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Page 4 of 10                                            Yilmaz et al. Hepatoma Res 2018;4:46  I  http://dx.doi.org/10.20517/2394-5079.2018.49


               Table 1. Recommendations for cirrhotic adults
                                                                       Time interval
                Continent    Guidelines             Modality                              Exceptions
                                                                        (months)
                North America AASLD-2017  US with or without AFP       6          Child-Pugh stage C unless awaiting
                                                                                  liver transplantation
                          CASL-2014       US                           6          Same as AASLD
                Asia      APASL-2017      US and AFP                   6          Severe liver diseases/other co-
                                                                                  morbidities (ineligible for curative
                                                                                  therapy)
                          CHINESE-2017    US and AFP                   6          NS
                          JSH-2015*       Extremely-high risk patients: (HBV/HCV
                                          cirrhosis)
                                          - US and three Tm markers (AFP/PIVKA-II/ 3-4
                                          AFP-L3)
                                          - CT or MRI (optional)      6-12        NS
                                          High risk patients: (cirrhosis of another
                                          etiology)
                                          US and three tumor markers (AFP/PIVKA-  6
                                          II, AFP-L3)
                          JSH-LCSG-2014   Recommend EOB-MRI instead of CT or MR  Same as JSH  NS
                Europe    EASL-2018**     US                           6          Same as AASLD
                          SPANISH-2016 (AEEH,  US                      6          NS
                          SEOM, SERAM,
                          SERVEI and SETH)
                          SEOM-2015       US                           6          Same as AASLD
                          ESMO-ESDO-2012   US                          6          NS
               *3rd JSH-HCC guidelines, 2013 update; **in press. HBV: hepatitis B virus; HCV: hepatitis C virus; AFP: alpha-fetoprotein; NS: not specified;
               US: ultrasound; PIVKA-II: proteins induced by vitamin K absence; CT: computed tomography; MRI: magnetic resonance imaging; EOP-
               MRI: gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOBDTPA)-enhanced magnetic resonance imaging

               Selected guidelines from Spain (consensus document from The Spanish Association for the Study of the
               Liver (AEEH), Spanish Society of Medical Oncology (SEOM), The Spanish Society of Medical Radiology
               (SERAM), The Spanish Society of Vascular and International Radiology (SERVEI), The Spanish Society of
               Liver Transplantation (SETH)-2016 and European Society for Medical Oncology (ESMO)/European Society
               of Digestive Oncology (ESDO)-2012 recommend every 6 months US examination to patients with or without
               cirrhosis, and specify the theory behind this recommendation [35,36] . However; SEOM-2015 guideline excluded
                                                                                      [37]
               Child C patients from screening (unless awaiting for liver transplantation) like EASL .

               This section was summarized in Table 1.

               Recommendations for non-cirrhotic adults
               A small proportion of patients with HCC is diagnosed in the non-cirrhotic liver (NCL) with the risk of be-
               ing less than 1% annually in patients with chronic hepatitis without significant fibrosis, in contrast to 3%-7%
               annually when the patient develops cirrhosis [26,35,38] . HCC in NCL ranges widely from 7% to 54% according
                                                                        [39]
               to the etiology of the liver disease and varies of the geographic areas . While viral hepatitis is pre-screened
               with decrease in the east as known, metabolic causes predominate in the west.

               As compared to cirrhotic HCC, it has lower prevalence of the three main risk factors (hepatitis B and C virus
               infections and alcohol abuse), with an increased prevalence of other etiological factors, such as non-alcoholic
               fatty liver diseases, obesity and type 2 diabetes mellitus, exposure to genotoxic substances-aflatoxin, tobacco,
               sex hormones, inherited diseases and genetic mutations [2,3,11,26,30,36,38-40] .

               In contrast to cirrhotic, NCL-HCC are more suitable for surgical treatments even in more advanced tumour
               stage at the time of diagnosis, since it is generally detected at a symptomatic stage due to unsettled scheduled
               screening program in these groups [2,38,39] .
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