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Page 2 of 7 Ballestri et al. Metab Target Organ Damage 2023;3:13 https://dx.doi.org/10.20517/mtod.2023.21

[1]
steatohepatitis (NASH), which also features inflammation and hepatocellular ballooning . Of concern,
[2]
global NAFLD burdens have increased since 1990 , accounting for direct and indirect financial costs.
Alarmingly, compared to individuals with NAFLD, NASH patients exhibit increased odds of developing
[3]
cirrhosis and mortality owing to liver-related causes , which supports the importance of differentiating
NASH from steatosis. This differential diagnosis requires liver biopsy, although this procedure is invasive
and not invariably safe, and thus cannot be used in epidemiological studies . Imaging techniques, such as
[4]
nuclear magnetic resonance (NMR) proton density fat fraction, are deemed to be the surrogate reference
standard for the evaluation of NAFLD . However, drawbacks of NMR imaging comprise high costs, limited
[5]
sampling of hepatic regions, susceptibility to motion artifacts from the heart, time consumption, and
[6]
uneven availability across various institutions and countries . Taken collectively, issues with liver biopsy
and inconvenience with NMR make ultrasonographic techniques an excellent non-invasive imaging
modality for use in the NAFLD arena . Point-of-Care ultrasound (POCUS) refers to the use of echography
[7]
to diagnose problems wherever a patient is being treated, conducted by a non-radiologist physician who is
directly involved in the patient's care . However, the application of POCUS in the field of NAFLD has been
[8]
limited so far.

In 2012, Ballestri et al. conceived a novel ultrasound-based scoring system that they named
ultrasonographic fatty liver indicator (US-FLI) . US-FLI was based on the ultrasound semeiotics as follows:
[9]
(severity of) liver-kidney contrast, posterior attenuation (of ultrasound beam), (difficult) visualization of the
diaphragm, vessel blurring, (difficult) visualization of gallbladder wall, and focal sparing . US-FLI could
[9]
range from 2 to 8, and NAFLD was identified by a score ≥ 2. [Figures 1 and 2 reproduced, with permission
from Ballestri et al. ]. Interestingly, US-FLI was correlated with metabolic variables [homeostasis model
[9]
(HOMA), insulin, serum uric acid, ferritin, alanine transaminase (ALT), and bilirubin. Moreover, US-FLI
was also associated with some histological features [such as steatosis extent and nonalcoholic steatohepatitis
(NASH), except for fibrosis]. At multivariate analysis, US-FLI independently predicted NASH (OR 2.236; P
= 0.007) and a US-FLI < 4 excluded severe NASH at histology with a negative predictive value of 94%.

Sourianarayanane and McCullough have recently validated US-FLI as a marker of NASH in the setting of
POCUS delivered by primary care providers . In their study, these authors found that US-FLI can reliably
[10]
stratify NASH patients. This important study is only the last adjunct to a series of studies summarized in
Table 1.

Taken collectively, the studies illustrated above [7,9-13] offer a complete outlook of the points of strengths and
weaknesses of US-FLI. The former include high reproducibility [9,13] , applicability to the pediatric
population and to the point-of-care setting , its strong association with metabolic derangements [9,11,12] ,
[10]
[12]
different grades of hepatic steatosis assessed with transient elastography , and important liver histology
[6]
endpoints, notably including its capacity to differentiate bland steatosis from true NASH [7,9,10,11] . As a result,
US-FLI outperforms the fatty liver index (FLI) , a validated non-invasive biomarker proposed by
[13]
Bedogni et al., to help in picking out those subjects to submit to hepatic ultrasonography scanning to
confirm steatosis (and whose scope has now been expanded to many other areas) and represents an
[14]
invaluable tool for triaging those patients in whom hepatic biopsy for suspected NASH is indicated. Coming
to the limitations, US-FLI reportedly has limited accuracy among patient populations with obesity, given
[7]
that these individuals often exhibit scores ≥ 5 . Moreover, US-FLI was devised at a time when the
dichotomy bland steatosis vs. NASH was deemed the key research and clinical question to address.
However, over time, assessment of fibrosis has become comparatively more important given that fibrosis
dictates the hepatic and extra-hepatic outcomes of NAFLD, and several biomarkers and algorithms are