Hepatology International

, Volume 6, Issue 1, pp 379–385 | Cite as

Clinical significance of serum autoantibodies in patients with NAFLD: results from the nonalcoholic steatohepatitis clinical research network

  • Raj Vuppalanchi
  • Robert J. Gould
  • Laura A. Wilson
  • Aynur Unalp-Arida
  • Oscar W. Cummings
  • Naga Chalasani
  • Kris V. Kowdley
  • Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)
Original Article



Some studies have suggested that autoantibodies might define a subcategory and phenotype of nonalcoholic fatty liver disease (NAFLD) associated with advanced histological features. We evaluated the relationship between the presence of serum autoantibodies and liver histology in a large cohort of well-characterized patients with NAFLD.


A total of 864 NAFLD patients participating in two prospective multicentre clinical studies underwent testing for serum autoantibodies within 24 months of a liver biopsy. Liver histology was compared between the patients with and without ANA ≥ 1:160 or ASMA ≥ 1:40 or both.


Autoantibodies were present in 182 patients (21%). There was no difference in age, gender, race, body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), or history of diabetes between the two groups. Biopsies in subjects with autoantibodies were less likely to have moderate-to-severe steatosis (i.e., >33%) compared to controls (57.1 vs. 43.0%, P value = 0.0006). Lobular inflammation (46.7 vs. 47.5%), ballooning degeneration (38.5 vs. 42.5%), and advanced fibrosis (33.2 vs. 29.3%) were not different between the two groups. Histologic evidence of ‘definite’ NASH did not differ significantly between the two groups (55.5 vs. 58.9%). After adjusting for age, gender, BMI, race, and diabetes, the presence of autoantibodies was independently associated with lower prevalence of moderate-to-severe steatosis [odds ratio (OR), 0.58; 95% confidence interval (CI), 0.41–0.82; P = 0.01].


Autoantibodies are frequently positive in NAFLD in the absence of autoimmune hepatitis and their occurrence is not associated with more advanced histologic features.


Autoantibodies NASH NAFLD Liver histology 



Nonalcoholic fatty liver disease


Nonalcoholic steatohepatitis


Pioglitazone versus Vitamin E versus Placebo for the treatment of non diabetic patients with NASH

Supplementary material

12072_2011_9277_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 14 kb)


