Diagnostic Histopathology
Volume 14, Issue 12 , Pages 586-597 , December 2008

Pathology of fatty liver: differential diagnosis of non-alcoholic fatty liver disease

References 

  1. Panel . Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285:2486–2497
  2. Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40:1387–1395
  3. Weston SR, Leyden W, Murphy R, et al. Racial and ethnic distribution of nonalcoholic fatty liver in persons with newly diagnosed chronic liver disease. Hepatology. 2005;41:372–379
  4. Patton HM, Sirlin C, Behling C, Middleton MS, Schwimmer JB, Lavine JE. Pediatric nonalcoholic fatty liver disease: a critical appraisal of current data and implications for future research. J Pediatr Gastroenterol Nutr. 2006;43:413–427
  5. Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world - a growing challenge. N Engl J Med. 2007;356:213–215
  6. Mandayam S, Jamal MM, Morgan TR. Epidemiology of alcoholic liver disease. Semin Liver Dis. 2004;24:217–232
  7. Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology. 2006;43(2 Suppl 1):S99–S112
  8. 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
  9. Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–1321
  10. 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
  11. Merriman RB, Ferrell LD, Patti MG, et al. Correlation of paired liver biopsies in morbidly obese patients with suspected nonalcoholic fatty liver disease. Hepatology. 2006;44:874–880
  12. Mofrad P, Contos MJ, Haque M, et al. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology. 2003;37:1286–1292
  13. Brunt EM. Grading and staging the histopathological lesions of chronic hepatitis: the Knodell histology activity index and beyond. Hepatology. 2000;31:241–246
  14. Brunt EM. Liver biopsy interpretation for the gastroenterologist. Curr Gastroenterol Rep. 2000;2:27–32
  15. Ishak KG. Chronic hepatitis: morphology and nomenclature. Mod Pathol. 1994;7:690–713
  16. Brunt EM, Ramrakhiani S, Cordes BG, et al. Concurrence of histologic features of steatohepatitis with other forms of chronic liver disease. Mod Pathol. 2003;16:49–56
  17. Sanyal AJ, Contos MJ, Sterling RK, et al. Nonalcoholic fatty liver disease in patients with hepatitis C is associated with features of the metabolic syndrome. Am J Gastroenterol. 2003;98:2064–2071
  18. Levitsky J, Mailliard ME. Diagnosis and therapy of alcoholic liver disease. Semin Liver Dis. 2004;24:233–247
  19. Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980;55:434–438
  20. Chitturi S, Abeygunasekera S, Farrell GC, et al. NASH and insulin resistance: insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology. 2002;35:373–379
  21. Marchesini G, Bugianesi E, Forlani G, et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology. 2003;37:917–923
  22. Burt AD, Mutton A, Day CP. Diagnosis and interpretation of steatosis and steatohepatitis. Semin Diagn Pathol. 1998;15:246–258
  23. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999;116:1413–1419
  24. Younossi ZM, Gramlich T, Liu YC, et al. Nonalcoholic fatty liver disease: assessment of variability in pathologic interpretations. Mod Pathol. 1998;11:560–565
  25. Brunt EM, Neuschwander-Tetri BA, Oliver D, Wehmeier KR, Bacon BR. Nonalcoholic steatohepatitis: histologic features and clinical correlations with 30 blinded biopsy specimens. Hum Pathol. 2004;35:1070–1082
  26. Brunt EM. Nonalcoholic steatohepatitis. Semin Liver Dis. 2004;24:3–20
