What is currently known about stage IV well-differentiated liver cancer with no cirrhosis? —Elizabeth Laursen Roesler, BSN, RN

Incidence of hepatocellular carcinoma (HCC) in the noncirrhotic liver (NCL) is less than 20%. HCC is often moderately or well differentiated and occurs as a solitary large mass. HCCs that develop in a liver with mild or no fibrosis may share these characteristics. Nonalcoholic fatty liver disease (NAFLD) without cirrhosis is an independent risk factor for HCC and is becoming more of a risk factor than NAFLD with cirrhosis. Similarly, HCC complicating the metabolic syndrome and arising in nonfibrotic livers often remain well differentiated despite a larger size. The alpha-fetoprotein (AFP) is normal more often than not.

The prognosis of HCC in NCL is better than that for HCC with cirrhosis; 5-year survival is approximately 50%. Prognosis is best for the patient with a small HCC, especially when no major vascular vessel invasion occurs and limited nodules are present. Although intrahepatic recurrence occurs frequently and should be aggressively sought and treated, there is a major role for repeat hepatic resection and a lesser role for hepatic transplantation, where results are poorer.

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A few groups have investigated biomarkers that may distinguish the molecular pathogenesis of HCC in cirrhotic vs. noncirrhotic livers. As far as stage IV disease is concerned, as for HCC in the setting of cirrhosis, the disease is incurable; however, treatments such as sorafenib (Nexavar), which is approved for advanced HCC, may be better tolerated when cirrhosis is not present and therefore more efficacious. —Donald R. Fleming, MD