  1. 1.
    Clark JM, Brancati FL, Diehl AM. The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol 2003;98(5):960–967PubMedCrossRefGoogle Scholar
  2. 2.
    Browning JD. Statins and hepatic steatosis: perspectives from the Dallas Heart Study. Hepatology 2006;44(2):466–471PubMedCrossRefGoogle Scholar
  3. 3.
    McCullough AJ. The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease. Clin Liver Dis 2004;8(3):521–33. viiiPubMedCrossRefGoogle Scholar
  4. 4.
    Emanuele E. Is biopsy always necessary? Toward a clinico-laboratory approach for diagnosing nonalcoholic steatohepatitis in obesity. Hepatology 2008;48(6):2086–2087 (author reply 2087)PubMedCrossRefGoogle Scholar
  5. 5.
    Yilmaz Y, Kedrah AE, Ozdogan O. Cytokeratin-18 fragments and biomarkers of the metabolic syndrome in nonalcoholic steatohepatitis. World J Gastroenterol 2009;15(35):4387–4391PubMedCrossRefGoogle Scholar
  6. 6.
    Anty R, et al. A new composite model including metabolic syndrome, alanine aminotransferase and cytokeratin-18 for the diagnosis of non-alcoholic steatohepatitis in morbidly obese patients. Aliment Pharmacol Ther 2010;32(11–12):1315–1322PubMedCrossRefGoogle Scholar
  7. 7.
    Angulo P, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 2007;45(4):846–854PubMedCrossRefGoogle Scholar
  8. 8.
    Rosenberg WM, et al. Serum markers detect the presence of liver fibrosis: a cohort study. Gastroenterology 2004;127(6):1704–1713PubMedCrossRefGoogle Scholar
  9. 9.
    Guha IN, et al. Noninvasive markers of fibrosis in nonalcoholic fatty liver disease: validating the European Liver Fibrosis Panel and exploring simple markers. Hepatology 2008;47(2):455–460PubMedCrossRefGoogle Scholar
  10. 10.
    Ratziu V, et al. Diagnostic value of biochemical markers (FibroTest-FibroSURE) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease. BMC Gastroenterol 2006;6:6PubMedCrossRefGoogle Scholar
  11. 11.
    Adams LA, Lindor KD, Angulo P. The prevalence of autoantibodies and autoimmune hepatitis in patients with nonalcoholic fatty liver disease. Am J Gastroenterol 2004;99(7):1316–1320PubMedCrossRefGoogle Scholar
  12. 12.
    Yatsuji S, et al. Diagnosing autoimmune hepatitis in nonalcoholic fatty liver disease: is the international autoimmune hepatitis group scoring system useful? J Gastroenterol 2005;40(12):1130–1138PubMedCrossRefGoogle Scholar
  13. 13.
    Niwa H, et al. Clinicopathological significance of antinuclear antibodies in non-alcoholic steatohepatitis. Hepatol Res 2007;37(11):923–931PubMedCrossRefGoogle Scholar
  14. 14.
    Bacon BR, et al. Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology 1994;107(4):1103–1109PubMedGoogle Scholar
  15. 15.
    Caldwell SH, et al. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology 1999;29(3):664–659PubMedCrossRefGoogle Scholar
  16. 16.
    Laroussi N, et al. Non alcoholic steatohepatitis: a multifactorial, frequent, paucysymptomatic liver disease with a fibrotic outcome. Gastroenterol Clin Biol 2002;26(5):475–479PubMedGoogle Scholar
  17. 17.
    Cotler SJ, et al. Prevalence and significance of autoantibodies in patients with non-alcoholic steatohepatitis. J Clin Gastroenterol 2004;38(9):801–804PubMedCrossRefGoogle Scholar
  18. 18.
    Loria P, et al. Non-organ-specific autoantibodies in nonalcoholic fatty liver disease: prevalence and correlates. Dig Dis Sci 2003;48(11):2173–2181PubMedCrossRefGoogle Scholar
  19. 19.
    Loria P, Carulli N, Lonardo A. The prevalence of autoantibodies and autoimmune hepatitis in patients with nonalcoholic fatty liver disease letters to the editor. Am J Gastroenterol 2005;5(100):1200–1201CrossRefGoogle Scholar
  20. 20.
    Adams A, Angulo P. Insulin resistance, auto-antibodies, and nonalcoholic fatty liver disease, response to letter. Am J Gastroenterol 2005;100(5):1201–1202CrossRefGoogle Scholar
  21. 21.
    Nonalcoholic Steatohepatitis Clinical Research Network. Hepatology 2003;37:244.Google Scholar
  22. 22.
    Chalasani NP, et al. Pioglitazone versus vitamin E versus placebo for the treatment of non-diabetic patients with non-alcoholic steatohepatitis: PIVENS trial design. Contemp Clin Trials 2009;30(1):88–96PubMedCrossRefGoogle Scholar
  23. 23.
    Tan EM, et al. Range of antinuclear antibodies in “healthy” individuals. Arthritis Rheum 1997;40(9):1601–1611PubMedCrossRefGoogle Scholar
  24. 24.
    Kleiner DE, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41(6):1313–1321PubMedCrossRefGoogle Scholar
  25. 25.
    Syn WK, et al. Accumulation of natural killer T cells in progressive nonalcoholic fatty liver disease. Hepatology 2010;51(6):1998–2007Google Scholar
  26. 26.
    Naito T, et al. Simultaneous activation of natural killer T cells and autoantibody production in mice injected with denatured syngeneic liver tissue. Clin Exp Immunol 2002;129(3):397–404PubMedCrossRefGoogle Scholar
  27. 27.
    Fujii Y et al. Co-appearance of autoantibody-producing B220(low) B cells with NKT cells in the course of hepatic injury. Cell Immunol 2010;260(2):105–112Google Scholar
  28. 28.
    Satoh M, Del Vazquez-Mercado M, Chan EK. Clinical interpretation of antinuclear antibody tests in systemic rheumatic diseases. Mod Rheumatol 2009;19(3):219–228PubMedCrossRefGoogle Scholar
  29. 29.
    Patton HM, et al. Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis. Gastroenterology 2008;135(6):1961e2–1971e2CrossRefGoogle Scholar

Copyright information

© Asian Pacific Association for the Study of the Liver 2011

Authors and Affiliations

  • Raj Vuppalanchi
    • 1
  • Robert J. Gould
    • 2
  • Laura A. Wilson
    • 3
  • Aynur Unalp-Arida
    • 3
  • Oscar W. Cummings
    • 1
  • Naga Chalasani
    • 1
  • Kris V. Kowdley
    • 2
  • Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)
  1. 1.Indiana University School of MedicineIndianapolisUSA
  2. 2.Centre for Liver Disease, Virginia Mason Medical CentreSeattleUSA
  3. 3.Department of EpidemiologyJohns Hopkins Bloomberg School of Public HealthBaltimoreUSA

Personalised recommendations