  27. Hui JM, Sud A, Farrell GC, et al. Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression. [corrected] Gastroenterology. 2003;125:1695–1704
  28. Kashireddy PR, Rao MS. Sex differences in choline-deficient diet-induced steatohepatitis in mice. Exp Biol Med (Maywood). 2004;229:158–162
  29. Svegliati-Baroni G, Candelaresi C, Saccomanno S, et al. A model of insulin resistance and nonalcoholic steatohepatitis in rats: role of peroxisome proliferator-activated receptor-alpha and n-3 polyunsaturated fatty acid treatment on liver injury. Am J Pathol. 2006;169:846–860
  30. Feldstein AE, Canbay A, Angulo P, et al. Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology. 2003;125:437–443
  31. Ramalho RM, Cortez-Pinto H, Castro RE, et al. Apoptosis and Bcl- 2 expression in the livers of patients with steatohepatitis. Eur J Gastroenterol Hepatol. 2006;18:21–29
  32. 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
  33. Younossi ZM, Gorreta F, Ong JP, et al. Hepatic gene expression in patients with obesity-related non-alcoholic steatohepatitis. Liver Int. 2005;25:760–771
  34. Teli MR, Day CP, Burt AD, Bennett MK, James OF. Determinants of progression to cirrhosis or fibrosis in pure alcoholic fatty liver. Lancet. 1995;346:987–990
  35. Fromenty B, Grimbert S, Mansouri A, et al. Hepatic mitochondrial DNA deletion in alcoholics: association with microvesicular steatosis. Gastroenterology. 1995;108:193–200
  36. Pessayre D, Berson A, Fromenty B, Mansouri A. Mitochondria in steatohepatitis. Semin Liver Dis. 2001;21:57–69
  37. Torbenson M, Chen YY, Brunt E, et al. Glycogenic hepatopathy: an underrecognized hepatic complication of diabetes mellitus. Am J Surg Pathol. 2006;30:508–513
  38. Li MK, Crawford JM. The pathology of cholestasis. Semin Liver Dis. 2004;24:21–42
  39. Caldwell SH, Swerdlow RH, Khan EM, et al. Mitochondrial abnormalities in non-alcoholic steatohepatitis. J Hepatol. 1999;31:430–434
  40. Sanyal AJ, Campbell-Sargent C, Mirshahi F, et al. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology. 2001;120:1183–1192
  41. Brunt EM, Kleiner DE, Behling C, Wilson L, Lavine JE, Neuschwander-Tetri BA, et al. Portal inflammation in NAFLD: correlations from the NASH CRN database. Presented, AASLD, 2006. Hepatology. 2006;44:655A
  42. Itoh S, Yougel T, Kawagoe K. Comparison between nonalcoholic steatohepatitis and alcoholic hepatitis. Am J Gastroenterol. 1987;82:650–654
  43. Richardson MM, Jonsson JR, Powell EE, et al. Progressive fibrosis in nonalcoholic steatohepatitis: association with altered regeneration and a ductular reaction. Gastroenterology. 2007;133:80–90
  44. Brunt EM. Alcoholic and nonalcoholic steatohepatitis. Clin Liver Dis. 2002;6:399–420vii
  45. Weltman MD, Farrell GC, Hall P, Ingelman-Sundberg M, Liddle C. Hepatic cytochrome P450 2E1 is increased in patients with nonalcoholic steatohepatitis. Hepatology. 1998;27:128–133
  46. Weltman MD, Farrell GC, Liddle C. Increased hepatocyte CYP2E1 expression in a rat nutritional model of hepatic steatosis with inflammation. Gastroenterology. 1996;111:1645–1653
  47. Pinto HC, Baptista A, Camilo ME, Valente A, Saragoca A, de Moura MC. Nonalcoholic steatohepatitis. Clinicopathological comparison with alcoholic hepatitis in ambulatory and hospitalized patients. Dig Dis Sci. 1996;41:172–179
  48. Thung SNGM. Alcoholic hepatitis vs. nonalcoholic steatohepatitis. In:  Thung SN editors. Differential diagnosis in pathology: liver disorders. New York: Igaku-Shoin; 1995;p. 24–26
