Adjuvant Everolimus in High-Risk Hepatocellular Carcinoma After Curative Resection (SEVERANCE Trial)

Inclusion Criteria: * Alkaline phosphatase level \> 2.5 times the ULN * Proteinuria defined as a urine protein-to-creatinine ratio \> 1.0 g/gCr or ≥ 2+ on urine dipstick * Patients who received systemic therapy prior to hepatic resection * Prior treatment with anti-CTLA-4, anti-PD-1, or anti-PD-L1 therapies * Renal impairment with estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73m² (based on MDRD formula) * Total cholesterol \> 350 mg/dL or triglycerides \> 500 mg/dL * History of severe acute (within the past 4 weeks) or chronic hypersensitivity reactions requiring treatment to everolimus or drugs with a similar chemical structure * Pregnant or breastfeeding women, women who are possibly pregnant, or women of childbearing potential who are unable to use highly effective contraception† during the study period and for 8 weeks after the last dose * Any condition deemed by the investigator to render the patient unsuitable for participation in the clinical trial * Highly effective contraception is defined as methods with a failure rate of less than 1% per year, including bilateral tubal occlusion, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices (IUDs), and copper IUDs. Methods such as calendar-based methods, ovulation prediction, symptothermal methods, and post-ovulation methods are not considered adequate contraception. Exclusion Criteria: * Patients diagnosed with combined hepatocellular-cholangiocarcinoma (HCC-CCC) * Presence of clinically significant ascites * History of hepatic encephalopathy * History of variceal bleeding within 6 months prior to hepatic resection * Autoimmune diseases or immunodeficiency disorders * Serious cardiovascular diseases, including acute myocardial infarction, acute coronary syndrome, stroke, or heart failure of New York Heart Association (NYHA) Class II or higher * History of malignancies other than HCC within the past 5 years * Patients with hereditary metabolic disorders such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption * Patients currently taking medication for psychiatric disorders * Absolute neutrophil count (ANC) \< 1500/μL or platelet count \< 75,000/μL * AST, ALT, or total bilirubin levels \> 3 times the upper limit of normal (ULN) * Alkaline phosphatase level \> 2.5 times the ULN * Proteinuria defined as a urine protein-to-creatinine ratio \> 1.0 g/gCr or ≥ 2+ on urine dipstick * Patients who received systemic therapy prior to hepatic resection * Prior treatment with anti-CTLA-4, anti-PD-1, or anti-PD-L1 therapies * Renal impairment with estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73m² (based on MDRD formula) * Total cholesterol \> 350 mg/dL or triglycerides \> 500 mg/dL * History of severe acute (within the past 4 weeks) or chronic hypersensitivity reactions requiring treatment to everolimus or drugs with a similar chemical structure * Pregnant or breastfeeding women, women who are possibly pregnant, or women of childbearing potential who are unable to use highly effective contraception† during the study period and for 8 weeks after the last dose * Any condition deemed by the investigator to render the patient unsuitable for participation in the clinical trial * Highly effective contraception is defined as methods with a failure rate of less than 1% per year, including bilateral tubal occlusion, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices (IUDs), and copper IUDs. Methods such as calendar-based methods, ovulation prediction, symptothermal methods, and post-ovulation methods are not considered adequate contraception.