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Intestinal Inflammation Does Not Predict Nonalcoholic Fatty Liver Disease Severity in Inflammatory Bowel Disease Patients

Abstract

Background and Aim

Nonalcoholic fatty liver disease (NAFLD) is a common cause of hepatic steatosis in patients with inflammatory bowel disease (IBD). Both metabolic syndrome (MetS) and intestinal inflammation are implicated in NAFLD pathogenesis.

Methods

We performed a retrospective cohort study of patients with IBD and NAFLD seen in our health system from January 1997 to December 2011 to examine associations between IBD severity and phenotype; MetS; and NAFLD fibrosis as estimated by the NAFLD Fibrosis Score (NFS).

Results

A total of 84 patients were included in our analysis (24 UC, 60 CD). 23% of patients had MetS. IBD patients with MetS were significantly older at the time of IBD diagnosis (44 vs. 33, p = 0.005) and NAFLD diagnosis (55 vs. 47, p = 0.018). IBD patients with MetS had higher ALT (54 vs. 38 U/L, p = 0.02) and AST (52 vs. 35 U/L, p = 0.004). Comparing MetS patients to non-MetS IBD patients, there was no significant difference between IBD medication use (i.e., steroids, anti-TNFs, and immunomodulators) or NAFLD medication use, other than statins. Both UC and CD patients with concomitant MetS had significantly higher NFS scores than non-MetS patients: UC (−0.4 vs. −2.5, p = 0.02) and CD (−0.8 vs. −2.3, p = 0.03). IBD disease severity, disease location, or IBD medication use was associated with NAFLD severity.

Conclusions

To our knowledge, this is the first study to demonstrate that NAFLD severity in both UC and CD IBD patients is associated with the presence of MetS but not with the severity of IBD.

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References

  1. Carr RM, Oranu A, Khungar V. Nonalcoholic fatty liver disease: pathophysiology and management. Gastroenterol Clin North Am. 2016;45:639–652.

    Article  PubMed  Google Scholar 

  2. Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012;55:2005–2023.

    Article  PubMed  Google Scholar 

  3. Abu-Shanab A, Quigley EM. The role of the gut microbiota in nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2010;7:691–701.

    Article  PubMed  Google Scholar 

  4. Gabele E, Dostert K, Hofmann C, et al. DSS induced colitis increases portal LPS levels and enhances hepatic inflammation and fibrogenesis in experimental NASH. J Hepatol. 2011;55:1391–1399.

    Article  PubMed  Google Scholar 

  5. Bargiggia S, Maconi G, Elli M, et al. Sonographic prevalence of liver steatosis and biliary tract stones in patients with inflammatory bowel disease: study of 511 subjects at a single center. J Clin Gastroenterol. 2003;36:417–420.

    Article  PubMed  Google Scholar 

  6. U.S. Food and Drug Administration CfDEaRIal, August 24, 1998. Retrieved July 16, 2016. http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/ucm107700.pdf.

  7. Long MD, Crandall WV, Leibowitz IH, et al. Prevalence and epidemiology of overweight and obesity in children with inflammatory bowel disease. Inflamm Bowel Dis. 2011;17:2162–2168.

    Article  PubMed  Google Scholar 

  8. Yorulmaz E, Adali G, Yorulmaz H, Ulasoglu C, Tasan G, Tuncer I. Metabolic syndrome frequency in inflammatory bowel diseases. Saudi J Gastroenterol. 2011;17:376–382.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Broome U, Glaumann H, Hultcrantz R. Liver histology and follow up of 68 patients with ulcerative colitis and normal liver function tests. Gut. 1990;31:468–472.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  10. Eade MN, Cooke WT, Williams JA. Liver disease in Crohn’s disease. A study of 100 consecutive patients. Scand J Gastroenterol. 1971;6:199–204.

    CAS  Article  PubMed  Google Scholar 

  11. Koca SS, Bahcecioglu IH, Poyrazoglu OK, Ozercan IH, Sahin K, Ustundag B. The treatment with antibody of TNF-alpha reduces the inflammation, necrosis and fibrosis in the non-alcoholic steatohepatitis induced by methionine- and choline-deficient diet. Inflammation. 2008;31:91–98.

    CAS  Article  PubMed  Google Scholar 

  12. Satapathy SK, Garg S, Chauhan R, et al. Beneficial effects of tumor necrosis factor-alpha inhibition by pentoxifylline on clinical, biochemical, and metabolic parameters of patients with nonalcoholic steatohepatitis. Am J Gastroenterol. 2004;99:1946–1952.

