Caren van Roekel

38 Chapter 2 Hepatotoxicity is the most important adverse event after radioembolization, but a clear definition is often lacking. Braat et al have proposed the following grading for hepatotoxicity after radioembolization (74): • Grade 0: no liver toxicity (i.e. no CTCAE toxicity grade changes over baseline) • Grade 1: minor liver toxicity, limited to increased aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and/or γ-glutamyl transpeptidase levels (all not exceedingly newly developed grade 1 CTCAE toxicity) • Grade 2: moderate liver toxicity, with a self-limiting course. No medical intervention necessary. • Grade 3: REILD, manageable with noninvasive treatments such as diuretics, ursodeoxycholic acid, and steroids • Grade 4: REILD necessitating invasive medical treatment such as paracentesis, transfusions, hemodialysis or a transjugular intrahepatic portosystemic shunt • Grade 5: fatal REILD The most frequent side effect of radioembolization is the post-embolization syndrome, which consists of fatigue, nausea, vomiting, anorexia, fever and abdominal pain. These effects are usually mild and self-limiting within two weeks. The post-embolization syndrome occurs in up to 55% of patients (75). Another common side effect is a transient elevation of liver enzymes (75). In a retrospective analysis of 58 patients with diverse hepatic malignancies, Roberson et al. found that a decreased pretreatment albumin and an elevated pretreatment INR were associated with the development of severe liver toxicity after radioembolization (76). Gabrielson et al. evaluated toxicity after radioembolization in patients with hepatocellular carcinoma. They found that a pretreatment elevation of bilirubin and an elevation of the transaminases (ALT/AST) were associated with a higher risk of a decline in liver function after treatment (77). Laboratory abnormalities usually go without associated clinical side effects (78). However, when laboratory toxicities are associated with ascites, this may be a sign of a much more serious complication: radioembolization- induced liver disease (REILD) (Figure 6).