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.
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, Won‑Ho
Kim1
Title of original paper Histological severity of nonalcoholic fatty liver disease is associated with 10‑year 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.