Elucidating the association between nonalcoholic fatty liver disease and incidence of inflammatory bowel disease: a focus on systemic inflammation

Sihyun Kim; Jong Pil Im

doi:10.5217/ir.2024.00204

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Editorial IBD Elucidating the association between nonalcoholic fatty liver disease and incidence of inflammatory bowel disease: a focus on systemic inflammation: Sihyun Kim, Jong Pil Im^,; Intestinal Research 2025;23(1):3-5.
DOI: https://doi.org/10.5217/ir.2024.00204
Published online: January 24, 2025

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea

Correspondence to Jong Pil Im, Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea. E-mail: jpim0911@snu.ac.kr

• Received: December 1, 2024 • Accepted: January 15, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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REFERENCES

See the article "Association between nonalcoholic fatty liver disease and incidence of inflammatory bowel disease: a nationwide population‑based cohort study" on page 76.

Nonalcoholic fatty liver disease (NAFLD) has emerged as a significant global health concern, with prevalence estimates ranging from 25% to 30% worldwide [1]. This condition, characterized by excessive hepatic fat accumulation in the absence of significant alcohol consumption, encompasses a spectrum from simple steatosis to nonalcoholic steatohepatitis (NASH), which can progress to fibrosis, cirrhosis, and hepatocellular carcinoma [2]. The pathogenesis of NAFLD is multifactorial, involving genetic predisposition, insulin resistance, obesity, dyslipidemia, and sedentary lifestyle. These factors contribute to hepatic lipid accumulation and subsequent inflammatory processes [2]. In parallel, inflammatory bowel disease (IBD), comprising ulcerative colitis and Crohn’s disease, represents a chronic relapsing-remitting disorder of the gastrointestinal tract [3]. The incidence of IBD has been increasing globally, particularly in newly industrialized countries adopting Westernized lifestyles [3]. The etiology of IBD is complex, involving genetic susceptibility, environmental factors, and immune dysregulation [4]. Recent studies have suggested a potential association between NAFLD and IBD, hypothesizing that systemic inflammation and metabolic disturbances common to both conditions may underlie this link [3].

In this issue of Intestinal Research, Wang et al. [5] provide a robust exploration of this potential association. Utilizing data from Taiwan’s National Health Insurance Research Database spanning from 2000 to 2015, the researchers conducted a retrospective cohort study involving 45,403 patients with NAFLD and 181,612 matched controls without NAFLD. The study aimed to investigate the risk of developing IBD among patients with NAFLD and to identify potential risk factors associated with this development. The findings revealed that patients with NAFLD had a 2.245-fold increased risk of developing IBD compared to controls. Subgroup analysis indicated a 2.260-fold increased risk for ulcerative colitis and a 2.231-fold increased risk for Crohn’s disease among NAFLD patients. Additionally, comorbidities such as diabetes mellitus, dyslipidemia, obesity, and obstructive sleep apnea were significantly associated with an elevated risk of IBD in the NAFLD cohort. Notably, patients with both NAFLD and liver cirrhosis exhibited a higher risk of developing IBD compared to those without cirrhosis, highlighting a potential interplay between hepatic and systemic inflammation in driving IBD pathogenesis.

This study presents several strengths that lend credibility to its findings. The use of a nationwide database ensures a large sample size, enhancing the statistical power to detect associations even for relatively rare outcomes like IBD. Furthermore, the 4:1 matching ratio for controls based on sex, age, and inclusion date reduces selection bias, ensuring comparability between groups. The longitudinal design, with a follow-up period spanning up to 16 years, provides a temporal framework for assessing the development of IBD following NAFLD diagnosis. This methodological rigor and the inclusion of multivariable Cox regression analyses to adjust for potential confounders, such as comorbidities and demographic factors, strengthen the causal inference between NAFLD and IBD risk.

