Hepatic steatosis and steatohepatitis: Are they really two distinct entities?

Current Hepatitis Reports

Volumn 13, Issue 2, 2014, Pages 151-158

  Fielding, Cory M ^a   Angulo, Paul ^a  

^a UNIVERSITY OF KENTUCKY   (United States)

Author keywords

Cirrhosis; Hepatitis; Hepatocellular; Insulin resistance; Liver; NAFLD; NASH; Non alcoholic fatty liver disease; Non alcoholic steatohepatitis; Obesity; Review; Steatohepatitis; Steatosis; Transplant

Indexed keywords

ALANINE AMINOTRANSFERASE; ALPHA TOCOPHEROL; AMIODARONE; ASPARTATE AMINOTRANSFERASE; GFT 505; METFORMIN; OBETICHOLIC ACID; OMEGA 3 FATTY ACID; PENTOXIFYLLINE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR AGONIST; PIOGLITAZONE; PLACEBO; TETRACYCLINE; UNCLASSIFIED DRUG; VALPROIC ACID;

BLADDER CANCER; CARDIOVASCULAR DISEASE; COMPUTER ASSISTED TOMOGRAPHY; FATTY LIVER; FRACTURE; HEART FAILURE; HEPATITIS; HUMAN; HYPERTRIGLYCERIDEMIA; INCIDENTAL FINDING; LIFESTYLE MODIFICATION; LIVER BIOPSY; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; LIVER FIBROSIS; LIVER TRANSPLANTATION; NONALCOHOLIC FATTY LIVER; NUCLEAR MAGNETIC RESONANCE IMAGING; OSTEOPOROSIS; PATHOPHYSIOLOGY; PROGNOSIS; REVIEW; RISK FACTOR; STEATOHEPATITIS; TOTAL PARENTERAL NUTRITION;

EID: 84905675588     PISSN: 15403416     EISSN: 15410706     Source Type: Journal    
DOI: 10.1007/s11901-014-0227-5     Document Type: Review

References (89)

