme results in asymptomatic patients. N Engl J Med 342: 1266–1271CrossRefPubMedGoogle Scholar
  3. 3.
    Clark JM, Brancati FL, Diehl AM (2003) The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastro 98: 960–967CrossRefGoogle Scholar
  4. 4.
    Ioannou GN, Boyko EJ, Lee SP (2006) The prevalence and predictors of elevated serum aminotransferase activity in the United States in 1999–2002. Am J Gastroenterol 101: 76–82CrossRefPubMedGoogle Scholar
  5. 5.
    Lobstein S, Kaiser T, Liebert U et al (2008) Prevalence, aetiology and associated co-morbidities of elevated aminotransferases in a german cohort of orthopaedic surgery patients. Z Gastroenterol 46: 415–420CrossRefPubMedGoogle Scholar
  6. 6.
    Schlosser B, Domke D, Möckel M et al (2009) High prevalence of chronic hepatitis C virus (HCV) infection in a german metropolitan area: a prospective screening analysing 7683 patients. J Hepatol 50 (S1): S156CrossRefGoogle Scholar
  7. 7.
    Cornberg M, Protzer U, Dollinger MM et al (2007) Prophylaxis, diagnosis and therapy of hepatitis B virus (HBV) infection: the German guidelines for the management of HBV infection. Z Gastroenterol 45: 1281–1328CrossRefPubMedGoogle Scholar
  8. 8.
    Ghany MG, Strader DB, Thomas DL, Seeff LB (2009) American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update Hepatology 49: 1335–1374Google Scholar
  9. 9.
    Prati D, Taioli E, Zanella A et al (2002) Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med 137: 1–9PubMedGoogle Scholar
  10. 10.
    Kim WR, Flamm SL, Di Biscegli AM, Bodenheimer HC (2008) Serum activity of alanine aminotransferase (ALT) as indicator of health and disease. Hepatology 47: 1363–1370CrossRefPubMedGoogle Scholar
  11. 11.
    Lee TH et al (2008) Serum aminotransferase activity and mortality risk in a Unites States community. Hepatology 47: 880–887CrossRefPubMedGoogle Scholar
  12. 12.
    Goessling W, Massaro JM, Vasan RS et al (2008) Aminotransferase levels and 20-year risk of metabolic syndrome, diabetes, and cardiovascular disease. Gastroenterology 135: 1935–1944CrossRefPubMedGoogle Scholar
  13. 13.
    Ioannou GN (2008) Implications of elevated serum alanine aminotransferase levels: think outside the liver. Gastroenterology 135: 1851–1854CrossRefPubMedGoogle Scholar
  14. 14.
    Brenner H, Rothenbacher D, Arndt V et al (1997) Distribution, determinants, and prognostic value of gamma-glutamyltransferase for all-cause mortality in a cohort of construction workers from southern Germany. Prev Med 26: 305–310CrossRefPubMedGoogle Scholar
  15. 15.
    Ruttmann E, Brant LJ, Concin H, Vorarlberg Health Monitoring and Promotion Program Study Group et al (2005) Gamma-glutamyltransferase as a risk factor for cardiovascular disease mortality: an epidemiological investigation in a cohort of 163,944 Austrian adults. Circulation 112: 2130–2137CrossRefPubMedGoogle Scholar
  16. 16.
    Fraser A, Ebrahim S, Smith GD, Lawlor DA (2007) A comparison of associations of alanine aminotransferase and gamma-glutamyltransferase with fasting glucose, fasting insulin, and glycated hemoglobin in women with and without diabetes. Hepatology 46: 158–165CrossRefPubMedGoogle Scholar
  17. 17.
    Strasak AM, Kelleher CC, Klenk J, Vorarlberg Health Monitoring and Promotion Program Study Group et al (2008) Longitudinal change in serum gamma-glutamyltransferase and cardiovascular disease mortality: a prospective population-based study in 76,113 Austrian adults. Arterioscler Thromb Vasc Biol 28: 1857–1865CrossRefPubMedGoogle Scholar
  18. 18.
    Fraser A, Harris R, Sattar N et al (2009) Alanine aminotransferase, gamma-glutamyltransferase, and incident diabetes: the British Women’s Heart and Health Study and meta-analysis. Diabetes Care 32: 741–750CrossRefPubMedGoogle Scholar
  19. 19.
    Ruhl CE, Everhart JE (2009) Elevated serum alanine aminotransferase and gamma-glutamyltransferase and mortality in the United States population. Gastroenterology 136: 477–485CrossRefPubMedGoogle Scholar
  20. 20.
    Kaplan MM (2002) Alanine aminotransferase levels: what’s normal? Ann Intern Med 137: 49–50PubMedGoogle Scholar
  21. 21.
    Pettersson J, Hindorf U, Persson P et al (2008) Muscular exercise can cause highly pathological liver function tests in healthy men. Br J Clin Pharmacol 65: 253–259CrossRefPubMedGoogle Scholar
  22. 22.
    Ohtsuka T, Tsutsumi M, Fukumura A et al (2005) Use of serum carbohydrate-deficient transferring values to exclude alcoholic hepatis from non-alcoholic steatohepatitis: a pilot study. Alcohol Clin Exp Res 29: 236S–239SPubMedGoogle Scholar
