Clinical Practice Guidelines for Hepatocellular Carcinoma Differ between Japan, United States, and Europe

The main differences between the surveillance and diagnostic algorithms of Europe and USA and those of Japan can be summarized as follows. 1) Whereas the European and American guidelines propose a surveillance interval of 6 months regardless of whether the patient has cirrhosis, the Japanese guidelines propose a shorter interval of 3-4 months for cirrhotic patients. Because of this, more cases of small HCCs are detected in Japan compared with Europe and America. 2) The surveillance methods also differ. Whereas the three tumor markers AFP, PIVKA-II, and AFP-L3 are used in addition to ultrasound in Japan, not even AFP is recommended in Europe and America, and PIVKA-II and AFP-L3 are not recommended because these tests are not routinely available outside Japan. 3) The Japanese guidelines recommend EOB-MRI or dynamic CT be performed every 6-12 months for surveillance for cirrhotic patients. 4) The European and American diagnostic guidelines recommend prompt biopsy when typical features of liver cancer are not observed, whereas the Japanese guidelines recommend more sophisticated imaging, such as hepatobiliary-phase EOB-MRI or Sonazoid CEUS. 5) Another major difference is that even hypovascular pathologically early HCC is diagnosed with EOB-MRI or biopsy in Japan. 6) The Japanese guidelines propose that when HCC cannot be detected with ultrasound, screening with EOB-MRI should be done every 6-12 months. This has enabled the detection of a large number of very small HCCs, including hypovascular pathologically early HCC. The Japanese treatment algorithm's are different and considered to be superior to the European and American treatment algorithms for the following reasons. 1) Consensus-based treatment algorithm provides a treatment option for hypovascular pathologically early HCC. 2) When used in combination with TACE, ablation is still indicated as a treatment for patients with ≤ 3 nodules that are >3 cm.