Clinical Aspects of Fatty Liver Disease

ABSTRACT

The global emergence of obesity as an epidemic has made fatty liver disease a public health problem in the Western world. The increased incidence of obesity has been paralleled by an increase in metabolic syndrome in the same cohort of patients. The net consequence of insulin resistance in a large majority of these obese individuals is hepatic steatosis, which over time in a proportion of these patients progresses to steatohepatitis and cirrhosis. Despite the increased awareness among physicians regarding its presence, the diagnostic process has been hampered by the lack of sensitive and specific population-based screening tests. Liver biopsy remains the gold standard for diagnosis as well as for grading and staging of the disease process but its precise role in the diagnostic conundrum continues to be debated.

KEYWORDS

Nonalcoholic fatty liver disease - steatohepatitis - insulin resistance - obesity - alanine aminotransferase - aspartate aminotransferase - metabolic syndrome - cirrhosis - gastric bypass - hepatitis C

REFERENCES

• 1 Marceau P, Biron S, Hould F S et al.. Liver pathology and the metabolic syndrome X in severe obesity.  J Clin Endocrinol Metab. 1999;  84 1513-1517
• 2 Knobler H, Schattner A, Zhornicki T et al.. Fatty liver-an additional and treatable feature of the insulin resistance syndrome.  QJM. 1999;  92 73-79
• 3 Andersen T, Gluud C. Liver morphology in morbid obesity: a literature study.  Int J Obes. 1984;  8 97-106
• 4 Marchesini G, Brizi M, Morselli-Labate A M et al.. Association of nonalcoholic fatty liver disease with insulin resistance.  Am J Med. 1999;  107 450-455
• 5 Flegal K M, Carroll M D, Ogden C L, Johnson C L. Prevalence and trends in obesity among US adults, 1999-2000.  JAMA. 2002;  288 1723-1727
• 6 Wanless I R, Lentz J S. Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors.  Hepatology. 1990;  12 1106-1110
• 7 Foster K J, Griffith A H, Dewbury K, Price C P, Wright R. Liver disease in patients with diabetes mellitus.  Postgrad Med J. 1980;  56 767-772
• 8 Adler M, Schaffner F. Fatty liver hepatitis and cirrhosis in obese patients.  Am J Med. 1979;  67 811-816
• 9 Ludwig J, Viggiano T R, McGill D B, Oh B J. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease.  Mayo Clin Proc. 1980;  55 434-438
• 10 Bacon B R, Farahvash M J, Janney C G, Neuschwander-Tetri B A. Nonalcoholic steatohepatitis: an expanded clinical entity.  Gastroenterology. 1994;  107 1103-1109
• 11 Falck-Ytter Y, Younossi Z M, Marchesini G, McCullough A J. Clinical features and natural history of nonalcoholic steatosis syndromes.  Semin Liver Dis. 2001;  21 17-26
• 12 Brunt E M. Nonalcoholic steatohepatitis: definition and pathology.  Semin Liver Dis. 2001;  21 3-16
• 13 Younossi Z M, Gramlich T, Liu Y C et al.. Nonalcoholic fatty liver disease: assessment of variability in pathologic interpretations.  Mod Pathol. 1998;  11 560-565
• 14 Contos M J, Choudhury J, Mills A S, Sanyal A J. The histologic spectrum of nonalcoholic fatty liver disease.  Clin Liver Dis. 2004;  8 481-500
• 15 Powell E E, Cooksley W G, Hanson R, Searle J, Halliday J W, Powell L W. The natural history of nonalcoholic steatohepatitis: a follow-up study of forty-two patients for up to 21 years.  Hepatology. 1990;  11 74-80
• 16 Loguercio C, De Girolomo V, de Sio I et al.. Non-alcoholic fatty liver disease in an area of southern Italy: main clinical, histological, and pathophysiological aspects.  J Hepatol. 2001;  35 568-574 , Erratum in: J Hepatol. 2002;  36 713