However, while the study’s strengths are evident, several limitations warrant careful consideration. The reliance on ICD codes for identifying NAFLD and IBD, without histopathological confirmation, raises concerns about diagnostic accuracy. NAFLD encompasses a spectrum of disease severity, including simple steatosis and NASH, but the lack of stratification within the NAFLD cohort precludes analysis of whether the association with IBD differs by disease severity. Additionally, the study population was exclusively Taiwanese, limiting the generalizability of findings to other ethnic and racial groups with potentially distinct genetic and environmental risk factors. The absence of detailed data on medication use, including treatments for metabolic comorbidities or IBD, is another limitation, as these interventions could confound the observed associations. Moreover, lifestyle factors such as diet and physical activity, which are known to influence both NAFLD and IBD risk, were not captured in the dataset, representing another potential source of unmeasured confounding.

The findings of this study have important clinical implications. NAFLD has traditionally been viewed as a hepatic manifestation of systemic metabolic dysfunction, but its association with IBD underscores the need for a more comprehensive approach to patient care [3]. Gastroenterologists and hepatologists should work collaboratively to develop screening strategies for early detection of IBD in patients with NAFLD, particularly those with additional risk factors such as diabetes, dyslipidemia, and obesity. Such multidisciplinary care models can facilitate timely diagnosis and intervention, potentially improving outcomes for patients at the intersection of these 2 chronic inflammatory conditions. Furthermore, the coexistence of multiple metabolic and inflammatory risk factors highlights the necessity of proactive monitoring and intervention strategies.

From a research perspective, understanding the biological mechanisms linking NAFLD and IBD is critical. Both conditions are characterized by systemic inflammation, altered immune responses, and disruptions in the gut-liver axis [4]. Investigating the interplay between gut microbiota, hepatic lipid metabolism, and pro-inflammatory cytokine pathways could provide novel insights into their shared pathogenesis [4]. For instance, dysbiosis in the gut microbiome and the role of microbial metabolites warrant further exploration to uncover potential therapeutic targets.

In conclusion, the study provides compelling evidence for an association between NAFLD and an increased risk of IBD, underscoring the importance of recognizing NAFLD as a systemic condition with implications beyond the liver. The robust methodology and large sample size strengthen the findings, while the limitations highlight the need for further research. Looking ahead, a multidisciplinary approach that integrates metabolic and inflammatory disease management is essential to optimize care for individuals with these interconnected chronic diseases.

NOTES

Funding Source

The author received no financial support for the research, authorship, and/or publication of this article.

Conflict of Interest

Im JP is editorial board member of the journal but was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.

Data Availability Statement

Not applicable.

Author Contributions

Conceptualization: Kim S, Im JP. Original draft: Kim S. Review and editing: Im JP. Approval of final manuscript: Kim S, Im JP.

REFERENCES

1. Nagata T, Funakoshi S, Morihara D, et al. Malnutrition and inflammation status in nonobese patients with inflammatory bowel disease are associated with nonalcoholic fatty liver disease: a retrospective study. Intest Res 2023;21:471–480.Article PubMed PMC PDF
2. Aggarwal K, Singh B, Goel A, et al. Complex dichotomous links of nonalcoholic fatty liver disease and inflammatory bowel disease: exploring risks, mechanisms, and management modalities. Intest Res 2024;22:414–427.Article PubMed PMC PDF
3. Boustany A, Rahhal R, Mitri J, et al. The impact of nonalcoholic fatty liver disease on inflammatory bowel disease-related hospitalization outcomes: a systematic review. Eur J Gastroenterol Hepatol 2023;35:1067–1074.Article PubMed
4. Di Vincenzo F, Del Gaudio A, Petito V, Lopetuso LR, Scaldaferri F. Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review. Intern Emerg Med 2024;19:275–293.Article PubMed PMC PDF
5. Wang YH, Chung CH, Huang TY, et al. Association between nonalcoholic fatty liver disease and incidence of inflammatory bowel disease: a nationwide population‑based cohort study. Intest Res 2025;23:76–84.Article PubMed PDF

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Elucidating the association between nonalcoholic fatty liver disease and incidence of inflammatory bowel disease: a focus on systemic inflammation

Intest Res. 2025;23(1):3-5. Published online January 24, 2025

DOI: https://doi.org/10.5217/ir.2024.00204

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Elucidating the association between nonalcoholic fatty liver disease and incidence of inflammatory bowel disease: a focus on systemic inflammation