Skip to main content
Top
Published in: Hepatology International 1/2012

01-01-2012 | Original Article

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

Authors: 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)

Published in: Hepatology International | Issue 1/2012

Login to get access

Abstract

Purpose

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.

Methods

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.

Results

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].

Conclusion

Autoantibodies are frequently positive in NAFLD in the absence of autoimmune hepatitis and their occurrence is not associated with more advanced histologic features.
Appendix
Available only for authorised users
Literature
1.
go back to reference Clark JM, Brancati FL, Diehl AM. The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol 2003;98(5):960–967PubMedCrossRef Clark JM, Brancati FL, Diehl AM. The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol 2003;98(5):960–967PubMedCrossRef
2.
go back to reference Browning JD. Statins and hepatic steatosis: perspectives from the Dallas Heart Study. Hepatology 2006;44(2):466–471PubMedCrossRef Browning JD. Statins and hepatic steatosis: perspectives from the Dallas Heart Study. Hepatology 2006;44(2):466–471PubMedCrossRef
3.
go back to reference McCullough AJ. The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease. Clin Liver Dis 2004;8(3):521–33. viiiPubMedCrossRef McCullough AJ. The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease. Clin Liver Dis 2004;8(3):521–33. viiiPubMedCrossRef
4.
go back to reference 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)PubMedCrossRef 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)PubMedCrossRef
5.
go back to reference Yilmaz Y, Kedrah AE, Ozdogan O. Cytokeratin-18 fragments and biomarkers of the metabolic syndrome in nonalcoholic steatohepatitis. World J Gastroenterol 2009;15(35):4387–4391PubMedCrossRef Yilmaz Y, Kedrah AE, Ozdogan O. Cytokeratin-18 fragments and biomarkers of the metabolic syndrome in nonalcoholic steatohepatitis. World J Gastroenterol 2009;15(35):4387–4391PubMedCrossRef
6.
go back to reference 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):1315–1322PubMedCrossRef 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):1315–1322PubMedCrossRef
7.
go back to reference Angulo P, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 2007;45(4):846–854PubMedCrossRef Angulo P, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology 2007;45(4):846–854PubMedCrossRef
8.
go back to reference Rosenberg WM, et al. Serum markers detect the presence of liver fibrosis: a cohort study. Gastroenterology 2004;127(6):1704–1713PubMedCrossRef Rosenberg WM, et al. Serum markers detect the presence of liver fibrosis: a cohort study. Gastroenterology 2004;127(6):1704–1713PubMedCrossRef
9.
go back to reference 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):455–460PubMedCrossRef 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):455–460PubMedCrossRef
10.
go back to reference 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;6:6PubMedCrossRef 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;6:6PubMedCrossRef
11.
go back to reference 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):1316–1320PubMedCrossRef 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):1316–1320PubMedCrossRef
12.
go back to reference 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):1130–1138PubMedCrossRef 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):1130–1138PubMedCrossRef
13.
go back to reference Niwa H, et al. Clinicopathological significance of antinuclear antibodies in non-alcoholic steatohepatitis. Hepatol Res 2007;37(11):923–931PubMedCrossRef Niwa H, et al. Clinicopathological significance of antinuclear antibodies in non-alcoholic steatohepatitis. Hepatol Res 2007;37(11):923–931PubMedCrossRef
14.
go back to reference Bacon BR, et al. Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology 1994;107(4):1103–1109PubMed Bacon BR, et al. Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology 1994;107(4):1103–1109PubMed
15.
go back to reference Caldwell SH, et al. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology 1999;29(3):664–659PubMedCrossRef Caldwell SH, et al. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology 1999;29(3):664–659PubMedCrossRef
