Toxic hepatitis in metastatic breast cancer patient using ribociclib and denosumab

by Selleckchem | Jun 09 2023

Hepatotoxicity is observed due to cyclin-dependent kinase (CDK4/6) inhibitors used to treat hormone receptor-positive metastatic breast cancer. However, it should not be ignored that denosumab may be hepatotoxic, although it is rare.

Case Report: A 73-year-old female patient with breast cancer with axillary lymph node, adrenal gland and bone metastases was started on ribociclib letrozole and denosumab treatment. Ribociclib treatment was discontinued due to grade 4 hepatotoxicity during treatment, but liver function tests did not decrease. After discontinuation of denosumab treatment, alanine aminotransferase and aspartate aminotransferase values regressed to baseline values.

Management and Outcome: Despite the discontinuation of ribociclib treatment, other causes of liver toxicity were investigated due to persistence of hepatic transaminases and elevation. Autoimmune hepatitis markers were negative. Hepatobiliary USG did not reveal any pathological findings except hepatosteatosis. Liver biopsy was performed to determine the etiology. Pathology result was compatible with acute hepatocellular damage (in favor of toxic hepatitis). A decrease in liver values was detected after discontinuation of denosumab treatment.

Discussion: Although cases with improvement in liver enzymes have been reported after discontinuation of ribociclib, no improvement in hepatotoxicity was observed in our case. Since the liver biopsy was toxic hepatitis, it was thought that other drugs used by the patient might cause this toxicity, and a significant decrease was observed in liver values after discontinuation of denosumab. Denosumab-induced liver toxicity is very rare, and there are only a limited number of cases in the literature.

Comments:

Thank you for providing the case report. It describes a rare instance of hepatotoxicity associated with the use of denosumab in a patient with breast cancer and metastases. While hepatotoxicity has been observed with cyclin-dependent kinase (CDK4/6) inhibitors such as ribociclib, this case suggests that denosumab, although uncommon, may also be hepatotoxic.

In the case, a 73-year-old female patient with hormone receptor-positive metastatic breast cancer was started on ribociclib, letrozole, and denosumab treatment. Ribociclib was discontinued due to grade 4 hepatotoxicity, but liver function tests did not improve. After stopping denosumab, liver enzyme values returned to baseline. Further investigations were carried out to determine the cause of the persistent liver toxicity, including ruling out autoimmune hepatitis. The liver biopsy indicated acute hepatocellular damage consistent with toxic hepatitis, and a subsequent decrease in liver values was observed following discontinuation of denosumab.

It's important to note that denosumab-induced liver toxicity is very rare, and there are only a limited number of cases reported in the literature. Monitoring liver function tests is generally recommended during treatment with denosumab, as well as other medications that may have hepatotoxic potential.

In this case, the hepatotoxicity observed may have been attributed to denosumab, but it is crucial to consider other potential causes as well. Adverse drug reactions can vary among individuals, and it is important for healthcare professionals to closely monitor patients and assess for any signs of liver toxicity during treatment.