Surveillance is not required in patients who had not developed cirrhosis at the time of successful HCV treatment. Ultrasono-graphy of the liver is the best available tool for surveillance for HCC, although sensitivity and specificity are limited at 65–80%

and 90% respectively. Other limitations of the technique are operator dependency, decreased NVP-BKM120 quality in obese patients and decreased sensitivity in patients with cirrhosis. Periodic measurement of serum AFP is only recommended if ultrasonography is not available: there is no single cut-off level that is both sensitive and specific enough for the presence of HCC. However, because of the limitations of US, many clinicians still favour the combination of US and AFP. A sudden rise of AFP and/or a high level of AFP deserves further radiological diagnostics (4-phase CT scanning) in case US is not conclusive. The interval between ultrasounds is determined by the growth rate of the tumour: the aim is to diagnose HCC between its earliest visibility on US and the time it has reached 2 cm in diameter. From biological studies, this window is 6–12 months. Most clinical evidence does not show added benefit for surveillance intervals of 6 months

over 12 months and AASLD’s recommendation to screen at 6 months’ interval is based on data in hepatitis B. Evidence in haemophilia.  Santagostino et al. performed a non-randomized, two-arm study in persons with haemophilia, in which they compared surveillance intervals of 6 and 12 months [27]. They used both US and AFP. More cases of HCC were diagnosed in the 6-month group (0.40% vs. 0.14% per year), but in both groups tumours MLN8237 molecular weight were multinodular and long-term survival was only seen in patients who had undergone orthotopic liver transplantation

see more (OLT). Too few HCC were diagnosed for a meaningful comparison of the two strategies: in the 12-month group, two patients died and one was a long-term survivor; in the 6-month group, one patient was recently diagnosed, one died, one was on the waiting list for OLT and two were long-term survivors. The Santagostino study was designed after an earlier cohort study by the same group tested annual screening with US and AFP [18]. In this study, all HCC were late stage disease without options for curative treatment. It should of course be noted that treatment options have increased after these two studies were performed. Recommendation.  We perform yearly US combined with twice-yearly AFP measurement in all haemophilia patients with chronic hepatitis C, including those in whom cirrhosis has not been diagnosed. We do this because fibrosis without cirrhosis is also associated with HCC and because present diagnostic methods (including non-invasive tests) cannot reliably exclude cirrhosis. We also continue surveillance in patients who have successfully been treated for HCV, as we did not exclude cirrhosis in most of them before treatment.