Primary liver cancer, mostly hepatocellular carcinoma, remains a difficult-to-treat cancer. Incidence of liver cancer varies geographically and parallels with the geographic prevalence of viral hepatitis. A number of staging systems have been developed, reflecting the heterogeneity of primary liver cancer, regional preferences, and regional variations in resectability or transplant eligibility. Multimodality treatments are available for this heterogeneous malignancy, and there are variations in the management recommendations for liver cancers across specialties and geographic regions. Novel treatment strategies have merged with the advance of new treatment modalities. This work focuses on reviewing the incidence, staging, and treatment of liver cancer.

Liver cancer is a cancer that originates in the liver, and is an aggressive tumor that frequently occurs in the setting of chronic liver disease and cirrhosis. Primary liver cancer, or hepatocellular carcinoma (HCC), is the fifth most common cancer in males and the seventh most common cancer in females, and is the third leading cause of cancer-related death worldwide. The incidence of liver cancer is increasing in the United States, reaching an annual incidence of 4.5 per 100,000 in 2005. Despite advances in its treatment, liver cancer remains one of the most difficult cancers to treat. For patients with early HCC, surgery, local destructive therapies, and liver transplantation provide curative potential. However, recurrence of HCC remains a major problem after curative treatment, reaching an incidence of more than 70% at 5 yr. Even in patients with early, small HCC (<3 cm) receiving surgery, the 5-yr survival rate is not satisfactory (47% to 53%). Typically, HCC is often diagnosed at an advanced stage, and many patients with advanced stage are not eligible for the curative therapies. Moreover, traditional systemic chemotherapy shows low efficacy and little survival benefits. The approval of a multikinase inhibitor, sorafenib, has shown some survival benefit in patients with advanced HCC and preserved liver function, highlighting a promising molecular targeted strategy .

Treatment of liver cancer is now multidisciplinary, and multimodel treatment options are chosen generally on an individualized basis according to the complex interplay of tumor stage and the extent of underlying liver disease, as well as the patient’s overall general health. There are variations in the recommendations for the management of liver cancers across the specialties and geographic regions. Heterogeneity in management of liver cancer exists across the various guidelines from the United States (National Comprehensive Cancer Network [NCCN]), Europe (European Association for the Study of the Liver-European Organization for Research and Treatment of Cancer [EASL-EORTC]), and Asia (consensus statement from the Asian Oncology Summit 2009 [AOS]) . This work focuses on reviewing the incidence, monitoring, and treatment of liver cancer.

INCIDENCE OF LIVER CANCER

Globally, the incidence of liver cancer is more than twice as high in males as in females. The highest liver cancer rates are found in East and Southeast Asia and in Middle and Western Africa, whereas rates are low in South-Central and Western Asia, as well as Northern and Eastern Europe. These regional differences in incidence of liver cancer reflect regional variations in exposure to hepatitis viruses and environmental pathogens. In developing countries, hepatitis B virus (HBV) infection accounts for about 60% of the total liver cancer in developing countries, whereas hepatitis C virus (HCV) infection accounts for about 33% of total liver cancer. The incidence of liver cancer is increasing in the United States and Central Europe, possibly because of the obesity epidemic and the increase in HCV infection through continued transmission by injecting drug users. In the United States and several other low-risk Western countries, alcohol-related cirrhosis and possibly nonalcoholic fatty liver disease, associated with obesity, are thought to account for the majority of liver cancer. In contrast, liver cancer incidence rates have decreased in some historically high-risk areas, possibly because of the vaccine . A universal infant hepatitis vaccination program initiated in 1984 in Taiwan has significantly reduced liver cancer incidence rates in children aged 6–19 yr, showing an age- and sex-adjusted relative risk of 0.31 for persons vaccinated at birth.