• 17 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
• 18 Neuschwander-Tetri B A, Caldwell S H. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference.  Hepatology. 2003;  37 1202-1219 , Erratum in: Hepatology. 2003;  38 536
• 19 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
• 20 Nomura H, Kashiwagi S, Hayashi J, Kajiyama W, Tani S, Goto M. Prevalence of fatty liver in a general population of Okinawa, Japan.  Jpn J Med. 1988;  27 142-149
• 21 Tazawa Y, Noguchi H, Nishinomiya F, Takada G. Serum alanine aminotransferase activity in obese children.  Acta Paediatr. 1997;  86 238-241
• 22 Underwood Ground K E. Prevalence of fatty liver in healthy male adults accidentally killed.  Aviat Space Environ Med. 1984;  55 59-61
• 23 Oshibuchi M, Nishi F, Sato M, Ohtake H, Okuda K. Frequency of abnormalities detected by abdominal ultrasound among Japanese adults.  J Gastroenterol Hepatol. 1991;  6 165-168
• 24 Yano E, Tagawa K, Yamaoka K, Mori M. Test validity of periodic liver function tests in a population of Japanese male bank employees.  J Clin Epidemiol. 2001;  54 945-951
• 25 Bellentani S, Saccoccio G, Masutti F et al.. Prevalence of and risk factors for hepatic steatosis in Northern Italy.  Ann Intern Med. 2000;  132 112-117
• 26 Shen L, Fan J G, Shao Y et al.. Prevalence of nonalcoholic fatty liver among administrative officers in Shanghai: an epidemiological survey.  World J Gastroenterol. 2003;  9 1106-1110
• 27 Clark J M, Brancati F L, Diehl A M. The prevalence and etiology of elevated aminotransferase levels in the United States.  Am J Gastroenterol. 2003;  98 960-967
• 28 Galambos J T, Wills C E. Relationship between 505 paired liver tests and biopsies in 242 obese patients.  Gastroenterology. 1978;  74 1191-1195
• 29 Nomura F, Ohnishi K, Satomura Y et al.. Liver function in moderate obesity-study in 534 moderately obese subjects among 4613 male company employees.  Int J Obes. 1986;  10 349-354
• 30 Baldridge A D, Perez-Atayde A R, Graeme-Cook F, Higgins L, Lavine J E. Idiopathic steatohepatitis in childhood: a multicenter retrospective study.  J Pediatr. 1995;  127 700-704
• 31 Teli M R, James O F, Burt A D, Bennett M K, Day C P. The natural history of nonalcoholic fatty liver: a follow-up study.  Hepatology. 1995;  22 1714-1719
• 32 Matteoni C A, Younossi Z M, Gramlich T, Boparai N, Liu Y C, McCullough A J. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity.  Gastroenterology. 1999;  116 1413-1419
• 33 Ruhl C E, Everhart J E. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States.  Gastroenterology. 2003;  124 71-79
• 34 Flegal K M, Carroll M D, Kuczmarski R J, Johnson C L. Overweight and obesity in the United States: prevalence and trends, 1960-1994.  Int J Obes Relat Metab Disord. 1998;  22 39-47
• 35 Caldwell S H, Harris D M, Patrie J T, Hespenheide E E. Is NASH underdiagnosed among African Americans?.  Am J Gastroenterol. 2002;  97 1496-1500
• 36 Ruhl C E, Everhart J E. Epidemiology of nonalcoholic fatty liver.  Clin Liver Dis. 2004;  8 501-519
• 37 Struben V M, Hespenheide E E, Caldwell S H. Nonalcoholic steatohepatitis and cryptogenic cirrhosis within kindreds.  Am J Med. 2000;  108 9-13
• 38 Lee J H, Reed D R, Price R A. Familial risk ratios for extreme obesity: implications for mapping human obesity genes.  Int J Obes Relat Metab Disord. 1997;  21 935-940
• 39 Trevisan R, Vedovato M, Tiengo A. The epidemiology of diabetes mellitus.  Nephrol Dial Transplant. 1998;  13(suppl 8) 2-5
