If this results in a typical image, HCC is diagnosed. If this is also inconclusive, biopsy is needed. This approach has been validated by a number of studies. The main limitation
is that 30–40% of HCC is missed on fine needle biopsy . Repeated biopsies are often necessary. Other problems of biopsy include the risk of needle track seeding (2.7% Ivacaftor clinical trial in a recent meta-analysis ) and the difficulty to differentiate HCC from high-grade dysplastic nodules on small biopsy samples. In persons with haemophilia, the risk of bleeding and requirement of coagulation factor concentrates need to be considered . The most widely used staging system for HCC is the Barcelona Clinic Liver Cancer (BCLC) staging scheme (Table 1) . Recommendation. We follow the AASLD recommendations for diagnosis. The diagnostic work-up and indications for biopsy are not different from those in patients without haemophilia. Removal of the tumour(s), prior to spreading outside the liver is the only option for cure. This can be achieved by surgical resection, local ablation or liver transplantation. The first two can only be considered in selected cases with one or two nodules and relative adequate function of the cirrhotic liver. Impaired liver
function and regenerative capacity in combination with the precancerous condition of the liver make the outcome less than optimal. Liver transplantation is in itself the best option as it both cures the cirrhosis and removes both malignant and premalignant lesions. However, patient characteristics, donor shortage and (potential) tumour spread outside the liver buy Deforolimus may preclude this option. If local ablation or resection are not feasible, most liver transplant centres only accept patients for liver transplantation if the tumour load is not outside the so-called Milan
criteria: one solitary HCC lesion ≤5 cm or maximum three lesions ≤3 cm, no gross vascular invasion and no regional node or distant metastases . The different treatment modalities are discussed in more detail below. Only a small minority of patients with HCC in the setting of HCV infection are good candidates for resection, because most will have cirrhosis and liver dysfunction. Patients with cirrhosis but still well-preserved liver function Sodium butyrate can be eligible, if their bilirubin and portal blood pressure are normal. In that case, 5-year survival can exceed 70%, while in less rigorously selected patients, 5-year survival is about 50% . Recurrence of HCC, either a true recurrence of the same tumour or de novo HCC, is eventually seen in up to 70% of patients who undergo resection. Adjuvant therapy, either before or after surgery, does not reduce this rate . Data on the treatment of recurrence are scarce, although liver transplantation might be an option in some patients. Evidence in haemophilia.