Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Visceral adiposity and insulin resistance are independent predictors of the presence of non-cirrhotic NAFLD-related portal hypertension

International Journal of Obesity volume 35, pages 270–278 (2011)Cite this article

Subjects

Abstract

Introduction:

We previously demonstrated in an animal model that steatosis, in the absence of fibrosis, induces a significant rise in portal pressure, indicating substantial changes in liver hemodynamics. As assessment of portal pressure is an invasive procedure, non-invasive parameters are needed to identify patients at risk.

Aims:

To study the portal pressure in nonalcoholic fatty liver disease patients and to identify factors that are possibly related to steatosis-induced changes in liver hemodynamics.

Materials and methods:

Patients presenting with a problem of overweight or obesity, and in whom non-invasive investigations showed signs of liver involvement, were proposed for transjugular hepatic vein catheterization and liver biopsy. The biopsy was scored according to the Nonalcoholic Steatohepatitis Clinical Research Network Scoring System.

Results:

A total of 50 consecutive patients were studied. Their mean age was 47.9±1.8 years; 31 (62%) were female. Hepatic venous pressure gradient was normal in 36 (72%) and elevated in 14 (28%) patients. The degree of steatosis was the only histological parameter that differed significantly between the two groups (P=0.016), and was a predictor of the presence of portal hypertension (PHT) in regression analysis (P=0.010). Comparing normal versus portal hypertensive patients, waist circumference (117±2 versus 128±4 cm, P=0.005), waist–hip ratio (0.96±0.06 versus 1.04±0.03, P=0.003), visceral fat (229±15 versus 292±35 cm2, P=0.022), fasting insulin (15.4±1.7 versus 21.8±2.4 μU ml−1, P=0.032), fasting c-peptide (1.22±0.06 versus 1.49±0.09 nmol l−1, P=0.035) and homeostasis model assessment–insulin resistance (HOMA IR) (3.28±0.29 versus 4.81±0.57, P=0.019) were significantly higher. Age, gender, liver enzymes, ferritin and high-sensitive C-reactive protein were not significantly different. In regression analysis, waist circumference (P=0.008) and HOMA IR (P=0.043) were independent predictors of PHT.

Conclusions:

Estimates of both visceral adiposity and IR are predictors for the presence of PHT, related to the degree of steatosis, and may help in identifying patients who are at risk of developing steatosis-related complications.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Angulo P . Non-alcoholic fatty liver disease. N Engl J Med 2002; 346: 1221–1231.

    Article  CAS  Google Scholar 

  2. Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F, Carucci P et al. Expanding the natural history of non-alcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 2002; 123: 134–143.

    Article  Google Scholar 

  3. Selzner M, Clavien P . Fatty liver in liver transplantation and surgery. Semin Liver Dis 2001; 21: 105–113.

    Article  CAS  Google Scholar 

  4. Behrns K, Tsiotos G, DeSouza N, Krishna M, Ludwig J, Nagorney D . Hepatic steatosis as a potential risk factor for major hepatic resections. J Gastrointest Surg 1998; 2: 292–298.

    Article  CAS  Google Scholar 

  5. Rao M, Papreddy K, Abecassis M, Hashimoto T . Regeneration of liver with marked fatty change following partial hepatectomy in rats. Dig Dis Sci 2001; 46: 1821–1826.

    Article  CAS  Google Scholar 

  6. Selzner M, Rüdiger H, Sindram D, Madden J, Clavien . Mechanisms of ischemic injury are different in the steatotic and normal rat liver. Hepatology 2000; 32: 1281–1288.

    Article  Google Scholar 

  7. Choi S, Diehl AM . Role of inflammation in non-alcoholic steatohepatitis. Curr Opin Gastroenterol 2005; 21: 702–707.

    Article  Google Scholar 

  8. Seifalian A, Chidambaram V, Rolles K, Davidson B . In vivo demonstration of impaired microcirculation in steatotic human liver grafts. Liver Transpl Surg 1998; 4: 71–77.

    Article  CAS  Google Scholar 

  9. McCuskey RS, Ito Y, Robertson GR, McCuskey MK, Perry M, Farrell GC . Hepatic microvascular dysfunction during evolution of dietary steatohepatitis in mice. Hepatology 2004; 40: 386–393.

    Article  Google Scholar 

  10. Francque S, Wamutu S, Chatterjee S, Van Marck E, Herman A, Ramon A et al. Non-alcoholic steatohepatitis induces non-fibrosis related portal hypertension associated with splanchnic vasodilation and signs of a hyperdynamic circulation in vitro and in vivo in a rat model. Liver Int 2010; 30: 365–375.

    Article  CAS  Google Scholar 

  11. Lebrec D, Moreau R . Pathogenesis of portal hypertension. Eur J Gastroenterol Hepatol 2001; 13: 309–311.

    Article  CAS  Google Scholar 

  12. Laleman W, Van Landeghem L, Wilmer A, Fevery J, Nevens F . Portal hypertension: from pathophysiology to clinical practice. Liver Int 2005; 25: 1070–1090.

