Nonalcoholic fatty liver disease: What the pathologist can tell the clinician

Digestive Diseases

Volumn 30, Issue SUPPL. 1, 2012, Pages 61-68

  Brunt, Elizabeth M ^a  

^a WASHINGTON UNIVERSITY   (United States)

Author keywords

Ballooning; Fibrosis; Histopathology; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis

Indexed keywords

IRON;

APOPTOSIS; ARTICLE; DISEASE COURSE; END STAGE LIVER DISEASE; FATTY LIVER; HEPATITIS; HUMAN; HYPERFERRITINEMIA; INFLAMMATORY CELL; KUPFFER CELL; LABORATORY TEST; LIPOGRANULOMA; LIVER BIOPSY; LIVER CELL CARCINOMA; LIVER CELL DAMAGE; LIVER FIBROSIS; LIVER GRAFT; LIVER HISTOLOGY; LIVER INJURY; METABOLIC SYNDROME X; NATURAL KILLER T CELL; NONALCOHOLIC FATTY LIVER; PATHOLOGIST; PREVALENCE; PRIORITY JOURNAL; RETICULOENDOTHELIAL SYSTEM; SCREENING; STEATOSIS; STEM CELL; VIRUS HEPATITIS;

BIOLOGICAL MARKERS; FATTY LIVER; GENETIC PREDISPOSITION TO DISEASE; HUMANS; LIVER; LIVER CIRRHOSIS; PATHOLOGY, CLINICAL;

EID: 84867714394     PISSN: 02572753     EISSN: 14219875     Source Type: Journal    
DOI: 10.1159/000341127     Document Type: Article

References (99)

