Z Gastroenterol 2010; 48(4): 486-498
DOI: 10.1055/s-0029-1245278
Leitlinie

© Georg Thieme Verlag KG Stuttgart · New York

Histopathologische Diagnose der nicht alkoholischen und alkoholischen Fettlebererkrankung

Histopathological Diagnose of Non-alcoholic and Alcoholic Fatty Liver DiseaseA. Tannapfel1 , H. Denk2 , H.-P. Dienes3 , C. Langner2 , P. Schirmacher4 , M. Trauner5 , B. Flott-Rahmel1
  • 1Institut für Pathologie, Ruhr-Universität Bochum
  • 2Institut für Pathologie, Medizinische Universität Graz
  • 3Institut für Pathologie, Universität zu Köln
  • 4Pathologisches Institut, Universitätsklinikum Heidelberg
  • 5Klinische Abteilung für Gastroenterologie und Hepatologie, Medizinische Universität Graz
Further Information

Publication History

Manuskript eingetroffen: 21.12.2009

Manuskript akzeptiert: 10.2.2010

Publication Date:
29 March 2010 (online)

Zusammenfassung

Eine alkoholische (AFL) und eine nicht alkoholische Fettleber (NAFL) zeichnen sich durch eine Einlagerung von Lipiden in die Hepatozyten aus. Bei einer Beteiligung von > 5 % der Hepatozyten spricht man von „Verfettung”, bei > 50 % von einer „Fettleber”. Eine zusätzliche Entzündungsreaktion mit hepatozytärer Ballonierung führt zur alkoholischen (ASH) oder nicht alkoholischen (NASH) Steatohepatitis. Eine ASH bzw. NASH kann zur Fibrose oder Zirrhose führen. In der klinischen Praxis ist es bislang allein auf Basis nicht invasiver Tests nicht möglich, zwischen Steatose und Steatohepatitis zu unterscheiden. Eine Steatohepatitis liegt dann vor, wenn neben der Steatose gemischtzellige entzündliche Infiltrate in den Leberläppchen nachweisbar sind und zusätzlich eine Leberzellschädigung in Form einer Ballonierung vorliegt. Die Leberbiopsie ist der „Goldstandard” bei der Sicherung der Diagnose sowie der Bestimmung der entzündlichen Aktivität und möglichen Fibrose einer Fettlebererkrankung. Die Indikation zur Biopsie sollte den möglichen Informationsgewinn durch die Biopsie und seine Konsequenzen im Vergleich zu Aufwand und Komplikationsrate berücksichtigen und daher im klinischen Kontext gestellt werden.

Abstract

Alcoholic fatty liver (AFL) as well as non-alcoholic fatty liver (NAFL) are characterised by deposition of lipids into hepatocytes. The diagnosis of steatosis is made if lipid deposition exceeds 5 % of hepatocytes, in case of more than 50 % it is called ”fatty liver”. An additional inflammatory reaction, with ballooning of hepatocytes, leads to alcoholic steatohepatitis (ASH) or non-alcoholic steatohepatitis (NASH). Both ASH or NASH may lead to fibrosis or cirrhosis. To date in clinical practice it is not possible to differentiate between steatosis and steatohepatitis just on the basis of non-invasive tests. Steatohepatitis is present if, along with steatosis, both inflammatory infiltrates of mixed cells in the small liver lobules and liver cell injury in terms of ballooning can be detected. Liver biopsy represents the ”gold standard” for confirming the diagnosis and to determine inflammatory activity and potential fibrosis of fatty liver disease. Indications for biopsy should take into account the possible information and its consequences as compared to expense and complication rate and therefore should be assessed in the clinical context.

