Intest Res.  2025 Jan;23(1):76-84. 10.5217/ir.2023.00078.

Association between nonalcoholic fatty liver disease and incidence of inflammatory bowel disease: a nationwide population‑based cohort study

• Wang YH
• Chung CH
• Huang TY
• Chang CF
• Yang CW
• Chien WC
• Cheng YC

• KMID: 2564398
• DOI: http://doi.org/10.5217/ir.2023.00078

Abstract

Background/Aims
Nonalcoholic fatty liver disease (NAFLD) is a common disease with severe inflammatory processes associated with numerous gastrointestinal diseases, such as inflammatory bowel disease (IBD). Therefore, we investigated the relationship between NAFLD and IBD and the possible risk factors associated with the diagnosis of IBD.
Methods
This longitudinal nationwide cohort study investigated the risk of IBD in patients with NAFLD alone. General characteristics, comorbidities, and incidence of IBD were also compared.
Results
Patients diagnosed with NAFLD had a significant risk of developing IBD compared to control individuals, who were associated with a 2.245-fold risk of the diagnosis of IBD and a 2.260- and 2.231-fold of increased diagnosis of ulcerative colitis and Crohn’s disease, respectively (P< 0.001). The cumulative risk of IBD increased annually during the follow-up of patients with NAFLD (P< 0.001).
Conclusions
Our results emphasize that NAFLD significantly impacts its incidence in patients with NAFLD. If patients with NAFLD present with risk factors, such as diabetes mellitus and dyslipidemia, these conditions should be properly treated with regular follow-ups. Furthermore, we believe that these causes may be associated with the second peak of IBD.

Keyword

Non-alcoholic fatty liver disease; Inflammatory bowel disease; Ulcerative colitis; Crohn disease

Figure

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  Fig. 1. Flowchart of the patient selection in this cohort. NAFLD, nonalcoholic fatty live disease; IBD, Inflammatory bowel disease.

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  Fig. 2. Kaplan-Meier curve for cumulative risks of inflammatory bowel disease (IBD) among patients aged ≥18 years, stratified by nonalcoholic fatty live disease (NAFLD) using the log-rank test. Zero of the X-axis was defined as the disease name of NAFLD registered in the database. Furthermore, the observation starting point for the non-NAFLD group is similar to that for the study group.

Reference

1. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease: meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016; 64:73–84.

2. Graham DB, Xavier RJ. Pathway paradigms revealed from the genetics of inflammatory bowel disease. Nature. 2020; 578:527–539.

3. GBD 2017 Inflammatory Bowel Disease Collaborators. The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020; 5:17–30.

4. Ng SC, Shi HY, Hamidi N, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017; 390:2769–2778.

5. Yen HH, Weng MT, Tung CC, et al. Epidemiological trend in inflammatory bowel disease in Taiwan from 2001 to 2015: a nationwide populationbased study. Intest Res. 2019; 17:54–62.

6. Ritaccio G, Stoleru G, Abutaleb A, et al. Nonalcoholic fatty liver disease is common in IBD patients however progression to hepatic fibrosis by noninvasive markers is rare. Dig Dis Sci. 2021; 66:3186–3191.

7. Stojsavljević S, Gomerčić Palčić M, Virović Jukić L, Smirčić Duvnjak L, Duvnjak M. Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol. 2014; 20:18070–18091.

8. Schaffner F, Thaler H. Nonalcoholic fatty liver disease. Prog Liver Dis. 1986; 8:283–298.

9. Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc. 1980; 55:434–438.

10. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999; 116:1413–1419.

11. Sennello JA, Fayad R, Morris AM, et al. Regulation of T cellmediated hepatic inflammation by adiponectin and leptin. Endocrinology. 2005; 146:2157–2164.

12. Giby VG, Ajith TA. Role of adipokines and peroxisome proliferator-activated receptors in nonalcoholic fatty liver disease. World J Hepatol. 2014; 6:570–579.

13. Shabani P, Emamgholipour S, Doosti M. CTRP1 in liver disease. Adv Clin Chem. 2017; 79:1–23.

14. Balmer ML, Joneli J, Schoepfer A, Stickel F, Thormann W, Dufour JF. Significance of serum adiponectin levels in patients with chronic liver disease. Clin Sci (Lond). 2010; 119:431–436.

15. Tarantino G, Savastano S, Colao A. Hepatic steatosis, lowgrade chronic inflammation and hormone/growth factor/adipokine imbalance. World J Gastroenterol. 2010; 16:4773–4783.

