Histopathology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

World Journal of Gastroenterology

Volumn 20, Issue 42, 2014, Pages 15539-15548

  Takahashi, Yoshihisa ^a   Fukusato, Toshio ^a  

^a TEIKYO UNIVERSITY   (Japan)

Author keywords

Histopathology; Interobserver variation; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Pediatric

Indexed keywords

IRON;

ACIDOPHILE; ARTICLE; CELL VACUOLE; DIAGNOSTIC PROCEDURE; DIFFERENTIAL DIAGNOSIS; DISEASE CLASSIFICATION; EOSINOPHIL; GLYCOGENATED NUCLEUS; GOLD STANDARD; HEPATITIS; HISTOLOGY; HISTOPATHOLOGY; HUMAN; LIPOGRANULOMA; LIVER BIOPSY; LIVER CELL DAMAGE; LIVER FIBROSIS; MEGAMITOCHONDRIA; NONALCOHOLIC FATTY LIVER; PEDIATRICS; STEATOSIS; ALCOHOLIC FATTY LIVER; ANIMAL; BIOPSY; CARCINOMA, HEPATOCELLULAR; DISEASE COURSE; LIVER; LIVER NEOPLASMS; NON-ALCOHOLIC FATTY LIVER DISEASE; OBSERVER VARIATION; PATHOLOGY; PREDICTIVE VALUE; PROGNOSIS; REPRODUCIBILITY; SEVERITY OF ILLNESS INDEX;

ANIMALS; BIOPSY; CARCINOMA, HEPATOCELLULAR; DIAGNOSIS, DIFFERENTIAL; DISEASE PROGRESSION; FATTY LIVER, ALCOHOLIC; HUMANS; LIVER; LIVER NEOPLASMS; NON-ALCOHOLIC FATTY LIVER DISEASE; OBSERVER VARIATION; PREDICTIVE VALUE OF TESTS; PROGNOSIS; REPRODUCIBILITY OF RESULTS; SEVERITY OF ILLNESS INDEX;

EID: 84912138352     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v20.i42.15539     Document Type: Article

References (65)

1. Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, Natale S, Vanni E, Villanova N, Melchionda N, Rizzetto M. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003; 37: 917-923 [PMID: 12668987 DOI: 10.1053/jhep.2003.50161]
2. Abdelmalek MF, Diehl AM. Nonalcoholic fatty liver disease as a complication of insulin resistance. Med Clin North Am 2007; 91: 1125-1149, ix [PMID: 17964913]
3. Neuschwander-Tetri BA. Fatty liver and the metabolic syndrome. Curr Opin Gastroenterol 2007; 23: 193-198 [PMID: 17268250 DOI: 10.1097/MOG.0b013e32801421a9]
4. Takahashi Y, Fukusato T. Pediatric nonalcoholic fatty liver disease: Overview with emphasis on histology. World J Gastroenterol 2010; 16: 5280-5285 [PMID: 21072890 DOI: 10.3748/wjg.v16.i42.5280]
5. Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: From steatosis to cirrhosis. Hepatology 2006; 43: S99-S112 [PMID: 16447287 DOI: 10.1002/hep.20973]
6. Cohen JC, Horton JD, Hobbs HH. Human fatty liver disease: Old questions and new insights. Science 2011; 332: 1519-1523 [PMID: 21700865 DOI: 10.1126/science.1204265]
7. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: Summary of an AASLD Single Topic Conference. Hepatology 2003; 37: 1202-1219 [PMID: 12717402 DOI: 10.1053/jhep.2003.50193]
8. Brunt EM, Tiniakos DG. Alcoholic and non-alcoholic fatty liver disease. In: Odze RD, Goldblum JR, Crawford JM. Pathology of the GI tract, liver, biliary tract and pancreas. Philadelphia: Saunders, 2009: 1087-1114
9. Neuschwander-Tetri BA, Clark JM, Bass NM, Van Natta ML, Unalp-Arida A, Tonascia J, Zein CO, Brunt EM, Kleiner DE, McCullough AJ, Sanyal AJ, Diehl AM, Lavine JE, Chalasani N, Kowdley KV. Clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease. Hepatology 2010; 52: 913-924 [PMID: 20648476 DOI: 10.1002/hep.23784]
10. Sanyal AJ, Brunt EM, Kleiner DE, Kowdley KV, Chalasani N, Lavine JE, Ratziu V, McCullough A. Endpoints and clinical trial design for nonalcoholic steatohepatitis. Hepatology 2011; 54: 344-353 [PMID: 21520200 DOI: 10.1002/hep.24376]
11. Patton HM, Lavine JE, Van Natta ML, Schwimmer JB, Kleiner D, Molleston J. Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis. Gastroenterology 2008; 135: 1961-1971.e2 [PMID: 19013463 DOI: 10.1053/j.gastro.2008.08.050]
12. Schwimmer JB, Behling C, Newbury R, Deutsch R, Nievergelt C, Schork NJ, Lavine JE. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology 2005; 42: 641-649 [PMID: 16116629 DOI: 10.1002/hep.20842]
13. Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: A proposal for grading and staging the histological lesions. Am J Gastroenterol 1999; 94: 2467-2474 [PMID: 10484010 DOI: 10.1111/j.1572-0241.1999.01377.x]
14. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41: 1313-1321 [PMID: 15915461 DOI: 10.1002/hep.20701]
15. Brunt EM, Kleiner DE, Wilson LA, Belt P, Neuschwander-Tetri BA. Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: Distinct clinicopathologic meanings. Hepatology 2011; 53: 810-820 [PMID: 21319198 DOI: 10.1002/hep.24127]
16. Yeh MM, Brunt EM. Pathology of nonalcoholic fatty liver disease. Am J Clin Pathol 2007; 128: 837-847 [PMID: 17951208 DOI: 10.1309/RTPM1PY6YGBL2G2R]
17. Bondini S, Kleiner DE, Goodman ZD, Gramlich T, Younossi ZM. Pathologic assessment of non-alcoholic fatty liver disease. Clin Liver Dis 2007; 11: 17-23, vii [PMID: 17544969 DOI: 10.1016/j.cld.2007.02.002]
18. Tandra S, Yeh MM, Brunt EM, Vuppalanchi R, Cummings OW, Unalp-Arida A, Wilson LA, Chalasani N. Presence and significance of microvesicular steatosis in nonalcoholic fatty liver disease. J Hepatol 2011; 55: 654-659 [PMID: 21172393 DOI: 10.1016/j.jhep.2010.11.021]
19. Chalasani N, Wilson L, Kleiner DE, Cummings OW, Brunt EM, Unalp A; NASH Clinical Research Network. Relationship of steatosis grade and zonal location to histological features of steatohepatitis in adult patients with non-alcoholic fatty liver disease. J Hepatol 2008; 48: 829-834 [PMID: 18321606 DOI: 10.1016/j.jhep.2008.01.016]
