Spontaneous intracerebral hemorrhage associated with lenvatinib in advanced hepatocellular carcinoma without conventional risk factors: a case report literature review.

Lenvatinib is a multi-target tyrosine kinase inhibitor widely used in the treatment of advanced hepatocellular carcinoma (HCC). Its anti-angiogenic effects, however, may increase the risk of hemorrhagic events. Intracranial hemorrhage (ICH) during lenvatinib therapy is rare and remains poorly characterized. We report a case of spontaneous lobar ICH in a 54-year-old man with hepatitis B virus-related liver cirrhosis and advanced HCC with lung metastases. The patient was initially treated with atezolizumab-based therapy followed by lenvatinib due to disease progression. After seven months of treatment, he presented with a headache and visual disturbances. Brain magnetic resonance imaging (MRI) revealed a large lobar ICH in the right parieto-occipito-temporal region without evidence of metastatic tumor or vascular abnormalities. MRI spectroscopy did not support a malignant etiology. Although mild-to-moderate thrombocytopenia (platelet count 90, 000/µL) was observed, it was insufficient to fully explain the hemorrhage. The lesion initially improved but exacerbated subsequently, leading to discontinuation of lenvatinib. This case supports a possible association between lenvatinib therapy and spontaneous intracerebral hemorrhage even in the absence of hypertension or structural brain lesions, highlighting the need for constant vigilance in patients who present new neurological symptoms during treatment.