Novel Use of N-Acetylcysteine in Management of Tyrosine Kinase Inhibitor Induced Acute Liver Injury.

Abstract

Tyrosine kinase inhibitors (TKIs) have been adopted in the treatment of a variety of malignancies. Despite their popularity, the underlying mechanism of the adverse effects seen with the use of TKIs is not completely understood. Acute liver injury is a known side effect of many of these drugs. Some papers have demonstrated that N-acetylcysteine may have a role in non-acetaminophen induced acute liver failure (NAI-ALF). There is little evidence supporting the use of N-acetylcysteine in the treatment of tyrosine kinase inhibitor-induced acute liver injury. This case report adds to the limited body of existing knowledge.We present a 67-year-old Caucasian female with a past medical history of anxiety, hyperlipidemia, in utero exposure to diethylstilbestrol (DES), and well-differentiated angiosarcoma of the right breast. She achieved remission for approximately six years after mastectomy with adjuvant chemotherapy and radiation. Subsequent surveillance imaging revealed new hepatic and cervical lesions. Further investigation with cutaneous biopsy near the occipital region confirmed recurrent metastatic angiosarcoma. The patient was started on high-dose pazopanib and initially tolerated the TKI without any adverse effects. However, after approximately two weeks of therapy, she began to experience dark colored urine, myalgias, and fatigue. These symptoms, along with significant elevations in liver enzymes (alanine transaminase of 1377 units/L, aspartate transaminase of 1212 units/L), prompted admission for evaluation of acute liver injury. The etiology of the acute liver injury was suspected to be secondary to TKI therapy. Treatment with intravenous N-acetylcysteine was initiated for non-acetaminophen induced acute liver failure (NAI-ALF) and resulted in a dramatic improvement in transaminases before discharge.Evidence suggests that there is a beneficial role for N-acetylcysteine in the management of NAI-ALF. However, when it comes specifically to the management of TKI induced acute liver injury, there is limited evidence to support its use. This case report highlights a possible use of N-acetylcysteine in the management of TKI mediated acute liver injury. Additional studies should be conducted to determine the role N-acetylcysteine plays in the management of TKI mediated liver injury.