Shushan Wang1, Qing Xu2, Kankan Qu1, Jun Wang2, Zhenhe Zhou2. 1. The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Department of Pharmacy, Binhu District, Wuxi City, Jiangsu Province, China. 2. The Affiliated Wuxi Mental Health Center of Nanjing Medical University, Department of Psychiatry, Binhu District, Wuxi City, Jiangsu Province, China.
Abstract
RATIONALE: Liver function monitoring is recommended when agomelatine is prescribed, although liver enzymes are not considered predictive biomarkers. Most patients present with acute liver injury, with only a few presenting with levels of liver enzymes that are over 30 times the upper limit of normal. The patient-specific risk factors that are associated with liver injury remain unclear. Thus, this report provides new insights into the mechanism of agomelatine-induced acute hepatocellular injury based on cytochrome P450 family 1 subfamily A member 2 (CYP1A2) polymorphism. PATIENT CONCERNS: We present a case of acute hepatocellular injury in a 75-year-old man who was taking agomelatine at a dose of 50 mg/qn. All hepatitis virus test results were negative. No history of liver disease was observed. As CYP1A2 is the main metabolic enzyme of agomelatine, CYP1A2 AA (rs762551) genetic polymorphism was analyzed. DIAGNOSIS: The patient's transaminases level exceeded the critical value on day 72 after starting oral agomelatine. INTERVENTIONS: The patient received intravenous magnesium isoglycyrrhizinate, a liver cell-protecting agent, followed by the withdrawal of agomelatine. OUTCOMES: There was an improvement in the levels of the liver enzymes and no subsequent organ dysfunction was observed. LESSONS: Here, we report a case of acute hepatocellular injury characterized by a very high aspartate aminotransferase level. Periodic liver function testing throughout the treatment period can help in the rapid and appropriate diagnosis of acute liver injury, particularly in the absence of typical clinical manifestations. Agomelatine hepatic toxicity might be related to an idiosyncratic metabolic reaction that depends on individual patient differences. As it is the main metabolic enzyme of agomelatine, CYP1A2 genetic polymorphism may contribute to liver injury by affecting its metabolites.
RATIONALE: Liver function monitoring is recommended when agomelatine is prescribed, although liver enzymes are not considered predictive biomarkers. Most patients present with acute liver injury, with only a few presenting with levels of liver enzymes that are over 30 times the upper limit of normal. The patient-specific risk factors that are associated with liver injury remain unclear. Thus, this report provides new insights into the mechanism of agomelatine-induced acute hepatocellular injury based on cytochrome P450 family 1 subfamily A member 2 (CYP1A2) polymorphism. PATIENT CONCERNS: We present a case of acute hepatocellular injury in a 75-year-old man who was taking agomelatine at a dose of 50 mg/qn. All hepatitis virus test results were negative. No history of liver disease was observed. As CYP1A2 is the main metabolic enzyme of agomelatine, CYP1A2 AA (rs762551) genetic polymorphism was analyzed. DIAGNOSIS: The patient's transaminases level exceeded the critical value on day 72 after starting oral agomelatine. INTERVENTIONS: The patient received intravenous magnesium isoglycyrrhizinate, a liver cell-protecting agent, followed by the withdrawal of agomelatine. OUTCOMES: There was an improvement in the levels of the liver enzymes and no subsequent organ dysfunction was observed. LESSONS: Here, we report a case of acute hepatocellular injury characterized by a very high aspartate aminotransferase level. Periodic liver function testing throughout the treatment period can help in the rapid and appropriate diagnosis of acute liver injury, particularly in the absence of typical clinical manifestations. Agomelatine hepatic toxicity might be related to an idiosyncratic metabolic reaction that depends on individual patient differences. As it is the main metabolic enzyme of agomelatine, CYP1A2 genetic polymorphism may contribute to liver injury by affecting its metabolites.