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Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized advanced cancer management. Nevertheless, the generalized use of these medications has led to an increase in the incidence of adverse immune-mediated events and the liver is one of the most frequently affected organs. Liver involvement associated with the administration of immunotherapy is known as immune-mediated hepatitis (IMH), whose incidence and clinical characteristics have been described by different authors. It often presents as mild elevations of amino transferase levels, seen in routine blood tests, that spontaneously return to normal, but it can also manifest as severe transaminitis, possibly leading to the permanent discontinuation of treatment. The aim of the following review was to describe the most up-to-date concepts regarding the epidemiology, diagnosis, risk factors, and progression of IMH, as well as its incidence in different types of common cancers, including hepatocellular carcinoma. Treatment recommendations according to the most current guidelines are also provided.
Assuntos
Carcinoma Hepatocelular , Hepatite A , Hepatite , Neoplasias Hepáticas , Humanos , Hepatite/epidemiologia , Hepatite/etiologia , Hepatite/terapia , Carcinoma Hepatocelular/etiologia , Imunoterapia/efeitos adversos , Neoplasias Hepáticas/complicaçõesRESUMO
El uso de esteroides anabólicos de forma ilícita es un problema en aumento caracterizado por la falta de conocimiento sobre los potenciales efectos secundarios a estos productos. El uso ilegal de los mismos ha llevado a un infra diagnóstico de los eventos adversos, dentro de los más frecuentes se ha encontrado la hepatotoxicidad. Se presenta el caso de un hombre adulto maduro deportista aficionado quien fue hospitalizado por ictericia y enfermedad hepática inducida por medicamentos en relación al uso de esteroides anabólicos en dosis elevadas. La prevención de la lesión hepática inducida por fármacos (DILI) implica educar a los pacientes que toman fármacos hepatotóxicos sobre su uso seguro, enseñar los signos y síntomas asociados con la lesión hepática, así como, la educación a la población vulnerable en prevenir la automedicación o el uso ilegal de estas sustancias.
The use of anabolic steroids in an illicit way is a growing problem characterized by the lack of knowledge about the potential side effects of these products. Their illegal use has led to under diagnosis of adverse events, among the most frequent of which was hepatotoxicity. We present the case of a mature adult male amateur athlete who was hospitalized for jaundice and drug-induced liver disease in relation to the use of high-dose anabolic steroids. The prevention of drug-induced liver damage (DILI) training the susceptible population about the dangers of self-medication and illegal drug use, as well as educating the vulnerable population to prevent self-medication. or the illegal use of these substances.
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Over the last years, pembrolizumab has been one of the checkpoint inhibitors that have revolutionized the management of unresectable malignancies given its successful rate of disease control. This drug has become part of the standard of care in several types of cancers, however, the side effects are an emerging concern for physicians managing patients with cancer. Immune mediated injury of these drugs can target virtually any organ. Liver injury is an important side effect of these drugs that can be life threatening and needs to be well recognized. Here we report a case of an 85-year-old male with medical history of stage 3 laryngeal carcinoma who presented with severe liver injury secondary to pembrolizumab.
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Anticorpos Monoclonais Humanizados , Médicos , Masculino , Humanos , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversosRESUMO
INTRODUCTION AND AIM: Drug-induced liver injury (DILI) is a diagnosis based on the ruling out of potential liver diseases and consolidated by establishing causality through the temporal relation between a potentially hepatotoxic substance and altered liver biochemistry. Incidence fluctuates greatly worldwide, with very few reports of causal agents of DILI in Colombia. A retrospective study on patients treated at the Centro de Estudios en Salud (CES), within the time frame of January 2015 and June 2020, was conducted to document the causal substances of DILI in patients with liver biopsy and to correlate the types of histologic patterns with the biochemical pattern of liver injury (R ratio). RESULTS: Of the 254 adult patients with liver biopsy and no tumor etiology, 20 patients were identified as cases of DILI (7.87%). The two most frequently found causal substances were efavirenz, in three HIV-positive patients, and Moringa oleifera (moringa), in two patients. There was a statistically significant association between cholestatic patterns (pâ¯=â¯0.037) and mixed patterns (pâ¯=â¯0.031), in the comparison of the histopathologic categories and the R ratio. CONCLUSION: To the best of our knowledge, there are no reports on DILI secondary to Moringa oleifera (moringa). The R ratio could be a useful tool, in relation to the histologic pattern of injury, in cases of mixed and cholestatic patterns.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Hepatopatias , Adulto , Humanos , Estudos Retrospectivos , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , ColômbiaRESUMO
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.
