Chemoembolization With or Without Antiviral Therapy for Unresectable HBV-related HCC With Low HBV DNA Replication
Chemoembolization With or Without Antiviral Therapy for Unresectable HBV-related HCC With Low HBV DNA Replication
Although it is commonly accepted that antiviral therapy should be commenced before or during
 hepatocellular carcinoma (HCC) treatment if the patients have high viral loads and elevated
 ALT or total bilirubin values with signs of cirrhosis, the dilemma exists when HBV DNA and
 liver function (such as ALT, AST, TBIL) remains low level. Whether antiviral therapy make
 sense or not in these patients with no signs of hepatitis or high viral replication remains
 unclear, especially for the relatively advanced stage HCC patients receiving TACE. Thus, the
 investigators carried out this prospective control study to compare the survivals for
 patients after TACE between with or without antiviral therapy.
In highly endemic areas, hepatitis B virus (HBV) infection plays a primary role in the
 etiology of HCC and is frequently observed in HCC patients. Patients with HBV-related HCC
 usually have a history of chronic HBV infection. Chemotherapy for other malignancies has been
 associated with HBV reactivation. Furthermore, in end stage liver disease due to HBV, levels
 of HBV replication have been correlated with liver function. For TACE, reports on HBV
 reactivation have been inconsistent. Some studies have demonstrated HBV reactivation, some
 have not , and others have shown decreased HBV DNA levels . The exact mechanism by which this
 occurs is still unknown. Although anti-HBV therapy has been reported to suppress HBV
 reactivation in various clinical settings with immunosuppressive conditions, few reports were
 concerned with the TACE treatment of HBV-related HCC. Also, the long-term effects of
 antiviral therapy in relatively advanced HCC patients after HCC remains unclear.

 Although it is commonly accepted that antiviral therapy should be commenced before or during
 HCC treatment if the patients have high viral loads and elevated ALT or total bilirubin
 values with signs of cirrhosis, the dilemma exists when HBV DNA and liver function (such as
 ALT, AST, TBIL) remains low level. Therefore, we would call for the establishment of clinical
 practice guidelines on the antiviral therapy in HBV-related HCC patients, especially a
 consensus on the indications to administer nucleosides analogs (NAs).

 Thus , the purpose of the investigators' study is to prospectively study the efficacy of
 nucleosides analogs (NAs) in transcatheter arterial chemoembolization for nonresectable
 hepatocellular carcinoma with relatively low HBV DNA replication and Child-Pugh grade A based
 on multivariate analysis of prognostic factors. The HBV DNA and liver function parameters
 will be monitored closely. Once the reactivation occurs in the control group, antiviral
 therapy would be administered immediately. The study had a interim analysis to allow the
 trial to be stopped if significant differences were detected. The accumulated data were
 examined when half patient was enrolled in the clinical trial.
Inclusion Criteria:

 Male or female patients from 18 to 75 years of age with a diagnosis of HCC. A diagnosis of
 HCC based on the diagnostic criteria for HCC used by the European Association for the Study
 of the Liver (EASL).

 The patient has not been previously treated with surgery, radiation therapy, radiofrequency
 ablation, percutaneous ethanol or acetic acid injection, or cryoablation, or any other
 treatment with chemotherapeutic agents or sorafenib.

 The patient has not been previously treated with any anti-viral agents, including
 interferon or nucleosides analogs (NAs).

 Adults patients with a diagnosis of HCC which is not amenable to surgical resection ,local
 ablative therapy or any other radically cured treatment.

 The MDT group of HCC agree to administer TACE in this patient.

 Patients must have at least one tumor lesion that can be accurately measured according to
 EASL criteria.

 No serious concurrent medical illness.

 Unresectable TNM stage Ⅲ or Ⅳ disease.

 Zubrod-ECOG-WHO performance status: 0 or 1. and the estimated survival more than 4 months.

 Not pregnant or breast-feeding patients

 No significant renal impairment (creatinine clearance < 30 mL/minute) or patients on
 dialysis

 No current infections requiring antibiotic therapy

 Not on anticoagulation or suffering from a known bleeding disorder

 No unstable coronary artery disease or recent MI

 Ability to understand the protocol and to agree to and sign a written informed consent
 document

 The following laboratory parameters at baseline:

 Platelet count ≥ 70,000/µL

 Hemoglobin ≥ 8.5 g/dL

 Absolute neutrophil count (ANC) >1,500/mm3

 Total bilirubin ≤ 1.5 mg/dL Serum albumin ≥ 35 g/L

 Serum creatinine ≤ 1.5 x upper limit of normal

 PT prolong time less than 3 seconds

 Cirrhotic status of Child-Pugh class A only

 ALT<2×upper limit of normal

 Hepatitis B surface antigen positive

 If hepatitis B e antigen positive, HBV DNA level <2000IU/mL; If hepatitis B e antigen
 negative, HBV-DNA<200IU/mL.

 Exclusion Criteria:

 - History of HIV or HCV infection.

 History of organ allograft

 Known or suspected allergy to the investigational agents or any agent given in association
 with this trial.

 Evidence of bleeding diathesis.

 Patients with clinically significant gastrointestinal bleeding within 30 days prior to
 study entry.

 Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of study entry.

 Serious non-healing wound, ulcer, or bone fracture

 Known central nervous system tumors including metastatic brain disease

 Any event > grade 2 National Cancer Institute [NCI]-Common Terminology Criteria for Adverse
 Events [CTCAE] version 3.0

 Severe complication after TACE.

 History of hepatotoxic medication within 8 wk prior to the current treatment.

 History of corticosteroid administration.