  49. Falck-Ytter Y, Younossi ZM, Marchesini G, McCullough AJ. Clinical features and natural history of nonalcoholic steatosis syndromes. Semin Liver Dis. 2001;21:17–26
  50. Schwimmer JB, Behling C, Newbury R, et al. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology. 2005;42:641–649
  51. Yip WW, Burt AD. Alcoholic liver disease. Semin Diagn Pathol. 2006;23:149–160
  52. Goodman ZD, Ishak KG. Histopathology of hepatitis C virus infection. Semin Liver Dis. 1995;15:70–81
  53. Adinolfi LE, Gambardella M, Andreana A, Tripodi MF, Utili R, Ruggiero G. Steatosis accelerates the progression of liver damage of chronic hepatitis C patients and correlates with specific HCV genotype and visceral obesity. Hepatology. 2001;33:1358–1364
  54. Castera L, Hezode C, Roudot-Thoraval F, et al. Worsening of steatosis is an independent factor of fibrosis progression in untreated patients with chronic hepatitis C and paired liver biopsies. Gut. 2003;52:288–292
  55. Monto A, Alonzo J, Watson JJ, Grunfeld C, Wright TL. Steatosis in chronic hepatitis C: relative contributions of obesity, diabetes mellitus, and alcohol. Hepatology. 2002;36:729–736
  56. Moriya K, Yotsuyanagi H, Shintani Y, et al. Hepatitis C virus core protein induces hepatic steatosis in transgenic mice. J Gen Virol. 1997;78:1527–1531
  57. 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
  58. Loria P, Lonardo A, Leonardi F, et al. Non-organ-specific autoantibodies in nonalcoholic fatty liver disease: prevalence and correlates. Dig Dis Sci. 2003;48:2173–2181
  59. McFarlane IG. Autoimmune hepatitis: diagnostic criteria, subclassifications, and clinical features. Clin Liver Dis. 2002;6:605–621
  60. Reid AE. Nonalcoholic steatohepatitis. Gastroenterology. 2001;121:710–723
  61. Bonkovsky HL, Jawaid Q, Tortorelli K, et al. Non-alcoholic steatohepatitis and iron: increased prevalence of mutations of the HFE gene in non-alcoholic steatohepatitis. J Hepatol. 1999;31:421–429
  62. Bugianesi E, Manzini P, D’Antico S, et al. Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver. Hepatology. 2004;39:179–187
  63. Zelber-Sagi S, Nitzan-Kaluski D, Halpern Z, Oren R. NAFLD and hyperinsulinemia are major determinants of serum ferritin levels. J Hepatol. 2007;46:700–707
  64. 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
  65. Franzese A, Vajro P, Argenziano A, et al. Liver involvement in obese children. Ultrasonography and liver enzyme levels at diagnosis and during follow-up in an Italian population. Dig Dis Sci. 1997;42:1428–1432
  66. Mager DR, Roberts EA. Nonalcoholic fatty liver disease in children. Clin Liver Dis. 2006;10:109–131vi-vii
  67. Nobili V, Marcellini M, Devito R, et al. NAFLD in children: a prospective clinical-pathological study and effect of lifestyle advice. Hepatology. 2006;44:458–465
  68. Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999–2002. JAMA. 2004;291:2847–2850
  69. Schwimmer JB, Deutsch R, Rauch JB, Behling C, Newbury R, Lavine JE. Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease. J Pediatr. 2003;143:500–505
  70. Moran JR, Ghishan FK, Halter SA, Greene HL. Steatohepatitis in obese children: a cause of chronic liver dysfunction. Am J Gastroenterol. 1983;78:374–377
  71. Baldridge AD, Perez-Atayde AR, Graeme-Cook F, Higgins L, Lavine JE. Idiopathic steatohepatitis in childhood: a multicenter retrospective study. J Pediatr. 1995;127:700–704
  72. Manton ND, Lipsett J, Moore DJ, Davidson GP, Bourne AJ, Couper RT. Non-alcoholic steatohepatitis in children and adolescents. Med J Aust. 2000;173:476–479
