Abemaciclib/fulvestrant

Abstract

Decompensated liver failure and cerebral oedema secondary to hepatic thrombotic portal venopathy : case report A 54-year-old woman developed decompensated liver failure and cerebral oedema secondary to hepatic thrombotic portal venopathy. The woman had a history of grade-II invasive lobular carcinoma (ILC), high alcohol intake, chronic kidney disease and hypertension. For ILC, she initially underwent bilateral mastectomy and unilateral axillary lymph node dissection (pT3pN2a). It was followed by five cycles of adjuvant FEC-T chemotherapy included fluorouracil, epirubicin, cyclophosphamide and docetaxel, and radiotherapy. She also received adjuvant endocrine therapy. Eventually, 4.5 years after the initial diagnosis, she presented with isolated cervical lymph node ILC metastasis. Staging CT scans demonstrated no other distant disease. Thereafter, she started receiving oral abemaciclib 150mg twice daily and IM fulvestrant 500mg injection. However, eleven days after the initiation of combination palliative therapy, she developed headache, blurred vision and hyperpyrexia. Subsequently, the woman was admitted. Upon admission, abemaciclib and fulvestrant were discontinued. Extensive investigations were unremarkable. Her prothrombin time was increased and she became anaemic with evidence of haemolysis. Serum ALP and bilirubin levels were >5 ULN. Her eGRF was 39 mL/min. Despite supportive therapy including inotropic support, ventilation and renal dialysis, she was rapidly deteriorated and she had multiorgan (including hepatic) failure. A CT head scan demonstrated severe cerebral oedema. Eight days after the initial presentation, her supportive care was withdrawn and she died. To determine the cause of death, a coronial postmortem was performed. During postmortem, the most evident finding on macroscopic assessment was the cut surface of the liver, which showed diffuse areas of small antemortem thrombus formation. The brain weighed 1240g and was diffusely swollen with effacement of the sulcal-gyral pattern. There was no evidence of intracranial metastatic carcinoma. Both cerebellar tonsils demonstrated evidence of haemorrhagic change, consistent with intracranial herniation. The medial aspects of the occipital lobes also showed haemorrhagic change and discoloration, consistent with compression of the posterior cerebral arteries secondary to raised intracranial pressure. Histological sections of the liver demonstrated acute antemortem portal vein thrombus formation with massive expansion of the portal tracts. In some areas, the portal veins were seen to herniate toward the adjacent hepatic parenchyma. The appearances were of an acute thrombotic portal venopathy and areas of hepatic necrosis. The cerebellum demonstrated parenchymal haemorrhage and some Purkinje cell ischemic injury consistent with downward cerebellar herniation. Based on the aforementioned findings, the cause of death was concluded as decompensated liver failure and cerebral oedema secondary to hepatic thrombotic portal venopathy (noncirrhotic portal hypertension), and these were attributed to abemaciclib and fulvestrant chemotherapy. This case report was submitted to the Medicines and Healthcare products Regulatory Agency, UK (MHRA).