• 40 Castellano G, Garfia C, Gomez-Coronado D et al.. Diffuse fatty liver in familial heterozygous hypobetalipoproteinemia.  J Clin Gastroenterol. 1997;  25 379-382
• 41 Ogata H, Akagi K, Baba M et al.. Fatty liver in a case with heterozygous familial hypobetalipoproteinemia.  Am J Gastroenterol. 1997;  92 339-342
• 42 Kagimoto T, Higaki T, Nagata K, Morino Y, Takatsuki K. An interesting syndrome of hemolytic anemia, degeneration of the liver and diabetes associated with a high red cell Mg-ATPase, detected by 31P NMR spectroscopy.  NMR Biomed. 1989;  2 93-97
• 43 Angulo P, Keach J C, Batts K P, Lindor K D. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis.  Hepatology. 1999;  30 1356-1362
• 44 Lyznicki J M, Young D C, Riggs J A, Davis R M. Obesity: assessment and management in primary care.  Am Fam Physician. 2001;  63 2185-2196
• 45 Lakka H M, Laaksonen D E, Lakka T A et al.. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men.  JAMA. 2002;  288 2709-2716
• 46 Pi-Sunyer F X. The obesity epidemic: pathophysiology and consequences of obesity.  Obes Res. 2002;  10(suppl 2) 97S-104S
• 47 George D K, Goldwurm S, MacDonald G A et al.. Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis.  Gastroenterology. 1998;  114 311-318
• 48 Younossi Z M, Gramlich T, Bacon B R et al.. Hepatic iron and nonalcoholic fatty liver disease.  Hepatology. 1999;  30 847-850
• 49 Bonkovsky H L, 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
• 50 Noguchi H, Tazawa Y, Nishinomiya F, Takada G. The relationship between serum transaminase activities and fatty liver in children with simple obesity.  Acta Paediatr Jpn. 1995;  37 621-625
• 51 Charlton M, Sreekumar R, Rasmussen D, Lindor K, Nair K S. Apolipoprotein synthesis in nonalcoholic steatohepatitis.  Hepatology. 2002;  35 898-904
• 52 Clark J M, Brancati F L, Diehl A M. Nonalcoholic fatty liver disease.  Gastroenterology. 2002;  122 1649-1657
• 53 Prati D, Taioli E, Zanella A et al.. Updated definitions of healthy ranges for serum alanine aminotransferase levels.  Ann Intern Med. 2002;  137 1-10
• 54 Garcia-Monzon C, Martin-Perez E, Iacono O L et al.. Characterization of pathogenic and prognostic factors of nonalcoholic steatohepatitis associated with obesity.  J Hepatol. 2000;  33 716-724
• 55 Daniel S, Ben M en, achem T, Vasudevan G, Ma C K, Blumenkehl M. Prospective evaluation of unexplained chronic liver transaminase abnormalities in asymptomatic and symptomatic patients.  Am J Gastroenterol. 1999;  94 3010-3014
• 56 Skelly M M, James P D, Ryder S D. Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology.  J Hepatol. 2001;  35 195-199
• 57 Lee R G. Nonalcoholic steatohepatitis: a study of 49 patients.  Hum Pathol. 1989;  20 594-598
• 58 Diehl A M, Goodman Z, Ishak K G. Alcohollike liver disease in nonalcoholics. A clinical and histologic comparison with alcohol-induced liver injury.  Gastroenterology. 1988;  95 1056-1062
• 59 Tajiri K, Takenawa H, Yamaoka K, Yamane M, Marumo F, Sato C. Nonalcoholic steatohepatitis masquerading as autoimmune hepatitis.  J Clin Gastroenterol. 1997;  25 538-540
• 60 Saadeh S, Younossi Z M, Remer E M et al.. The utility of radiological imaging in nonalcoholic fatty liver disease.  Gastroenterology. 2002;  123 745-750
• 61 Yajima Y, Ohta K, Narui T, Abe R, Suzuki H, Ohtsuki M. Ultrasonographical diagnosis of fatty liver: significance of the liver-kidney contrast.  Tohoku J Exp Med. 1983;  139 43-50
• 62 Saverymuttu S H, Joseph A E, Maxwell J D. Ultrasound scanning in the detection of hepatic fibrosis and steatosis.  Br Med J (Clin Res Ed). 1986;  292 13-15
• 63 Mathiesen U L, Franzen L E, Aselius H et al.. Increased liver echogenicity at ultrasound examination reflects degree of steatosis but not of fibrosis in asymptomatic patients with mild/moderate abnormalities of liver transaminases.  Dig Liver Dis. 2002;  34 516-522
• 64 Mendler M H, Bouillet P, Le Sidaner A et al.. Dual-energy CT in the diagnosis and quantification of fatty liver: limited clinical value in comparison to ultrasound scan and single-energy CT, with special reference to iron overload.  J Hepatol. 1998;  28 785-794
• 65 Bydder G M, Chapman R W, Harry D, Bassan L, Sherlock S, Kreel L. Computed tomography attenuation values in fatty liver.  J Comput Tomogr. 1981;  5 33-35
• 66 Piekarski J, Goldberg H I, Royal S A, Axel L, Moss A A. Difference between liver and spleen CT numbers in the normal adult: its usefulness in predicting the presence of diffuse liver disease.  Radiology. 1980;  137 727-729
• 67 Ducommun J C, Goldberg H I, Korobkin M, Moss A A, Kressel H Y. The relation of liver fat to computed tomography numbers: a preliminary experimental study in rabbits.  Radiology. 1979;  130 511-513
• 68 Galambos J T. Natural history of alcoholic hepatitis 3. Histological changes.  Gastroenterology. 1972;  63 1026-1035
• 69 Jacobs J E, Birnbaum B A, Shapiro M A et al.. Diagnostic criteria for fatty infiltration of the liver on contrast-enhanced helical CT.  AJR Am J Roentgenol. 1998;  171 659-664
• 70 Johnston R J, Stamm E R, Lewin J M, Hendrick R E, Archer P G. Diagnosis of fatty infiltration of the liver on contrast enhanced CT: limitations of liver-minus-spleen attenuation difference measurements.  Abdom Imaging. 1998;  23 409-415
• 71 Outwater E K, Blasbalg R, Siegelman E S, Vala M. Detection of lipid in abdominal tissues with opposed-phase gradient-echo images at 1. 5 T: techniques and diagnostic importance.  Radiographics. 1998;  18 1465-1480
• 72 Longo R, Pollesello P, Ricci C et al.. Proton MR spectroscopy in quantitative in vivo determination of fat content in human liver steatosis.  J Magn Reson Imaging. 1995;  5 281-285
• 73 Sorbi D, McGill D B, Thistle J L, Therneau T M, Henry J, Lindor K D. An assessment of the role of liver biopsies in asymptomatic patients with chronic liver test abnormalities.  Am J Gastroenterol. 2000;  95 3206-3210
• 74 Reid A L, Webb G R, Hennrikus D, Fahey P P, Sanson-Fisher R W. Detection of patients with high alcohol intake by general practitioners.  Br Med J (Clin Res Ed). 1986;  293 735-737
• 75 Lewis K O, Paton A. ABC of alcohol: tools of detection.  Br Med J (Clin Res Ed). 1981;  283 1531-1532
• 76 Salaspuro M. Use of enzymes for the diagnosis of alcohol-related organ damage.  Enzyme. 1987;  37 87-107
• 77 Nalpas B, Vassault A, Le Guillou A et al.. Serum activity of mitochondrial aspartate aminotransferase: a sensitive marker of alcoholism with or without alcoholic hepatitis.  Hepatology. 1984;  4 893-896
• 78 Nalpas B, Vassault A, Charpin S, Lacour B, Berthelot P. Serum mitochondrial aspartate aminotransferase as a marker of chronic alcoholism: diagnostic value and interpretation in a liver unit.  Hepatology. 1986;  6 608-614
• 79 Storey E L, Anderson G J, Mack U, Powell L W, Halliday J W. Desialylated transferrin as a serological marker of chronic excessive alcohol ingestion.  Lancet. 1987;  1 1292-1294
• 80 Contos M J, Cales W, Sterling R K et al.. Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis.  Liver Transpl. 2001;  7 363-373
