Atrial Fibrillation Is Highly Prevalent Yet Undertreated in Patients With Biopsy-proven Nonalcoholic Steatohepatitis

Maureen Whitsett; Jane Wilcox; Amy Yang; Lihui Zhao; Mary Rinella; Lisa B. VanWagner


Liver International. 2019;39(5):933-940. 

In This Article

Abstract and Introduction


Background & Aims: Nonalcoholic steatohepatitis (NASH) is associated with increased cardiovascular disease. Atrial fibrillation is a prominent risk marker for underlying cardiovascular disease with a prevalence of 2% in patients <65 years old. Atrial fibrillation prevalence in NASH is unknown. We sought to assess the prevalence and impact of atrial fibrillation on healthcare utilization in NASH.

Methods: Patients were identified from a tertiary care centre Electronic Database from 2002 to 2015. International Classification of Diseases 9 (ICD9) codes identified comorbidities and atrial fibrillation. Descriptive statistics were used to compare characteristics between patients with NASH with and without atrial fibrillation.

Results: Of 9108 patients with ICD9 diagnosis of NASH, 215 (2.3%, mean age 57 years, 32% male) had biopsy-proven NASH. Atrial fibrillation prevalence was 4.6%. Patients with NASH and atrial fibrillation had a higher prevalence of heart failure (54.5% vs 8.8%, P < 0.001) and cerebrovascular (27.3% vs 2.0%, P < 0.001) or vascular disease (54.5% vs 13.2%, P = 0.002), compared to NASH without atrial fibrillation. All patients with NASH and atrial fibrillation had a CHA2DS2VASc score ≥2 indicating high stroke risk and need for anticoagulation. Eight of 10 patients were eligible for anticoagulation and 5 of 8 (62.5%) received appropriate therapy.

Conclusion: Atrial fibrillation prevalence is two-fold higher in patients with NASH compared to the general population. Patients with NASH have a high risk of stroke; however, many do not receive appropriate guideline-directed therapy. Future studies are needed to identify whether guideline-based management of atrial fibrillation in NASH reduces cardiovascular morbidity and mortality.


Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among patients with nonalcoholic fatty liver disease (NAFLD) and its severe form, nonalcoholic steatohepatitis (NASH), which may lead to hepatic fibrosis and cirrhosis.[1] Hepatic fibrosis increases risk for liver-related and CVD mortality in patients with NAFLD/NASH. Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. An estimated 3.03 million people in the United States have AF, and the prevalence increases as patients age ranging from 0.5% to 12%.[2,3] The inflammatory milieu of NAFLD[4–6] may contribute to cardiac remodelling and lead to the development of arrhythmias.[7,8] Recently, Targher et al[9,10] demonstrated in two separate studies that NAFLD, diagnosed by ultrasonography, is associated with an increased prevalence and incidence of AF among patients with type 2 diabetes. In a prospective population-based study from Finland, researchers also found that ultrasound-diagnosed NAFLD was independently associated with the risk of incident AF independent of confounders including age, sex, body mass index (BMI) and diabetes status.[11] However, these findings have not been replicated in all population-based large cohorts. For example, the Framingham Heart Study and Study of Health in Pomerania (SHIP) showed no association between AF and either computerized tomography (CT) or ultrasound-diagnosed hepatic steatosis.[12,13] The prevalence and impact of AF in biopsy-proven NASH are unknown.

Most studies which examine clinical outcomes in patients with AF and coexisting liver disease are derived from the transplant population. Patients with AF who undergo liver transplantation have increased cardiovascular morbidity and mortality, greater need for post-operative intensive care unit level care, and lengthier hospitalizations.[14–17] There is a paucity of data which specifically examine the impact of AF on healthcare utilization in the non-transplant NASH population. Because patients with NASH have risk factors for the development of cardiac abnormalities, it is prudent to better characterize this group further to fully understand how management of these patients might impact morbidity and mortality.

The purpose of the current study was to determine the prevalence of AF among patients with NASH, to assess the impact of AF on healthcare utilization in patients with NASH, and to determine what, if any, guideline-based therapy patients with concomitant NASH and AF are receiving. We hypothesized that given the propensity for patients with NASH to develop arrhythmias, the prevalence of AF in patients with NASH will exceed that of the general population. Additionally, patients with NASH and AF will have a higher comorbidity burden and healthcare utilization than patients with NASH alone.