Hepatocellular carcinoma is the most common form of primary liver cancer. It occurs most commonly in the setting of underlying hepatic cirrhosis. The lesions are highly vascular and may be multifocal or solitary. There are few associated symptoms until the lesion becomes large; therefore, all patients with underlying cirrhosis or diseases associated with a progression towards cirrhosis should undergo regular screening for this malignancy. Associated paraneoplastic syndromes include erythrocytosis, hypercalcemia, hypoglycemia, carcinoid syndrome, dysfibrinogenemia, and cryoglobulinemia. Therapy has evolved from simple resection, to various forms of radiofrequency ablation techniques, theraspheres with radiation therapy, intralesional chemotherapy with arterial embolization, sorafenib, or orthotopic liver transplantation. The latter option offers the added benefit to also treat the underlying hepatic cirrhosis.

Every cirrhotic patient should be considered for HCC surveillance. Cirrhotic patients with diabetes mellitus and/or obesity are at higher risk for HCC development. Continued alcohol use is another risk factor for the development of HCC in cirrhotic patients. Determining when surveillance should begin is problematic. Many liver diseases are diagnosed early with only fibrosis or minimal hepatic damage on biopsy specimens. Following the AST/ALT and AST/platelet ratios are helpful to determine when the underlying liver damage is progressing when an earlier biopsy specimen is not consistent with a cirrhotic liver. An AST/ALT ratio greater than 1.3 or an AST/platelet ratio greater than 1.5 are suggestive of progression towards cirrhosis. Chronic hepatitis B is unusual since HCC can precede cirrhosis and these patients require close observation.

HCC surveillance is accomplished with serial hepatic ultrasonography with or without serum alpha-feto protein (AFP) determinations. The AFP is insensitive when the HCC lesion is less than 2 cm in size; therefore minor elevations of AFP are non-diagnostic.

The diagnosis may be established without the need for biopsy when lesions are greater than 2 cm in size if two imaging studies reveal a hypervascular lesion or if one is consistent with HCC and the serum AFP is greater than 400 ng/mL. Lesions larger than 2 cm with a low AFP require biopsy. Smaller lesions, less than 1 cm in size have a low malignant potential and can be followed with serial ultrasonography every three months with the diagnosis developing if the lesions progress. Intermediate lesions (between 1 to 2 cm in size) will require biopsy. Determination of the patient’s Child-Pugh score helps when determining the course of treatment, as the health of the remaining liver is an important variable in post-treatment prognosis.

Managing patients after effective diagnosis and treatment of HCC is complex since these patients are still at risk for recurrence as HCC is multifocal and the remaining hepatic tissue after treatment is still cirrhotic. Therefore continued surveillance is the rule. Orthotopic liver transplantation recipients are the exception as their cirrhotic liver has been replaced; however, if they still suffer from treatment resistant chronic hepatitis B or C, the transplanted liver is at risk for progression towards cirrhosis. All cirrhotic patients should be counseled to maintain an ideal body weight.