16.
go back to reference Laroussi N, et al. Non alcoholic steatohepatitis: a multifactorial, frequent, paucysymptomatic liver disease with a fibrotic outcome. Gastroenterol Clin Biol 2002;26(5):475–479PubMed Laroussi N, et al. Non alcoholic steatohepatitis: a multifactorial, frequent, paucysymptomatic liver disease with a fibrotic outcome. Gastroenterol Clin Biol 2002;26(5):475–479PubMed
17.
go back to reference Cotler SJ, et al. Prevalence and significance of autoantibodies in patients with non-alcoholic steatohepatitis. J Clin Gastroenterol 2004;38(9):801–804PubMedCrossRef Cotler SJ, et al. Prevalence and significance of autoantibodies in patients with non-alcoholic steatohepatitis. J Clin Gastroenterol 2004;38(9):801–804PubMedCrossRef
18.
go back to reference Loria P, et al. Non-organ-specific autoantibodies in nonalcoholic fatty liver disease: prevalence and correlates. Dig Dis Sci 2003;48(11):2173–2181PubMedCrossRef Loria P, et al. Non-organ-specific autoantibodies in nonalcoholic fatty liver disease: prevalence and correlates. Dig Dis Sci 2003;48(11):2173–2181PubMedCrossRef
19.
go back to reference 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):1200–1201CrossRef 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):1200–1201CrossRef
20.
go back to reference Adams A, Angulo P. Insulin resistance, auto-antibodies, and nonalcoholic fatty liver disease, response to letter. Am J Gastroenterol 2005;100(5):1201–1202CrossRef Adams A, Angulo P. Insulin resistance, auto-antibodies, and nonalcoholic fatty liver disease, response to letter. Am J Gastroenterol 2005;100(5):1201–1202CrossRef
21.
go back to reference Nonalcoholic Steatohepatitis Clinical Research Network. Hepatology 2003;37:244. Nonalcoholic Steatohepatitis Clinical Research Network. Hepatology 2003;37:244.
22.
go back to reference 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):88–96PubMedCrossRef 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):88–96PubMedCrossRef
23.
go back to reference Tan EM, et al. Range of antinuclear antibodies in “healthy” individuals. Arthritis Rheum 1997;40(9):1601–1611PubMedCrossRef Tan EM, et al. Range of antinuclear antibodies in “healthy” individuals. Arthritis Rheum 1997;40(9):1601–1611PubMedCrossRef
24.
go back to reference Kleiner DE, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41(6):1313–1321PubMedCrossRef Kleiner DE, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41(6):1313–1321PubMedCrossRef
25.
go back to reference Syn WK, et al. Accumulation of natural killer T cells in progressive nonalcoholic fatty liver disease. Hepatology 2010;51(6):1998–2007 Syn WK, et al. Accumulation of natural killer T cells in progressive nonalcoholic fatty liver disease. Hepatology 2010;51(6):1998–2007
26.
go back to reference 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):397–404PubMedCrossRef 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):397–404PubMedCrossRef
27.
go back to reference 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):105–112 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):105–112
28.
go back to reference Satoh M, Del Vazquez-Mercado M, Chan EK. Clinical interpretation of antinuclear antibody tests in systemic rheumatic diseases. Mod Rheumatol 2009;19(3):219–228PubMedCrossRef Satoh M, Del Vazquez-Mercado M, Chan EK. Clinical interpretation of antinuclear antibody tests in systemic rheumatic diseases. Mod Rheumatol 2009;19(3):219–228PubMedCrossRef
29.
go back to reference Patton HM, et al. Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis. Gastroenterology 2008;135(6):1961e2–1971e2CrossRef Patton HM, et al. Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis. Gastroenterology 2008;135(6):1961e2–1971e2CrossRef
Metadata
Title
Clinical significance of serum autoantibodies in patients with NAFLD: results from the nonalcoholic steatohepatitis clinical research network
Authors
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)
Publication date
01-01-2012
Publisher
Springer-Verlag
Published in
Hepatology International / Issue 1/2012
Print ISSN: 1936-0533
Electronic ISSN: 1936-0541
DOI
https://doi.org/10.1007/s12072-011-9277-8

Other articles of this Issue 1/2012

Hepatology International 1/2012 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine