Chemotherapy-Induced Hepatotoxicity

Idiosyncratic drug-induced liver injury (DILI) caused by xenobiotics (drugs, herbals and dietary supplements) is an uncommon cause of liver disease presenting with a wide range of phenotypes and disease severity, acute hepatitis mimicking viral hepatitis to autoimmune hepatitis, steatosis, fibrosis or rare chronic vascular syndromes. Disease severity ranges from asymptomatic liver test abnormalities to acute liver failure. DILI has been traditionally classified in predictable or intrinsic (dose-related) or unpredictable (not dose-related) mechanisms. Few prospective studies are assessing the real prevalence and incidence of hepatotoxicity in the general population. DILI registries represent useful networks used for the study of liver toxicity, aimed at improving the understanding of causes, phenotypes, natural history, and standardized definitions of hepatotoxicity. Although most of the registries do not carry out population-based studies, they may provide important data related to the prevalence of DILI, and also may be useful to compare features from different countries. With the support of the Spanish Registry of Hepatotoxicity, our Latin American Registry (LATINDILI) was created in 2011, and more than 350 DILI patients have been recruited to date. This position paper describes the more frequent drugs and herbs-induced DILI in Latin America, mainly focusing on several features of responsible medicaments. Also, we highlighted the most critical points on the management of hepatotoxicity in general and those based on findings from our Latin American experience in particular.

The liver is the most commonly involved organ in metastases from a wide variety of solid tumors. The use of biologically and cellularly complex liver tissue systems have shown that tumor cell behavior and therapeutic responses are modulated within the liver microenvironment and in ways distinct from the behaviors in the primary locations. These microphysiological systems have provided unexpected and powerful insights into the tumor cell biology of metastasis. However, neither the tumor nor the liver exist in an isolated tissue situation, having to function within a complete body and respond to systemic events as well as those in other organs. To examine the influence of one organ on the function of other tissues, microphysiological systems are being linked. Herein, we discuss extending this concept to tumor metastases by integrating complex models of the primary tumor with the liver metastatic environment. In addition, inflammatory organs and the immune system can be incorporated into these multi-organ systems to probe the effects on tumor behavior and cancer treatments.

La lesión hepática inducida por fármacos debida a quimioterapia es una causa importante de morbilidad en enfermos oncológicos aunque sus manifestaciones clínicas son poco conocidas.

El objetivo del presente estudio fue determinar las características (formas de presentación, gravedad y tipo de lesión) de la hepatotoxicidad por quimioterapia en niños tratados por cáncer.

Se incluyó en el estudio a un total de 22 enfermos oncológico en los que, tras descartar otras causas de aumento de transaminasas (infecciosa, metabólica, autoinmune o hereditaria), se concluye, según la escala de causalidad CIOMS, que se trata de un episodio posible, probable o definido de lesión hepática por fármacos.

Todos los niños tuvieron más de un episodio de hepatotoxicidad, en total se analizan 98 episodios. Metotrexato fue el fármaco implicado con mayor frecuencia. El patrón histológico de daño predominante fue hepatocelular. Solo 2 episodios fueron clasificados de graves.

La hepatotoxicidad idiosincrásica por quimioterapia es frecuente, la tendencia es a la recidiva con la reexposición y, aunque no suele tener consecuencias importantes, la elevada frecuencia hace aconsejable establecer algoritmos de seguridad estandarizados con controles muy estrictos de enzimas hepáticas durante los períodos de alto riesgo de quimioterapia.

Drug-induced liver injury due to chemotherapy is an important cause of morbidity in cancer patients, although its clinical manifestations are poorly understood.

The objective of the present study was to determine the characteristics (forms of presentation, severity, and type of injury) of hepatotoxicity due to chemotherapy in children treated for cancer.

A total of 22 oncological patients were included in the study, after ruling out other causes of increased transaminases (infectious, metabolic, autoimmune, or hereditary), according to the CIOMS causality scale, it is concluded that it was a possible, probable or definite episode of hepatic injury by drugs.

All children had more than one episode of hepatotoxicity, and a total of 98 episodes are analysed. Methotrexate was the most commonly implicated drug. The histological pattern of predominant damage was hepatocellular. Only 2 episodes were classified as serious.

Idiosyncratic hepatotoxicity due to chemotherapy is frequent, with a tendency to relapse with re-exposure. Although it does not usually have important consequences, the high frequency makes it advisable to establish standardised safety algorithms with very strict monitoring of liver enzymes during high periods of risk in chemotherapy.