Clinical implications of basic research in hepatocellular carcinoma

Clinical vignette A 58-year old Caucasian female has compensated hepatitis C related cirrhosis. Her surveillance ultrasound showed hypodense liver nodules and subsequent triple phase CT scan showed five tumor nodules with diameters ranging from 3-5 cms involving both hepatic lobes. The nodules showed characteristic radiologic findings on the CT scan and she was diagnosed with hepatocellular carcinoma (HCC) based on non-invasive criteria. There was also associated right portal vein tumor thrombosis. Her functional capacity at diagnosis was slightly limited, but she was capable of performing all activities of daily living and self-care. Her laboratory tests at diagnosis were as follows: sodium 129 mmol/L, potassium 3.6 mmol/L, blood urea nitrogen 22 mg/dL, creatinine 1.0 mg/dL, albumin 2.9 g/dl, bilirubin 1.8 mg/dl, alanine aminotransferase 87 U/L, aspartate aminotransferase 68 U/L, alkaline phosphatase 139 U/L, white blood cell 3.5 x 10⁹/L, hemoglobin 10.4, platelet count 73 x 10⁹/L, international normalized ratio 1.9 and alpha-fetoprotein 5200 ng/ml. An upper endoscopy was negative for esophageal or gastric varices. Based on the tumor burden, presence of macrovascular invasion, ECOG performance status of 1 and Child-Pugh class A she was classified to have BCLC stage C HCC. She was started on sorafenib therapy at 400 mg oral twice daily but unfortunately this had to be discontinued since she experienced severe diarrhea and skin rash. She now returns for follow-up and requests information on the available therapeutic options. This particular case scenario is not uncommon and does raise several clinically relevant questions:Should her liver lesions have been biopsied for diagnosis?Are there any serum or tissue biomarkers that could have helped in prognostication?Was sorafenib the best first option for her and were there any biomarkers that could have predicted the adverse reactions she experienced?What other potential therapies will be available for her in the near future? This review provides a comprehensive overview of the current state of HCC management and also examines the clinical implications of recent basic research in HCC.