In the latter years in hepatology, due to new, very potent
antiviral drugs that can eradicate or control viral replication in chronic
hepatitis C and B patients, witnessed a change in focus has been witnessed:
from chronic viral hepatitis to fatty liver
disease. NAFLD (non-alcoholic fatty liver
disease) affects approximately
one quarter of the population in developed
countries, while NASH (non-alcoholic
steato-hepatitis) is present
in approximatively 2-4% [1,2].
Despite the fact that the course of NASH is quite long, the patients can
develop liver cirrhosis and later hepatocellular carcinoma. In the last years, hepatologists have
focused on how to
find the
patients at risk for NAFLD and NASH, how to predict their evolution and
maybe to stratify the
risk, considering that a huge
cohort of asymptomatic subjects (millions of people in an area) are dealt with
at any one time.
The answer to the first question – how to find them? – is to
evaluate the patients at risk for NAFLD and NASH: firstly the overweight
and obese patients;
secondly patients with type 2
diabetes: thirdly patients with metabolic syndrome and, of course, dyslipidemic
subjects (many of them having all these risk factors) [3,4]. The second question
is how to identify the subjects at risk to progress toward advanced liver
disease. The general practitioner (GP) is the first gate of this strategy,
being in direct contact with these patients, then the diabetologist who has
most patients at risk under surveillance, usually for a long time (type 2 diabetes
patients and dyslipidemic subjects), also the cardiologist who
is following-up patients
with metabolic syndrome. Finally, the hepatologist/gastroenterologist – whose duty
is to establish the disease severity, the prognosis and the best treatment approach
for these patients.
The first step in screening the population at risk is to find
liver steatosis; the second – to find if this fatty infiltration has a significant impact on
the liver; and finally – for
prognosis, to find if fibrosis is present. The first aim – to discover steatosis and to estimate its severity
– can be
easily and inexpensively
reached by using liver
ultrasonography (US). No expensive
ultrasound machines and no
large ultrasound experience are required. The sensitivity of
liver US for discovering and quantifying steatosis ranges between 60-80%, even higher for severe steatosis [5],
influenced by the physician’s
experience. In centers where a FibroScan
device is available, a more objective evaluation of steatosis can be performed
using CAP (Controlled Attenuation Parameter). For CAP, cut-off values were
calculated for different degrees of steatosis, with accuracy ranging from 80 to
85% [6,7]. In patients undergoing CT or MRI for other purposes, both techniques
can give valuable information concerning
the severity of fatty
infiltration of the liver, but none of them are screening tools.
Considering the availability,
the low cost,
and the relatively good
sensitivity of US, it seems to be the best method to screen for steatosis in
the general population. US can be performed by specialists or by a GP. The
criticism for US can be that its accuracy is at its best only if fatty infiltration
exceeds 20%. But considering carefully the increased echogenicity of the liver
with posterior attenuation and the liver/right kidney gradient, the method is
quite sensitive, at least for experienced people [8].
The next question is
how can inflammation, and especially fibrosis,
be assessed in patients with risk factors for NAFLD. A surrogate for inflammation
can be the level of
aminotransferases (ASAT/ALAT ratio), useful for general
practice and especially
for GP’s screening. We must advise
the GP, the diabetologist
and cardiologist, that any small
increase of aminotransferases in risk subjects must be evaluated by the
hepatologist. Other more sophisticated
biological tests can
be used, such
as the NAFLD test or FibroMax.
Some of them are expensive (FibroMax) and not widely available. Cytokeratin 18
was proposed as a surrogate test
for infammation detection and
NASH [9].
But let’s focus our
discussion on liver fibrosis! This is the most important aspect, since it gives
the prognosis. Liver fibrosis can be assessed by liver biopsy or non-invasively.
But how can we speak about liver biopsy when NAFLD is an epidemic disease, with
millions of cases?
This method is too
invasive for daily
practice and can lead to complications [10]. What about
liver elastography? Lately it has became a
fashion! During ILC
Amsterdam 2017, many papers and discussion were focused on this
topic. More than 10 years ago,
Transient Elastography (TE)
arrived on the market,
performed with a
FibroScan device. It
evaluates liver stiffness as a
marker of fibrosis. Many papers demonstrated
its good value of initially in chronic viral hepatitis and
later also in
NAFLD [11]. The
new XL probe (for obese
subjects), that completed the M probe, improved the method’s feasibility to
more than 90% [12]. Thus, the vast
majority of patients can be evaluated for fbrosis severity by TE. Cut-off
values for various stages of fibrosis were calculated for different etiologies,
so that TE became a “a must to
have” in clinical hepatological practice.
During the last 5 years, other US based elastographic techniques
were developed: point shear wave elastography (pSWE) or real time elastography
(2D-SWE), all integrated into ultrasound machines, can provide liver steatosis and
liver stiffness evaluation
in the same
session.
Very recently, an update on the EFSUMB Guidelines and recommendations
on liver elastography have been published
[13]. We expect that in the
next few years, ultrasound systems with stiffness evaluation will be common in
daily practice. The cost of such a system is still high (despite the
fact that some
companies have introduced the elastographic module in
their mid-class ultrasound machines), but
many hepatologists (and
maybe GPs) would like
to have such a system
to evaluate a pathology that is increasing annually. The maintenance
cost for such a system is very low and
thus it can be used for a long
time, without supplementary costs. One of the companies released very recently
an ultrasound system able to perform both 2D-SWE and TE. Another company tried to
combine pSWE and 2D-SWE in the same ultrasound machine.
Thus, very soon, the hepatologist (radiologist, diabetologist,
maybe the cardiologist, or GP) will be
able to start screening people at risk,
in order to find significant liver
steatosis and significant
liver fibrosis using
ultrasound machines and liver
elastography. In some areas, such as the USA, where a lot of energy
has been invested in Magnetic Resonance Elastography (MRE), this method can be
a competitor. But it is still very expensive and probably not suitable for screening purposes. The competition will
be between the FibroScan with CAP (that quantifies steatosis and fibrosis
severity) and ultrasound machines with elastography modules. Probably the analysis
of the acquisition and maintenance costs will be the decisive factor. Of
course, there is a place also for biological tests, but maybe decreasing
the cost for complex tests (such as FibroMax) should be recommended.
In centers where systems are able to evaluate the severity
of liver steatosis and liver fibrosis, I believe
that it is the moment
to start screening
for the presence
of fatty liver and fibrosis in patients with risk factors (type 2 diabetes,
obese, dyslipidemia, metabolic
syndrome) [14]. Early diagnosis of significant disease is the best moment
to start therapy (life style changes or drug therapy).
NAFLD is the more prevalent disease in hepatology now, in the
developed world, and now is the time to start the fight against this disease!
