Dili is rare amongst patients without liver metastases receiving cancer treatment in Iceland: a population-based cohort study.

BACKGROUND: There is limited information on the frequency of idiosyncratic drug-liver injury (DILI) among cancer patients. The aim of the study was to evaluate the frequency of DILI due to cancer treatment in a population-based setting. MATERIAL AND METHODS: All patients diagnosed with genitourinary cancer, breast cancer or metastatic malignant melanoma in 2007-2018 were matched with a database containing laboratory results for all major hospitals in Iceland. Medical chart review was performed for cases with ALT/AST ≥5× upper limit of normal (ULN), ALP ≥2× ULN or bilirubin ≥2× ULN. Patients with liver-, and/or bone metastases and isolated elevations of ALP and patients with other etiologies of liver enzyme elevations were excluded. Cases with a RUCAM score of probable or highly probable were included. RESULTS: Among 4956 patients, 840 patients had liver enzyme elevations. Overall, nine (0.2%) cases of DILI were identified, seven women (78%), median age 59 years (IQR 52-66). Four patients had kidney cancer, four breast cancer and one metastatic prostate cancer. In eight cases, a single agent was implicated: Pazopanib (n = 3), axitinib, docetaxel, gemcitabine, letrozole and paclitaxel. In all cases, the treatment was interrupted or discontinued due to the liver injury. No patient developed jaundice or liver failure and no death was linked to DILI. Time to normalization of liver enzymes was 17 days (IQR 25-120). CONCLUSION: DILI was found to be rare and no cases of severe liver injury occurred. However, approximately 90% of patients switched to another treatment which might have affected prognosis.

Drug-induced liver injury: Pathogenesis, epidemiology, clinical features, and practical management.

Drug-induced liver injury (DILI) is an important but rare adverse event which can range from mild liver enzyme elevations to liver failure, transplantation or death. A large proportion of commonly used medications, in addition to herbal and dietary supplements, can cause liver injury. DILI has been categorized as direct or idiosyncratic but indirect liver injury has emerged as a third type of drug-induced liver injury. These types of liver injury may warrant different clinical approach and treatment. Associations of HLA genotypes and risk of DILI have highlighted the importance of the immune system in the pathogenesis of DILI. Furthermore, novel agents affecting the immune response can lead to liver injury, often associated with autoimmune features in serologic tests and liver biopsies. Overall, the diagnosis of DILI remains a challenge as it is requires detailed case evaluation in addition to reviewing the hepatotoxic potentials and clinical signatures of the implicated agents. Biochemical profiles vary between agents and although individual drugs tend to portray a consistent clinicopathologic signature, many drugs have multiple signatures. Thanks to multicenter prospective studies on DILI and websites in the public domain such as LiverTox, physicians are provided with tools to investigate suspected DILI cases to increase the likelihood of establishing adiagnosis. The pathogenesis of DILI, epidemiology and current challenges in the diagnosis and management of the disease are reviewed in the paper.