1 Department of Internal Medicine, Case Western Reserve University/MetroHealth Medical Center, Cleveland, OH 44109, United States.
2 Department of Hematology and Oncology, Cleveland Clinic/Akron General Medical Center, Akron, OH 44307, United States.
3 Department of Pathology, University of Florida, Gainsville, FL 32611, United States.
4 Division of Gastroenterology and Hepatology, Case Western Reserve University/MetroHealth Medical Center, Cleveland, OH 44109, the United States. firstname.lastname@example.org.
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, which in turns accounts for the sixth most common cancer worldwide. Despite being the 6th most common cancer it is the second leading cause of cancer related deaths. HCC typically arises in the background of cirrhosis, however, about 20% of cases can develop in a non-cirrhotic liver. This particular subgroup of HCC generally presents at an advanced stage as surveillance is not performed in a non-cirrhotic liver. HCC in non-cirrhotic patients is clinically silent in its early stages because of lack of symptoms and surveillance imaging; and higher hepatic reserve in this population. Interestingly, F3 fibrosis in non-alcoholic fatty liver disease, hepatitis B virus and hepatitis C virus infections are associated with high risk of developing HCC. Even though considerable progress has been made in the management of this entity, there is a dire need for implementation of surveillance strategies in the patient population at risk, to decrease the disease burden at presentation and improve the prognosis of these patients. This comprehensive review details the epidemiology, risk factors, clinical features, diagnosis and management of HCC in non-cirrhotic patients and provides future directions for research.