Transarterial chemoembolization (TACE) based on drug-eluting beads (DEB-TACE) is widely used for unresectable hepatocellular carcinoma (HCC). However, the long-term survival is still low after DEB-TACE treatment. In recent years, lenvatinib and anti-PD-1 have exhibited potential therapeutic effects for advanced HCC. And sorafenib is the standard drug for advanced HCC. Combining targeted drugs or immunotherapies with DEB-TACE may provide synergistic effects and facilitate the development of personalized medicine. Therefore, this prospective study aims to investigate the safety and efficacy of DEB-TACE plus sorafenib or lenvatinib or PD-1 Inhibitor for unresectable HCC.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Most patients with HCC are diagnosed as advanced stage or unresectable disease because of the lack of signs and symptoms. Despite significant research efforts, only a few effective treatment approaches have been developed for HCC. Conventional transarterial chemoembolization (cTACE) is widely used as a palliative treatment for inoperable HCC. TACE based on drug-eluting beads (DEB-TACE) has recently been introduced into the clinic. This technique relies on drug-loaded microspheres to embolize and release antitumor medication gradually and locally in order to maximize local ischemia and tumor necrosis. Nowadays, many RCTs and meta-analyses found DEB-TACE is associated with higher overall survival than cTACE for unresectable HCC. However, the long-term survival is still low after DEB-TACE treatment. In recent years, targeted drugs (such as sorafenib, lenvatinib) and immune checkpoint inhibitor (anti-PD-1) have exhibited potential therapeutic effects for advanced HCC. Lenvatinib is non-inferior to sorafenib in overall survival in untreated advanced HCC. Combining targeted drugs or immunotherapies with conventional therapeutic approaches may provide synergistic effects and facilitate the development of personalized medicine. However, it is still unknown which is the best combining treatment. Therefore, this prospective study aims to investigate the safety and efficacy of DEB-TACE plus sorafenib or lenvatinib or PD-1 Inhibitor for unresectable HCC.

Inclusion Criteria:

• Age 18 - 75 years
• Patients with unresectable primary hepatocellular carcinoma.
• With Child-Pugh A liver function.

Exclusion Criteria:

• Patients received targeted drugs, anti-PD1, or anti-PD-L1 treatment.
• Patients with recurrent hepatocellular carcinoma.
• Patient compliance is poor.
• The blood supply of tumor lesions is absolutely poor or arterial-venous shunt that TACE can not be performed.
• Known history of human immunodeficiency virus (HIV) infection.
• Known Central Nervous System tumors including metastatic brain disease.
• Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.
• History of organ allograft.
• Known or suspected allergy to the investigational agent or any agent given in association with this trial.
• Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study.
• Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study drug. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial.

Outcomes assessor will be blinded about patients' allocation.