20. Brunt EM. Alcoholic and nonalcoholic steatohepatitis. Clin Liver Dis 2002; 6: 399-420, vii [PMID: 12122863]
21. Brunt EM. Nonalcoholic fatty liver disease: What the pathologist can tell the clinician. Dig Dis 2012; 30 Suppl 1: 61-68 [PMID: 23075870 DOI: 10.1159/000341127]
22. Brunt EM, Kleiner DE, Wilson LA, Unalp A, Behling CE, Lavine JE, Neuschwander-Tetri BA. Portal chronic inflammation in nonalcoholic fatty liver disease (NAFLD): A histologic marker of advanced NAFLD-Clinicopathologic correlations from the nonalcoholic steatohepatitis clinical research network. Hepatology 2009; 49: 809-820 [PMID: 19142989 DOI: 10.1002/hep.22724]
23. Rakha EA, Adamson L, Bell E, Neal K, Ryder SD, Kaye PV, Aithal GP. Portal inflammation is associated with advanced histological changes in alcoholic and non-alcoholic fatty liver disease. J Clin Pathol 2010; 63: 790-795 [PMID: 20819880 DOI: 10.1136/jcp.2010.079145]
24. Brunt EM. Pathology of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 2010; 7: 195-203 [PMID: 20195271 DOI: 10.1038/nrgastro.2010.21]
25. Lackner C, Gogg-Kamerer M, Zatloukal K, Stumptner C, Brunt EM, Denk H. Ballooned hepatocytes in steatohepatitis: The value of keratin immunohistochemistry for diagnosis. J Hepatol 2008; 48: 821-828 [PMID: 18329127 DOI: 10.1016/j.jhep.2008.01.026]
26. Skoien R, Richardson MM, Jonsson JR, Powell EE, Brunt EM, Neuschwander-Tetri BA, Bhathal PS, Dixon JB, O'Brien PE, Tilg H, Moschen AR, Baumann U, Brown RM, Couper RT, Manton ND, Ee LC, Weltman M, Clouston AD. Heterogeneity of fibrosis patterns in non-alcoholic fatty liver disease supports the presence of multiple fibrogenic pathways. Liver Int 2013; 33: 624-632 [PMID: 23356584 DOI: 10.1111/liv.12100]
27. Tiniakos DG. Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis: Histological diagnostic criteria and scoring systems. Eur J Gastroenterol Hepatol 2010; 22: 643-650 [PMID: 19478676 DOI: 10.1097/MEG.0b013e32832ca0cb]
28. Argo CK, Northup PG, Al-Osaimi AM, Caldwell SH. Systematic review of risk factors for fibrosis progression in nonalcoholic steatohepatitis. J Hepatol 2009; 51: 371-379 [PMID: 19501928 DOI: 10.1016/j.jhep.2009.03.019]
29. Caldwell SH, Lee VD, Kleiner DE, Al-Osaimi AM, Argo CK, Northup PG, Berg CL. NASH and cryptogenic cirrhosis: A histological analysis. Ann Hepatol 2009; 8: 346-352 [PMID: 20009134]
30. Caldwell SH, Oelsner DH, Iezzoni JC, Hespenheide EE, Battle EH, Driscoll CJ. Cryptogenic cirrhosis: Clinical characterization and risk factors for underlying disease. Hepatology 1999; 29: 664-669 [PMID: 10051466]
31. Poonawala A, Nair SP, Thuluvath PJ. Prevalence of obesity and diabetes in patients with cryptogenic cirrhosis: A casecontrol study. Hepatology 2000; 32: 689-692 [PMID: 11003611]
32. Struben VM, Hespenheide EE, Caldwell SH. Nonalcoholic steatohepatitis and cryptogenic cirrhosis within kindreds. Am J Med 2000; 108: 9-13 [PMID: 11059435 DOI: 10.1016/S0002-9343(99)00315-0]
33. Ong J, Younossi ZM, Reddy V, Price LL, Gramlich T, Mayes J, Boparai N. Cryptogenic cirrhosis and posttransplantation nonalcoholic fatty liver disease. Liver Transpl 2001; 7: 797-801 [PMID: 11552214 DOI: 10.1053/jlts.2001.24644]
34. Brunt EM, Tiniakos DG. Histopathology of nonalcoholic fatty liver disease. World J Gastroenterol 2010; 16: 5286-5296 [PMID: 21072891 DOI: 10.3748/wjg.v16.i42.5286]
35. Pinto HC, Baptista A, Camilo ME, Valente A, Saragoça A, de Moura MC. Nonalcoholic steatohepatitis. Clinicopathological comparison with alcoholic hepatitis in ambulatory and hospitalized patients. Dig Dis Sci 1996; 41: 172-179 [PMID: 8565753]
36. Feldstein AE, Gores GJ. Apoptosis in alcoholic and nonalcoholic steatohepatitis. Front Biosci 2005; 10: 3093-3099 [PMID: 15970563]
