Liver stiffness, but not fatty liver disease, linked to atrial fibrillation

Fatty liver disease does not seem to contribute to prevalent or incident atrial fibrillation (AF), but higher liver stiffness does, particularly among individuals without steatosis, reports a recent study.

“This association might be driven by venous congestion instead of fibrogenesis, but this awaits further validation,” the researchers said. “We recommend assessing cardiovascular health in participants with high liver stiffness, especially in the absence of overt liver disease.”

This study included participants attending the abdominal ultrasound program between 2009-2014 within the Rotterdam Study, a large prospective ongoing cohort. Those with no AF data or >20-percent missing data across analysis variable were excluded.

Ultrasound, transient elastography, and 12-lead electrocardiograms were used to assess steatosis, liver stiffness, and AF, respectively. Incident AF was based on medical records and complete until 2014. Finally, the researchers quantified the associations between fatty liver disease and AF using logistic and Cox regression.

A total of 5,825 participants (mean age 69.5 years, 42.9 percent male) met the eligibility criteria, of whom 35.7 percent had steatosis, 7.0 percent had prevalent AF, and 73.3 percent had available liver stiffness measurement. [J Hepatol 2022;77:931-938]

In fully adjusted models, steatosis showed no significant association with prevalent AF (odds ratio [OR], 0.80, 95 percent confidence interval [CI], 0.62‒1.03). Such findings were consistent for nonalcoholic or metabolic dysfunction-related fatty liver disease.

In contrast, liver stiffness significantly correlated with prevalent AF (OR, 1.09 per kPa, 95 percent CI, 1.03‒1.16), but this finding only persisted among individuals without steatosis (OR, 1.18 per kPa, 95 percent CI, 1.08‒1.29). Of note, no associations existed between steatosis and incident AF (hazard ratio, 0.88, 95 percent CI, 0.59‒1.33; follow-up, 2.1 years).

“Fatty liver disease is undisputedly associated with fibrogenesis as reflected by higher liver stiffness,” the researchers said. “A few studies have already investigated the association of fibrosis or liver stiffness with AF.”

One such study was conducted among 76 Finnish older adults and demonstrated an association between liver stiffness and AF. In another analysis, markers for fibrosis (ie, fibrosis-4 [FIB-4] and aspartate aminotransferase-to-platelet ratio index) significantly correlated with AF among patients with nonalcoholic fatty liver disease. [PLoS One 2017;12:e0173855; Sci Rep 2020;10:5023]

“However, using biomarker-based algorithms to assess fibrosis limits the possibility for accurate adjustment, given that those algorithms themselves include relevant predictors for AF (eg, FIB-4 includes age),” the researchers said.

Although liver stiffness is not a direct measurement for fibrosis, it may be affected by portosystemic congestion, inflammation, cholestasis, and central venous pressure. [J Hepatol 2010;52:206-210; Clin Gastroenterol Hepatol 2019;17:54-64.e51; Hepatology 2007;45:1290-1297]

“The latter is of particular interest since individuals with AF have higher right atrium pressure, which is associated with (subclinical) venous congestion in the liver,” the researchers said. [J Card Fail. 2018; 24: 177-185; J Am Heart Assoc 2020;9:e016689]

“Since this study indicates that increased liver stiffness may result from conditions originally not linked with liver disease, further research is required to determine if the same liver stiffness cut-offs for fibrosis are applicable in participants with concomitant atrial fibrillation,” they added.