Non-alcoholic fatty liver disease linked to higher risk of blood clots in healthy adults

A recent Scientific Reports study investigates the association between nonalcoholic fatty liver disease (NAFLD) and the prevalence of venous thromboembolism (VTE) among healthy Korean adults.

Study: Association of nonalcoholic fatty liver disease and venous thromboembolic disease in healthy adults in Korea: A nationwide study. Image Credit: ART-ur / Shutterstock.com

What is NAFLD?

NAFLD includes many liver diseases, such as cirrhosis, steatosis, and nonalcoholic steatohepatitis (NASH). Although NAFLD is associated with the accumulation of fats in the liver, it often affects many other organs in the body.

For example, NAFLD has been linked with manifestations of cardiovascular disease (CVD), colorectal cancer, metabolic syndrome, type 2 diabetes, chronic kidney disease, obstructive sleep apnea, and polycystic ovary syndrome.

Venous thromboembolism (VTE) is associated with Virchow’s triad, which includes hypercoagulability, venous stasis, and endothelial cell damage. A recent report states that VTE has become a leading cause of global deaths. Several factors that increase the risk of VTE include trauma, age, immobility, oral contraceptives, cancer, obesity, and genetic or acquired thrombophilia. 

Although many studies have evaluated the association between fatty liver and increased VTE risk, most outcomes were based on a small sample size.

About the study

The current study used data from the National Health Insurance Service-National Sample Cohort 2.0 (NHIS-NSC 2.0). The NHIS is a compulsory health insurance program that provides medical care coverage to all Korean residents, which amounts to about 97% of the total population.

Four databases have been linked to this cohort and provide information on the demographics, medical claims with diagnoses, hospitalization and treatment, check-ups, and medical institutions.

All individuals above 18 years of age are recommended to undergo health screening in Korea. This health screening comprises laboratory tests, physical examinations, chest radiography, and a questionnaire to obtain health-related behaviors and medical history.

The current study included individuals who underwent national health check-ups more than once between 2009 and 2014. All individuals with liver disease were selected for this study. Participants were taking medication for their condition, including lipid-lowering agents.

Study findings

Based on the eligibility criteria, a total of 472,212 participants were included in the study. The study cohort was divided into four groups in accordance with fatty liver index (FLI) quartile values, including the first (Q1), second (Q2), third (Q3), and fourth (Q4) quartiles. FLI is regarded as a surrogate marker for fatty liver. 

In the four quartiles, an increase in the body mass index (BMI), percentage of men, number of current smokers, and amounts of alcohol consumption was observed. Participants with higher FLI values were associated with higher fasting glucose levels, blood pressures, and gamma-glutamyl transferase (GGT) levels.

Compared to those with lower FLI values, higher FLI values were linked to greater comorbidities. Thus, unfavorable lipid profiles were associated with elevated FLI values.

VTE occurs in older adults with more comorbidities. Typically, this group of individuals exhibits a higher BMI, as well as aspartate aminotransferase (AST), cholesterol, AST/alanine transaminase (ALT) ratio, and blood glucose levels. Importantly, alcohol consumption, physical activity, and ALT were not linked with VTE development. 

These findings indicate that FLI is associated with an increased risk of VTE development. Since the liver secretes many factors linked with coagulation and fibrinolysis pathways, NAFLD may be associated with a hypercoagulable state. Although the exact mechanism responsible for this association is unclear, it is possible that chronic liver inflammation could disrupt the coagulation system.

Previous studies have highlighted an increase in individual procoagulant factors, particularly VIII, IX, XI, and XII, in NAFLD patients irrespective of their age, BMI, and sex. NAFLD severity has been linked to thrombin generation, which is a universal coagulation process.

A sequential increase in thrombin generation based on NAFLD form was reported. For example, in the most advanced form of NAFLD, the highest levels of factor VIII and lowest protein C levels were recorded.

Conclusions

The current study has some limitations, including the consideration of only FLI as a biomarker for fatty liver without performing any diagnostic tests. Notably, liver biopsy is the gold standard for NAFLD diagnosis; however, this process is invasive and expensive.

Since this is an observational study, the causal relationship between NAFLD and increased VTE risks was not uncovered. Therefore, future research must focus on elucidating the causality.

Despite these limitations, the study findings indicate that individuals with a higher FLI value, even without a significant liver disease, were at a higher risk of VTE as compared to those with lower FLI values.