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Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/terapia , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Diagnóstico Diferencial , Humanos , América Latina , Guias de Prática Clínica como Assunto , Sistema de Registros , Fatores de RiscoRESUMO
Coronavirus disease 2019 (COVID-19), an infection caused by severe acute respiratory syndrome coronavirus-type 2 (SARS-CoV-2), has emerged as a serious threat to public health. Liver transplant (LT) recipients may be at increased risk of acquisition of SARS-CoV-2 infection and higher morbidity and mortality due to constant contact with health-care services, the use of immunosuppressants and frequent comorbidities. In the first part of this review we discuss (1) the epidemiology and risk factors for SARS-CoV-2 infection in LT recipients; (2) the clinical and laboratory features of COVID-19 in this specific population, highlighting differences in presenting signs and symptoms with respect to general populations and (3) the natural history and prognostic factors in LT recipients hospitalized with COVID-19, with particular focus on the possible role of immunosuppression. Thereafter, we review the potential therapeutic options for COVID-19 treatment and prevention. Specifically, we give an overview of current practice in immunosuppressant regimen changes, showing the potential benefits of this strategy, and explore safety and efficacy issues of currently approved drugs in LT recipients. The last topic is dedicated to the potential benefits and pitfalls of vaccination.
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Drug-induced liver injury (DILI) is a rare entity associated with high morbidity and mortality. It includes a broad spectrum of clinical patterns, from acute hepatitis to cirrhosis. Among the common associated drugs are antimicrobial like anti-TBC, antineoplastic, CNS agents and non-steroidal anti-inflammatory drugs. Establishing causality between DILI and a certain drug is a challenge. Some scoring systems have been evaluated, considering RUCAM score as the gold standard. We present the case of a 35-year-old woman with a history of a high-grade glioma treated with surgery and chemotherapy with lomustine, procarbazine and vincristine. She evolved with altered liver tests, predominantly cholestatic pattern, but asymptomatic. Etiologic study negative and abdominal imaging were normal. The liver biopsy was compatible with 40% ductopenia, without inflammatory elements. We consider DILI associated with the use of lomustine, with RUCAM score suggesting. After discontinuing chemotherapy and using ursodeoxycholic acid for the treatment of cholestasis there was an improvement in liver tests. There is limited evidence in the literature regarding hepatotoxicity associated with lomustine, mainly in experimental animal models. Cases of cholestatic hepatotoxicity have been described with the use of other similar nitrosureas. In relation to procarbazine and vincristine, DILI is reported mainly reversible and predominantly with hepatocellular pattern, not consistent with our case. We find it interesting to communicate with review of the literature about it.
El daño hepático inducido por drogas (DILI) es una entidad poco frecuente, con alta morbimortalidad asociada. Incluye un amplio espectro de patrones clínicos, desde hepatitis aguda a cirrosis. Dentro de los fármacos frecuentemente asociados se encuentran antibióticos como anti-TBC, agentes antineoplásicos, de acción en el SNC y anti-inflamatorios no esteroidales. Establecer una causalidad entre DILI y una determinada droga constituye un desafío. Para ello, se han evaluado diversos sistemas de puntuación, considerándose gold estándar el RUCAM score. Se presenta el caso de una mujer de 35 años de edad con antecedentes de glioma de alto grado operado y en quimioterapia con lomustina, procarbazina y vincristina. En su evolución presenta alteración de pruebas hepáticas de predominio colestásico de manera asintomática, con estudio etiológico causal negativo e imagenológico normal. La biopsia hepática fue compatible con ductopenia de 40% sin elementos inflamatorios. Se plantea DILI asociado al uso de lomustina con un score de RUCAM sugerente, decidiéndose interrumpir sus ciclos de quimioterapia e inicia tratamiento con ácido ursodesoxicólico, presentando mejoría progresiva de pruebas hepáticas. Existe evidencia limitada en la literatura en relación a hepatotoxicidad asociada a este fármaco, principalmente en modelos experimentales, y con el uso de otras nitrosureas similares se han descrito casos de hepatotoxicidad de predominio colestásico. En relación con procarbazina y vincristina existen reportes de DILI principalmente reversible y con patrón de predominio hepatocelular, lo que no es concordante con nuestro caso, por lo cual nos parece de interés comunicarlo con revisión de la literatura al respecto.
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Humanos , Feminino , Adulto , Colestase/induzido quimicamente , Antineoplásicos Alquilantes/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Lomustina/efeitos adversos , Colestase/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/diagnósticoRESUMO
La isoniazida se utiliza para el tratamiento o profilaxis de la tuberculosis; sin embargo, su uso puede asociarse con reacciones hepáticas adversas. La hepatitis clínicamente manifiesta sucede en 0,5%-1% de los pacientes que reciben isoniazida como monoterapia. En este artículo se describe el caso de un paciente con enfermedad de Crohn que cursó con hepatotoxicidad grave por isoniazida, y se hace una revisión de la literatura al respecto
Isoniazid is used for treatment or prophylaxis of tuberculosis but may be associated with adverse hepatic reactions. Clinically manifest hepatitis occurs in 0.5%-1% of patients who receive isoniazid as monotherapy. This article describes the case of a patient with Crohns disease who experienced severe hepatotoxicity due to isoniazid. It also reviews the literature.
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Humanos , Masculino , Pessoa de Meia-Idade , Doença de Crohn , Hepatite , Isoniazida , LiteraturaRESUMO
Drug induced liver injury (DILI) is a rare but well recognized serious adverse reaction. Pre-marketing studies may not detect liver injury, and DILI becomes very often apparent after the drug is launched to the market. Specific biomarkers for DILI prediction or diagnosis are not available. Toxic liver reactions present with a wide spectrum of phenotypes and severity, and our knowledge on the mechanisms underlying idiosyncratic reactions and individual susceptibility is still limited. To overcome these limitations, country-based registries and multicenter research networks have been created in Europe and North America. Reliable epidemiological data on DILI in Latin America (LA), a region with a large variety of ethnic groups, were however lacking. Fortunately, a LA network of DILI was set up in 2011, with the support of the Spanish DILI Registry from the University of Malaga. The primary aim of the Latin DILI Network (LATINDILIN) Registry was to prospectively identify bona fide DILI cases and to collect biological samples to study genetic biomarkers. Physicians involved in the project must complete a structured report form describing the DILI case presentation and follow-up which is submitted to a Coordinator Center in each country, where it is further assessed for completeness. During the last four years, several LA countries (Argentina, Uruguay, Chile, Mexico, Paraguay, Brazil, Ecuador, Peru, Venezuela and Colombia) have joined the network and committed with this project. At that point, to identify both our strengths and weaknesses was a very important issue. In this review, we will describe how the LATINDILI Registry was created. The aims and methods to achieve these objectives will be discussed in depth. Additionally, both the difficulties we have faced and the strategies to solve them will be also pinpointed. Finally, we will report on our preliminary results, and discuss ideas to expand and to keep running this network.
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Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Sistema de Registros , Doença Hepática Induzida por Substâncias e Drogas/etnologia , Humanos , Cooperação Internacional , América do Sul , EspanhaRESUMO
In Mexico, herbal products are commonly used as therapeutic tools. The analysis of several publications reveals that there are dozens of different herbs and herbal products used for different reasons, some of which have been implicated in causing toxic liver disease. However, methodological aspects limit the attribution of causality, and the precise incidence and clinical manifestations of herb-induced liver injury have not been well characterized. This review outlines the history of traditional herbal medicine in Mexico, critically summarizes the mechanisms and adverse effects of commonly used herbal plants, and examines the regulatory issues regarding the legal use of these products.