1. Gaidos JKJ, Hillner BE, Sanyal AJ: A decision analysis study of the value of a liver biopsy in nonalcoholic steatohepatitis. Liver Int 2008; 28: 650-658. (Pubitemid 351541097)
2. Brunt EM, Neuschwander-Tetri BA, Burt AD: Fatty liver disease: Alcoholic and nonalcoholic; in Burt AD, Portmann B, Ferrell L (eds): MacSween's Pathology of the Liver, ed 6. Philadelphia, Churchill Livingstone, 2011, pp 293-361.
3. Neuschwander-Tetri BA, Clark JM, Bass NM, van Natta ML, Unalp-Arida A, Tonascia J, Zein CO, Brunt EM, Kleiner DE, Mc-Cullough AJ, Sanyal AJ, Diehl AM, Lavine JE, Chalasani N, Kowdley KV, NASH Clinical Research Network: Clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease. Hepatology 2010; 52: 913-924.
4. Fracanzani AL, Valenti L, Bugianesi E, Andreoletti M, Colli A, Vanni E, Bertelli C, Fatta E, Bignamini D, Marchesini G, Fargion S: Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: A role for insulin resistance and diabetes. Hepatology 2008; 48: 792-798.
5. Shalhub S, Parsee A, Gallagher SF, Haines KL, Willkomm C, Brantley SG, Pinkas H, Saff-Koche L, Murr MM: The importance of routine liver biopsy in diagnosing nonalcoholic steatohepatitis in bariatric patients. Obes Surg 2004; 14: 54-59. (Pubitemid 38130716)
6. Mofrad P, Contos MJ, Haque M, Sargeant C, Fisher RA, Luketic VA, Sterling RK, Shiffman ML, Stravitz RT, Sanyal AJ: Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology 2003; 37: 1286-1292. (Pubitemid 36667307)
7. Cotler SJ, Kanji K, Keshavarzian A, Jensen DM, Jakate S: Prevalence and significance of autoantibodies in patients with non-alcoholic steatohepatitis. J Clin Gastroenterol 2004; 38: 801-804. (Pubitemid 39274184)
8. Loria P, Carulli L, Lonardo A: The prevalence of autoantibodies and autoimmune hepatitis in patients with nonalcoholic fatty liver disease. Am J Gastroenterol 2005; 100: 1200-1201. (Pubitemid 40769063)
9. Adams LA, Lindor KD, Angulo P: The prevalence of autoantibodies and autoimmune hepatitis in patients with nonalcoholic fatty liver disease. Am J Gastroenterol 2004; 99: 1316-1320. (Pubitemid 39062269)
10. Vuppalanchi R, Gould RJ, Wilson LA, Unalp-Arida A, Cummings OW, Chalasani N, Kowdley KV, Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN): Clinical significance of serum autoantibodies in patients with NAFLD: Results from the nonalcoholic steatohepatitis clinical research network. Hepatol Int 2011, E-pub ahead of print.
11. Kowdley KV, Belt P, Wilson LA, Yeh MM, Neuschwander-Tetri BA, Chalasani N, Sanyal AJ, Nelson JE, for the NASH Clinical Research Network: Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease. Hepatology 2012; 55: 77-85.
12. Skelly MM, James PD, Ryder SD: Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology. J Hepatol 2001; 35: 195-199. (Pubitemid 32803474)
13. Teixeira A, Bellodi-Privato M, Carvalheira J, Pilla V, Pareja J, D'Albuquerque L: The incapacity of the surgeon to identify NASH in bariatric surgery makes biopsy mandatory. Obes Surg 2009; 19: 1678-1684.
14. Bedossa P, Moucari R, Chelbi E, Asselah T, Paradis V, Vidaud M, Cazals-Hatem D, Boyer N, Valla D, Marcellin P: Evidence for a role of nonalcoholic steatohepatitis in hepatitis C: A prospective study. Hepatology 2007; 46: 380-387. (Pubitemid 47344772)
15. Ong JP, Younossi ZM, Speer C, Olano A, Gramlich T, Boparai N: Chronic hepatitis C and superimposed nonalcoholic fatty liver disease. Liver 2001; 21: 266-271. (Pubitemid 32677383)
16. Sanyal AJ, Contos MJ, Sterling RK, Luketic VA, Shiffman ML, Stravitz RT, Mills AS: Nonalcoholic fatty liver disease in patients with hepatitis C is associated with features of the metabolic syndrome. Am J Gastroenterol 2003; 98: 2064-2071. (Pubitemid 37185807)
17. Brunt EM, Ramrakhiani S, Cordes BG, Neuschwander-Tetri BA, Janney CG, Bacon BR, Di Bisceglie AM: Concurrence of histologic features of steatohepatitis with other forms of chronic liver disease. Mod Pathol 2003; 16: 49-56. (Pubitemid 36152686)