37. Zatloukal K, Stumptner C, Fuchsbichler A, Fickert P, Lackner C, Trauner M, Denk H. The keratin cytoskeleton in liver diseases. J Pathol 2004; 204: 367-376 [PMID: 15495250 DOI: 10.1002/path.1649]
38. Zatloukal K, French SW, Stumptner C, Strnad P, Harada M, Toivola DM, Cadrin M, Omary MB. From Mallory to Mallory-Denk bodies: What, how and why? Exp Cell Res 2007; 313: 2033-2049 [PMID: 17531973 DOI: 10.1016/j.yexcr.2007.04.024]
39. Denk H, Stumptner C, Zatloukal K. Mallory bodies revisited. J Hepatol 2000; 32: 689-702 [PMID: 10782920 DOI: 10.1016/S0168-8278(00)80233-0]
40. Brunt EM. Non-alcoholic fatty liver disease: What's new under the microscope? Gut 2011; 60: 1152-1158 [PMID: 21303916 DOI: 10.1136/gut.2010.218214]
41. Valenti L, Fracanzani AL, Bugianesi E, Dongiovanni P, Galmozzi E, Vanni E, Canavesi E, Lattuada E, Roviaro G, Marchesini G, Fargion S. HFE genotype, parenchymal iron accumulation, and liver fibrosis in patients with nonalcoholic fatty liver disease. Gastroenterology 2010; 138: 905-912 [PMID: 19931264 DOI: 10.1053/j.gastro.2009.11.013]
42. Nelson JE, Wilson L, Brunt EM, Yeh MM, Kleiner DE, Unalp-Arida A, Kowdley KV. Relationship between the pattern of hepatic iron deposition and histological severity in nonalcoholic fatty liver disease. Hepatology 2011; 53: 448-457 [PMID: 21274866 DOI: 10.1002/hep.24038]
43. Le TH, Caldwell SH, Redick JA, Sheppard BL, Davis CA, Arseneau KO, Iezzoni JC, Hespenheide EE, Al-Osaimi A, Peterson TC. The zonal distribution of megamitochondria with crystalline inclusions in nonalcoholic steatohepatitis. Hepatology 2004; 39: 1423-1429 [PMID: 15122772 DOI: 10.1002/hep.20202]
44. Richardson MM, Jonsson JR, Powell EE, Brunt EM, Neuschwander-Tetri BA, Bhathal PS, Dixon JB, Weltman MD, Tilg H, Moschen AR, Purdie DM, Demetris AJ, Clouston AD. Progressive fibrosis in nonalcoholic steatohepatitis: Association with altered regeneration and a ductular reaction. Gastroenterology 2007; 133: 80-90 [PMID: 17631134 DOI: 10.1053/j.gastro.2007.05.012]
45. Gill RM, Belt P, Wilson L, Bass NM, Ferrell LD. Centrizonal arteries and microvessels in nonalcoholic steatohepatitis. Am J Surg Pathol 2011; 35: 1400-1404 [PMID: 21836480 DOI: 10.1097/PAS.0b013e3182254283]
46. Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C. Prevalence of fatty liver in children and adolescents. Pediatrics 2006; 118: 1388-1393 [PMID: 17015527 DOI: 10.1542/peds.2006-1212]
47. Park HS, Han JH, Choi KM, Kim SM. Relation between elevated serum alanine aminotransferase and metabolic syndrome in Korean adolescents. Am J Clin Nutr 2005; 82: 1046-1051 [PMID: 16280437]
48. Tominaga K, Kurata JH, Chen YK, Fujimoto E, Miyagawa S, Abe I, Kusano Y. Prevalence of fatty liver in Japanese children and relationship to obesity. An epidemiological ultrasonographic survey. Dig Dis Sci 1995; 40: 2002-2009 [PMID: 7555456]
49. Giorgio V, Prono F, Graziano F, Nobili V. Pediatric non alcoholic fatty liver disease: Old and new concepts on development, progression, metabolic insight and potential treatment targets. BMC Pediatr 2013; 13: 40 [PMID: 23530957 DOI: 10.1186/1471-2431-13-40]
50. Nobili V, Marcellini M, Devito R, Ciampalini P, Piemonte F, Comparcola D, Sartorelli MR, Angulo P. NAFLD in children: A prospective clinical-pathological study and effect of lifestyle advice. Hepatology 2006; 44: 458-465 [PMID: 16871574 DOI: 10.1002/hep.21262]
51. Carter-Kent C, Yerian LM, Brunt EM, Angulo P, Kohli R, Ling SC, Xanthakos SA, Whitington PF, Charatcharoenwitthaya P, Yap J, Lopez R, McCullough AJ, Feldstein AE. Nonalcoholic steatohepatitis in children: A multicenter clinicopathological study. Hepatology 2009; 50: 1113-1120 [PMID: 19637190 DOI: 10.1002/hep.23133]