  23. 23.
    Berg PA, Stechemesser E, Strienz J (1981) Hypergammaglobulinämische chronisch aktive Hepatitis mit Nachweis von Leber-Pankreas-spezifischen Autoantikörpern. Verh Dtsch Ges Inn Med 87: 857–864Google Scholar
  24. 24.
    Stechemesser E, Klein R, Berg PA (1993) Characterization and clinical relevance of liver-pancreas antibodies in autoimmune hepatitis. Hepatology 18: 1–9CrossRefPubMedGoogle Scholar
  25. 25.
    Wies I, Brunner S, Henninger J et al (2000) Identification of target antigen for SLA/LP autoantibodies in autoimmune hepatitis. Lancet 355: 1510–1515CrossRefPubMedGoogle Scholar
  26. 26.
    Klein R, Berg PA (2009) Significance of antibodies to soluble liver/liver pancreas antigen: experiences in Germany. Liver International (Epub ahead of print)Google Scholar
  27. 27.
    Hennes EM, Zeniya M, Czaja AJ, International Autoimmune Hepatitis Group et al (2008) Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology 48: 169–176CrossRefPubMedGoogle Scholar
  28. 28.
    EASL clinical Practice Guidelines (2009) Management of cholestatic liver diseases. J Hepatol 51: 237–267CrossRefGoogle Scholar
  29. 29.
    Ludwig J (1991) Small-duct primary sclerosing cholangitis. Semin Liver Dis 11: 11–17CrossRefPubMedGoogle Scholar
  30. 30.
    Nikolaidis NL, Giouleme OI, Tziomalos KA et al (2005) Small-duct primary sclerosing cholangitis. A single-center seven-year experience. Dig Dis Sci 50: 324–326CrossRefPubMedGoogle Scholar
  31. 31.
    Radice A, Sinico RA (2005) Antineutrophil cytoplasmic antibodies (ANCA). Autoimmunity 38: 93–103CrossRefPubMedGoogle Scholar
  32. 32.
    Herrmann T, Smolarek C, Gehrke S et al (1991) Hämochromatose und Morbus Wilson. Internist 40: 513–521CrossRefGoogle Scholar
  33. 33.
    Müller T, Koppikar S, Taylor RM et al (2007) Re-evaluation of the penicillamine challenge test in the diagnosis of Wilson’s disease in children. J Hepatol 47: 270–276CrossRefPubMedGoogle Scholar
  34. 34.
    Merle U, Schaefer M, Ferenci P, Stremmel W (2007) Clinical presentation, diagnosis and long-term outcome of Wilson’s disease: a cohort study. Gut 56: 115–120CrossRefPubMedGoogle Scholar
  35. 35.
    Halangk J, Witt H, Puhl G et al (2009) Heterozygous alpha-1 antitrypsin deficiency as an inherited risk factor in the development of chronic liver disease. J Hepatol 50 (Suppl 1): A162CrossRefGoogle Scholar
  36. 36.
    Beutler E, Hoffbrand VA, Cook JD (2003) Iron Deficiency and Overload. Hematology 40–61Google Scholar
  37. 37.
    Deugnier Y, Brissot P, Loréal O (2008) Iron and the liver: Update 2008. J Hepatol 48: S113-S123CrossRefPubMedGoogle Scholar
  38. 38.
    Skelly MM, James PD, Ryder SD (2001) Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology. J Hepatol 35: 195-199CrossRefPubMedGoogle Scholar
  39. 39.
    Mathiesen UL, Franzén LE, Frydén A et al (1999) The Clinical Significance of slightly to mederately increate liver transaminasi values in asymptomatic patients. Scand J Gastroenterol 1: 85–91Google Scholar
  40. 40.
    Dancygier H (2006) Nichtalkoholische Fettlebererkrankungen. Gastroenterol 1: 221–230CrossRefGoogle Scholar
  41. 41.
    Pusl T, Göke B (2007) Neue Therapiemöglichkeiten bei nicht-alkoholischer Fettleber. Diabetologe 3: 202–210CrossRefGoogle Scholar
  42. 42.
    Dunn W, Xu R, Schwimmer JB (2008) Modest wine consumption and decreased prevalence of suspected non-alcoholic liver disease. Hepatology 47: 1947–1954CrossRefPubMedGoogle Scholar
  43. 43.
    Umemura T, Zen Y, Hamano H et al (2007) mmunoglobin G4-hepatopathy: association of immunoglobin G4-bearing plasma cells in liver with autoimmune pancreatitis. Hepatology 46: 463–471 Umemura T, Zen Y, Hamano H et al (2007) IgG4 associated autoimmune hepatitis: a differential diagnosis for classical autoimmune hepatitis. Gut 56: 1471–1472CrossRefPubMedGoogle Scholar
  44. 44.
    Umemura T, Zen Y, Hamano H et al (2007) mmunoglobin G4-hepatopathy: association of immunoglobin G4-bearing plasma cells in liver with autoimmune pancreatitis. Hepatology 46: 463–471CrossRefPubMedGoogle Scholar
  45. 45.
    Rubio-Tapia A, Murray JA (2007) The liver in celiac disease. Hepatology 46: 1650–1658CrossRefPubMedGoogle Scholar

Copyright information

© Springer Medizin Verlag 2009

Authors and Affiliations

  1. 1.Medizinische Klinik m.S. Hepatologie und GastroenterologieCharité-Universitätsmedizin Berlin, Campus Virchow-KlinikumBerlinDeutschland

Personalised recommendations