Literatur

  • 1 Adams L A, Talwalkar J A. Diagnostic evaluation of nonalcoholic fatty liver disease.  J Clin Gastroenterol. 2006;  40 34-38
  • 2 AGA . American Gastroenterological Association medical position statement: nonalcoholic fatty liver disease.  Gastroenterology. 2002;  123 1702-1704
  • 3 Alfire M E, Treem W R. Nonalcoholic fatty liver disease.  Pediatr Ann. 2006;  35 290-299
  • 4 Aloia T, Sebagh M, Plasse M. et al . Liver histology and surgical outcomes after preoperative chemotherapy with fluorouracil plus oxaliplatin in colorectal cancer liver metastases.  J Clin Oncol. 2006;  24 4983-4990
  • 5 Angulo P, Hui J M, Marchesini G. et al . The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD.  Hepatology. 2007;  45 846-854
  • 6 Angulo P, Lindor K D. Non-alcoholic fatty liver disease.  J Gastroenterol Hepatol. 2002;  17 S186-S190
  • 7 Bacon B R, Farahvash M J, Janney C G. et al . Nonalcoholic steatohepatitis: an expanded clinical entity.  Gastroenterology. 1994;  107 1103-1109
  • 8 Baumann U. Die kindliche Fettlebererkrankung.  Dtsch Ärzteblatt. 2005;  102 A2634-A2639
  • 9 Bellentani S, Bedogni G, Miglioli L. et al . The epidemiology of fatty liver.  Eur J Gastroenterol Hepatol. 2004;  16 1087-1093
  • 10 Bonekamp S, Kamel I, Solga S. et al . Can imaging modalities diagnose and stage hepatic fibrosis and cirrhosis accurately?.  J Hepatol. 2009;  50 17-35
  • 11 Brunt E M. Nonalcoholic steatohepatitis: definition and pathology.  Semin Liver Dis. 2001;  21 3-16
  • 12 Brunt E M. Alcoholic and nonalcoholic steatohepatitis.  Clin Liver Dis. 2002;  6 399-420
  • 13 Brunt E M. Pathology of fatty liver disease.  Mod Pathol. 2007;  20 S40-S48 (S 01)
  • 14 Brunt E M. Nonalcoholic steatohepatitis: pathologic features and differential diagnosis.  Semin Diagn Pathol. 2005;  22 330-338
  • 15 Brunt E M. Pathology of nonalcoholic steatohepatitis.  Hepatol Res. 2005;  33 68-71
  • 16 Brunt E M, Janney C G, Di Bisceglie A M. et al . Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions.  Am J Gastroenterol. 1999;  94 2467-2474
  • 17 Brunt E M, Neuschwander-Tetri B A, Oliver D. et al . Nonalcoholic steatohepatitis: histologic features and clinical correlations with 30 blinded biopsy specimens.  Hum Pathol. 2004;  35 1070-1082
  • 18 Brunt E M, Ramrakhiani S, Cordes B G. et al . Concurrence of histologic features of steatohepatitis with other forms of chronic liver disease.  Mod Pathol. 2003;  16 49-56
  • 19 Brunt E M, Tiniakos D G. Pathology of steatohepatitis.  Best Pract Res Clin Gastroenterol. 2002;  16 691-707
  • 20 Brunt E M, Tiniakos D G. Pathological features of NASH.  Front Biosci. 2005;  10 1475-1484
  • 21 Burt A D, Mutton A, Day C P. Diagnosis and interpretation of steatosis and steatohepatitis.  Semin Diagn Pathol. 1998;  15 246-258
  • 22 Caldwell S H, Oelsner D H, Iezzoni J C. et al . Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease.  Hepatology. 1999;  29 664-669
  • 23 Castera L, Forns X, Alberti A. Non-invasive evaluation of liver fibrosis using transient elastography.  J Hepatol. 2008;  48 835-847
  • 24 Chitturi S, Abeygunasekera S, Farrell G C. et al . NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome.  Hepatology. 2002;  35 373-379
  • 25 Church T S, Kuk J L, Ross R. et al . Association of cardiorespiratory fitness, body mass index, and waist circumference to nonalcoholic fatty liver disease.  Gastroenterology. 2006;  130 2023-2030
  • 26 Cortez-Pinto H, Moura M C, Day C P. Non-alcoholic steatohepatitis: from cell biology to clinical practice.  J Hepatol. 2006;  44 197-208
  • 27 Dancygier de H. Pathogenese und Therapie der nichtalkoholischen Fettlebererkrankungen.  Dtsch Ärzteblatt. 2006;  103 A1301-A1307
  • 28 Day C P. Non-alcoholic fatty liver disease: current concepts and management strategies.  Clin Med. 2006;  6 19-25
  • 29 Day C P. Pathogenesis of steatohepatitis.  Best Pract Res Clin Gastroenterol. 2002;  16 663-678
  • 30 Day C P, James O F. Steatohepatitis: a tale of two ”hits”?.  Gastroenterology. 1998;  114 842-845
