Weighing the benefits of hepatocellular carcinoma surveillance against potential harms Daniel Geh,1,* Fahd A Rana,2,* Helen L Reeves1,3 1Northern Institute for Cancer Research, Newcastle University Medical School, Newcastle upon Tyne, UK; 2The Liver Unit, Freeman Hospital, Newcastle upon Tyne, UK; 3The Hepatopancreatobiliary Multidisciplinary Team, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK *These authors contributed equally to this work Abstract: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and usually occurs in people with liver cirrhosis. Both the incidence and mortality of HCC are increasing worldwide, making it a growing public health issue. HCC diagnosed at an early stage has a far better prognosis than HCC diagnosed at a late stage, mainly because early stage HCC can be treated with potentially curative therapies such as resection and transplantation. This makes surveillance for HCC in patients with liver cirrhosis an important strategy in improving outcomes. Serial measurements of serum alpha fetoprotein (AFP) and abdominal ultrasound (US) are the established methods of surveillance. Surveillance using a combination of these techniques has reasonable sensitivity and specificity and reduces mortality from HCC by varying degrees, depending on the patient population. However, there are potential harms. The main harms result from false-positive and false-negative results. False-positive results commit patients to undergo further, potentially invasive and ultimately unnecessary diagnostic testing – which has both financial and emotional costs. False-negative results can have devastating consequences for patients who later present with more advanced HCC. Obesity is increasingly prevalent and reduces the sensitivity of US in detecting HCC. Obesity-associated non-alcoholic fatty liver disease (NAFLD) presents an additional challenge, where HCC can develop in the absence of cirrhosis. As surveillance with US and AFP is not cost-effective in NAFLD without cirrhosis, it is not advocated. These aspects will be reviewed. Keywords: hepatocellular carcinoma, liver cirrhosis, surveillance, NAFLD, screening