1. Angulo P. GI epidemiology: nonalcoholic fatty liver disease. Aliment Pharmacol Ther. 2007;25(8):883-9.
2. Kotronen A, Yki-Järvinen H. Fatty liver: a novel component of the metabolic syndrome. Arterioscler Thromb Vasc Biol. 2008;28(1):27-38.
3. 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(6):1387-95. (Pubitemid 39657013)
4. Williams CD, Stengel J, Asike MI, et al. 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(1):124-31.
5. Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011;34(3):274-85.
6. • Charlton MR, Burns JM, Pedersen RA, et al. Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States. Gastroenterology. 2011;14(4):1249-53. This paper showed NASH is on a trajectory to become the most common indication for liver transplantation.
7. Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980;55(7):434-8. (Pubitemid 10057164)
8. Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002;346(16):1221-31.
9. Marchesini G, Marzocchi R. Metabolic syndrome and NASH. Clin Liver Dis. 2007 Feb;11(1):105-17, ix. (Pubitemid 46829976)
10. Loria P, Lonardo A, Anania F. Liver and diabetes. Avicious circle. Hepatol Res. 2013;43(1):51-64.
11. Lottenberg AM, Afonso Mda S, Lavrador MS, Machado RM, Nakandakare ER. The role of dietary fatty acids in the pathology of metabolic syndrome. J Nutr Biochem. 2012;23(9):1027-40.
12. Sevastianova K, Santos A, Kotronen A, et al. Effect of short-term carbohydrate overfeeding and long-term weight loss on liver fat in overweight humans. Am J Clin Nutr. 2012;96(4):727-34.
13. Guglielmi FW, Boggio-Bertinet D, Federico A, et al. Total parenteral nutrition-related gastroenterological complications. Dig Liver Dis. 2006;38(9):623-42. (Pubitemid 44356260)
14. Naini BV, Lassman CR. Total parenteral nutrition therapy and liver injury: a histopathologic study with clinical correlation. Hum Pathol. 2012;43(6):826-33.
15. Anthérieu S, Rogue A, Fromenty B, Guillouzo A, Robin MA. Induction of vesicular steatosis by amiodarone and tetracycline is associated with up-regulation of lipogenic genes in HepaRG cells. Hepatology. 2011;53(6):1895-905.
16. Verrotti A, D'Egidio C, Mohn A, Coppola G, Chiarelli F. Weight gain following treatment with valproic acid: pathogenetic mechanisms and clinical implications. Obes Rev. 2011;12(5):e32-43.
17. Abenavoli L,Milic N, De Lorenzo A, Luzza F. A pathogenetic link between non-alcoholic fatty liver disease and celiac disease. Endocrine. 2013;43(1):65-7.
18. Day CP, James OF. Steatohepatitis: a tale of two "hits"? Gastroenterology. 1998;114(4):842-5.
19. Tilg H, Moschen AR. Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology. 2010;52(5):1836-46.
20. Larter CZ, Chitturi S, Heydet D, Farrell GC. A fresh look at NASH pathogenesis. Part 1: the metabolic movers. J Gastroenterol Hepatol. 2010;25(4):672-90.
21. Ibrahim SH, Kohli R, Gores GJ. Mechanisms of lipotoxicity in NAFLD and clinical implications. J Pediatr Gastroenterol Nutr. 2011;53(2):131-40.
22. Samuel VT, Petersen KF, Shulman GI. Lipid-induced insulin resistance: unravelling the mechanism. Lancet. 2010;375(9733):2267-77.
23. Wong VW, Wong GL, Choi PC, et al. Disease progression of nonalcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years. Gut. 2010;59(7):969-74.
24. Pais R, Charlotte F, Fedchuk L, et al. A systematic review of follow-up biopsies reveals disease progression in patients with non-alcoholic fatty liver. J Hepatol. 2013. doi:10.1016/j.jhep.2013.04.027.
25. 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(1):132-8. (Pubitemid 40038911)
26. Angulo P. Long-termmortality in nonalcoholic fatty liver disease: is liver histology of any prognostic significance? Hepatology. 2010;51(2):373-5.
27. • Yilmaz Y. Review article: is non-alcoholic fatty liver disease a spectrum, or are steatosis and non-alcoholic steatohepatitis distinct conditions? Aliment Pharmacol Ther. 2012;36(9):815-23. Excellent review article defining simple steatosis and NASH as separate pathophysiological entities.
28. Newton JL, Jones DE, Henderson E, et al. Fatigue in nonalcoholic fatty liver disease (NAFLD) is significant and associates with inactivity and excessive daytime sleepiness but not with liver disease severity or insulin resistance. Gut. 2008;57(6):807-13. (Pubitemid 351716975)
29. • Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology. 2012;142(7):1592-609. Practice guidelines providing insight into the diagnosis and management of NAFLD for general practitioners and specialists.
30. Sheth SG, Flamm SL, Gordon FD, Chopra S. AST/ALT ratio predicts cirrhosis in patients with chronic hepatitis C virus infection. Am J Gastroenterol. 1998;93(1):44-8. (Pubitemid 29065511)
31. Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology. 1999;30(6):1356-62.
32. Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45(4):846-54. (Pubitemid 46631552)
33. Musso G, Gambino R, Cassader M, Pagano G. Meta-analysis: natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity. Ann Med. 2011;43(8):617-49.
