S1587 The Impact of Nonalcoholic Fatty Liver Disease on Inflammatory Bowel Disease-Related Hospitalization Outcomes: A Systematic Review

Introduction: Nonalcoholic fatty liver disease (NAFLD) has been the subject of intensive research efforts as it has become the most common liver disease worldwide. Evidence suggests that patients with inflammatory bowel disease (IBD) are at higher risk of developing NAFLD. However, there is limited information currently available on how NAFLD may affect the clinical course of IBD. The aim of this systematic review is to characterize the association of NAFLD on IBD-related hospitalization outcomes in patients afflicted by both conditions (NAFLD+IBD). Methods: All observational studies assessing IBD-related hospitalization outcomes in patients with NAFLD were included. Studies with both inpatient or outpatient data were included in the systematic review but analyzed separately. Exclusion criteria were studies published in languages other than English or French, or those involving pediatric population. For studies involving inpatients, primary outcomes were IBD-related hospitalization length of stay, need for surgery, readmission rates, inpatient mortality, and hospitalization costs. For studies involving patients initially followed as outpatients, primary outcomes also included IBD-related hospitalization rates. Results: Overall, 3,252 citations were retrieved and 7 studies met the inclusion criteria (1,574,937 patients) (Figure 1); all were observational, of high quality, and originated in the United Sates. Measurable outcomes reported in these studies were few and with insufficient similarity across studies to complete a quantitative assessment. Only 1 study reports NAFLD severity. Two studies suggested a higher rate of hospitalization for patients with both NAFLD and IBD compared to IBD alone (incidence rate ratio of 1.54; 95% CI: 1.33-1.79) (Table 1). Conclusion: This is the first systematic review to date that evaluates any possible association of NAFLD with IBD-related hospitalization outcomes. Despite the paucity and low quality of available data, our findings indicate that NAFLD may be associated with worse outcomes amongst IBD patients (especially Crohn’s disease). Besides metabolic risk factors common for both diseases, specific IBD-related mechanisms hypothesized to explain this association include micronutrient deficiencies, total parenteral nutrition after bowel resections, and chronic use of IBD medications. Further and higher certainty of evidence is needed for better characterization of such clinical impact.Figure 1.: Preferred reporting items for systematic reviews (PRISMA) of study selection. Abbreviations: ACG, American College of Gastroenterology; DDW, Digestive Disease Week. Table 1. - Study characteristics Authors, Year, Country Type of Study Patients selection Hospitalization Rate Hospitalization Length of Stay Need for surgery Readmission In-patient Mortality Hospitalization Cost Studies including outpatients McHenry et al. 2019 (USA) Prospective (abstract) Included: CD patients propectively enrolled (12 months) at the time of staging MRE at tertiary referral center for IBD, Excluded: Alternative liver disease etiologies (a) aHR=2.5; 95% CI=(1.3-4.9); P< 0.05 Not reported aHR=2.6; 95% CI=(1.4-5.0); P< 0.05 Not reported Not reported Not reported Young et al. 2015 (USA) Retrospective (abstract) Included: Patients aged 19 years and above with CD and followed at least 1 year at the institution's IBD Center between 2000 and 2013, Excluded: Patients with a chronic liver condition other than NAFLD IRR=1.54; 95% CI=(1.33-1.79); P< 0.0001 and aIRR=1.69; 95% CI=(1.40-2.03); P< 0.0001 Not reported Not reported Not reported Not reported Not reported Sourianarayanane et al. 2013 (USA) Retrospective Included: Patients with IBD and abdominal imaging performed at the institution, Excluded: Patients who had other types of liver diseases or who had a prior diagnosis of a liver disease other than NAFLD Not reported Not reported NAFLD present: 55.3% vs NAFLD absent: 55.3%; P=0.99 and aOR=3.7; 95% CI=(1.5-9.3); P=0.005 (b) Not reported Not reported Not reported Studies including inpatients Abomhya et al. 2022 (USA) Retrospective