The purpose of this study is to evaluate the safety and tolerability of escalating doses of mapatumumab in combination with sorafenib in subjects with advanced Hepatocellular Carcinoma who are positive for hepatitis B surface antigen or hepatitis C antibody.

Inclusion Criteria:

• Moderate liver disease
• Test positive for hepatitis B surface antigen or hepatitis C antibody
• Locally advanced unresectable/untransplantable or metastatic hepatocellular carcinoma
• Age 18 years or older

Exclusion Criteria:

• Received investigational (not yet approved by a regulatory authority) or non-investigational agent to treat hepatocellular carcinoma.
• Received radiation therapy within 4 weeks before randomization
• Major surgery within 4 weeks before randomization
• Minor surgery within 2 weeks before randomization
• Systemic steroids within 1 week before randomization
• Hepatic encephalopathy, per the investigator's evaluation
• History of clinically significant gastrointestinal bleeding requiring procedural intervention within 4 weeks before enrollment
• History of any infection requiring hospitalization or antibiotics within 2 weeks before randomization
• Known brain or spinal cord metastases
• History of other cancers within 5 years before enrollment
• Pregnant or breast-feeding women
• Known HIV infection