16. Gao B, Tsukamoto H. Inflammation in alcoholic and nonalcoholic fatty liver disease: friend or foe? Gastroenterology. 2016; 150:1704–1709.

17. Chang ML, Yang Z, Yang SS. Roles of adipokines in digestive diseases: markers of inflammation, metabolic alteration and disease progression. Int J Mol Sci. 2020; 21:8308.

18. Barnes EL, Loftus EV Jr, Kappelman MD. Effects of race and ethnicity on diagnosis and management of inflammatory bowel diseases. Gastroenterology. 2021; 160:677–689.

19. Olivier I, Theodorou V, Valet P, Castan-Laurell I, Ferrier L, Eutamène H. Modifications of mesenteric adipose tissue during moderate experimental colitis in mice. Life Sci. 2014; 94:1–7.

20. Al-Hassi HO, Bernardo D, Murugananthan AU, et al. A mechanistic role for leptin in human dendritic cell migration: differences between ileum and colon in health and Crohn’s disease. Mucosal Immunol. 2013; 6:751–761.

21. Obeid S, Wankell M, Charrez B, et al. Adiponectin confers protection from acute colitis and restricts a B cell immune response. J Biol Chem. 2017; 292:6569–6582.

22. Fousekis FS, Katsanos KH, Theopistos VI, et al. Hepatobiliary and pancreatic manifestations in inflammatory bowel diseases: a referral center study. BMC Gastroenterol. 2019; 19:48.

23. Wald A. Is chronic use of stimulant laxatives harmful to the colon? J Clin Gastroenterol. 2003; 36:386–389.

24. Wang Y, Song J, Bian H, et al. Apelin promotes hepatic fibrosis through ERK signaling in LX-2 cells. Mol Cell Biochem. 2019; 460:205–215.

25. Han S, Wang G, Qiu S, et al. Increased colonic apelin production in rodents with experimental colitis and in humans with IBD. Regul Pept. 2007; 142:131–137.

26. Zou ZY, Shen B, Fan JG. Systematic review with meta-analysis: epidemiology of nonalcoholic fatty liver disease in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2019; 25:1764–1772.

27. Hoffmann P, Jung V, Behnisch R, Gauss A. Prevalence and risk factors of nonalcoholic fatty liver disease in patients with inflammatory bowel diseases: a cross-sectional and longitudinal analysis. World J Gastroenterol. 2020; 26:7367–7381.

28. Principi M, Iannone A, Losurdo G, et al. Nonalcoholic fatty liver disease in inflammatory bowel disease: prevalence and risk factors. Inflamm Bowel Dis. 2018; 24:1589–1596.

29. Beger HG, Mayer B, Poch B. Resection of the duodenum causes long-term endocrine and exocrine dysfunction after Whipple procedure for benign tumors: results of a systematic review and meta-analysis. HPB (Oxford). 2020; 22:809–820.

30. Szathmári M, Vásárhelyi B, Treszl A, Tulassay T, Tulassay Z. Association of dehydroepiandrosterone sulfate and testosterone deficiency with bone turnover in men with inflammatory bowel disease. Int J Colorectal Dis. 2002; 17:63–66.

31. Mintziori G, Poulakos P, Tsametis C, Goulis DG. Hypogonadism and non-alcoholic fatty liver disease. Minerva Endocrinol. 2017; 42:145–150.

32. McGowan CE, Jones P, Long MD, Barritt AS 4th. 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.

33. Greuter T, Manser C, Pittet V, Vavricka SR, Biedermann L; on behalf of Swiss IBDnet, an official working group of the Swiss Society of Gastroenterology. Gender differences in inflammatory bowel disease. Digestion. 2020; 101(Suppl 1):98–104.

34. Soon IS, Molodecky NA, Rabi DM, Ghali WA, Barkema HW, Kaplan GG. The relationship between urban environment and the inflammatory bowel diseases: a systematic review and meta-analysis. BMC Gastroenterol. 2012; 12:51.

35. Koido S, Ohkusa T, Saito H, et al. Seasonal variations in the onset of ulcerative colitis in Japan. World J Gastroenterol. 2013; 19:9063–9068.

36. Johnston RD, Logan RF. What is the peak age for onset of IBD? Inflamm Bowel Dis. 2008; 14(Suppl 2):S4–S5.