Semin Liver Dis 2008; 28(4): 380-385
DOI: 10.1055/s-0028-1091982
© Thieme Medical Publishers

Hepatic, Cardiovascular, and Endocrine Outcomes of the Histological Subphenotypes of Nonalcoholic Fatty Liver Disease

Eitan Rubinstein1 , Joel E. Lavine1 , Jeffrey B. Schwimmer1
  • 1Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California, San Diego; and the Department of Gastroenterology, Rady Children's Hospital, San Diego, California
Further Information

Publication History

Publication Date:
27 October 2008 (online)

ABSTRACT

This review covers the diagnosis and outcomes of histological subphenotypes of nonalcoholic fatty liver disease (NAFLD) including nonalcoholic steatohepatitis (NASH) in both children and adults. Serious outcomes of NAFLD include cirrhosis, hepatocellular carcinoma, coronary heart disease, and diabetes. The ability to determine differential outcomes by NAFLD subtypes is dependent upon both the adequate assessment of histological subtypes, as well as the appropriate measure of the outcome of interest. Steatohepatitis, which can only be diagnosed by liver biopsy, has a greater risk for both hepatic and systemic complications than simple steatosis. Differences in subphenotypes between children and adults and among children have only recently been described. Careful future attention should be given to determine their influence on clinical outcomes. Enhanced understanding of the epidemiology of NAFLD subphenotypes may help organize collaborative efforts between hepatologists, pathologists, cardiologists, endocrinologists, and primary care physicians to develop clinical management protocols.

