Hepatocellular carcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up.

The oncologic community is faced with a steady increase in the incidence of hepatocellular carcinoma (HCC) [1]. Liver cancer represents the sixth most common cancer in the world (749 000 new cases) and the third cause of cancer-related death (692 000 cases). The incidence varies from 3 out of 100 000 in Western countries, to more than 15 out of 100 000 in certain areas of the world, mapping the geographical distribution of viral hepatitis B (HBV) and hepatitis C (HCV), the most important causes of chronic liver disease and HCC [2]. Most cases arise in those regions with limited resources. The incidence of HCC increases progressively with advancing age in all populations, with a strong male preponderance. The association of chronic liver disease and HCC represents the basis for preventive strategies, including universal vaccination at birth against hepatitis B , programs to stop transmission and early antiviral eradication of viral hepatitis B and C [III, A]. It is unclear whether HBV vaccination will result in a decline in HCC as was seen in Taiwan, given the importance of other risk factors in Europe, such as alcoholic and non-alcoholic fatty liver disease. The control of other risk factors for chronic liver disease and cancer is more difficult to implement, such as cutting down on the consumption of alcohol and programs aiming at a healthier lifestyle in the light of the obesity pandemic [3, 4]. In Africa, reduction of exposure to aflatoxin B1, especially in HBV-infected individuals, may lower the risk of HCC. HCC may evolve from subclasses of adenomas, and in <10% of cases HCC occurs in a normal liver. Surveillance of HCC involves the repeated application of screening tools in patients at risk for HCC and aims for the reduction in mortality of this patient population. The success of surveillance is influenced by the incidence of HCC in the target population, the availability and acceptance of efficient diagnostic tests and the availability of effective treatment. Costeffectiveness studies suggest surveillance of HCC is warranted in cirrhotic patients irrespective of its etiology [5]. Surveillance of non-cirrhotic patients is also advocated, especially in HBV carriers with serum viral load >10 000 copies/ml [6] or HCVinfected patients with bridging fibrosis (F3) [III, A]. Patients with HCV infection and advanced fibrosis remain at risk for HCC even after achieving sustained virological response following antiviral treatment [III, A]. Japanese cohort studies have shown that surveillance by abdominal ultrasound resulted in an average size of the detected tumors of 1.6 ± 0.6 cm, with <2% of the cases exceeding 3 cm [7]. In the Western world and in less experienced centers, sensitivity of finding early-stage HCC by ultrasound is considerably less effective [8]. There are no data to support the use of contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) for surveillance. In many centers, ultrasound surveillance is complemented with the determination of serum alphafetoprotein (AFP), which can lead to a 6%–8% gain in the tumor detection rate but at the price of false-positive results. A randomized, controlled trial (RCT) of Chinese patients with chronic hepatitis B infection compared surveillance (ultrasound and serum AFP measurements every 6 months) versus no surveillance [9]. Despite low compliance with the surveillance program (55%), HCC-related mortality was reduced by 37% in the surveillance arm. Considering the most appropriate surveillance interval, a randomized study comparing a 3versus 6-month based schedule failed to detect any differences [10]. Therefore, surveillance of patients at risk for HCC should be carried out by abdominal ultrasound every 6 months [I, A].