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. Author manuscript; available in PMC: 2020 Dec 1.
Published in final edited form as: Clin Gastroenterol Hepatol. 2019 Mar 12;17(13):2816–2818. doi: 10.1016/j.cgh.2019.02.045

Crohn’s Disease is Associated with an Increased Prevalence of Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study using Magnetic Resonance Proton Density Fat Fraction Mapping

Scott McHenry 1, Yeshika Sharma 2,3, Ankita Tirath 4, Richard Tsai 5, Aaron Mintz 5, Tyler J Fraum 5, Amber Salter 6, Jeffrey D Browning 7, Avegail G Flores 1, Nicholas O Davidson 1, Kathryn J Fowler 5,8, Matthew A Ciorba 1,a, Parakkal Deepak 1,a,*
PMCID: PMC7539260  NIHMSID: NIHMS1631969  PMID: 30876963

Introduction:

Nonalcoholic fatty liver disease (NAFLD) commonly coexists with Crohn’s disease (CD); however, it remains unclear if it is more prevalent than would be expected as ultrasound surveys of CD patients report a very wide range of prevalence (9-40%)1–3. To address this uncertainty, we performed a prospective, cross-sectional survey of NAFLD in CD patients by generating Magnetic Resonance Proton Density Fat Fraction (MR-PDFF) maps as compared to two control populations. MR-PDFF provides a quantitative, sensitive and specific (97% and 100%, respectively) radiographic surrogate for liver fat4.

Methods:

Consecutive CD patients were enrolled during staging MR enterography (MRE) at Washington University Inflammatory Bowel Disease (IBD) Center’s network of outpatient clinics in St. Louis, MO, USA, from 6/1/2017 – 5/31/18. The exclusion criteria included an alternative etiology of liver disease or greater than moderate alcohol use.

To increase the generalizability of our results, we used two control populations. The first control population was a retrospective hospital and clinic based cohort, which was selected from a previously published database of all abdominal MRs performed at Washington University in St. Louis between 2013 to 20145. A second control population was drawn from participants from the Dallas Heart Study (DHS), a population-based probability sample recruited between 2000 to 20026. For each control population, a random 2:1 sample was chosen for analysis.

For the CD patients and internal controls, MR examinations included gradient recall echo low flip angle proton density weighted images, and PDFF maps were obtained7. For the controls from the DHS, fat quantification was by 1H MR spectroscopy (MRS), which shows excellent agreement with the PDFF method8. The primary outcome was the proportion with >5.5% liver fat (NAFLD).

Results:

After applying the inclusion/exclusion criteria, 311 subjects with CD, 622 internal controls and 622 DHS controls were studied. NAFLD was diagnosed in 38% of the Crohn’s patients compared to 30% from the internal controls and 28% from the DHS (p = 0.010 and 0.002, respectively; see Figure 1.A). This was most pronounced in lean subjects with BMI <25 kg/m2 where NAFLD was present in 20% of CD patients compared to 10% of either control population (p = 0.024 and 0.013, respectively; see Figure 1.A). After multivariate logistic regression adjusting for BMI, age, sex and ethnicity, CD independently predicted NAFLD compared to our internal controls [OR of 2.5 (95% CI 1.8 – 3.5, p = <0.001)] or DHS controls [OR of 1.6 (95% CI 1.1 – 2.3, p = 0.008)]. A hypothesis generating observation was that NAFLD with an elevated FIB-4 score (>1.3) was also significantly greater in the CD patients (11 % vs 5%; p <0.001; see Figure 1.B).

Figure 1:

Figure 1:

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A Overall Rates of NAFLD are Higher in Crohn’s Disease

B Crohn’s Disease Patients Have Higher Rates of NAFLD with an Elevated Fibrosis-4 Score

Footnotes: NAFLD, nonalcoholic fatty liver disease; BMI, body mass index; DHS, Dallas Heart Study

Discussion:

Here we report findings from the largest and only study to use the non-invasive and quantitative MR-PDFF method to assess the prevalence of NAFLD in a cohort of patients with Crohn’s. We clearly show that CD is an independent risk factor for NAFLD. The prevalence of NAFLD with an elevated FIB-4 score was also significantly higher than would be expected with the caveat that this score has not been validated against histology in this population.

The strengths of our study include a large consecutively recruited population of CD patients along with the inclusion of both clinic-based and population-based control populations to limit healthy-volunteer and sick-patient selection bias, respectively. The key difference between our study and most previously published studies is our use of an imaging technology (MR-PDFF) with markedly increased sensitivity and specificity4.

Our study has several limitations. This was a single tertiary referral centers population of CD patients that were selected at the time of staging MRE, which may not be generalizable to CD patients at other centers or with colon-only distribution. This limitation is mitigated as there was no difference in percent liver fat when comparing those with colon-only distribution or as stratified by clinical severity as assessed by the Harvey Bradshaw index.

Further study of CD patients with NAFLD may shed light on the underlying pathophysiology and identify therapeutic targets associated with the “lean” NAFLD phenotype in the population at large. Though prior studies hypothesize a role of micronutrient deficiencies, total parenteral nutrition and chronic glucocorticoid use, our results do not support such a pathophysiology to explain the greater than expected prevalence of NALFD in the CD population; however, we do acknowledge that the aim of this study was not to clarify the disease-specific mechanisms that are predisposing to hepatic steatosis but are actively pursuing this line of questioning.

Funding statements and Acknowledgements:

SM is supported by an Institutional National Research Service Award (T32-DK007130-45). NOD supported by grants DK-56260, HL-38180 and DK-112378. PD is supported by a Junior Faculty Development Award from the American College of Gastroenterology. M.A.C. is supported by DK109384, a Crohn’s and Colitis Foundation Daniel H Present Senior Research Award (Ref. 370763) and philanthropic support from the Givin’ it all for Guts Foundation (https://qivinitallforquts.org) and the Lawrence C. Pakula MD IBD Research Innovation and Education Fund. The work performed in this paper was additionally supported by grants provided by the National Institute of Health through the Washington University in Saint Louis’ Digestive Disease Research Core (P30 DK052574). Additional grant support for the REDCap database was provided by the Clinical and Translational Science Award (UL1 TR000448) and Siteman Cancer Center Support Grant (P30-CA091842). This work supported in part by grant UL1TR001105 from the National Center for Advancing Translational Science, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Center for Translational Medicine, The University of Texas Southwestern Medical Center and its affiliated academic and health care centers, the National Center for Advancing Translational Sciences, or the National Institutes of Health.

Footnotes

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