  73. Lindor KD, Kowdley KV, Heathcote EJ, et al. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology. 2004;39:770–778
  74. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002;346:1221–1231
  75. 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
  76. Brunt EM. Nonalcoholic steatohepatitis: pathologic features and differential diagnosis. Semin Diagn Pathol. 2005;22:330–338
  77. Promrat K, Lutchman G, Uwaifo GI, et al. A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology. 2004;39:188–196
  78. Huang MA, Greenson JK, Chao C, et al. One-year intense nutritional counseling results in histological improvement in patients with non-alcoholic steatohepatitis: a pilot study. Am J Gastroenterol. 2005;100:1072–1081
  79. Lutchman G, Modi A, Kleiner DE, et al. The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis. Hepatology. 2007;46:424–429
  80. Dixon JB, Bhathal PS, Hughes NR, O’Brien PE. Nonalcoholic fatty liver disease: improvement in liver histological analysis with weight loss. Hepatology. 2004;39:1647–1654
  81. Brunt EM, Clouston AD. Histologic features of fatty liver disease. In:  Bataller R editors. International hepatology updates: nonalcoholic steatohepatitis. Barcelona: Permanyer Press; 2007;p. 95–110
  82. Leevy CM. Fatty liver: a study of 270 patients with biopsy proven fatty liver and review of the literature. Medicine (Balt). 1962;41:249–276
  83. Galambos JT. Natural history of alcoholic hepatitis. 3. Histological changes. Gastroenterology. 1972;63:1026–1035
  84. Czaja AJ. Recurrence of nonalcoholic steatohepatitis after liver transplantation. Liver Transpl Surg. 1997;3:185–186
  85. Molloy RM, Komorowski R, Varma RR. Recurrent nonalcoholic steatohepatitis and cirrhosis after liver transplantation. Liver Transpl Surg. 1997;3:177–178
  86. Carson K, Washington MK, Treem WR, Clavien PA, Hunt CM. Recurrence of nonalcoholic steatohepatitis in a liver transplant recipient. Liver Transpl Surg. 1997;3:174–176
  87. Kim WR, Poterucha JJ, Porayko MK, Dickson ER, Steers JL, Wiesner RH. Recurrence of nonalcoholic steatohepatitis following liver transplantation. Transplantation. 1996;62:1802–1805
  88. Contos MJ, Cales W, Sterling RK, et al. Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis. Liver Transpl. 2001;7:363–373
  89. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology. 2003;37:1202–1219
  90. Watt KD, McCashland TM. Transplantation in the alcoholic patient. Semin Liver Dis. 2004;24:249–255
  91. Burra P, Mioni D, Cecchetto A, et al. Histological features after liver transplantation in alcoholic cirrhotics. J Hepatol. 2001;34:716–722
  92. Everson G, Bharadhwaj G, House R, et al. Long-term follow-up of patients with alcoholic liver disease who underwent hepatic transplantation. Liver Transpl Surg. 1997;3:263–274
  93. Pageaux GP, Bismuth M, Perney P, et al. Alcohol relapse after liver transplantation for alcoholic liver disease: does it matter?. J Hepatol. 2003;38:629–634
  94. Conjeevaram HS, Hart J, Lissoos TW, et al. Rapidly progressive liver injury and fatal alcoholic hepatitis occurring after liver transplantation in alcoholic patients. Transplantation. 1999;67:1562–1568
  95. Savolainen V, Perola M, Lalu K, Penttila A, Virtanen I, Karhunen PJ. Early perivenular fibrogenesis - precirrhotic lesions among moderate alcohol consumers and chronic alcoholics. J Hepatol. 1995;23:524–531

PII: S1756-2317(08)00167-9

doi: 10.1016/j.mpdhp.2008.09.005

Diagnostic Histopathology
Volume 14, Issue 12 , Pages 586-597 , December 2008