34. • Kim D, Kim WR, Kim HJ, Therneau TM. Association between noninvasive fibrosis markers and mortality among adults with nonalcoholic fatty liver disease in the United States. Hepatology. 2013;57(4):1357-65. An outstanding analysis of a sample representative of the general United States population determining both the prevalence of advanced fibrosis and the accuracy of the NAFLD fibrosis score in predicting long-term mortality.
35. Treeprasertsuk S, Björnsson E, Enders F, Suwanwalaikorn S, Lindor KD. NAFLD fibrosis score: a prognostic predictor for mortality and liver complications among NAFLD patients. World J Gastroenterol. 2013;19(8):1219-29.
36. •• Angulo P, Bugianesi E, Bjornsson ES, Charatcharoenwitthaya P, Mills PR, Barrera F, et al. Simple noninvasive systems predict longterm outcomens of patients with nonalcoholic fatty liver disease. Gastroenterology. 2013;145(4):782-9. Study demonstrating the high accuracy of the NAFLD fibrosis score in predicting longterm risk to develop liver-related complications and overall mortality in patients with NAFLD.
37. Grattagliano I, Ubaldi E, Napoli L, et al. Utility of noninvasive methods for the characterization of nonalcoholic liver steatosis in the family practice. The "VARES" Italian multicenter study. Ann Hepatol. 2013;12(1):70-7.
38. • Chen J, Zhu Y, Zheng Q, Jiang J. Serum cytokeratin-18 in the diagnosis of non-alcoholic steatohepatitis: A meta-analysis. Hepatol Res. 2013. doi:10.1111/hepr.12197Meta-analysis showing CK-18 fragments are a useful non-invasive way to screen for NASH. ..
39. Grandison GA, Angulo P. Can NASH be diagnosed, graded and staged noninvasively? Clin Liver Dis. 2012;16(3):567-85.
40. .• Castera L, Vilgrain V, Angulo P. Noninvasive evaluation of NAFLD. Nat Rev Gastroenterol Hepatol. 2013;10(11):666-75. An thorough review of the available noninvasive tools to evaluate patients with NAFLD.
41. Kim D, Kim WR, Talwalkar JA, Kim HJ, Ehman RL. Advanced fibrosis in nonalcoholic fatty liver disease: noninvasive assessment with MR elastography. Radiology. 2013;268(2):411-9.
42. Chen J, Talwalkar JA, Yin M, Glaser KJ, Sanderson SO, Ehman RL. Early detection of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease by using MR elastography. Radiology. 2011;259(3):749-56.
43. 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(6):1313-21. (Pubitemid 40770284)
44. Brunt EM, Kleiner DE, Wilson LA, Belt P, Neuschwander-Tetri BA. NASH Clinical Research Network (CRN). Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology. 2011;53(3):810-20.
45. Fukusato T, Fukushima J, Shiga J, et al. Interobserver variation in the histopathological assessment of nonalcoholic steatohepatitis. Hepatol Res. 2005;33(2):122-7. (Pubitemid 41799788)
46. Janiec DJ, Jacobson ER, Freeth A, Spaulding L, Blaszyk H. Histologic variation of grade and stage of non-alcoholic fatty liver disease in liver biopsies. Obes Surg. 2005;15(4):497-501. (Pubitemid 40605072)
47. Ratziu V, Charlotte F, Heurtier A, et al. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology. 2005;128(7):1898-906. (Pubitemid 40824701)
48. Rahimi RS, Landaverde C. Nonalcoholic fatty liver disease and the metabolic syndrome: clinical implications and treatment. Nutr Clin Pract. 2013;28(1):40-51.
49. Hickman IJ, Clouston AD, Macdonald GA, et al. Effect of weight reduction on liver histology and biochemistry in patients with chronic hepatitis C. Gut. 2002;51(1):89-94. (Pubitemid 34717750)
50. 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(5):1072-81. (Pubitemid 40769044)
51. Promrat K, Kleiner DE, Niemeier HM, et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology. 2010;51(1):121-9.
52. Rodriguez B, Torres DM, Harrison SA. Physical activity: an essential component of lifestyle modification in NAFLD. Nat Rev Gastroenterol Hepatol. 2012;9(12):726-31.
53. Hattar LN, Wilson TA, Tabotabo LA, Smith EO, Abrams SH. Physical activity and nutrition attitudes in obese Hispanic children with non-alcoholic steatohepatitis. World J Gastroenterol. 2011;17(39):4396-403.
54. Kistler KD, Brunt EM, Clark JM, et al. Physical activity recommendations, exercise intensity, and histological severity of nonalcoholic fatty liver disease. Am J Gastroenterol. 2011;106(3):460-8. quiz 469.
55. Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med. 2010;363(14):1341-50.
56. Lonardo A, Sookoian S, Chonchol M, Loria P, Targher G. Cardiovascular and Systemic Risk in Nonalcoholic Fatty Liver Disease - Atherosclerosis as a Major Player in the Natural Course of NAFLD. Curr Pharm Des. 2013;19(29):5177-92.
57. Bonora E, Targher G. Increased risk of cardiovascular disease and chronic kidney disease in NAFLD. Nat Rev Gastroenterol Hepatol. 2012;9(7):372-81.
58. Treeprasertsuk S, Leverage S, Adams LA, et al. The Framingham risk score and heart disease in nonalcoholic fatty liver disease. Liver Int. 2012;32(6):945-50.
59. Hallsworth K, Hollingsworth KG, Thoma C, et al. Cardiac structure and function are altered in adults with non-alcoholic fatty liver disease. J Hepatol. 2013;58(4):757-62.