18. Weston SR, Leyden W, Murphy R, Bass NM, Bell BP, Manos MM, Terrault NA: Racial and ethnic distribution of nonalcoholic fatty liver in persons with newly diagnosed chronic liver disease. Hepatology 2005; 41: 372-379. (Pubitemid 40165382)
19. Charlton M, Kasparova P, Weston S, Lindor K, Maor-Kendler Y, Wiesner RH, Rosen CB, Batts KP: Frequency of nonalcoholic steatohepatitis as a cause of advanced liver disease. Liver Transpl 2001; 7: 608-614. (Pubitemid 32677885)
20. Kallwitz ER, Guzman G, TenCate V, Vitello J, Layden-Almer J, Berkes J, Patel R, Layden TJ, Cotler SJ: The histologic spectrum of liver disease in African-American, non-Hispanic White and Hispanic obesity surgery patients. Am J Gastroenterol 2009; 104: 64-69.
21. Mohanty SR, Troy TN, Huo D, O'Brien BL, Jensen DM, Hart J: Influence of ethnicity on histological differences in nonalcoholic fatty liver disease. J Hepatol 2009; 50: 797-804.
22. Giday SA, Shiny Z, Naab T, Smoot D, Banks A: Frequency of nonalcoholic fatty liver disease and degree of hepatic steatosis in African-American patients. J Natl Med Assoc 2006; 98: 1613-1615. (Pubitemid 44682953)
23. 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. (Pubitemid 46393782)
24. Williams CD, Stengel J, Asike MI, Torres DM, Shaw J, Contreras M, Landt CL, Harrison SA: Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: A prospective study. Gastroenterology 2011; 140: 124-131.
25. Fassio E, Alvarez E, Dominguez N, Landeira G, Longo C: Natural history of nonalcoholic steatohepatitis: A longitudinal study of repeat liver biopsies. Hepatology 2004; 40: 820-826. (Pubitemid 39288114)
26. Adams LA, Sanderson S, Lindor KD, Angulo P: The histological course of nonalcoholic fatty liver disease: A longitudinal study of 103 patients with sequential liver biopsies. J Hepatol 2005; 42: 132-138. (Pubitemid 40038911)
27. Ekstedt M, Franzen LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, Kechagias S: Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006; 44: 865-873. (Pubitemid 46489550)
28. Pais R, Pascale A, Fedchuck L, Charlotte F, Poynard T, Ratziu V: Progression from isolated steatosis to steatohepatitis and fibrosis in nonalcoholic fatty liver disease. Clin Res Hepatol Gastroenterol 2011; 35: 23-28.
29. Dam-Larsen S, Becker U, Franzmann MB, Larsen K, Christoffersen P, Bendtsen F: Final results of a long-term, clinical follow-up in fatty liver patients. Scand J Gastroenterol 2009; 44: 1236-1243.
30. Feldstein AE, Charatcharoenwitthaya P, Treeprasertsuk S, Benson JT, Enders FB, Angulo P: The natural history of non-alcoholic fatty liver disease in children: A follow-up study for up to 20 years. Gut 2009; 58: 1538-1544.
31. Marchesini G, Marzocchi R, Agostini F, Bugianesi E: Nonalcoholic fatty liver disease and the metabolic syndrome. Curr Opin Lipidol 2005; 16: 421-427. (Pubitemid 41017626)
32. Schwimmer JB, Pardee PE, Lavine JE, Blumkin AK, Cook S: Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease. Circulation 2008; 118: 277-283.
33. Hossain N, Afendy A, Stepanova M, Nader F, Srishord M, Rafiq N, Goodman Z, Younossi Z: Independent predictors of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol 2009; 7: 1224-1229.e2.
34. Sanyal AJ, Brunt EM, Kleiner DE, Kowdley KV, Chalasani N, Lavine JE, Ratziu V, Mc-Cullough A: Endpoints and clinical trial design for nonalcoholic steatohepatitis. Hepatology 2011; 54: 344-353.
35. Brunt EM: Nonalcoholic steatohepatitis. Semin Liver Dis 2004; 24: 3-20. (Pubitemid 38496045)
36. Boursier J, Chaigneau J, Roullier V, Lainé F, Sandrini J, Michalak S, Hubert I, Dib N, Oberti F, Bertrais S, Hunault G, Deugnier Y, Rousselet MC, Cavaro-Ménard C, Gallois Y, Aubé C, Calès P, Study Group UNAMMETABOL: Steatosis degree, measured by morphometry, is linked to other liver lesions and metabolic syndrome components in patients with NAFLD. Eur J Gastroenterol Hepatol 2011; 23: 974-981.
