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Page 2 of 11 Garg et al. Hepatoma Res 2019;5:39 I http://dx.doi.org/10.20517/2394-5079.2019.009

Conclusion: NAFLD associated HCC demonstrate less frequent portal venous washout on CT which may affect their
imaging diagnosis.

Keywords: Hepatocellular carcinoma, computed tomography, fatty liver, inter-rater agreement, non-alcoholic fatty
liver disease

INTRODUCTION
Hepatocellular carcinoma (HCC) is the second most common cause of cancer related death worldwide,
[1,2]
with increasing mortality rates in Europe, North America, South America and Africa . Imaging plays
a pivotal role in management of HCC and is an established method for diagnosis with radiological
hallmarks on contrast enhanced multiphase computed tomography (CT) or magnetic resonance imaging
(MRI). The imaging hallmark features include arterial phase hyper enhancement (APHE), portal venous
phase washout (PVWO) and/or delayed phase washout (DPWO), and presence of enhancing capsule.
Based on some or all of the three features, several guidelines have been developed for the non-invasive
imaging diagnosis and standardization in reporting of observations suspicious for HCC such as European
Association for the Study of the Liver (EASL), European Organization for Research and Treatment of
Cancer, Organ Procurement and Transplantation Network (OPTN), American Association for the Study
of Liver Diseases (AASLD) and Liver Imaging Reporting and Data System. It should be noted that EASL
does not recognize capsule as a major imaging feature of HCC. However, these guidelines have only been
validated in patients with most commonly recognized risk factors for development of HCC including,
[3-8]
alcoholic cirrhosis and chronic viral hepatitis and not in non-alcoholic fatty liver disease (NAFLD) .
Although most HCCs (75%-90%) develop in cirrhosis resulting from chronic hepatitis B or C infections
[9]
and alcoholic injury , an estimated 4%-22% of HCC occur in the setting of NAFLD [10-12] . NAFLD has now
become the most common cause chronic liver disease in developed countries [13,14] . Given its increasing
prevalence worldwide, NAFLD may become the most common chronic liver disease associated with HCC.

NAFLD is a spectrum of disease ranging simple non-alcoholic fatty liver (NAFL) to non-alcoholic
[15]
steatohepatitis (NASH) that can progress to cirrhosis . NAFL is considered to have minimal risk of
progression to cirrhosis and liver failure, while NASH can progress to cirrhosis, liver failure and develop
HCC. NASH is thought to be a common underlying cause of cryptogenic cirrhosis as the patients with
cryptogenic cirrhosis are comprised mostly of patients with metabolic risk factors including obesity,
[15]
metabolic syndrome and diabetes , but other etiologies such as burnt-out autoimmune hepatitis and
occult alcoholism may also result in cryptogenic cirrhosis [16-18] . HCCs are known to occur in patients with
NAFLD in the absence of cirrhosis [10,19-21] and these HCCs may not meet the imaging criteria based on the
[22]
current guidelines including LIRADs .

The effect of hepatic steatosis in NAFLD on the imaging features of HCC has not yet been fully explored.
For example, hepatic steatosis may decrease the liver attenuation on CT and as a result, washout
observation may be absent or less conspicuous which could render the LIRADSv2017 imaging criteria not
applicable [22-25] . HCCs can also occur in the absence of cirrhosis in patients with NAFLD as mentioned
earlier. Therefore based on these premises, the purpose of our study was to determine the major imaging
features of HCC on multiphase CT and the inter-observer agreement in patients with NAFLD.

METHODS
In this institutional review board (IRB) approved (ID: 15-004925), HIPPA-compliant retrospective study.
Written informed consent for retrospective review of data was waived.