Page 73 - Read Online

Page 2 of 15 Osho et al. Hepatoma Res 2020;6:55 I http://dx.doi.org/10.20517/2394-5079.2020.42

INTRODUCTION
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the fourth leading cause
[1]
of cancer-related death worldwide . Common risk factors for the development of HCC include alcohol
use, chronic hepatitis B (HBV) or hepatitis C infection, and nonalcoholic fatty liver disease (NAFLD).
Prognosis for HCC depends on tumor stage at diagnosis; curative treatment options for early stage tumors
provide 5-year survival exceeding 70%, whereas late stage HCC is only amenable to palliative therapies
with a median survival of 2-3 years. Imaging plays a central role in the management of patients with HCC,
including surveillance, diagnosis, and assessing treatment response. The aim of this review is to discuss best
practices for imaging along the care spectrum of HCC.

ROLE OF IMAGING FOR HCC SURVEILLANCE
Given the strong association between early detection and improved survival, the American Association for
the Study of Liver Diseases (AASLD) and European Association for the Study of Liver (EASL) recommend
HCC surveillance in at-risk patients, including subgroups with chronic HBV and those with cirrhosis from
[2,3]
any etiology . HCC surveillance is supported by a large randomized controlled trial (RCT) in patients
[4]
with HBV that showed a 37% reduction in mortality . Although there is no similar RCT among patients
with cirrhosis, several cohort studies have highlighted an association between surveillance and improved
early detection, curative treatment receipt, and overall survival .
[5]

Ultrasound for HCC surveillance
The preferred imaging modality for HCC surveillance across all major professional liver organizations
worldwide has been, and remains, abdominal ultrasound [2,3,6,7] . Ultrasound has many advantages including
being readily available, inexpensive, and non-invasive with a favorable safety profile. A systematic
review of test modalities for HCC surveillance found that ultrasound has a high sensitivity of 94%
to detect HCC at any stage; however, its sensitivity to detect early stage HCC is significantly lower at
only 63% . Furthermore, the wide variation in ultrasound sensitivity between studies highlights the
[8]
operator-dependent nature of the examination. High ultrasound quality relies heavily on the experience
of the individual performing the ultrasound examination as well as the radiologist interpreting the
examination [9,10] . These challenges have been observed in breast cancer screening, with ultrasound being
more useful than mammography in women with dense breast tissue, but one of its limitations being
[11]
variable quality based on inherent operator dependence . Standardization of examination technique
[12]
and establishment of minimum reporting requirements, as has been done for breast ultrasonography ,
[13]
can improve the quality of ultrasound-based screenings . For HCC, regional differences have been
[8]
observed in ultrasound sensitivity and align with differences in technique . In the U.S., ultrasound is
typically performed by technicians with select frozen images interpreted by a radiologist at a later time,
[14]
whereas physicians in other regions of the world often perform and interpret ultrasound in real time .
Recent data have also highlighted the impact of patient characteristics on ultrasound effectiveness. In a
retrospective cohort study of 941 patients undergoing surveillance ultrasound, 191 (20.3%) were deemed to
[15]
be of inadequate quality for exclusion of HCC lesions . In multivariable analysis, inadequate ultrasound
quality was associated with obesity and alcohol- or nonalcoholic steatohepatitis (NASH)-related cirrhosis,
suggesting that inadequate ultrasound quality and poor sensitivity may be more common as the prevalence
of obesity and NASH continue to rise globally [16,17] . Since this study, the Liver Imaging Reporting and
Data System (LI-RADS) has proposed that ultrasound assessment and reporting include an ultrasound
visualization score, including score A (no or minimal limitation), score B (moderate limitations that may
obscure small masses), and score C (severe limitations that significantly lower sensitivity for focal liver
lesions). The visualization score is based on liver heterogeneity, beam attenuation or shadowing, proportion
of liver visualized, and proportion of diaphragm visualized. Routine reporting of visualization is an
important step that helps clinicians interpret ultrasound results; however, further data are needed to verify