Healthy Adults More Prone To Blood Clots If They Suffer From Non-Alcoholic Fatty Liver Disease


A recent study published in Scientific Reports explores the link between nonalcoholic fatty liver disease (NAFLD) and the occurrence of venous thromboembolism (VTE) in healthy Korean adults.


All About NAFLD

Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of liver disorders such as cirrhosis, steatosis, and nonalcoholic steatohepatitis (NASH), characterized by the accumulation of fats in the liver. However, its impact extends far beyond hepatic complications, affecting various organs in the body.

Notably, NAFLD has been linked to diverse health issues including cardiovascular disease (CVD), colorectal cancer, metabolic syndrome, type 2 diabetes, chronic kidney disease, obstructive sleep apnea, and polycystic ovary syndrome. This broad range of associations underscores the systemic nature of NAFLD, emphasizing the need for comprehensive understanding and management.

Additionally, venous thromboembolism (VTE), a condition involving blood clots in the veins, is closely associated with Virchow’s triad, which includes factors like hypercoagulability, venous stasis, and endothelial cell damage. Alarmingly, recent reports indicate that VTE has emerged as a leading global cause of death. Several risk factors contribute to the development of VTE, including trauma, advanced age, immobility, oral contraceptive use, cancer, obesity, and genetic or acquired thrombophilia, highlighting the complex interplay of biological and lifestyle factors in its occurrence.

While numerous studies have explored the connection between fatty liver and increased VTE risk, it is crucial to note that most of these investigations have been limited by small sample sizes. This limitation underscores the importance of further research efforts aimed at unraveling the intricate relationship between NAFLD and VTE, potentially paving the way for more effective prevention and treatment strategies in the future.


About the Study Made

In the conducted research, data sourced from the National Health Insurance Service-National Sample Cohort 2.0 (NHIS-NSC 2.0) was utilized. This particular cohort is derived from the NHIS, a mandatory health insurance initiative that extends medical coverage to virtually the entire Korean populace, encompassing approximately 97% of the total population.

The NHIS-NSC 2.0 integrates information from four databases, offering a comprehensive overview of various aspects such as demographics, medical claims specifying diagnoses, records of hospitalization and treatment, routine check-ups, and details about medical institutions involved in patient care.

In the context of Korean healthcare, it is customary for individuals aged 18 years and above to undergo regular health screenings. These screenings are inclusive of an array of assessments, including laboratory tests, physical examinations, chest radiography, and a structured questionnaire designed to gather pertinent information about health-related behaviors and medical history.

For the purposes of this study, the focus was on individuals who had undergone these national health check-ups multiple times within the timeframe of 2009 to 2014. The study specifically targeted individuals afflicted with liver disease, a condition for which they were receiving treatment, including the use of lipid-lowering agents. The utilization of this rich dataset enabled the researchers to delve into the nuances of liver disease management and its correlation with the prescribed medications, providing valuable insights into this critical aspect of public health.


Findings of the Study

In this study, a comprehensive analysis was conducted on 472,212 participants, focusing on their eligibility criteria and fatty liver index (FLI) quartile values. The cohort was divided into four groups (Q1, Q2, Q3, and Q4) based on FLI values, which serve as a surrogate marker for fatty liver. The research revealed notable correlations between FLI values and various factors such as body mass index (BMI), gender distribution, smoking habits, and alcohol consumption. Higher FLI values were consistently associated with elevated fasting glucose levels, blood pressures, and gamma-glutamyl transferase (GGT) levels among participants.

Furthermore, individuals with higher FLI values exhibited a higher prevalence of comorbidities and unfavorable lipid profiles, highlighting the connection between FLI and health complications. The study also explored the occurrence of venous thromboembolism (VTE) in older adults with comorbidities. Interestingly, higher FLI values were linked to an increased risk of VTE development in this population.

The association between FLI and VTE risk suggests a potential link between non-alcoholic fatty liver disease (NAFLD) and a hypercoagulable state. The liver, which secretes various factors related to coagulation and fibrinolysis pathways, may play a role in this phenomenon. Although the exact mechanism remains unclear, chronic liver inflammation might disrupt the coagulation system, leading to a predisposition for VTE.

Previous studies have highlighted specific procoagulant factors (such as VIII, IX, XI, and XII) in NAFLD patients, regardless of their age, BMI, or sex. Additionally, the severity of NAFLD has been associated with thrombin generation, a fundamental coagulation process. The research reported a sequential increase in thrombin generation based on the form of NAFLD, with the most advanced stage showing the highest levels of factor VIII and the lowest levels of protein C.

This sheds light on the intricate relationship between FLI values, NAFLD, and the risk of developing VTE. These findings underscore the importance of further research to elucidate the underlying mechanisms, potentially leading to targeted interventions for individuals at risk of VTE due to liver-related factors.


Conclusions Reached

The present study possesses certain constraints, one of which is the reliance solely on FLI as a biomarker for fatty liver, without resorting to any definitive diagnostic procedures. It’s crucial to note that liver biopsy stands as the gold standard for diagnosing Non-Alcoholic Fatty Liver Disease (NAFLD); however, this method is both invasive and financially burdensome.

Given the observational nature of this study, it falls short of establishing a direct cause-and-effect relationship between NAFLD and the heightened risk of Venous Thromboembolism (VTE). Consequently, it is imperative for forthcoming research endeavors to delve into unraveling the intricacies of this causality.

Notwithstanding these limitations, the study’s outcomes had signified a noteworthy discovery. They suggest that individuals exhibiting elevated FLI values, even in the absence of overt liver disease, face a significantly higher risk of developing VTE when contrasted with those having lower FLI values. This insight, despite the study’s constraints, underscores the potential importance of monitoring FLI values as an indicator of VTE susceptibility, even in cases where apparent liver disease might not be present.