  • 31 DeLeve L D, Shulman H M, McDonald G B. Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease).  Semin Liver Dis. 2002;  22 27-42
  • 32 Dufour J F, Oneta C M. Alcoholic and non-alcoholic steatohepatitis.  Ther Umsch. 2004;  61 505-512
  • 33 Duvnjak M, Lerotic I, Barsic N. et al . Pathogenesis and management issues for non-alcoholic fatty liver disease.  World J Gastroenterol. 2007;  13 4539-4550
  • 34 Edmison J, McCullough A J. Pathogenesis of non-alcoholic steatohepatitis: human data.  Clin Liver Dis. 2007;  11 75-104
  • 35 Falck-Ytter Y, Younossi Z M, Marchesini G. et al . Clinical features and natural history of nonalcoholic steatosis syndromes.  Semin Liver Dis. 2001;  21 17-26
  • 36 Farrell G C, Larter C Z. Nonalcoholic fatty liver disease: from steatosis to cirrhosis.  Hepatology. 2006;  43 S99-S112
  • 37 Friedrich-Rust M, Ong M F, Martens S. et al . Performance of transient elastography for the staging of liver fibrosis: a meta-analysis.  Gastroenterology. 2008;  134 960-974
  • 38 Gentilucci U V, Santini D, Vincenzi B. et al . Chemotherapy-induced steatohepatitis in colorectal cancer patients.  J Clin Oncol. 2006;  24 5467-5468
  • 39 Gramlich T, Kleiner D E, McCullough A J. et al . Pathologic features associated with fibrosis in nonalcoholic fatty liver disease.  Hum Pathol. 2004;  35 196-199
  • 40 Harrison S A, Torgerson S, Hayashi P H. The natural history of nonalcoholic fatty liver disease: a clinical histopathological study.  Am J Gastroenterol. 2003;  98 2042-2047
  • 41 Hubscher S G. Role of liver biopsy in the assessment of non-alcoholic fatty liver disease.  Eur J Gastroenterol Hepatol. 2004;  16 1107-1115
  • 42 Joy D, Thava V R, Scott B B. Diagnosis of fatty liver disease: is biopsy necessary?.  Eur J Gastroenterol Hepatol. 2003;  15 539-543
  • 43 Kacerovsky M, Roden M. Nichtalkoholische Fettleber.  Diabetologe. 2007;  3 176-183
  • 44 Karoui M, Penna C, min-Hashem M. et al . Influence of preoperative chemotherapy on the risk of major hepatectomy for colorectal liver metastases.  Ann Surg. 2006;  243 1-7
  • 45 Kleiner D E, Brunt E M, Van Natta M. et al . Design and validation of a histological scoring system for nonalcoholic fatty liver disease.  Hepatology. 2005;  41 1313-1321
  • 46 Lackner C, Gogg-Kamerer M, Zatloukal K. et al . Ballooned hepatocytes in steatohepatitis: the value of keratin immunohistochemistry for diagnosis.  J Hepatol. 2008;  48 821-828
  • 47 Ludwig J, McGill D B, Lindor K D. Review: nonalcoholic steatohepatitis.  J Gastroenterol Hepatol. 1997;  12 398-403
  • 48 Ludwig J, Viggiano T R, McGill D B. et al . Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease.  Mayo Clin Proc. 1980;  55 434-438
  • 49 Matteoni C A, Younossi Z M, Gramlich T. et al . Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity.  Gastroenterology. 1999;  116 1413-1419
  • 50 Medina J, Fernandez-Salazar L I, Garcia-Buey L. et al . Approach to the pathogenesis and treatment of nonalcoholic steatohepatitis.  Diabetes Care. 2004;  27 2057-2066
  • 51 Mendez-Sanchez N, Arrese M, Zamora-Valdes D. et al . Current concepts in the pathogenesis of nonalcoholic fatty liver disease.  Liver Int. 2007;  27 423-433
  • 52 Mendler M H, Kanel G, Govindarajan S. Proposal for a histological scoring and grading system for non-alcoholic fatty liver disease.  Liver Int. 2005;  25 294-304
  • 53 Mofrad P, Contos M J, Haque M. et al . Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values.  Hepatology. 2003;  37 1286-1292
  • 54 Moss A, Wabitsch M, Kromeyer-Hauschild K. et al . Prevalence of overweight and adiposity in German school children.  Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2007;  50 1424-1431
  • 55 Nakano H, Oussoultzoglou E, Rosso E. et al . Sinusoidal injury increases morbidity after major hepatectomy in patients with colorectal liver metastases receiving preoperative chemotherapy.  Ann Surg. 2008;  247 118-124
  • 56 Neuschwander-Tetri B A. Evolving pathophysiologic concepts in nonalcoholic steatohepatitis.  Curr Gastroenterol Rep. 2002;  4 31-36