Included: CD patients discharged from US hospitals between 2016 and 2018, Excluded: Age< 18, those with missing principal diagnoses, missing information, repeat readmissions, and alcoholic fatty liver Not applicable NAFLD present: mLOS=4, IQR=(2-6) vs NALFD absent: mLOS=3, IQR=(2-6); P< 0.001 Not reported NAFLD present: 15.6% vs NAFLD absent: 11.1%; P< 0.001 and aOR=1.6; 95% CI=(1.3-1.9); P< 0.001 NAFLD present: 2.2% vs NAFLD absent: 1.2%; P=0.004 and aOR=1.7; 95% CI=(1.1-2.6); P< 0.03 NAFLD present: mTC=32,305.5, IQR=(18,600-61,599) vs NAFLD absent: mTC=30,782, IQR=(16,847-58,667); P< 0.001 Chhoun et al. 2022 (USA) Retrospective (abstract) Included: Patients aged 18 years and above with diagnoses of IBD, Excluded: Not reported Not applicable aLOS=-1.01; 95% CI=(-1.23-1.22); P=0.95 Not reported Not reported aOR=0.64; 95% CI=(0.47-0.89); P< 0.009 TC=-1,572.96; 95% CI=(-4,773.51-1,627.59); P=0.33 Patel et al. 2020 (USA) Retrospective (abstract) Included: Adults with a principal discharge diagnosis of IBD, Excluded: Age less than 18, non-NAFLD chronic liver disease, December discharge, death during index admission, and missing data for lenfth of index admission Not applicable aOR=-0.10; 95% CI=(-0.54-0.34); P=0.661 Not reported aOR=0.79; 95% CI=(0.68–0.92); P=0.003 Not reported aOR=259; 95% CI=(-787-1,306); P=0.627 Noorian et al. 2022 (USA) Retrospective IBD patients in Model 1 (c) Not applicable CD: aLOS=0.71; 95% CI=(0.42-1.01); P< 0.01, UC: aLOS=0.64; 95% CI=(0.26-1.03); P< 0.01 CD: aHR=1.04; 95% CI=(0.86-1.26); P=0.65, UC: aHR=0.94; 95% CI=(0.71-1.25); P=0.68 CD: aHR=1.90; 95% CI=(1.76-2.04); P< 0.01, UC: aHR=1.65; 95% CI=(1.46-1.86); P< 0.01 Not reported CD: COC=7,312; 95% CI=(3,950-10,674); P< 0.01, UC: COC=9,392; 95% CI=(4,121-14,662); P< 0.01 IBD patients in Model 2 (d) Not applicable CD: aLOS=0.71; 95% CI=(0.41-1.01); P< 0.01, UC: aLOS=0.61; 95% CI=(0.23-1.00); P< 0.01 CD: aHR=1.05; 95% CI=(0.86-1.27); P=0.64, UC: aHR=0.94; 95% CI=(0.71-1.25); P=0.69 CD: aHR=1.89; 95% CI=(1.76-2.04); P< 0.01, UC: aHR=1.64; 95% CI=(1.46-1.86); P< 0.01 Not reported CD: COC=7,223; 95% CI=(3,851-10,594); P< 0.01, UC: COC=9,172; 95% CI=(3,962-14,382); P< 0.01 IBD patients in Model 3 (e) Not applicable CD: aLOS=0.72; 95% CI=(0.42-1.02); P< 0.01, UC: aLOS=0.59; 95% CI=(0.21-0.98); P< 0.01 CD: aHR=1.05; 95% CI=(0.87-1.27); P=0.59, UC: aHR=0.96; 95% CI=(0.73-1.28); P=0.80 CD: aHR=1.89; 95% CI=(1.75-2.03); P< 0.01, UC: aHR=1.61; 95% CI=(1.42-1.82); P< 0.01 Not reported CD: COC=7,634; 95% CI=(4,236-11,031); P< 0.01, UC: COC=8,358; 95% CI=(3,200-13,516); P< 0.01 IBD patients in Model 4 (f) Not applicable CD: aLOS=0.72; 95% CI=(0.43-1.02); P< 0.01, UC: aLOS=0.62; 95% CI=(0.24-1.00); P< 0.01 CD: aHR=1.05; 95% CI=(0.87-1.27); P=0.64, UC: aHR=0.94; 95% CI=(0.71-1.25); P=0.80 CD: aHR=1.90; 95% CI=(1.76-2.04); P< 0.01, UC: aHR=1.64; 95% CI=(1.46-1.86); P< 0.01 Not reported CD: COC=7,354; 95% CI=(923-17,116); P< 0.03, UC: COC=8,358; 95% CI=(3,200-13,516); P< 0.01 Abbreviations: ACC, additional cost of care; aHR, adjusted hazard ratio; aIRR, adjusted incidence rate ratio; aLOS, additional length of stay in days; CI, confidence interval; CD, Crohn’s disease; HR, hazard ratio; COC, cost of care in USD; IBD, inflammatory bowel disease; IRR, incidence rate ratio; IQR, interquartile range; mLOS: median length of stay in days; MRE, magnetic resonance elastography; mTC, median total charges in USD; NAFLD, non-alcoholic fatty liver disease; OR: odds ratio; TC, total charges in USD; UC: ulcerative colitis.a: alcohol abuse, viral hepatitis, primary sclerosing cholangitis; b: small bowel surgery; c: adjusted for obesity, dyslipidemia, Charlson-Deyo comorbidity index, hospital characteristics, source of payment, patient income, and elective status of admission; d: adjusted for all variables of model 1 as well as NASH and cirrhosis; e: adjusted for all variables from model 1 but excluded patients with NASH and cirrhosis; f: adjusted for all variables of model 2 and common diagnosis in the top 3 diagnosis positions for admissions in which patients experienced death: sepsis, pneumonia, acute respiratory failure, and chronic kidney disease.

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