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Clinical Practice Guidelines and Real-Life Management of Hepatocellular Carcinoma in Japan

By: Julia Fiederlein Cipriano
Posted: Friday, May 12, 2023

Hironori Koga, MD, PhD, of Kurume University School of Medicine, Japan, and colleagues reviewed the management recommendations for hepatocellular carcinoma from the Japan Society of Hepatology’s 2021 Guidelines for Liver Cancer Treatment. Their survey, which was published in the journal Clinical and Molecular Hepatology, also introduced the real-life approaches that may prompt updates to these guidelines.  

Ultrasonography is a preferred surveillance modality, per the guidelines. In some cases, the addition of CT/MRI is recommended. The assessment of tumor markers, such as AFP-L3 fraction (a lectin-reactive fraction of alpha-fetoprotein) and DCP (des-gamma-carboxy prothrombin), is considered an important characteristic of the real-life Japanese surveillance system. In terms of staging, the guidelines include the modified Union for International Cancer Control system and the General Rules for the Clinical and Pathological Study of Primary Liver Cancer; however, the Barcelona Clinic Liver Cancer system is the most widely used method, both in Japan and other countries.

Per the guidelines, the treatment algorithm for hepatocellular carcinoma is based on five factors: hepatic functional reserve, extrahepatic metastasis, vascular invasion, tumor number, and tumor size. Curative therapy, transcatheter arterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), systemic therapy, and/or palliative care may be recommended based on these clinical characteristics.

In terms of curative therapy, radiofrequency ablation and hepatic resection have been found to demonstrate similar efficacy. Recent data revealed longer local recurrence–free periods with balloon-occluded versus conventional TACE; at a consensus meeting, the kinase inhibitor lenvatinib was approved for TACE-unsuitable patients with intermediate-stage disease. Although HAIC was the standard therapy for advanced disease, recent studies have evaluated it in combination with systemic treatments, such as sorafenib and lenvatinib.

According to the authors, further research is warranted to substantiate the effectiveness of stereotactic body radiation therapy and particle therapy for hepatocellular carcinoma. Data regarding the second-line systemic therapy options for patients who did not respond to treatment with the checkpoint inhibitor atezolizumab plus the monoclonal antibody bevacizumab are limited; however, both the monoclonal antibody ramucirumab and lenvatinib have demonstrated efficacy in this clinical context.

Disclosure: For full disclosures of the study authors, visit

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