Brain hemorrhage in patients with advanced hepatocellular carcinoma treated with atezolizumab and bevacizumab: two case reports

A combination of atezolizumab and bevacizumab is currently recommended for treating unresectable advanced-stage hepatocellular carcinoma (HCC), as it has demonstrated superior overall survival and progression-free survival compared to sorafenib. However, concerns have been raised regarding serious adverse events associated with bevacizumab, such as gastrointestinal perforation, fistula, hemorrhage, and arterial thromboembolism. In particular, patients with liver cirrhosis (LC) show an increased risk of variceal bleeding. However, brain hemorrhage associated with the use of bevacizumab in patients with HCC and LC is extremely rare. We encountered two cases of brain hemorrhage in patients with HCC and LC who underwent treatment with atezolizumab and bevacizumab. One patient had no history of hypertension, while the other patient had hypertension that was well-controlled with medication and an unruptured brain aneurysm located on the right side of the anterior communicating artery. Both patients experienced brain hemorrhage after two treatment cycles of atezolizumab with bevacizumab. One patient died due to brain hemorrhage, while the other patient recovered from subarachnoid hemorrhage with successful coil embolization. This case report suggests that if a patient has any high-risk factors associated with brain hemorrhage, physicians should thoroughly consider alternative treatment options for advanced HCC, as brain hemorrhage could be fatal.