60. Nseir W, Mahamid M. Statins in nonalcoholic fatty liver disease and steatohepatitis: updated review. Curr Atheroscler Rep. 2013;15(3):305.
61. .•• Singh S, Singh PP, Singh AG, Murad MH, Sanchez W. Statins are associated with a reduced risk of hepatocellular cancer: a systematic review and meta-analysis. Gastroenterology. 2013;144(2):323-32. Statin use decreased the likelihood of developing HCC by an adjusted odds ratio of 0.63.
62. Yilmaz Y, Colak Y, Kurt R, Senates E, Eren F. Linking nonalcoholic fatty liver disease to hepatocellular carcinoma: from bedside to bench and back. Tumori. 2013;99(1):10-6.
63. Belfort R, Harrison SA, Brown K, et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med. 2006;355(22):2297-307. (Pubitemid 44837778)
64. Aithal GP, Thomas JA, Kaye PV, et al. Randomized, placebo-controlled trial of pioglitazone in nondiabetic subjects with nonalcoholic steatohepatitis. Gastroenterology. 2008;135(4):1176-84.
65. Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010;362(18):1675-85.
66. Haukeland JW, Konopski Z, Eggesbø HB, et al. Metformin in patients with non-alcoholic fatty liver disease: a randomized, controlled trial. Scand J Gastroenterol. 2009;44(7):853-60.
67. Lavine JE, Schwimmer JB, Van Natta ML, et al. Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. JAMA. 2011;305(16):1659-68.
68. Klein EA, Thompson Jr IM, Tangen CM, et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 2011;306(14):1549-56.
69. Miller 3rd ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005;142:37-46.
70. Zein CO, Yerian LM, Gogate P, Lopez R, Kirwan JP, Feldstein AE, et al. Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo-controlled trial. Hepatology. 2011;54(5):1610-9.
71. Ku CS, Yang Y, Park Y, Lee J. Health benefits of blue-green algae: prevention of cardiovascular disease and nonalcoholic fatty liver disease. J Med Food. 2013;16(2):103-11.
72. Gutiérrez-Grobe Y, Chávez-Tapia N, Sánchez-Valle V, et al. High coffee intake is associated with lower grade nonalcoholic fatty liver disease: the role of peripheral antioxidant activity. Ann Hepatol. 2012;11(3):350-5.
73. Birerdinc A, Stepanova M, Pawloski L, Younossi ZM. Caffeine is protective in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2012;35(1):76-82.
74. Shavakhi A, Minakari M, Firouzian H, et al. Effect of a Probiotic and Metformin on Liver Aminotransferases in Non-alcoholic Steatohepatitis: A Double Blind Randomized Clinical Trial. Int J Prev Med. 2013;4(5):531-7.
75. Dunn W, Sanyal AJ, Brunt EM, et al. Modest alcohol consumption is associated with decreased prevalence of steatohepatitis in patients with non-alcoholic fatty liver disease (NAFLD). J Hepatol. 2012;57(2):384-91.
76. Moriya A, Iwasaki Y, Ohguchi S, et al. Alcohol consumption appears to protect against non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2011;33(3):378-88.
77. Völzke H.Multicausality in fatty liver disease: is there a rationale to distinguish between alcoholic and non-alcoholic origin? World J Gastroenterol. 2012;18(27):3492-501.
78. Zhu L, Baker SS, Gill C, et al. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH. Hepatology. 2013;57(2):601-9.
79. Söderberg C, Stål P, Askling J, et al. Decreased survival of subjects with elevated liver function tests during a 28-year follow-up. Hepatology. 2010;51(2):595-602.
80. Dam-Larsen S, Franzmann M, Andersen IB, et al. Long term prognosis of fatty liver: risk of chronic liver disease and death. Gut. 2004;53(5):750-5. (Pubitemid 38561456)
81. Ekstedt M, Franzén LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006;44(4):865-73. (Pubitemid 46489550)
82. Teli MR, James OF, Burt AD, Bennett MK, Day CP. The natural history of nonalcoholic fatty liver: a follow-up study. Hepatology. 1995;22(6):1714-9.
83. Charatcharoenwitthaya P, Lindor KD, Angulo P. The spontaneous course of liver enzymes and its correlation in nonalcoholic fatty liver disease. Dig Dis Sci. 2012;57(7):1925-31.
84. Merat S, Sotoudehmanesh R, Nouraie M, et al. Sampling error in histopathology findings of nonalcoholic fatty liver disease: a post mortem liver histology study. Arch Iran Med. 2012;15(7):418-21.
85. Ekstedt M, Franzén LE, Mathiesen UL, Kechagias S. Low clinical relevance of the nonalcoholic fatty liver disease activity score (NAS) in predicting fibrosis progression. Scand J Gastroenterol. 2012;47(1):108-15.
86. Bhala N, Angulo P, van der Poorten D, et al. The natural history of nonalcoholic fatty liver disease with advanced fibrosis or cirrhosis: an international collaborative study. Hepatology. 2011;54(4):1208-16.
87. Singal AK, Guturu P, Hmoud B, et al. Evolving frequency and outcomes of liver transplantation based on etiology of liver disease. Transplantation. 2013;95(5):755-60.
88. Agopian VG, Kaldas FM, Hong JC, et al. Liver transplantation for nonalcoholic steatohepatitis: the new epidemic. Ann Surg. 2012;256(4):624-33.
89. .• Dureja P, Mellinger J, Agni R, et al. NAFLD recurrence in liver transplant recipients. Transplantation. 2011;91(6):684-9. NAFLD recurred in 39% of patients after liver transplant, but survival was not affected..