Table 1.

Potential steps to mitigate overdiagnosis in HCC surveillance

Method	Example
Target screening to the at-risk population	AASLD and EASL guidelines recommend HCC surveillance in at risk populations (i.e., cirrhosis and select individuals with hepatitis B infection) and against routine screening in non-cirrhotic NAFLD or hepatitis C infection Risk stratification biomarkers may facilitate precision/tailored surveillance according to individual patient risk in the future
Avoid screening in patients with high competing risks of mortality	AASLD and EASL guidelines recommend avoiding HCC surveillance in patients with significant liver dysfunction (e.g., Child Pugh C cirrhosis) and those with high comorbidity
Appropriate frequency of screening	AASLD and EASL guidelines recommend HCC surveillance with ultrasound +/- AFP every 6 months (shorter intervals result in increased overdiagnosis)
Avoid screening and diagnostic tests that have high potential for overdiagnosis	AASLD and EASL guidelines recommend ultrasound instead of routine use of CT or MRI for surveillance Emerging early detection biomarkers may preserve high sensitivity for early HCC while reducing potential for overdiagnosis
Adhere to guideline recommendations for recall procedures	AASLD and EASL guidelines recommend repeat short-interval ultrasound in patients with sub-centimeter lesions and perform diagnostic imaging for those with lesions ≥1 cm and those with elevated AFP levels.
Strictly apply diagnostic criteria	AASLD and EASL guidelines recommend strict radiologic criteria (e.g., LI-RADS) for HCC diagnosis and using biopsy in cases where diagnosis is uncertain and LI-RADS has not been validated (e.g., non-cirrhosis, cardiac cirrhosis) AASLD and EASL guidelines recommend multidisciplinary discussion for patients with LR-4 observations and recommend against routine treatment
Assess tumor biology and identify indolent tumors that may not require treatment	Novel prognostic biomarkers and radiomics may help distinguish indolent versus aggressive HCC
Inform patients of the possibility of overdiagnosis, the balance of benefits and harms and enable shared decision making	Discuss benefits and harms of various HCC surveillance modalities according to the patient’s individual risk Counsel patients on the potential outcomes and limitations of surveillance tests