Screening for hepatocellular carcinoma in viral liver disease: Any new biomarkers on the horizon?

Professional society guidelines recommend semi-annual HCC surveillance to increase early HCC detection and receipt of curative treatment. Ultrasound remains the cornerstone of HCC surveillance tests but is limited by operator dependency and wide variation in sensitivity for early HCC detection. Although there has been increased use of alternative imaging modalities such as CT or MRI for HCC surveillance, their widespread use is limited by potential concerns including cost, radiologic capacity, and radiation or gadolinium accumulation. Alpha fetoprotein (AFP), the only biomarker to have undergone all five phases of biomarker evaluation, has insufficient sensitivity for use alone but can significantly improve early detection accuracy when used in combination with ultrasound. Other imaging tests, such as contrast-enhanced CT and MRI, have not been adequately evaluated as surveillance tests and should likely not be routinely used at this time given other potential concerns including radiation, gadolinium accumulation, cost, and radiologic capacity. Several serologic biomarkers, including multi-biomarker panels, have demonstrated promising results in phase II (case-control) studies, with some demonstrating sensitivities for early stage HCC exceeding that of imaging-based surveillance tests. The availability of at least two large prospective cohorts with stored clinically annotated serum and plasma samples should facilitate phase III validation among large cohorts of cirrhosis patients in the near future – a critical step to these biomarkers being available for routine use in clinical practice.