    CAS  Article  PubMed  Google Scholar 

  13. McGowan CE, Jones P, Long MD, Barritt A. Changing shape of disease: nonalcoholic fatty liver disease in Crohn’s disease-a case series and review of the literature. Inflamm Bowel Dis. 2012;18:49–54.

    Article  PubMed  Google Scholar 

  14. Bessissow T, Le NH, Rollet K, Afif W, Bitton A, Sebastiani G. Incidence and predictors of nonalcoholic fatty liver disease by serum biomarkers in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2016;22:1937–1944.

    Article  PubMed  Google Scholar 

  15. Sourianarayanane A, Garg G, Smith TH, Butt MI, McCullough AJ, Shen B. Risk factors of non-alcoholic fatty liver disease in patients with inflammatory bowel disease. J Crohns Colitis. 2013;7:e279–e285.

    Article  PubMed  Google Scholar 

  16. Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45:846–854.

    CAS  Article  PubMed  Google Scholar 

  17. Silverberg MS, Satsangi J, Ahmad T, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol. 2005;19:5A–36A.

    Article  PubMed  Google Scholar 

  18. Chalasani NP, Sanyal AJ, Kowdley KV, 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;30:88–96.

    CAS  Article  PubMed  Google Scholar 

  19. Ryan MC, Wilson AM, Slavin J, Best JD, Jenkins AJ, Desmond PV. Associations between liver histology and severity of the metabolic syndrome in subjects with nonalcoholic fatty liver disease. Diabetes Care. 2005;28:1222–1224.

    Article  PubMed  Google Scholar 

  20. Lichtenstein GR, Feagan BG, Cohen RD, et al. Serious infections and mortality in association with therapies for Crohn’s disease: TREAT registry. Clin Gastroenterol Hepatol. 2006;4:621–630.

    CAS  Article  PubMed  Google Scholar 

  21. Chitturi S, Farrell GC. Etiopathogenesis of nonalcoholic steatohepatitis. Semin Liver Dis. 2001;21:27–41.

    CAS  Article  PubMed  Google Scholar 

  22. Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362:1383–1395.

    CAS  Article  PubMed  Google Scholar 

  23. Truelove SC, Witts LJ. Cortisone in ulcerative colitis; final report on a therapeutic trial. Br Med J. 1955;2:1041–1048.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. Lichtenstein GR, Hanauer SB, Sandborn WJ. Practice parameters Committee of American College of G. Management of Crohn’s disease in adults. Am J Gastroenterol. 2009;104:465–483.

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Institutes of Health [K08-AA021424, P30 DK019525, and P30-DK050306 to RMC]; National Institutes of Health [K23 DK090209 to KF]; National Institutes of Health [T32 DK007066 to AO] and the Robert Wood Johnson Foundation [7158 to RMC].

Author's contribution

RMC, AP, CK, KF, and GRL helped in Planning and/or conducting the study; AP, HB, RMC, AP, and AO helped in collecting and/or interpreting data; RMC and AP contributed to drafting the manuscript. All authors (RMC, AP, HB, RR, KF, AP, AO, and GRL) approved the final submitted draft.

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Correspondence to Rotonya M. Carr.

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Conflict of interest

Dr. Gary R. Lichtenstein serves as consultant and/or participates in research for the following: Abbott Corporation, Abbvie, Actavis, Alaven, Celgene, Hospira, Luitpold/American Regent, Pfizer Pharmaceuticals, Prometheus Laboratories, Inc., Romark, Salix Pharmaceuticals, Valeant, Santarus, Receptos, Celgene, Shire Pharmaceuticals, Takeda, and UCB. Dr. Rotonya Carr is a sub-investigator on a research study sponsored by Intercept Pharmaceuticals.

Additional information

Rotonya M. Carr and Arpan Patel are co-first authors.

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Carr, R.M., Patel, A., Bownik, H. et al. Intestinal Inflammation Does Not Predict Nonalcoholic Fatty Liver Disease Severity in Inflammatory Bowel Disease Patients. Dig Dis Sci 62, 1354–1361 (2017). https://doi.org/10.1007/s10620-017-4495-0

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  • DOI: https://doi.org/10.1007/s10620-017-4495-0

Keywords

  • Inflammatory bowel disease
  • Crohn’s disease
  • Ulcerative colitis
  • Nonalcoholic fatty liver disease
  • NAFLD Fibrosis Score