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

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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.

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Abbreviations

NAFLD:

Nonalcoholic fatty liver disease

NASH:

Nonalcoholic steatohepatitis

PIVENS:

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

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Acknowledgements

The authors declare that they do not have anything to disclose regarding funding from industries or conflicts of interest with respect to this manuscript. This work is supported by the National Institute of Diabetes & Digestive & Kidney Diseases and the National Institute of Child health and Human Development. A list of members of the Nonalcoholic Steatohepatitis Clinical Research Network is located in Appendix. The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (grants U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713), and the National Institute of Child Health and Human Development (NICHD). Several clinical centres use support from General Clinical Research Centres or Clinical and Translational Science Awards in conduct of NASH CRN Studies (grants UL1RR024989, M01RR000750, M01RR00188, UL1RR02413101, M01RR000827, UL1RR02501401, M01RR000065, M01RR020359, DK-02957-KK).

Author information

Authors and Affiliations

  1. Indiana University School of Medicine, Indianapolis, IN, USA

    Raj Vuppalanchi, Oscar W. Cummings & Naga Chalasani

  2. Centre for Liver Disease, Virginia Mason Medical Centre, Seattle, WA, USA

    Robert J. Gould & Kris V. Kowdley

  3. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Laura A. Wilson & Aynur Unalp-Arida

Authors
  1. Raj Vuppalanchi
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  2. Robert J. Gould
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  3. Laura A. Wilson
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  4. Aynur Unalp-Arida
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  5. Oscar W. Cummings
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  6. Naga Chalasani
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  7. Kris V. Kowdley
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Consortia

Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN)

Corresponding author

Correspondence to Raj Vuppalanchi.

Electronic supplementary material

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Appendix: Members of the non-alcoholic steatohepatitis clinical research network

Appendix: Members of the non-alcoholic steatohepatitis clinical research network

Clinical centres

Baylor College of Medicine, Houston, TX: Stephanie Abrams, MD; Diana Arceo, MD, MS; Denise Espinosa; Leanel Angeli Fairly, RN.

Case Western Reserve University Clinical Centres:

  • MetroHealth Medical Centre, Cleveland, OH: Carol Hawkins, RN; Yao-Chang Liu, MD (2004–2009); Margaret Stager, MD

  • Cleveland Clinic Foundation, Cleveland, OH: Arthur J. McCullough, MD; Srinivasan Dasarathy, MD; Ruth Sargent, LPN

Children’s National Medical Centre, Washington DC: Parvathi Mohan, MD; Kavita Nair

Duke University Medical Centre, Durham, NC: Manal Abdelmalek, MD; Miriam Chitty, Anna Mae Diehl, MD; Marcia Gottfried, MD (2004–2008); Cynthia Guy, MD; Paul Killenberg, MD (2004–2008); Samantha Kwan; Yi-Ping Pan; Dawn Piercy, FNP; Melissa Smith

Indiana University School of Medicine, Indianapolis, IN: Elizabeth Byam, RN; Naga Chalasani, MD; Oscar W. Cummings, MD; Ann Klipsch, RN; Jean P. Molleston, MD; Linda Ragozzino, RN; Girish Subbarao, MD; Raj Vuppalanchi, MD

Johns Hopkins Hospital, Baltimore, MD: Kimberly Pfeifer; Ann Scheimann, MD; Michael Torbenson, MD

Seattle Children’s Hospital & Research Institute, WA: Melissa Coffey; Sarah Galdzicka, Karen Murray, MD; Melissa Young

St Louis University, St Louis, MO: Sarah Barlow, MD (2002–2007); Jose Derdoy, MD; Joyce Hoffmann; Debra King, RN; Andrea Morris; Joan Siegner, RN; Susan Stewart, RN; Brent A. Tetri, MD; Judy Thompson, RN

University of California San Diego, San Diego, CA: Cynthia Behling, MD, PhD; Lisa Clark, PhD, MPH; Janis Durelle; Tarek Hassanein, MD (2004–2009); Joel E. Lavine, MD, PhD; Rohit Loomba, MD; Susana Mendoza; Heather Patton, MD; Jeffrey B. Schwimmer, MD; Claude Sirlin, MD; Zobeida Palomares

University of California San Francisco, San Francisco, CA: Bradley Aouizerat, PhD; Kiran Bambha, MD; Nathan M. Bass, MD, PhD; Linda D. Ferrell, MD; Danuta Filipowski, MD; Raphael Merriman, MD; Mark Pabst; Monique Rosenthal; Philip Rosenthal, MD; Tessa Steel (2006–2008)

University of Washington Medical Centre, Seattle, WA: Matthew Yeh, MD, PhD

Virginia Commonwealth University, Richmond, VA: Sherry Boyett, RN; Melissa J. Contos, MD; Michael Fuchs, MD; Amy Jones; Velimir AC Luketic, MD; Bimalijit Sandhu, MD; Arun J. Sanyal, MD; Carol Sargeant, RN, MPH; Kimberly Selph; Melanie White, RN

Virginia Mason Medical Centre, Seattle, WA: Kris V. Kowdley, MD; Jody Mooney, MS; James Nelson, PhD; Sarah Ackermann; Cheryl Saunders, MPH; Vy Trinh; Chia Wang, MD

Washington University, St. Louis, MO: Elizabeth M. Brunt, MD

Resource centres

National Cancer Institute, Bethesda, MD: David E. Kleiner, MD, PhD

National Institute of Child Health and Human Development, Bethesda, MD: Gilman D. Grave, MD; Terry TK Huang, PhD, MPH

National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD: Edward C. Doo, MD; James E. Everhart, MD, MPH; Jay H. Hoofnagle, MD; Patricia R. Robuck, PhD, MPH (Project Scientist)

Johns Hopkins University, Bloomberg School of Public Health (Data Coordinating Centre), Baltimore, MD: Patricia Belt, BS; Frederick L. Brancati, MD, MHS (2003–2009); Jeanne M. Clark, MD, MPH; Ryan Colvin, MPH; Michele Donithan, MHS; Mika Green, MA; Rosemary Hollick (2003–2005); Milana Isaacson; Wana Kim; Alison Lydecker, MPH (2006–2008), Pamela Mann, MPH (2008–2009); Laura Miriel; Alice Sternberg, ScM; James Tonascia, PhD; Aynur Ünalp-Arida, MD, PhD; Mark Van Natta, MHS; Laura Wilson, ScM; Katherine Yates, ScM

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Vuppalanchi, R., Gould, R.J., Wilson, L.A. et al. Clinical significance of serum autoantibodies in patients with NAFLD: results from the nonalcoholic steatohepatitis clinical research network. Hepatol Int 6, 379–385 (2012). https://doi.org/10.1007/s12072-011-9277-8

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