REFERENCES

  • 1 Ludwig J, Viggiano T R, McGill D B, Oh B J. Nonalcoholic steatohepatitis: Mayo Clinic experience with a hitherto unnamed disease.  Mayo Clin Proc. 1980;  55(7) 434-438
  • 2 Sanyal A J. AGA technical review on nonalcoholic fatty liver disease.  Gastroenterology. 2002;  123(5) 1705-1725
  • 3 Matteoni C A, Younossi Z M, Gramlich T, Boparai N, Chang Liu Y, McCullough A J. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity.  Gastroenterology. 1999;  116(6) 1413-1419
  • 4 Brunt E M, Janney C G, Di Bisceglie A M, Neuschwander-Tetri B A, Bacon B R. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesion.  Am J Gastroenterol. 1999;  94(9) 2467-2474
  • 5 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(5) 700-704
  • 6 Rashid M, Roberts E A. Nonalcoholic steatohepatitis in children.  J Pediatr Gastroenterol Nutr. 2000;  30(1) 48-53
  • 7 Schwimmer J B, Deutsch R, Rauch J B, Behling C, Newbury R, Lavine J E. Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease.  J Pediatr. 2003;  143 500-505
  • 8 Schwimmer J B, Behling C, Newbury R et al.. Histopathology of pediatric nonalcoholic fatty liver disease.  Hepatology. 2005;  42 641-649
  • 9 Manco M, Bedogni G, Marcellini M et al.. Waist circumference correlates with liver fibrosis in children with non alcoholic steatohepatitis.  Gut. 2008;  , April 28 (Epub ahead of print)
  • 10 Nobili V, Marcellini M, Devito R et al.. NAFLD in children: a prospective clinical-pathological study and effect of lifestyle advice.  Hepatology. 2006;  44(2) 458-465
  • 11 Kleiner D E, Brunt E M, Van Natta M et al.. Design and validation of a histological scoring system for nonalcoholic fatty liver disease.  Hepatology. 2005;  41(6) 1313-1321
  • 12 Harrison S A, Torgerson S, Hayashi P H. The natural history of nonalcoholic fatty liver disease: a clinical histopathological study.  Am J Gastroenterol. 2003;  98(9) 2042-2047
  • 13 Lindor K D, Kowdley K V, Heathcote E J et al.. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial.  Hepatology. 2004;  39(3) 770-778
  • 14 Ratziu V, Charlotte F, Heurtier A et al.. Sampling variability of liver biopsy in nonalcoholic fatty liver disease.  Gastroenterology. 2005;  128 1898-1906
  • 15 Dam-Larsen S, Franzmann M, Andersen I B et al.. Long term prognosis of fatty liver: risk of chronic liver disease and death.  Gut. 2004;  53(5) 750-755
  • 16 Ratziu V, Giral P, Charlotte F et al.. Liver fibrosis in overweight patients.  Gastroenterology. 2000;  118(6) 1117-1123
  • 17 Ekstedt M, Franzen L E, Mathiesen U L et al.. Long-term follow-up of patients with NAFLD and elevated liver enzymes.  Hepatology. 2006;  44(4) 865-873
  • 18 Angulo P, Keach J C, Batts K P, Lindor K D. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis.  Hepatology. 1999;  30(6) 1356-1362
  • 19 Abrams G A, Kunde S S, Lazenby A J, Clements R H. Portal fibrosis and hepatic steatosis in morbidly obese subjects: a spectrum of nonalcoholic fatty liver disease.  Hepatology. 2004;  40(2) 475-483
  • 20 Kinugasa A, Tsunamoto K, Furukawa N, Sawada T, Kusunoki T, Shimada N. Fatty liver and its fibrous changes found in simple obesity of children.  J Pediatr Gastroenterol Nutr. 1984;  3(3) 408-414
  • 21 Marrero J A, Fontana R J, Su G L, Conjeevaram H S, Emick D M, Lok A S. NAFLD may be a common underlying liver disease in patients with hepatocellular carcinoma in the United States.  Hepatology. 2002;  36 1349-1354
  • 22 Bugianesi E. Non-alcoholic steatohepatitis and cancer.  Clin Liver Dis. 2007;  11 191-207
  • 23 Hashizume H, Sato K, Takagi H et al.. Primary liver cancers with nonalcoholic steatohepatitis.  Eur J Gastroenterol Hepatol. 2007;  19 827-834
  • 24 Regimbeau J M, Colombat M, Mognol P et al.. Obesity and diabetes as a risk factor for hepatocellular carcinoma.  Liver Transpl. 2004;  10 S69-S73
  • 25 Cuadrado A, Orive A, Garcia-Suarez C et al.. Non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma.  Obes Surg. 2005;  15 442-446
  • 26 Sanyal A J, Banas C, Sargeant C et al.. Similarities and differences in outcomes of cirrhosis due to nonalcoholic steatohepatitis and hepatitis C.  Hepatology. 2006;  43 682-689
  • 27 Zen Y, Katayanagi K, Tsuneyama K, Harada K, Araki I, Nakanuma Y. Hepatocellular carcinoma arising in non-alcoholic steatohepatitis.  Pathol Int. 2001;  51 127-131
  • 28 Bullock R E, Zaitoun A M, Aithal G P, Ryder S D, Beckingham I J, Lobo D N. Association of non-alcoholic steatohepatitis without significant fibrosis with hepatocellular carcinoma.  J Hepatol. 2004;  41 685-686
  • 29 Adams L A, Lymp J F, St. Sauver J et al.. The natural history of nonalcoholic fatty liver disease: a population based cohort study.  Gastroenterology. 2005;  129(1) 113-121
  • 30 Braegger C. NASH remains without a treatment … URSO they say.  J Pediatr Gastroenterol Nutr. 2004;  39(3) 305-306
  • 31 Molleston J P, White F, Teckman J, Fitzgerald J F. Obese children with steatohepatitis can develop cirrhosis in childhood.  Am J Gastroenterol. 2002;  97(9) 2460-2462
  • 32 Evans H M, Shaikh M G, McKiernan P J et al.. Acute fatty liver disease after suprasellar tumor resection.  J Pediatr Gastroenterol Nutr. 2004;  39(3) 288-291
  • 33 Adams L A, Feldstein A, Lindor K D, Angulo P. Nonalcoholic fatty liver disease among patients with hypothalamic and pituitary dysfunction.  Hepatology. 2004;  39(4) 909-914
  • 34 Jankowska I, Socha P, Pawlowska J et al.. Recurrence of non-alcoholic steatohepatitis after liver transplant in a 13-yr-old boy.  Pediatr Transplant. 2007;  11 796-798
  • 35 Jonas M M, Krawczuk L E, Kim H B, Lillehei C, Perez-Atayde A. Rapid recurrence of nonalcoholic fatty liver disease after transplantation in a child with hypopituitarism and hepatopulmonary syndrome.  Liver Transpl. 2005;  11 108-110
  • 36 Marchesini G, Bugianesi E, Forlani G et al.. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome.  Hepatology. 2003;  37(4) 917-923
  • 37 Targher G, Bertolini L, Padovani R, Rodella S, Arcaro G, Day C. Differences and similarities in early atherosclerosis between patients with non-alcoholic steatohepatitis and chronic hepatitis B and C.  J Hepatol. 2007;  46 1126-1132
  • 38 Aygun C, Kocaman O, Sahin T et al.. Evaluation of metabolic syndrome frequency and carotid artery intima-media thickness as risk factors for atherosclerosis in patients with nonalcoholic fatty liver disease.  Dig Dis Sci. 2008;  53(5) 1352-1357
  • 39 Targher G, Bertolini L, Poli F et al.. Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients.  Diabetes. 2005;  54(12) 3541-3546
  • 40 Kotronen A, Yki-Jarvinen H. Fatty liver: a novel component of the metabolic syndrome.  Arterioscler Thromb Vasc Biol. 2008;  28(1) 27-38
  • 41 Araya A V, Valera J M, Contreras J et al.. Alteraciones de la tolerancia a la glucose y frecuencia de syndrome metabolico en pacientes con enfermedad por higado graso no alcoholico.  Rev Med Chil. 2006;  134 1092-1098
  • 42 De Piano A, Prado W L, Caranti D A et al.. Metabolic and nutritional profile of obese adolescents with nonalcoholic fatty liver disease.  J Pediatr Gastroenterol Nutr. 2007;  44(4) 446-452
  • 43 Marchesini G, Brizi M, Bianchi G et al.. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome.  Diabetes. 2001;  50 1844-1850
  • 44 Fan J G, Li F, Cai X B, Peng Y D, Ao Q H, Gao Y. Effects of nonalcoholic fatty liver disease on the development of metabolic disorders.  J Gastroenterol Hepatol. 2007;  22(7) 1086-1091
  • 45 Friis-Liby I, Aldenborg F, Jerlstad P, Rundstrom K, Bjornsson E. High prevalence of metabolic complications in patients with non-alcoholic fatty liver disease.  Scand J Gastroenterol. 2004;  39(9) 864-869
  • 46 Targher G, Bertolini L, Rodella S et al.. Non-alcoholic fatty liver disease is independently associated with an increased prevalence of chronic kidney disease and proliferative/laser-treated retinopathy in type 2 diabetic patients.  Diabetologia. 2008;  51(3) 444-450
  • 47 Schwimmer J B, Deutsch R, Kahen T, Lavine J E, Stanley C, Behling C. Prevalence of fatty liver in children and adolescents.  Pediatrics. 2006;  118 1388-1393

Jeffrey B SchwimmerM.D. 

Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California

San Diego, 200 West Arbor Drive, San Diego, CA 92103-8450

Email: jschwimmer@ucsd.edu