Hepatocellular Carcinoma: The Search for an Optimal Screening Test.

Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer-related death, with a 5-year survival rate of 10%-12%. It usually develops in the setting of chronic liver disease (CLD), with chronic viral hepatitis, alcohol, and non-alcoholic fatty liver disease (NAFLD) being the most common risk factors. Some patients are at higher risk of developing hepatocellular cancer, so it is important to screen them regularly to diagnose the disease at an early stage and improve their chances for curative treatment. Six-monthly ultrasound with or without alpha-fetoprotein (AFP) is the currently recommended surveillance method. AFP has been used as a biomarker for liver cancer; however, it has low sensitivity and specificity, which necessitates the search for other, more accurate biomarkers. Promising biomarkers include lens culinaris agglutinin-reactive AFP, des-gamma-carboxy prothrombin, methylated DNA markers, plasma microRNA expression, circulating tumor DNA, and circulating tumor cells. In addition, combinations of biomarkers, like the GALAD score and the Doylestown algorithm, may help in the early detection of HCC. In this review, we summarize the screening tests for early detection of HCC that have been studied over the last decade.