37. Lackner C, Gogg-Kammerer 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.
38. Guy CD, Suzuki A, Burchette JL, Brunt EM, Abdelmalek MF, Cardona D, McCall SJ, Unalp A, Belt P, Ferrell LD, Diehl AM, Nonalcoholic Steatohepatitis Clinical Research Network: Costaining for keratins 8/18 plus ubiquitin improves detection of hepatocyte injury in nonalcoholic fatty liver disease. Hum Pathol 2012; 43: 790-800.
39. Caldwell S, Ikura Y, Dias D, Isomoto K, Yabu A, Moskaluk C, Pramoonjago P, Simmons W, Scruggs H, Rosenbaum N, Wilkinson T, Toms P, Argo CK, Al-Osaimi AM, Redick JA: Hepatocellular ballooning in NASH. J Hepatol 2010; 53: 719-723.
40. Tandra S, Yeh MM, Brunt EM, Vuppalanchi R, Cummings OW, Unalp-Arida A, Wilson LA, Chalasani N, NASH Clinical Research Network (NASH CRN): Presence and significance of microvesicular steatosis in nonalcoholic fatty liver disease. J Hepatol 2011; 55: 654-659.
41. Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Oliver D, Bacon BR: Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone. Hepatology 2003; 38: 1008-1017. (Pubitemid 37221684)
42. Marceau P, Biron S, Hould FS, Marceau S, Simard S, Thung SN, Kral JG: Liver pathology and the metabolic syndrome X in severe obesity. J Clin Endocrinol Metab 1999; 84: 1513-1517. (Pubitemid 30644245)
43. Promrat K, Lutchman G, Uwaifo GI, Freedman RJ, Soza A, Heller T, Doo E, Ghany M, Premkumar A, Park Y, Liang TJ, Yanovski JA, Kleiner DE, Hoofnagle JH: A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology 2004; 39: 188-196. (Pubitemid 38461481)
44. Brunt EM, Kleiner DE, Wilson LA, Unalp A, Behling CE, Lavine JE, Neuschwander-Tetri BA, NASH Clinical Research Network: 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.
45. 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.
46. Alisi A, Bedogni G, De Vito R, Comparcola D, Manco M, Nobili V: Relationship between portal chronic inflammation and disease severity in paediatric non-alcoholic fatty liver disease. Dig Liver Dis 2011; 43: 143-146.
47. Syn W-K, Oo YH, Pereira TA, Karaca GF, Jung Y, Omenetti A, Witek RP, Choi SS, Guy CD, Fearing CM, Teaberry V, Pereira FE, Adams DH, Diehl AM: Accumulation of natural killer T cells in progressive nonalcoholic fatty liver disease. Hepatology 2010; 51: 1998-2007.
48. Lefkowitch JH, Haythe J, Regent N: Kupffer cell aggregation and perivenular distribution in steatohepatitis. Mod Pathol 2002; 15: 699-704. (Pubitemid 34787304)
49. Itoh S, Yougel T, Kawagoe K: Comparison between nonalcoholic steatohepatitis and alcoholic hepatitis. Am J Gastroenterol 1987; 82: 650-654. (Pubitemid 17095826)
50. Yip WW, Burt AD: Alcoholic liver disease. Semin Diagn Pathol 2006; 23: 149-160. (Pubitemid 46176510)
51. Clouston AD, Powell EE: Interaction of nonalcoholic fatty liver disease with other liver diseases. Best Pract Res Clin Gastroenterol 2002; 16: 767-781.
52. Wieckowska A, Zein NN, Yerian LM, Lopez AR, McCullough AJ, Feldstein AE: In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease. Hepatology 2006; 44: 27-33. (Pubitemid 44049136)
53. Feldstein AE, Gores GJ: Apoptosis in alcoholic and nonalcoholic steatohepatitis. Front Biosci 2005; 10: 3093-3099. (Pubitemid 40910547)
54. Feldstein AE, Canbay A, Angulo P, Taniai M, Burgart LJ, Lindor KD, Gores GJ: Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology 2003; 125: 437-443. (Pubitemid 36929425)
55. Turlin B, Mendler MH, Moirand R, Guyader D, Guillygomarc'h A, Deugnier Y: Histologic features of the liver in insulin resistanceassociated iron overload. A study of 139 patients. Am J Clin Pathol 2001; 116: 263-270. (Pubitemid 33044332)
56. 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. (Pubitemid 29420675)
57. Yamauchi N, Itoh Y, Tanaka Y, Mizokami M, Minami M, Morita A, Toyama T, Yamaguchi K, Fujii H, Okanoue T: Clinical characteristics and prevalence of GB virus C, SEN virus, and HFE gene mutation in Japanese patients with nonalcoholic steatohepatitis. J Gastroenterol 2004; 39: 654-660. (Pubitemid 39149353)
