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DOI: 10.1055/s-0029-1245278
© Georg Thieme Verlag KG Stuttgart · New York
Histopathologische Diagnose der nicht alkoholischen und alkoholischen Fettlebererkrankung
Histopathological Diagnose of Non-alcoholic and Alcoholic Fatty Liver DiseasePublication 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.
Schlüsselwörter
nicht alkoholische Steatohepatitis - alkoholische Steatohepatitis - Chemotherapie - kindliche NASH - Ballonierung - Fibrose - Zirrhose - Differenzialdiagnose - Scoring - Leberbiopsie
Key words
non-alcoholic steatohepatitis - alcoholic steatohepatitis - chemotherapy - NASH in children - ballooning - fibrosis - cirrhosis - differential diagnosis - scoring - liver biopsy
Literatur
- 1
Adams L A, Talwalkar J A.
Diagnostic evaluation of nonalcoholic fatty liver disease.
J Clin Gastroenterol.
2006;
40
34-38
MissingFormLabel
- 2
AGA .
American Gastroenterological Association medical position statement: nonalcoholic
fatty liver disease.
Gastroenterology.
2002;
123
1702-1704
MissingFormLabel
- 3
Alfire M E, Treem W R.
Nonalcoholic fatty liver disease.
Pediatr Ann.
2006;
35
290-299
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 6
Angulo P, Lindor K D.
Non-alcoholic fatty liver disease.
J Gastroenterol Hepatol.
2002;
17
S186-S190
MissingFormLabel
- 7
Bacon B R, Farahvash M J, Janney C G. et al .
Nonalcoholic steatohepatitis: an expanded clinical entity.
Gastroenterology.
1994;
107
1103-1109
MissingFormLabel
- 8
Baumann U.
Die kindliche Fettlebererkrankung.
Dtsch Ärzteblatt.
2005;
102
A2634-A2639
MissingFormLabel
- 9
Bellentani S, Bedogni G, Miglioli L. et al .
The epidemiology of fatty liver.
Eur J Gastroenterol Hepatol.
2004;
16
1087-1093
MissingFormLabel
- 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
MissingFormLabel
- 11
Brunt E M.
Nonalcoholic steatohepatitis: definition and pathology.
Semin Liver Dis.
2001;
21
3-16
MissingFormLabel
- 12
Brunt E M.
Alcoholic and nonalcoholic steatohepatitis.
Clin Liver Dis.
2002;
6
399-420
MissingFormLabel
- 13
Brunt E M.
Pathology of fatty liver disease.
Mod Pathol.
2007;
20
S40-S48
(S 01)
MissingFormLabel
- 14
Brunt E M.
Nonalcoholic steatohepatitis: pathologic features and differential diagnosis.
Semin Diagn Pathol.
2005;
22
330-338
MissingFormLabel
- 15
Brunt E M.
Pathology of nonalcoholic steatohepatitis.
Hepatol Res.
2005;
33
68-71
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 19
Brunt E M, Tiniakos D G.
Pathology of steatohepatitis.
Best Pract Res Clin Gastroenterol.
2002;
16
691-707
MissingFormLabel
- 20
Brunt E M, Tiniakos D G.
Pathological features of NASH.
Front Biosci.
2005;
10
1475-1484
MissingFormLabel
- 21
Burt A D, Mutton A, Day C P.
Diagnosis and interpretation of steatosis and steatohepatitis.
Semin Diagn Pathol.
1998;
15
246-258
MissingFormLabel
- 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
MissingFormLabel
- 23
Castera L, Forns X, Alberti A.
Non-invasive evaluation of liver fibrosis using transient elastography.
J Hepatol.
2008;
48
835-847
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 27
Dancygier de H.
Pathogenese und Therapie der nichtalkoholischen Fettlebererkrankungen.
Dtsch Ärzteblatt.
2006;
103
A1301-A1307
MissingFormLabel
- 28
Day C P.
Non-alcoholic fatty liver disease: current concepts and management strategies.
Clin Med.
2006;
6
19-25
MissingFormLabel
- 29
Day C P.
Pathogenesis of steatohepatitis.
Best Pract Res Clin Gastroenterol.
2002;
16
663-678
MissingFormLabel
- 30
Day C P, James O F.