    Article  Google Scholar 

  13. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and β-cell functioning from fasting glucose and insulin concentrations in men. Diabetology 1985; 28: 412–419.

    Article  CAS  Google Scholar 

  14. van der Kooy K, Seidell JC . Techniques for the measurement of visceral fat: a practical guide. Int J Obes Relat Metab Disord 1993; 17: 187–196.

    CAS  Google Scholar 

  15. Bucombe JR, Hilson AJW . Radionuclide investigations of the liver. Oxford Textbook of Clinical Hepatology, 2nd edn. Oxford University Press: Oxford, UK, 1999. pp 579–588.

    Google Scholar 

  16. Merkel C, Bolognesi M, Bellon S, Bianca S, Honisch B, Lampe H et al. Aminopyrine breath test in the prognostic evaluation of patients with cirrhosis. Gut 1992; 33: 836–842.

    Article  CAS  Google Scholar 

  17. Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R et al. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003; 37: 917–923.

    Article  Google Scholar 

  18. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. 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.

    Article  Google Scholar 

  19. Alberti KG, Zimmet P, Shaw J, IDF Epidemiology Task Force Consensus Group. The metabolic syndrome—a new worldwide definition. Lancet 2005; 366: 1059–1062.

    Article  Google Scholar 

  20. Farrell G, George J, de la M Hall P, McCullough AJ . An introduction to NASH and related fatty liver disorders. Fatty Liver Disease; NASH and related disorders. Blackwell Publishing: USA, 2005; 1–12.

    Google Scholar 

  21. Cosgrove DO . Liver Anatomy. In: Cosgrove D, Meire H, Dewbury K (eds). Abdominal and General Ultrasound vol. 1, 3rd edn. Churchill Livingstone: New York, 1994. pp 227–242.

    Google Scholar 

  22. Bellentani S, Saccoccio G, Masutti F, Croce LS, Brandi G, Sasso F et al. Prevalence of and risk factors for hepatic steatosis in northern Italy. Ann Intern Med 2000; 132: 112–117.

    Article  CAS  Google Scholar 

  23. Dardenne AN . The spleen. In: Cosgrove D, Meire H, Dewbury K (eds). Abdominal and General Ultrasound vol. 1, 3rd edn. Churchill Livingstone: New York, 1994. pp 351–366.

    Google Scholar 

  24. Pratt DS, Kaplan MM . Evaluation of abnormal liver-enzyme results in asymptomatic patients. N Engl J Med 2000; 342: 1266–1271.

    Article  CAS  Google Scholar 

  25. Prati D, Taioli E, Zanella A, Della Torre E, Buttelli S, Del Vecchio E et al. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med 2002; 137: 1–10.

    Article  CAS  Google Scholar 

  26. Joy D, Thava VR, Scott BB . Diagnosis of fatty liver disease: is biopsy necessary? Eur J Gastroenterol Hepatol 2003; 15: 539–543.

    PubMed  Google Scholar 

  27. Kichian K, McLean R, Gramlich LM, Bailey RJ, Bain VG . Nonalcoholic fatty liver disease in patients investigated for elevated liver enzymes. Can J Gastroenterol 2003; 17: 38–42.

    Article  Google Scholar 

  28. Tawalkar JA . Motion—all patients with NASH need to have a liver biopsy: arguments for the motion. Can J Gastroenterol 2002; 16: 718–721.

    Article  Google Scholar 

  29. Campbell MS, Reddy KR . The evolving role of liver biopsy. Aliment Pharmacol Ther 2004; 20: 249–259.

    Article  CAS  Google Scholar 

  30. Kalambokis G, Manousou P, Vibhakorn S, Marelli L, Cholongitas E, Senzolo M et al. Transjugular liver biopsy—indications, adequacy, quality of specimens, and complications—A systematic review. J Hepatology 2007; 47: 284–294.

    Article  Google Scholar 

  31. Lebrec D, Godfarb G, Degott C, Rueff B, Benhamou JP . Transvenous liver biopsy: an experience based on 1000 hepatic tissue samplings with this procedure. Gastroenterology 1982; 83: 338–340.

    CAS  PubMed  Google Scholar 

  32. Groszmann R, Vorobioff JD, Gao H . Measurement of portal pressure: when, how and why to do it. Clin Liver Dis 2006; 10: 499–512.

    Article  Google Scholar 

  33. Bosch J, Garcia-Pagan JC, Berzigotti A, Abraldes JG . Measurement of portal pressure and its role in the management of chronic liver disease. Semin Liv Dis 2006; 26: 348–362.

    Article  Google Scholar 

  34. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW et al. for the nonalcoholic steatohepatitis clinical research network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41: 1313–1321.

    Article  Google Scholar 

  35. World Health Organisation (WHO). Obesity: preventing and managing the global epidemic report of a WHO consultation. WHO Technical Report Series 894. World Health Organisation: Geneva, 2000.

  36. Alberti KG, Zimmer P . Definition, diagnosis and classification of diabetes mellitus and its complications. Part I. Diagnosis and classification of diabetes mellitus. Provisional report of a WHO consultation. Diabet Med 1998; 15: 539–553.