58. 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.
59. Valenti L, Canavesi E, Galmozzi E, Dongiovanni P, Rametta R, Maggioni P, Maggioni M, Fracanzani AL, Fargion S: Beta-globin mutations are associated with parenchymal siderosis and fibrosis in patients with nonalcoholic fatty liver disease. J Hepatol 2010; 53: 927-933.
60. Valenti L, Swinkels DW, Burdick L, Dongiovanni P, Tjalsma H, Motta BM, Bertelli C, Fatta E, Bignamini D, Rametta R, Fargion S, Francanzani AL: Serum ferritin levels are associated with vascular damage in patients with nonalcoholic fatty liver disease. Nutr Metab Cardiovasc Dis 2011; 21: 568-575.
61. Sharp PA: New insights into the role of iron in the development of nonalcoholic fatty liver disease. Hepatology 2010; 52: 408-410.
62. Valenti L, Dongiovanni P, Piperno A, Fracanzani AL, Maggioni M, Rametta R, Loria P, Casiraghi MA, Suigo E, Ceriani R, Remondini E, Trombini P, Fargion S: Alpha 1-antitrypsin mutations in NAFLD: High prevalence and association with altered iron metabolism but not with liver damage. Hepatology 2006; 44: 857-864. (Pubitemid 46489549)
63. Bhattacharya R, Kowdley KV: Iron and HFE mutations in nonalcoholic steatohepatitis: Innocent bystanders or accessories to the crime? Gastroenterology 2003; 125: 615-616.
64. Deguti MM, Sipahi AM, Gayotto LCC, Palácios SA, Bittencourt PL, Goldberg AC, Laudanna AA, Carrilho FJ, Cançado EL: Lack of evidence for the pathogenic role of iron and HFE mutations in Brazilian patients with nonalcoholic steatohepatitis. Braz J Med Biol Res 2003; 36: 739-745. (Pubitemid 36874725)
65. Chitturi S, George J: Interaction of iron, insulin resistance, and nonalcoholic steatohepatitis. Curr Gastroenterol Rep 2003; 5: 18-25. (Pubitemid 38899267)
66. Chitturi S, Weltman M, Farrell GC, McDonald D, Kench J, Liddle C, Samarasinghe D, Lin R, Abeygunasekera S, George J: HFE mutations, hepatic iron, and fibrosis: Ethnicspecific association of NASH with C282Y but not with fibrotic severity. Hepatology 2002; 36: 142-149. (Pubitemid 34700771)
67. Fargion S, Mattioli M, Fracanzani AL, Sampietro M, Tavazzi D, Fociani P, Tajoli E, Valenti L, Fiorelli G: Hyperferritinemia, iron overload and multiple metabolic alterations identify patients at risk for nonalcoholic steatohepatitis. Am J Gastroenterol 2001; 96: 2448-2455. (Pubitemid 32769210)
68. Moirand R, Mendler MH, Guillygomarc'h A, Brissot P, Deugnier Y: Non-alcoholic steatohepatitis with iron: Part of insulin resistance-associated hepatic iron overload? J Hepatol 2000; 33: 1024-1026.
69. Blendis L, Oren R, Halpern Z: NASH: Can we iron out the pathogenesis? Gastroenterology 2000; 118: 981-983.
70. Ferrannini E: Insulin resistance, iron, and the liver. Lancet 2000; 355: 2181-2182. (Pubitemid 30394321)
71. Bonkovsky HL, Jawaid Q, Tortorelli K, LeClair P, Cobb J, Lambrecht RW, Banner BF: Non-alcoholic steatohepatitis and iron: Increased prevalence of mutations of the HFE gene in non-alcoholic steatohepatitis. J Hepatol 1999; 31: 421-429. (Pubitemid 29408723)
72. Fargion S: Dysmetabolic iron overload syndrome. Haematologica 1999; 84: 97-98. (Pubitemid 29479651)
73. Mendler MH, Turlin B, Moirand R, Jouanolle AM, Sapey T, Guyader D, LeGall JY, Brissot P, David V, Beugnier Y: Insulin resistance-associated hepatic iron overload. Gastroenterology 1999; 117: 1155-1163. (Pubitemid 29512675)
74. Younossi ZM, Gramlich T, Bacon BR, Matteoni CA, Boparai N, O'Neill R, McCullough AJ: Hepatic iron and nonalcoholic fatty liver disease. Hepatology 1999; 30: 847-850. (Pubitemid 29458269)
75. George DK, Goldwurm S, MacDonald GA, Cowley LL, Walker NI, Ward PJ, Jazwinski EC, Powell LW: Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis. Gastroenterology 1998; 114: 311-318. (Pubitemid 28093538)
76. Pietrangelo A: Iron in NASH, chronic liver diseases and HCC: How much iron is too much? J Hepatol 2009; 50: 249-251.