Steatohepatitis: a tale of two ”hits”?.
Gastroenterology.
1998;
114
842-845
MissingFormLabel
- 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
MissingFormLabel
- 32
Dufour J F, Oneta C M.
Alcoholic and non-alcoholic steatohepatitis.
Ther Umsch.
2004;
61
505-512
MissingFormLabel
- 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
MissingFormLabel
- 34
Edmison J, McCullough A J.
Pathogenesis of non-alcoholic steatohepatitis: human data.
Clin Liver Dis.
2007;
11
75-104
MissingFormLabel
- 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
MissingFormLabel
- 36
Farrell G C, Larter C Z.
Nonalcoholic fatty liver disease: from steatosis to cirrhosis.
Hepatology.
2006;
43
S99-S112
MissingFormLabel
- 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
MissingFormLabel
- 38
Gentilucci U V, Santini D, Vincenzi B. et al .
Chemotherapy-induced steatohepatitis in colorectal cancer patients.
J Clin Oncol.
2006;
24
5467-5468
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 43
Kacerovsky M, Roden M.
Nichtalkoholische Fettleber.
Diabetologe.
2007;
3
176-183
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 47
Ludwig J, McGill D B, Lindor K D.
Review: nonalcoholic steatohepatitis.
J Gastroenterol Hepatol.
1997;
12
398-403
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 56
Neuschwander-Tetri B A.
Evolving pathophysiologic concepts in nonalcoholic steatohepatitis.
Curr Gastroenterol Rep.
2002;
4
31-36
MissingFormLabel
- 57
Neuschwander-Tetri B A, Caldwell S H.
Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference.
Hepatology.
2003;
37
1202-1219
MissingFormLabel
- 58
Nocito A, El-Badry A M, Clavien P A.
When is steatosis too much for transplantation?.
J Hepatol.
2006;
45
494-499
MissingFormLabel
- 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
MissingFormLabel
- 60
Oneta C M, Dufour J F.
Diagnostik, Prognose und therapeutische Möglichkeiten der nicht-alkoholischen Fettlebererkrankung.
Schweiz Med Forum.
2003;
37
862-868
MissingFormLabel
- 61
Papandreou D, Rousso I, Mavromichalis I.
Update on non-alcoholic fatty liver disease in children.
Clin Nutr.
2007;
26
409-415
MissingFormLabel
- 62
Rashid M, Roberts E.
Nonalcoholic steatohepatitis in children.
J Pediatr Gastroenterol Nutr.
2000;
30
48-53
MissingFormLabel
- 63
Ratziu V, Charlotte F, Heurtier A. et al .
Sampling variability of liver biopsy in nonalcoholic fatty liver disease.
Gastroenterology.
2005;
128
1898-1906
MissingFormLabel
- 64
Reid A E.
Nonalcoholic steatohepatitis.
Gastroenterology.
2001;
121
710-723
MissingFormLabel
- 65
Roberts E A.
Steatohepatitis in children.
Best Pract Res Clin Gastroenterol.
2002;
16
749-765
MissingFormLabel
- 66
Roberts E A.
Non-alcoholic steatohepatitis in children.
Clin Liver Dis.
2007;
11
155-72
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 70
Schwimmer J B, Behling C, Newbury R. et al .
Histopathology of pediatric nonalcoholic fatty liver disease.
Hepatology.
2005;
42
641-649
MissingFormLabel
- 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
MissingFormLabel
- 72
Strassburg C P, Manns M P.
Approaches to liver biopsy techniques – revisited.
Semin Liver Dis.
2006;
26
318-327
MissingFormLabel
- 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
MissingFormLabel
- 74
Tannapfel A, Reinacher-Schick A.
Chemotherapy associated hepatotoxicity in the treatment of advanced colorectal cancer
(CRC).
Z Gastroenterol.
2008;
46
435-440
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 78
Wieckowska A, McCullough A J, Feldstein A E.
Noninvasive diagnosis and monitoring of nonalcoholic steatohepatitis: present and
future.
Hepatology.
2007;
46
582-589
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
Prof. Dr. Andrea Tannapfel
Institut für Pathologie, Ruhr-Universität Bochum
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