  • 57 Neuschwander-Tetri B A, Caldwell S H. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference.  Hepatology. 2003;  37 1202-1219
  • 58 Nocito A, El-Badry A M, Clavien P A. When is steatosis too much for transplantation?.  J Hepatol. 2006;  45 494-499
  • 59 Nordlinger B, Van Cutsem E, Rougier P. et al . Does chemotherapy prior to liver resection increase the potential for cure in patients with metastatic colorectal cancer? A report from the European Colorectal Metastases Treatment Group.  Eur J Cancer. 2007;  43 2037-2045
  • 60 Oneta C M, Dufour J F. Diagnostik, Prognose und therapeutische Möglichkeiten der nicht-alkoholischen Fettlebererkrankung.  Schweiz Med Forum. 2003;  37 862-868
  • 61 Papandreou D, Rousso I, Mavromichalis I. Update on non-alcoholic fatty liver disease in children.  Clin Nutr. 2007;  26 409-415
  • 62 Rashid M, Roberts E. Nonalcoholic steatohepatitis in children.  J Pediatr Gastroenterol Nutr. 2000;  30 48-53
  • 63 Ratziu V, Charlotte F, Heurtier A. et al . Sampling variability of liver biopsy in nonalcoholic fatty liver disease.  Gastroenterology. 2005;  128 1898-1906
  • 64 Reid A E. Nonalcoholic steatohepatitis.  Gastroenterology. 2001;  121 710-723
  • 65 Roberts E A. Steatohepatitis in children.  Best Pract Res Clin Gastroenterol. 2002;  16 749-765
  • 66 Roberts E A. Non-alcoholic steatohepatitis in children.  Clin Liver Dis. 2007;  11 155-72
  • 67 Rousselet M C, Michalak S, Dupre F. et al . Sources of variability in histological scoring of chronic viral hepatitis.  Hepatology. 2005;  41 257-264
  • 68 Sanyal A J, Banas C, Sargeant C. et al . Similarities and differences in outcomes of cirrhosis due to nonalcoholic steatohepatitis and hepatitis C.  Hepatology. 2006;  43 682-689
  • 69 Schwimmer J B. Definitive diagnosis and assessment of risk for nonalcoholic fatty liver disease in children and adolescents.  Semin Liver Dis. 2007;  27 312-318
  • 70 Schwimmer J B, Behling C, Newbury R. et al . Histopathology of pediatric nonalcoholic fatty liver disease.  Hepatology. 2005;  42 641-649
  • 71 Sonsuz A, Basaranoglu M, Ozbay G. Relationship between aminotransferase levels and histopathological findings in patients with nonalcoholic steatohepatitis.  Am J Gastroenterol. 2000;  95 1370-1371
  • 72 Strassburg C P, Manns M P. Approaches to liver biopsy techniques – revisited.  Semin Liver Dis. 2006;  26 318-327
  • 73 Tannapfel A, Geissler F, Witzigmann H. et al . Analysis of liver allograft rejection related genes using cDNA-microarrays in liver allograft specimen.  Transplant Proc. 2001;  33 3283-3284
  • 74 Tannapfel A, Reinacher-Schick A. Chemotherapy associated hepatotoxicity in the treatment of advanced colorectal cancer (CRC).  Z Gastroenterol. 2008;  46 435-440
  • 75 Targher G, Bertolini L, Rodella S. et al . Associations between plasma adiponectin concentrations and liver histology in patients with nonalcoholic fatty liver disease.  Clin Endocrinol (Oxf). 2006;  64 679-683
  • 76 Teli M R, James O F, Burt A D. et al . The natural history of nonalcoholic fatty liver: a follow-up study.  Hepatology. 1995;  22 1714-1719
  • 77 Vauthey J N, Pawlik T M, Ribero D. Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases.  J Clin Oncol. 2006;  24 2065-2072
  • 78 Wieckowska A, McCullough A J, Feldstein A E. Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and future.  Hepatology. 2007;  46 582-589
  • 79 Wieckowska A, Zein N N, Yerian L M. et al . In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease.  Hepatology. 2006;  44 27-33
  • 80 Younossi Z M, Jarrar M, Nugent C. et al . A Novel Diagnostic Biomarker Panel for Obesity-related Nonalcoholic Steatohepatitis (NASH).  Obes Surg. 2008;  18 1430-1437
  • 81 Zivkovic A M, German J B, Sanyal A J. Comparative review of diets for the metabolic syndrome: implications for nonalcoholic fatty liver disease.  Am J Clin Nutr. 2007;  86 285-300

Prof. Dr. Andrea Tannapfel

Institut für Pathologie, Ruhr-Universität Bochum

Bürkle-de-la-Camp Platz 1

44789 Bochum

Phone: ++ 49/2 34/3 02 48 00

Fax: ++ 49/2 34/3 02 48 09

Email: andrea.tannapfel@rub.de

    >