52. Takahashi Y, Inui A, Fujisawa T, Takikawa H, Fukusato T. Histopathological characteristics of non-alcoholic fatty liver disease in children: Comparison with adult cases. Hepatol Res 2011; 41: 1066-1074 [PMID: 22035383 DOI: 10.1111/j.1872-034X.2011.00855.x]
53. Molleston JP, Schwimmer JB, Yates KP, Murray KF, Cummings OW, Lavine JE, Brunt EM, Scheimann AO, Unalp-Arida A. Histological abnormalities in children with nonalcoholic fatty liver disease and normal or mildly elevated alanine aminotransferase levels. J Pediatr 2014; 164: 707-713. e3 [PMID: 24360992 DOI: 10.1016/j.jpeds.2013.10.071]
54. Nakano M, Fukusato T. Histological study on comparison between NASH and ALD. Hepatol Res 2005; 33: 110-115 [PMID: 16219486]
55. Fukusato T, Fukushima J, Shiga J, Takahashi Y, Nakano T, Maeyama S, Masayuki U, Ohbu M, Matsumoto T, Matsumoto K, Hano H, Sakamoto M, Kondo F, Komatsu A, Ishikawa T, Ohtake H, Takikawa H, Yoshimura K. Interobserver variation in the histopathological assessment of nonalcoholic steatohepatitis. Hepatol Res 2005; 33: 122-127 [PMID: 16890173]
56. Younossi ZM, Gramlich T, Liu YC, Matteoni C, Petrelli M, Goldblum J, Rybicki L, McCullough AJ. Nonalcoholic fatty liver disease: Assessment of variability in pathologic interpretations. Mod Pathol 1998; 11: 560-565 [PMID: 9647594]
57. Ratziu V, Charlotte F, Heurtier A, Gombert S, Giral P, Bruckert E, Grimaldi A, Capron F, Poynard T. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 2005; 128: 1898-1906 [PMID: 15940625 DOI: 10.1053/j.gastro.2005.03.084]
58. Wong VW, Vergniol J, Wong GL, Foucher J, Chan HL, Le Bail B, Choi PC, Kowo M, Chan AW, Merrouche W, Sung JJ, de Lédinghen V. Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology 2010; 51: 454-462 [PMID: 20101745 DOI: 10.1002/hep.23312]
59. Feldstein AE, Wieckowska A, Lopez AR, Liu YC, Zein NN, McCullough AJ. Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: A multicenter validation study. Hepatology 2009; 50: 1072-1078 [PMID: 19585618 DOI: 10.1002/hep.23050]
60. Kamada Y, Fujii H, Fujii H, Sawai Y, Doi Y, Uozumi N, Mizutani K, Akita M, Sato M, Kida S, Kinoshita N, Maruyama N, Yakushijin T, Miyazaki M, Ezaki H, Hiramatsu N, Yoshida Y, Kiso S, Imai Y, Kawada N, Takehara T, Miyoshi E. Serum Mac-2 binding protein levels as a novel diagnostic biomarker for prediction of disease severity and nonalcoholic steatohepatitis. Proteomics Clin Appl 2013; Epub ahead of print [PMID: 23775887 DOI: 10.1002/prca.201200137]
61. Guha IN, Parkes J, Roderick P, Chattopadhyay D, Cross R, Harris S, Kaye P, Burt AD, Ryder SD, Aithal GP, Day CP, Rosenberg WM. Noninvasive markers of fibrosis in nonalcoholic fatty liver disease: Validating the European Liver Fibrosis Panel and exploring simple markers. Hepatology 2008; 47: 455-460 [PMID: 18038452 DOI: 10.1002/hep.21984]
62. Yatsuji S, Hashimoto E, Tobari M, Taniai M, Tokushige K, Shiratori K. Clinical features and outcomes of cirrhosis due to non-alcoholic steatohepatitis compared with cirrhosis caused by chronic hepatitis C. J Gastroenterol Hepatol 2009; 24: 248-254 [PMID: 19032450 DOI: 10.1111/j.1440-1746.2008.05640.x]
63. Salomao M, Yu WM, Brown RS, Emond JC, Lefkowitch JH. Steatohepatitic hepatocellular carcinoma (SH-HCC): A distinctive histological variant of HCC in hepatitis C virusrelated cirrhosis with associated NAFLD/NASH. Am J Surg Pathol 2010; 34: 1630-1636 [PMID: 20975341 DOI: 10.1097/PAS.0b013e3181f31caa]
64. Salomao M, Remotti H, Vaughan R, Siegel AB, Lefkowitch JH, Moreira RK. The steatohepatitic variant of hepatocellular carcinoma and its association with underlying steatohepatitis. Hum Pathol 2012; 43: 737-746 [PMID: 22018903 DOI: 10.1016/j.humpath.2011.07.005]
65. Jain D, Nayak NC, Saigal S. Hepatocellular carcinoma in nonalcoholic fatty liver cirrhosis and alcoholic cirrhosis: Risk factor analysis in liver transplant recipients. Eur J Gastroenterol Hepatol 2012; 24: 840-848 [PMID: 22495397 DOI: 10.1097/MEG.0b013e3283534b40]