Incidence and Factors Associated with the Development of Non Alcoholic Fatty Liver Disease(NAFLD) Among Patients with Rheumatoid Arthritis

Ani John¹, Angela Witt Prehn², Hebatullah Tawfik², George W. Reed³ and Joel Kremer⁴, ¹School of Health Sciences, Walden University, Minneapolis, CA, ²School of Health Sciences, Walden University, Minneapolis, MN, ³Corrona, LLC, Southborough, MA, ⁴The Center for Rheumatology, Albany Medical College, Albany, NY

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Cardiovascular disease, hypertension, metabolic syndrome, methotrexate (MTX) and rheumatoid arthritis (RA)

Session Information

Date: Sunday, November 13, 2016

Title: Epidemiology and Public Health - Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: NAFLD is a leading cause of chronic liver disorders, unrelated to significant alcohol use. RA and NAFLD have shared risk factors such as age, gender, race/ethnicity, metabolic syndrome, obesity, diabetes, and dyslipidemia^1.Little is known about the incidence of NAFLD in patients with RA. This study determined the incidence rate, time to event, and factors associated with the development of NAFLD in this population.

Methods: Longitudinal data from the Corrona RA registry (2001-2014) of adults without NAFLD (n=17,481) were used in this retrospective analysis. The Fibrosis-4 index², a validated noninvasive tool, was used to determine the presence of NAFLD (score ³1.3) at baseline. Kaplan Meier and adjusted Cox proportional hazard analysis were used to determine the incidence rate, time to event, and the predictors associated with NAFLD. Factors identified apriori and significant variables from the unadjusted analysis were included in the multivariate analysis (see Table 2).

Results: At baseline, the mean age of the cohort was 54 years (SD 12.4); 88 % were Caucasian; 79% female; with an average RA disease duration of 8 years. The most prevalent comorbidities were hypertension (37%), dyslipidemia (22%), and metabolic syndrome (19%). About 72% had a BMI ≥25, 70% were currently using MTX, and 40% reported using alcohol. The cumulative overall incidence was 31%; mean time to NAFLD was 7 years, 1.4% with advanced disease (see Table 1). In the multivariate analysis (see Table 2), independent predictors for increased risk for NAFLD were age (middle and elderly), hypertension, CVD, dyslipidemia, metabolic syndrome, exercise, use of MTX, and non-MTX antirheumatic drugs. Factors associated with reduced risk of NAFLD were gender (female), BMI ≥25, all RA disease duration categories, having insurance and being divorced/separated.

Conclusion: During the study period of 13 years, a third of patients with RA in this study developed mild/moderate NAFLD in a fairly short period of time. RA patients with dyslipidemia, metabolic syndrome, hypertension and cardiovascular disease were at higher risk for developing NAFLD. The ubiquitous prevalence of NAFLD is an emerging public health challenge, highlights the need for early diagnosis and management of NAFLD.

Table1: Overall NAFLD Incidence Rates and Time to Event (N=40,300, n= 17481)
	Variable	Incidence Cases n (%)	Incidence Cases/ 1000PY [95% CI]	Time to Event (years) [95% CI]
	Overall NAFLD¹	5328 (30.5%)	95.03 [92.60, 97.45]	7.18 [7.09,7.29]
	Mild/Moderate NAFLD²	5079 (29.1%)	90.59 [88.21, 92.96]	7.35 [7,24,7.47]
	Advanced NAFLD³	249 (1.4%)	4.44 [3.89, 4.99]	12.84 [12.78,12.90]
	1-FIB-4 score ³ 1. 3; 2= FIB-4 score ³ 1. 3 but < 2.67; ³ 2.67= Advanced disease

Table 2: Adjusted Analyses -Significant Predictors for the development of NAFLD
Baseline Factors	Hazard Ratio	95.0% CI	p Value
Age* Referent Younger (18-<40)
Middle Age (40 -<60)	5.16	4.16, 6.40	< .001
Elderly (>=60)	13.94	11.22, 17.31	< .001
Gender (Female)	0. 81	0.76,0.86	< .001
Marital Status: Referent Single / Widowed
Divorced or Separated	0.87	0.79, 0.97	0.010
Insurance (yes) **	0.89	0.83, 0.95	0.001
Exercise (Yes)	1.09	1.02, 1.15	0.009
Hypertension **	1.11	1.04, 1.19	0.003
Cardiovascular Disease**	1.19	1.08, 1.31	0.001
Dyslipidemia *	1.31	1.20, 1.42	0.001
Obese (BMI >=25) *	0.84	0.79, 0.90	< .001
Metabolic Syndrome*	1.21	1.09, 1.35	0.001
Disease Duration** Referent Early RA
2 to 5 years	0.87	0.80, 0.94	0.001
5 to 10 years	0.87	0.80, 0.95	0.001
>10 years	0.88	0.82, 0.95	0.001
MTX use *	1.08	0.01, 1.16	0.021
cDMARD Use**	1.08	1.01, 1.15	0.027
BMI = Body Mass Index; CDAI = Clinical Disease Activity Index; MTX= Methotrexates; cDMARD = Conventional disease modifying antirheumatic drugs (excluding MTX). * – Identified apriori; ** met signific ance (p =value or +/_10% difference)

Reference ¹Ahmed, M.(2006). Rheumatoid arthritis induced-fatty liver theory: One reason for global increase in prevalence of diabetes. Medical Hypotheses,66(4),862-863. ²Shah, A.,et.al.,(2009). Use of the Fib-4 Index for non-invasive evaluation of fibrosis in nonalcoholic fatty liver disease. Clinical Gastroenterology And Hepatology. 7(10),1104.

Disclosure: A. John, None; A. W. Prehn, None; H. Tawfik, None; G. W. Reed, Corrona Research Foundation, 3; J. Kremer, Corrona Research Foundation, 3.

To cite this abstract in AMA style:

John A, Prehn AW, Tawfik H, Reed GW, Kremer J. Incidence and Factors Associated with the Development of Non Alcoholic Fatty Liver Disease(NAFLD) Among Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/incidence-and-factors-associated-with-the-development-of-non-alcoholic-fatty-liver-diseasenafld-among-patients-with-rheumatoid-arthritis/. Accessed .

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