77. 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.
78. Roskams T, Yang SQ, Koteish A, Durnez A, DeVos R, Huang X, Achten R, Verslype C, Diehl AM: Oxidative stress and oval cell accumulation in mice and humans with alcoholic and nonalcoholic fatty liver disease. Am J Pathol 2003; 163: 1301-1311. (Pubitemid 37175079)
79. Richardson MM, Jonsson JR, Powell EE, Brunt EM, Neuschwander-Tetri BA, Bhatal PS, Dixon JB, Weltman MD, Tilg H, Moschen AR, Purdie DM, Demetris AJ, Clouston AD: Progressive fibrosis in non-alcoholic steatohepatitis -altered regeneration and the ductular reaction. Gastroenterology 2007; 133: 80-90. (Pubitemid 47031146)
80. Syn WK, Jung Y, Omenetti A, Abdelmalek M, Guy CD, Yang L, Wang J, Witek RP, Fearing CM, Pereira TA, Teaberry V, Choi SS, Vancells JC, Karaca G, Diehl AM: Hedgehog-mediated epithelial-to-mesenchymal transition and fibrogenic repair in nonalcoholic fatty liver disease. Gastroenterology 2009; 137: 1478-1488.e8.
81. Jung Y, Diehl AM: Non-alcoholic steatohepatitis pathogenesis: Role of repair in regulating the disease progression. Dig Dis 2010; 28: 225-228.
82. Jung Y, Witek RP, Syn WK, Choi SS, Omenetti A, Premont R, Guy CD, Diehl AM: Signals from dying hepatocytes trigger growth of liver progenitors. Gut 2010; 59: 655-665.
83. Chiba M, Sasaki M, Kitamura S, Ikeda H, Sato Y, Nakanuma Y: Participation of bile ductular cells in the pathological progression of non-alcoholic fatty liver disease. J Clin Pathol 2011; 64: 564-570.
84. 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.
85. Washington K, Wright K, Shyr Y, Hunter EB, Olson S, Raiford DS: Hepatic stellate cell activation in nonalcoholic steatohepatitis and fatty liver. Hum Pathol 2000; 31: 822-828. (Pubitemid 30480453)
86. Abrams GA, Kunde SS, Lazenby AJ, Clements RH: Portal fibrosis and hepatic steatosis in morbidly obese subjects: A spectrum of nonalcoholic fatty liver disease. Hepatology 2004; 40: 475-483. (Pubitemid 39062866)
87. 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. (Pubitemid 41233657)
88. Loomba R, Sirlin CB, Schwimmer JB, Lavine JE: Advances in pediatric nonalcoholic fatty liver disease. Hepatology 2009; 50: 1282-1293.
89. Alisi A, Manco M, Vania A, Nobili V: Pediatric nonalcoholic fatty liver disease in 2009. J Pediatr 2009; 155: 469-474.
90. Mencin AA, Lavine JE: Nonalcoholic fatty liver disease in children. Curr Opin Clin Nutr Metab Care 2011; 14: 151-157.
91. Rashid M, Roberts EA: Nonalcoholic steatohepatitis in children. J Pediatr Gastroenterol Nutr 2000; 30: 48-53. (Pubitemid 30349945)
92. Nobili V, Marcellini M, Devito R, et al: NAFLD in children: A prospective clinicalpathological study and effect of lifestyle advice. Hepatology 2006; 44: 458-465. (Pubitemid 44214885)
93. 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: Nonalcoholic steatohepatitis in children: A multicenter clinicopathological study. Hepatology 2009; 50: 1113-1120.
94. 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.
95. Brunt EM, Kleiner DE, Wilson LA, Belt P, Neuschwander-Tetri BA, NASH Clinical Research Network (CRN): The NAS and the histopatholoic diagnosis of NASH: Distinct clinicopathologic meanings. Hepatology 2011; 53: 810-820.
96. Kleiner DE, Brunt EM, van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu Y-C, 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. (Pubitemid 40770284)
97. Adams LA, George J, Bugianesi E, Rossi E, DeBoer WB, van der Poorten D, Ching HLI, Bulsara M, Jeffrey GP: Complex noninvasive fibrosis models are more accurate than simple models in non-alcoholic fatty liver disease. J Gastroenterol Hepatol 2011; 26: 1536-1543.
98. Anstee QM, McPherson S, Day CP: How big a problem is non-alcoholic fatty liver disease? BMJ 2011; 343:d3897.
99. McPherson S, Stewart SF, Henderson E, Burt AD, Day CP: Simple noninvasive scoring systems can exclude advanced fibrosis in patients with nonalcoholic fatty liver disease. Gut 2010; 59: 1259-1265.