Department of Medicine, First Division of Gastroenterology, Centro AM e A Migliavacca for the Study of Liver Disease, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and Università degli Studi di Milano, Milan, Italy.
The only hope for a cure from hepatocellular carcinoma (HCC) rests on early diagnosis as it can be attained through semiannual surveillance with abdominal ultrasound (US) of patients at risk. While the strategy of semiannual screening rests on the growth rate of the tumor that in cirrhotic patients takes 6 months to double its volume, on average, the noninvasive radiological diagnosis of HCC is possible in cirrhotic patients with a de novo HCC and patients with chronic hepatitis B. More recently, metabolic diseases related to insulin resistance, including diabetes and obesity, have been recognized to be causally related to HCC as well, in most patients bridging HCC to the histopathological diagnosis of non-alcoholic steatohepatitis (NASH). While the endpoint of an early diagnosis is achieved quite easily in most patients with >1 cm HCC by computed tomography (CT) or magnetic resonance imaging (MRI) demonstrating the specific pattern of an intense contrast uptake during the arterial phase (wash-in) and contrast wash-out during the venous/delayed phase, nodules <1 cm in size are more difficult to diagnose, almost invariably requiring an enhanced follow up with three monthly examinations with US until they grow in size or change their echo pattern. Owing to the lack of robust controlled evidence demonstrating a clinical benefit of surveillance, the real support for screening for liver cancer comes from the striking differences in response to therapy between screened populations in whom HCC is diagnosed and treated at early stages and patients with more advanced, incidentally detected tumors. This notwithstanding, numerous barriers work against screening effectiveness, including limited or outdated knowledge, lack of financial incentives, and limited access to appropriate testing and treatment. Though strengthening prediction in individual patients is expected to improve the cost-effectiveness ratio of screening, the benefits of approaches like pretreatment patient stratification by clinical, histologic, and genetic scores remain uncertain, while the worthiness of excluding patients with severe comorbidities and aged individuals is still debated.