    Article  CAS  Google Scholar 

  37. Ducimetiere P, Eschwege E, Papoz L, Richard JL, Claude JR, Rosselin G . Relationship of plasma insulin levels to the incidence of myocardial infarction and coronary heart disease mortality in a middle-aged population. Diabetologia 1980; 19: 205–210.

    Article  CAS  Google Scholar 

  38. Puoti C, Bellis L . Steatosis and portal hypertension. Eur Rev Med Pharmacol Sci 2005; 9: 285–290.

    CAS  PubMed  Google Scholar 

  39. Després JP, Lemieux I, Prud’homme D . Treatment of obesity: need to focus on high risk abdominally obese patients. Br Med J 2001; 322: 716–720.

    Article  Google Scholar 

  40. Clark JM, Brancati FL, Diehl AM . Nonalcoholic fatty liver disease. Gastroenterology 2002; 122: 1649–1657.

    Article  Google Scholar 

  41. Rinella M, Alonso E, Rao S, Whitington P, Fryer J, Abecassis M et al. Body mass index as a predictor of hepatic steatosis in living liver donors. Liver Transplant 2001; 7: 409–413.

    Article  CAS  Google Scholar 

  42. Egushi Y, Egushi T, Mizuka T, Ide Y, Yasutake T, Iwakini R et al. Visceral fat accumulation and insulin resistance are important factors in non-alcoholic liver disease. J Gastroenterol 2006; 41: 462–469.

    Article  Google Scholar 

  43. Stranges S, Dorn JM, Muti P, Freudenheim JL, Farinaro E, Russell M et al. Body fat distribution, relative weight, and liver enzyme levels: a population-based study. Hepatology 2004; 39: 754–763.

    Article  Google Scholar 

  44. Ahima RS, Flier JS . Adipose tissue as an endocrine organ. Trends Endocrinol Metab 2000; 11: 327–332.

    Article  CAS  Google Scholar 

  45. Jarrar MH, Baranova A, Collantes R, Ranard B, Stepanova M, Bennett C et al. Adipokines and cytokines in non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2008; 27: 412–421.

    Article  CAS  Google Scholar 

  46. Neuschwander-Tetri BA . Fatty liver and the metabolic syndrome. Curr Opin Gastroenterol 2007; 23: 193–198.

    Article  CAS  Google Scholar 

  47. Bugianesi E, McCullough AJ, Marchesini G . Insulin resistance: a metabolic pathway to chronic liver disease. Hepatology 2005; 42: 987–1000.

    Article  CAS  Google Scholar 

  48. Verrijken A, Francque S, Mertens I, Talloen M, Peiffer F, Van Gaal L . Visceral adipose tissue and inflammation correlate with elevated liver tests in a cohort of overweight and obese patients. Int J Obes 2010; 34: 899–907.

    Article  CAS  Google Scholar 

  49. Francque S . Non-alcoholic fatty liver disease (NAFLD) and Non-alcoholic Steatohepatitis (NASH). In: Van Damme P, van Herck K, Michielsen P, Francque S, Shouval D (eds). Chronic Hepatitis & Other Liver Disease. Oxford Textbook of Public Health 5th edn. Oxford University Press: Oxford, UK, 2009. (Chapter 9) 16, pp 1249–1263.

    Google Scholar 

  50. de Marco R, Locatelli F, Zoppini G, Verlato G, Bonora E, Muggeo M . Cause-specific mortality in type 2 diabetes. The Verona Diabetes Study. Diabetes Care 1999; 22: 756–761.

    Article  CAS  Google Scholar 

  51. Abrams GA, Kunde SS, Lazenby AJ, Clements RH . Portal fibrosis and hepatic steatosis in morbidly obese subjects: a spectrum of non-alcoholic fatty liver disease. Hepatology 2004; 40: 475–483.

    Article  Google Scholar 

  52. Reaven GM . Role of insulin resistance in human diabetes. Diabetes 1988; 37: 1595–1607.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work is part of the project ‘Hepatic and adipose tissue and functions in the metabolic syndrome’ (HEPADIP), which is supported by the European Commission as an Integrated Project under the 6th Framework Program (Contract LSHM-CT-2005-018734).

Author information

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium

    S Francque, P Pelckmans & P Michielsen

  2. Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Antwerp, Belgium

    A Verrijken, I Mertens & L Van Gaal

  3. Department of Abdominal Surgery, Antwerp University Hospital, Antwerp, Belgium

    G Hubens

  4. Department of Pathology, Antwerp University Hospital, Antwerp, Belgium

    E Van Marck

Authors
  1. S Francque
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Verrijken
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I Mertens
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G Hubens
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E Van Marck
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P Pelckmans
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P Michielsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. L Van Gaal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S Francque.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Francque, S., Verrijken, A., Mertens, I. et al. Visceral adiposity and insulin resistance are independent predictors of the presence of non-cirrhotic NAFLD-related portal hypertension. Int J Obes 35, 270–278 (2011). https://doi.org/10.1038/ijo.2010.134

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2010.134

Keywords

Search

Advanced search

Quick links