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Organ Crosstalk: Hints of Potential Cardiovascular Disease Can Come from The Liver

Update 09.11.2022

New study suggests that the histological severity of non-alcoholic fatty liver disease predicts the risk of future cardiovascular events


The incidence of non-alcoholic fatty liver disease (NAFLD) has increased in Korea owing to a rise in metabolic and cardiovascular disorders (CVD). While NALFD exhibits different levels of tissue damage, there isn’t enough evidence to examine the association between the risk of CVD and the liver histological spectrum. A new study by Korean researchers delves into this association and shows that the severity of NAFLD is associated with a high risk of CVD in a large cohort of patients with biopsy-proven NAFLD.

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The potential explanations for the link between NAFLD and CVD include both complex interrelated pathways and common pathophysiological processes, such as endothelial dysfunction, systemic inflammation, oxidative stress, and cytokine imbalances.

Photo courtesy: Shutterstock


The liver, the largest internal organ in the human body, is central to all metabolic processes. The most common disease of the liver is non-alcoholic fatty liver disease (NAFLD), with the accumulation of fat being a key feature. A rise in metabolic disorders such as obesity and diabetes—combined with the increasing incidence of cardiovascular diseases, the most common cause of death among people with NAFLD—has led to an increase in the prevalence of NAFLD to 21.5% in 2016–17 in the Korean population.


The histological spectrum of NAFLD is wide, ranging from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), the latter of which can lead to cirrhosis and hepatocellular carcinoma. NASH is considered more aggressive than NAFL, and is associated with advanced fibrosis and an increased risk of cardiovascular disease (CVD). Several studies have been conducted to better understand the association between NAFLD and the risk of CVD. However, these studies did not incorporate detailed histological features determined through liver biopsies to accurately gauge the severity of NAFLD.


Now, in a recent study led by Dr. Won-Ho Kim from the Korea National Institute of Health, a team of researchers has taken a closer look at the association between the risk of CVD and different histological features of NAFLD. The study was supported by an intramural research grant from the Korea National Institute of Health (Grant number 2018-NI007-02), and its findings have been published in Hepatology International. Dr. Kim remarks on the novelty of this research, “To our knowledge, ours is the first study to reveal the prognostic role of detailed histological features in predicting the 10-year atherosclerotic CVD (ASCVD) risk in Koreans with biopsy-proven NAFLD.”


The researchers employed the Korean Risk Prediction Model for estimating ASCVD risk, a version of the 10-year ASCVD risk score calibrated for the Korean population. This model was used because the ASCVD risk equation put forth by the American College of Cardiology and the American Heart Association was developed primarily in a large cohort of non-Hispanic whites, which means that it might considerably overestimate the overall CVD risk in an Asian population. On performing an association analysis, the researchers found that participants with more than 10% ASCVD risk had a higher prevalence of NASH and advanced fibrosis compared with patients with less than 10% ASCVD risk.


As for the question of whether the histological severity of NAFLD can predict ASCVD risk, the researchers found higher chances of developing ASCVD in participants with NASH than those with NAFL (also known as simple steatosis). The severity of liver fibrosis, another candidate for the prediction of ASCVD, showed similar results.


Another interesting aspect the researchers explored was the interaction between the NAFLD activity score (NAS) and fibrosis severity on the risk of ASCVD. Their findings showed that the risk of ASCVD was additionally increased by the concurrence of advanced fibrosis regardless of the severity of NAFLD as determined by the NAS. Thus, advanced fibrosis may serve as a significant discriminator for predicting ASCVD independent of conventional metabolic risk factors. Dr. Kim says, “Although NAFL can be reversed to a healthier state by adequate lifestyle modifications, NASH with significant fibrosis is prone to progress to advanced NAFLD and cardiometabolic diseases such as diabetes mellitus and CVD. Therefore, it is of paramount importance to detect and manage patients at high risk for NASH or advanced fibrosis as early as possible.”


These findings highlight the need for further long-term observational studies to elucidate the definite causality between the histological spectrum of NAFLD and an increased risk of CVD among patients with NAFLD. Dr. Kim also emphasizes that there are currently no drugs that can effectively treat NASH and liver fibrosis, and therefore further research is needed to develop therapies against these diseases.



Reference

Authors                               Ji Hye Park1, Bo Kyung Koo2, Won Kim3, WonHo Kim1

Title of original paper          Histological severity of nonalcoholic fatty liver disease is associated with 10year risk for atherosclerotic cardiovascular disease

Journal                                Hepatology International

DOI                                     10.1007/s12072-021-10209-3

Affiliations                           1Division of Cardiovascular Disease Research, Department for Chronic Disease Convergence Research, 

                                             Korea National Institute of Health

                                           2Division of Endocrinology

                                           3Division of Gastroenterology and Hepatology, Department of Internal Medicine, Seoul National University College of Medicine,

                                             Metropolitan Government Boramae Medical Center


About National Institute of Health in Korea

The Korea National Institute of Health (KNIH), one of the major operating components of the Ministry of Health and Welfare, leads the nation’s medical research. Over the past seven decades, the KNIH has made unwavering efforts to enhance the public’s health and innovate biomedical research. The KNIH seeks to eradicate diseases and make people healthier. The KNIH establishes a scientific basis and evidence underlying health policy as well as provides national research infrastructures. We also promote public health research. To this end, we make efforts to enrich a health research environment by granting funds to research projects and keeping our resources, data, and facilities more open and accessible to researchers.


Website: http://www.nih.go.kr/eng/


About Dr. Won-Ho Kim

Dr. Won-Ho Kim is the Director of the Division of Cardiovascular Disease Research, Department for Chronic Disease Convergence Research, Korea National Institute of Health, Korea. His research interests lie in identifying the causes of cardio-metabolic diseases, including NAFLD, type 2 diabetes, hypertension, and cardiovascular diseases, as well as developing early prediction, diagnosis, and interventional indicators. To date, he has published more than 80 original papers in peer-review journals.

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