Hepatocellular carcinoma: overcoming challenges in disease management.

Hepatocellular carcinoma is the third most frequent cause of death from cancer and the eighth most commonly occurring cancer in the world. In the United States, hepatocellular carcinoma appears to be increasing along with evolution of chronic hepatitis infection, especially in the immigrant population, a major risk group. A disease of multifactorial etiology, hepatocellular carcinoma confers many management challenges. Hepatocarcinogenesis is a multistep process involving different genetic alterations that ultimately lead to malignant transformation of the hepatocyte. Early hepatocellular carcinoma is characteristically silent and slow growing with few symptoms until late in disease. Early and accurate diagnosis of hepatic tumors relies on clinical suspicion, screening protocols, serologic testing, radiologic imaging, and tissue confirmation. Lack of clinically validated biomarkers and clinical identification of hepatocellular carcinoma at advanced disease make diagnosis and treatment difficult. Advances in computed tomography and magnetic resonance imaging have markedly increased the sensitivity and specificity of testing, yet they are still flawed with a relatively high false-positive rate. Several surgical and nonsurgical therapies have been developed and used with varying degrees of success. Options include surgical resection, liver transplantation, local ablation therapies, and pharmaceutical interventions. At 5 years after resection, in those patients who are surgical candidates, the recurrence rate ranges between 30% and 60%. In patients with nonresectable disease, the prognosis is dismal, with a median survival of less than 12 months even with chemotherapy. The medical community faces numerous challenges in hepatocellular carcinoma and must work toward better management and multidisciplinary care of this complex disease.