OUTLINE FATTY LIVER DISEASE

FIGHTING THE FATTY LIVER WATCH AN ANIMATION AT:

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Increased levels of obesity are driving an epidemic of non-alcoholic fatty liver disease.
Understanding, diagnosing and treating this progressive condition are now priorities.
By Liam Drew; illustration by Lucy Reading-Ikkanda

CALORIES To heart
Blood exits through
hepatic veins to
From heart
Blood enters
through hepatic
NOT ALCOHOL inferior vena cava artery

An advanced stage of non-alcoholic

fatty liver disease (NAFLD) was first
described in 1980, confirming that
liver disease characterized by an
accumulation of fat can develop
in people who do not consume
excess alcohol1. Associated with Diaphragm
obesity and type 2 diabetes,
NAFLD is set to become the
most common cause of
serious liver disease in many
nations.
Liver

1 HEALTHY LIVER
The liver carries out many
tasks, including processing
nutrients absorbed from the
gut, and controlling the levels
Hepatocyte
of glucose, fat and protein in
the blood. It stores Nucleus
carbohydrates and a limited
amount of fat. Most liver cells
are hepatocytes, which can Small droplets
metabolize almost all types of From gut of fat
nutrient. A healthy hepatocyte To gut Blood carrying fat
contains a nucleus at its Bile secreted through hepatic and nutrients
centre and evenly distributed ducts into intestines directly or enters through
droplets of fat. gall bladder for storage hepatic portal vein

REVERSIBLE
Bloated hepatocyte
2 NAFLD
In NAFLD, hepatocytes Displaced nucleus
accumulate excess fat, a ~25%
process known as steatosis. Large droplets of the
Such fat can come from the of fat US population
diet, be made in the liver or have
be released by NAFLD2
insulin-resistant fatty Fatty liver
(adipose) tissue.

REVERSIBLE

3 NASH
If accumulated fat causes
stress and injury to hepatocytes, Collagen
fibres Up to 30%
non-alcoholic steatohepatitis
of people
(NASH) develops. Already-
with NAFLD
bloated hepatocytes swell
will develop
further and start to die, causing Inflamed, NASH2
inflammation. Scarring (fibrosis) dying
Fatty, inflamed liver
occurs as collagen fibres replace hepatocyte
dead cells.

IRREVERSIBLE

4 CIRRHOSIS Potentially
Over the years or decades, dead
reversable
hepatocytes are broken down Scarring Up to 20%
and scar tissue accumulates, of people with
which stiffens the liver and NASH may go
impairs its function. Known on to develop
as cirrhosis, this can lead Remnants of cirrhosis3
to liver failure and an Scarred and dead cells
increased risk of liver shrunken liver
cancer.

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 FATTY LIVER DISEASE OUTLINE

RISK FACTORS
Age, gender and genetics all contribute to a person’s risk of developing NAFLD and NASH. But the main risk factors are Adipocyte
obesity and diabetes, as well as other features of metabolic syndrome, including high blood pressure and insulin resistance.

OBESITY DIABETES AND

The link between obesity, its complications and NAFLD is strong. INSULIN RESISTANCE
As levels of obesity have increased, In healthy people,
NAFLD increases in prevalence with body Fat
so too has the prevalence of NAFLD4. insulin inhibits the
mass index, and is more common in men5. reservoir
breakdown and release
US population with obesity (%) Prevalence in US population (%) of fat by fat cells
Chronic liver disease in US Men (adipocytes).
caused by NAFLD (%) 75 Women 57

63
44
39
47

33 25
30
20 In people with insulin
22 17
resistance, fat is secreted
into the bloodstream,
8 7 from where it is taken up
by hepatocytes. Released
1988–1994 1999–2004 2005–2008 18.5–24.9 25–29.9 30–34.9 ≥35 fat
Body mass index

DIAGNOSIS
To determine the extent of NAFLD and associated fibrosis, and
to monitor patients’ responses to treatment — without using an Ultrasound
invasive liver biopsy — biomarker discovery and advances in probe
imaging technology are needed.

IN THE BLOOD ULTRASOUND Fatty liver Scarred and

Although current blood tests for Diagnostic tools that use Absorbs a large stiffened liver
liver disease can help to assess ultrasound technology can help to proportion of Shear waves travel more rapidly
the severity of NAFLD, researchers assess the health of the liver, but ultrasound waves through damaged tissue
are seeking new biomarkers with the fine resolution and sensitivity
concentrations that reliably of such techniques needs
correlate with disease activity. improvement.

MORE THAN
75 MILLION
HALTING NAFLD people in the
The cornerstones of NAFLD treatment are weight loss and increased amounts of exercise, but maintaining these lifestyle changes can United States may
be hard. NASH is now considered to be a serious condition that requires the development of targeted drugs. As a result, hundreds of have NAFLD2
trials of potential treatment strategies are under way.
GUT LIVER

Fat Gut–liver interactions Metabolic stress Inflammation Fibrosis

Inhibiting enzymes in the Modifying the gut Many drugs aim to reverse Drugs that block receptors Hepatic stellate cells in the
gut that break down fats microbiome with probiotic the accumulation of fat or its for chemokines released by liver mediate fibrosis. Drugs
(lipases) to limit the bacteria may promote damaging effects. Some white blood cells in the that block receptors on the
absorption of fat by blood, intestinal-wall integrity, mimic hormones; others liver (Kupffer cells), inhibit surfaces of these cells and
as well as bariatric surgery, preventing inflammation- block pathogenic signalling pro-inflammatory enzymes, antibodies that inactivate key
may aid weight loss to help causing bacterial products pathways or alter fat or reduce oxidative stress, fibrotic molecules are in
resolve NAFLD. from reaching the liver. processing directly. are being tested. development.

Lipase Bacterial products Damaged, stressed hepatocytes Kupffer cell Hepatic stellate cell

Gut
lumen

Absorbable fat droplets Epithelial cell Chemokines Fibrotic

matrix

Sources: 1. Ludwig, J., Viggiano, T. R., McGill, D. B. & Oh, B. J. Mayo Clin. Proc. 55, 434–438 (1980). 2. Younossi, Z. M. et al. Hepatology 64, 73-84 (2016). 3. Rinella, M. E. JAMA 313,
2263–2273 (2015). 4. Younossi, Z. M. et al. Clin. Gastroenterol. Hepatol. 9, 524–530 (2011). 5. Lazo, M. et al. Am. J. Epidemiol. 178, 38–45 (2013).

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