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Page 12 of 16 de Santis et al. Hepatoma Res 2019;5:1 I http://dx.doi.org/10.20517/2394-5079.2018.65

HCC IN NON-CIRRHOTIC PATIENTS
HCC occurring in non-cirrhotic livers is uncommon and the clinical presentation is very different from that
observed in cirrhosis. Since the tumor occurs in subjects not known to be at risk of HCC, the diagnosis is
generally delayed and therefore the tumor is larger than commonly seen in cirrhotic patients. The problem
is whether the radiological characteristics that are decisive for the diagnosis of HCC on cirrhosis can be
[40]
translated in this different clinical situation. Di Martino et al. retrospectively reviewed histopathological
and laboratory findings of 30 non-cirrhotic patients with 32 HCCs. MDCT and gadobenate dimeglumine
enhanced MRI were evaluated. Imaging patterns were compared directly with HCC findings in a matched
group of cirrhotic patients. The imaging appearance at MDCT and contrast-enhanced MRI was typical in
27 (84.3%) and 28 (87.5%) cases, respectively. Most lesions presented as a well-differentiated large solitary
mass, with well-defined margins, areas of necrosis and peripheral capsule. No significant differences in HCC
pattern were observed between cirrhotic and non-cirrhotic liver. But in the last EASL guidelines in non-
cirrhotic liver, imaging alone is not considered sufficient and histological assessment is required to establish
the diagnosis of HCC and has the additional advantage of providing further information regarding the
[28]
nontumourous liver tissue .

MODIFIED RESPONSE EVALUATION CRITERIA IN SOLID TUMORS FOR THE EVALUATION OF
HCC RESPONSE TO TREATMENTS
Radiology plays an important role not only for the diagnosis but also for the evaluation of the response
both to locoregional and to systemic treatments of HCC. Until 2010, EASL and AASLD have recommended
Response Evaluation Criteria In Solid Tumors (RECIST) and WHO criteria in their guidelines for the
management of HCC for the evaluation of response to treatment. The application of these criteria requires
the measurement of the major diameter of the HCC nodule/s. However, because of the relevance of the
necrotic portion of a treated nodule with respect to its global size, a new version of RECIST modified
for HCC, formally taking into account only the vital tissue in each HCC lesion, was published in
[41]
2010 . These criteria have been endorsed in 2012 by EASL and European Organisation for Research
and Treatment of Cancer (EORTC) in their guidelines and are currently still the gold standard for the
assessment of radiological response, confirmed in the last version of EASL guidelines [4,28] . The application
of modifiedRECIST (mRECIST) requires taking into account those HCC nodules which are clearly visible,
measurable and showing the typical “hallmark of wash-in and wash-out” as “target lesions”, while all
the HCC localizations not definitively measurable or with an atypical post-contrast appearance such as
intrahepatic lesions which show infiltrative behavior with poorly defined margins and poorly defined
hyperenhancement, malignant thrombosis, neoplastic ascites, adenopathies, very small and/or numerous
diffuse lesions, are to be considered “non target lesions”. According to mRECIST, only “target lesions” can
undergo a dimensional evaluation of their vital portion (tissue showing arterial hyperenhancement and
venous/delayed washout) by the measurement of its longest diameter. The response assessment is to be based
on the comparison of this size before and after the treatment. On the contrary, “non target lesions” can be
monitored over time on the basis of their absence/presence (i.e., neoplastic ascites) or of their measurement
according to RECIST (longest diameter of the lesion as a whole). With respect to “target lesions”, the possible
responses are: a complete response (CR) defined by the disappearance of all arterial hyperenhancement in
all target lesions; a partial response (PR) in the case of a reduction of at least 30% in the sum of the diameters
of the vital portions of the target lesions; progressive disease (PD) if an increase of at least 20% in the sum of
the longest diameters of all target lesions is observed; and stable disease (SD) if neither PR nor PD definition
criteria can be satisfied [Table 2].

With respect to “non-target lesions”: a CR will correspond to the disappearance of all enhancing tissue in
all of them, an incomplete response/SD is defined by the persistence of vital tissue in at least one “non target
lesion”; a PD is defined by the appearance of a new lesion or the unequivocal worsening of at least one of the