• 81 Drenick E J, Fisler J, Johnson D. Hepatic steatosis after intestinal bypass-prevention and reversal by metronidazole, irrespective of protein-calorie malnutrition.  Gastroenterology. 1982;  82 535-548
• 82 Drenick E J, Simmons F, Murphy J F. Effect on hepatic morphology of treatment of obesity by fasting, reducing diets and small-bowel bypass.  N Engl J Med. 1970;  282 829-834
• 83 Luyckx F H, Desaive C, Thiry A et al.. Liver abnormalities in severely obese subjects: effect of drastic weight loss after gastroplasty.  Int J Obes Relat Metab Disord. 1998;  22 222-226
• 84 Dixon J B, Bhathal P S, O'Brien P E. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese.  Gastroenterology. 2001;  121 91-100
• 85 Caldwell S H, Oelsner D H, Iezzoni J C, Hespenheide E E, Battle E H, Driscoll C J. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease.  Hepatology. 1999;  29 664-669
• 86 Poonawala A, Nair S P, Thuluvath P J. Prevalence of obesity and diabetes in patients with cryptogenic cirrhosis: a case-control study.  Hepatology. 2000;  32 689-692
• 87 Hui J M, Kench J G, Chitturi S et al.. Long-term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C.  Hepatology. 2003;  38 420-427
• 88 Hilden M, Juhl E, Thomsen A C, Christoffersen P. Fatty liver persisting for up to 33 years. A follow-up of the inversen-roholm liver biopsy material.  Acta Med Scand. 1973;  194 485-489
• 89 Itoh S, Yougel T, Kawagoe K. Comparison between nonalcoholic steatohepatitis and alcoholic hepatitis.  Am J Gastroenterol. 1987;  82 650-654
• 90 Propst A, Propst T, Zangerl G, Ofner D, Judmaier G, Vogel W. Prognosis and life expectancy in chronic liver disease.  Dig Dis Sci. 1995;  40 1805-1815
• 91 Poynard T, Ratziu V, McHutchison J et al.. Effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis in patients infected with hepatitis C.  Hepatology. 2003;  38 75-85
• 92 Bressler B L, Guindi M, Tomlinson G, Heathcote J. High body mass index is an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C.  Hepatology. 2003;  38 639-644
• 93 Rubbia-Brandt L, Quadri R, Abid K et al.. Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3.  J Hepatol. 2000;  33 106-115
• 94 Moriya K, Yotsuyanagi H, Shintani Y et al.. Hepatitis C virus core protein induces hepatic steatosis in transgenic mice.  J Gen Virol. 1997;  78(Pt 7) 1527-1531
• 95 Fujie H, Yotsuyanagi H, Moriya K et al.. Steatosis and intrahepatic hepatitis C virus in chronic hepatitis.  J Med Virol. 1999;  59 141-145
• 96 Shintani Y, Fujie H, Miyoshi H et al.. Hepatitis C virus infection and diabetes: direct involvement of the virus in the development of insulin resistance.  Gastroenterology. 2004;  126 840-848
• 97 Serfaty L, Andreani T, Giral P, Carbonell N, Chazouilleres O, Poupon R. Hepatitis C virus induced hypobetalipoproteinemia: a possible mechanism for steatosis in chronic hepatitis C.  J Hepatol. 2001;  34 428-434
• 98 Fernandez-Miranda C, Castellano G, Guijarro C et al.. Lipoprotein changes in patients with chronic hepatitis C treated with interferon-alpha.  Am J Gastroenterol. 1998;  93 1901-1904
• 99 Wyatt J, Baker H, Prasad P, Gong Y Y, Millson C. Steatosis and fibrosis in patients with chronic hepatitis C.  J Clin Pathol. 2004;  57 402-406
• 100 Hui J M, Sud A, Farrell G C et al.. Insulin resistance is associated with chronic hepatitis C virus infection and fibrosis progression.  Gastroenterology. 2003;  125 1695-1704
• 101 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
• 102 McCaughan G W. Recurrence of nonalcoholic steatohepatitis (NASH) post-liver transplantation.  Liver Transpl Surg. 1997;  3 683
