Nivolumab Plus Ipilimumab as Neoadjuvant Therapy for Hepatocellular Carcinoma (HCC)

Inclusion Criteria: 1. Histological diagnosis of HCC with potential for curative surgical resection fulfilling one of the following criteria: (A)Tumor(s) with macrovascular invasion. (B)Tumors with one of the following features: (B1)multiple tumors and bilateral lobes involvement, none more than 5 cm (B2)tumor number \> 3, none more than 5 cm (B3)multiple tumors none more than 5 cm, with significant portal hypertension (splenomegaly, esophageal varices or platelet \< 100,000/μL) (B4)solitary tumor \> 5 cm, with significant portal hypertension (splenomegaly, esophageal varices or platelet \< 100,000/μL) (B5)Other conditions that are considered high-risk for recurrence after surgery, e.g., direct diaphragmic invasion suspected by imaging。 2. No evidence of extra-hepatic metastases. 3. At least one measurable tumor, according to RECIST version 1.1, that has not been treated with any local procedure. 4. Prior percutaneous ethanol injection, radiofrequency ablation, transarterial embolization, or cryotherapy are allowed if aforementioned local therapy is given at least 4 weeks prior to enrollment and progressive or recurrent disease is documented. 5. Age \>= 20 years old. 6. ECOG performance status 0 or 1. 7. Child-Pugh class A liver function. 8. WBC \>=2,000/uL (stable, off any growth factor within 4 weeks of study drug administration) ; Platelet\>= 60,000/uL. 9. Liver transaminases (ALT and AST) \<= 5 times upper limit of normal values (ULN); total bilirubin \<=1.5 times ULN; serum creatinine\<=1.5 times ULN; creatinine clearance \> 50 mL/min (calculated by Cockcroft-Gault formula) 10. Subjects with chronic hepatitis B virus infection (HBV surface antigen (HBsAg) positive) must start antiviral therapy with nucleoside analogs (e.g., entecavir or tenofovir, according to current practice guidelines) before start of study drug treatment. 11. Signed informed consent. Exclusion Criteria: 1. Receiving concurrent anti-cancer therapy for HCC, which includes local therapy, systemic therapy, or other experimental therapy. 2. Local treatment including radiotherapy (except palliative radiotherapy), percutaneous ethanol injection, radiofrequency ablation, or transarterial embolization administered within 4 weeks prior to enrollment. 3. Major surgical procedure within 2 weeks or minor surgical procedure within 1 week prior to enrollment. 4. History of esophageal/gastric varices or active peptic ulcers that are considered to have high risk of bleeding. 5. History of upper gastrointestinal bleeding within 1 year. 6. Known human immunodeficiency virus (HIV) infection. 7. Major systemic diseases that the investigator considers inappropriate for participation. 8. History of other malignancies except those treated with curative intent for skin cancer (other than melanoma), in situ breast or in situ cervical cancer, or those treated with curative intent for any other cancer with no evidence of disease for 2 years. 9. Any active autoimmune disease or history of known autoimmune disease except for vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll 10. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol. 11. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody (or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways). 12. Requirement of systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. 13. Prior organ allograft or allogeneic bone marrow transplantation. 14. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation and in the judgment of the investigator would make the patient inappropriate for entry into this study.