title: Erlotinib-induced Hepatotoxicity-Clinical Presentation and Successful Management: A Case Report.
abstract: Drug-induced liver injury (DILI) is a common occurrence in clinical practice in the present era because of frequent use of drugs and increase in patients who have increased susceptibility to DILI (because of underlying non-alcoholic steatohepatitis [NASH], chronic hepatitis C, chronic hepatitis B and alcoholic liver disease). DILI is the most common reason for withdrawal of an approved drug from the market. The overall mortality rate among patients hospitalized for DILI is approximately 10%. Erlotinib, a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) is indicated for treatment of patients with locally advanced or metastatic non-small cell lung cancer and pancreatic cancer. The most common adverse effects associated with erlotinib use are rash and diarrhea. Liver function test (LFT) abnormalities are commonly associated with erlotinib use. Grade 2 (ALT elevations > 2.5-5× upper limit of normal [ULN]) LFT abnormalities are observed in around 4% of patients while Grade 3 (ALT < 5-20× ULN) are not reported. We report a case of acute hepatitis due to administration of erlotinib in 81-year-old gentleman diagnosed as having non-small cell lung cancer with metastasis to mediastinal lymph nodes and started on erlotinib 150 mg/day. This type of deep jaundice is very rare, and timely diagnosis and withdrawal of the drug saved the life of the patient. It is recommended that liver functions be closely monitored in those with hepatic impairment, who are also on other cytochrome P450 3A4 inhibitors such as ketoconazole, clarithromycin, voriconazole, etc. In conclusion, we report a case of DILI secondary to erlotinib with significant hyperbilirubinemia (> 5× ULN; grade 4) in absence of concomitant P450 inhibitor intake and liver metastases. As erlotinib is now commonly incorporated into treatment of advanced lung and pancreatic cancer, it is important that clinicians are aware of this potential complication in practice especially in elderly patients.
authors.affiliation: Chairman, Department of Gastroenterology, Sir Ganga Ram Hospital, New Delhi.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Arora
keywords: ALT, alanine aminotransferase; AST, aspartate aminotransferase; DILI, drug-induced liver injury; Drug-induced liver injury; EGFR, epidermal growth factor receptor; GGT, gamma-glutamyl transpeptidase; INR, international normalized ratio; LFT, liver function test; NASH, non-alcoholic steatohepatitis; ULN, upper limit of normal; epidermal growth factor receptor hepatotoxicity; tyrosine kinase inhibitor