• 103 Molloy R M, Komorowski R, Varma R R. Recurrent nonalcoholic steatohepatitis and cirrhosis after liver transplantation.  Liver Transpl Surg. 1997;  3 177-178
• 104 Carson K, Washington M K, Treem W R, Clavien P A, Hunt C M. Recurrence of nonalcoholic steatohepatitis in a liver transplant recipient.  Liver Transpl Surg. 1997;  3 174-176
• 105 Kim W R, Poterucha J J, Porayko M K, Dickson E R, Steers J L, Wiesner R H. Recurrence of nonalcoholic steatohepatitis following liver transplantation.  Transplantation. 1996;  62 1802-1805
• 106 D'Souza-Gburek S M, Batts K P, Nikias G A, Wiesner R H, Krom R A. Liver transplantation for jejunoileal bypass-associated cirrhosis: allograft histology in the setting of an intact bypassed limb.  Liver Transpl Surg. 1997;  3 23-27
• 107 Andersen T, Christoffersen P, Gluud C. The liver in consecutive patients with morbid obesity: a clinical, morphological, and biochemical study.  Int J Obes. 1984;  8 107-115
• 108 Kern W H, Payne J H, Dewind L T. Hepatic changes after small-intestinal bypass for morbid obesity.  Am J Clin Pathol. 1974;  61 763-768
• 109 White J J, Moxley RT I II, Pozefsky T, Lockwood D H. Transient kwaskiorkor: a cause of fatty liver following small bowel bypass.  Surgery. 1974;  75 829-840
• 110 Halloran L G, Hutcher N E, Levinson S A, Schatzki P F, Hume D M. Morphology of the liver before and after intestinal bypass for morbid obesity.  Surg Forum. 1974;  25 359-361
• 111 Marubbio Jr A T, Buchwald H, Schwartz M Z, Varco R. Hepatic lesions of central pericellular fibrosis in morbid obesity, and after jejunoileal bypass.  Am J Clin Pathol. 1976;  66 684-691
• 112 Baddeley R M. Results of jejuno-ileostomy for gross refractory obesity.  Br J Surg. 1976;  63 801-806
• 113 Salmon P A, Reedyk L. Fatty metamorphosis in patients with jejunoileal bypass.  Surg Gynecol Obstet. 1975;  141 75-84
• 114 Griffen Jr W O, Young V L, Stevenson C C. A prospective comparison of gastric and jejunoileal bypass procedures for morbid obesity.  Ann Surg. 1977;  186 500-509
• 115 Buckwalter J A. Clinical trial of jejunoileal and gastric bypass for the treatment of morbid obesity: four-year progress report.  Am Surg. 1980;  46 377-381
• 116 Ogden C L, Troiano R P, Briefel R R, Kuczmarski R J, Flegal K M, Johnson C L. Prevalence of overweight among preschool children in the United States, 1971 through 1994.  Pediatrics. 1997;  99 E1
• 117 Tominaga K, Kurata J H, Chen Y K et al.. Prevalence of fatty liver in Japanese children and relationship to obesity. An epidemiological ultrasonographic survey.  Dig Dis Sci. 1995;  40 2002-2009
• 118 Rashid M, Roberts E A. Nonalcoholic steatohepatitis in children.  J Pediatr Gastroenterol Nutr. 2000;  30 48-53
• 119 Sanyal A J. AGA technical review on nonalcoholic fatty liver disease.  Gastroenterology. 2002;  123 1705-1725
• 120 Silverman E M, Sapala J A, Appelman H D. Regression of hepatic steatosis in morbidly obese persons after gastric bypass.  Am J Clin Pathol. 1995;  104 23-31
• 121 Ranlov I, Hardt F. Regression of liver steatosis following gastroplasty or gastric bypass for morbid obesity.  Digestion. 1990;  47 208-214
• 122 Pinto H C, Baptista A, Camilo M E, Valente A, Saragoca A, de Moura M C. Nonalcoholic steatohepatitis. Clinicopathological comparison with alcoholic hepatitis in ambulatory and hospitalized patients.  Dig Dis Sci. 1996;  41 172-179
• 123 Laurin J, Lindor K D, Crippin J S et al.. Ursodeoxycholic acid or clofibrate in the treatment of non-alcohol-induced steatohepatitis: a pilot study.  Hepatology. 1996;  23 1464-1467