Diagnosis of a Case of Hepatotoxicity Due to Drugs and Herbal Supplements in a Hospital in Pasto, Colombia

The liver is a crucial organ in metabolism, and some substances can induce toxic hepatitis with high morbidity and mortality. Chemical and drug-induced liver disease is a diagnostic and therapeutic challenge since it requires extension studies to rule out other entities. We present the case of a 51-year-old female patient without underlying comorbidities, admitted due to symptoms of two-day evolution consisting of progressive jaundice, diarrheal episodes without acholia, or any other additional manifestation. Her condition was caused by the intake of nimesulide, two tablets a day for two days, for pain secondary to a mandibular cyst diagnosed in previous days. During her admission to the emergency room, the patient described chronic consumption of Herbalife® products daily for four years. She presented with elevated transaminases, prolonged prothrombin time (PT), and direct hyperbilirubinemia. Infectious and immunological diseases were ruled out. We decided to start antibiotic and vitamin K coverage. Finally, and by exclusion, a liver biopsy suggested an inflammatory process compatible with drug-induced hepatitis. The woman evolved favorably when the medication and dietary supplement were discontinued. In conclusion, this case constitutes an initial point in advancing research into hepatotoxicity by shared mechanisms of various substances simultaneously, such as what happened to the patient with the parallel use of Herbalife® and nimesulide.

El hígado es un órgano crucial en el metabolismo y algunas sustancias pueden inducir hepatitis toxica con alta morbimortalidad. La enfermedad hepática inducida por sustancias químicas y medicamentos es un desafío tanto diagnostico como terapéutico, puesto que requiere la realización de estudios de extensión para descartar otras entidades. A continuación se presenta el caso de una paciente femenina de 51 años sin comorbilidades de base, ingresada por clínica de 2 días de evolución consistente en ictericia progresiva, episodios diarreicos sin acolia ni otra manifestación adicional. Aparentemente, su cuadro fue provocado por la administración de nimesulida, 2 tabletas al día por 2 días, contra el dolor secundario a un quiste mandibular diagnosticado en días anteriores. Durante su ingreso a urgencias la paciente describió consumo crónico, a diario desde hace 4 años, de productos de Herbalife®. Cursa con elevación de transaminasas, prolongación del tiempo de protrombina (TP) e hiperbilirrubinemia directa. Se descartan enfermedades infecciosas e inmunológicas. Se decidió iniciar el cubrimiento antibiótico y vitamina K. Finalmente y por exclusión, se realizó una biopsia hepática que sugirió un proceso inflamatorio compatible con hepatitis inducida por fármacos. La mujer evolucionó favorablemente al suspender la medicación y el suplemento dietético referido. En conclusión, el caso expuesto constituye un punto inicial en el avance hacia la investigación en hepatotoxicidad por mecanismos compartidos de diversas sustancias simultáneamente, como lo sucedido a la paciente con el uso paralelo de Herbalife® y de nimesulida.

Homozygotes NAT2*5B slow acetylators are highly associated with hepatotoxicity induced by anti-tuberculosis drugs

BACKGROUND Distinct N-acetyltransferase 2 (NAT2) slow acetylators genotypes have been associated with a higher risk to develop anti-tuberculosis drug-induced hepatotoxicity (DIH). However, studies have not pointed the relevance of different acetylation phenotypes presented by homozygotes and compound heterozygotes slow acetylators on a clinical basis. OBJECTIVES This study aimed to investigate the association between NAT2 genotypes and the risk of developing DIH in Brazilian patients undergoing tuberculosis treatment, focusing on the discrimination of homozygotes and compound heterozygotes slow acetylators. METHODS/FINDINGS The frequency of NAT2 genotypes was analysed by DNA sequencing in 162 patients undergoing tuberculosis therapy. The mutation analyses revealed 15 variants, plus two new NAT2 mutations, that computational simulations predicted to cause structural perturbations in the protein. The multivariate statistical analysis revealed that carriers of NAT2*5/*5 slow acetylator genotype presented a higher risk of developing anti-tuberculosis DIH, on a clinical basis, when compared to the compound heterozygotes presenting NAT2*5 and any other slow acetylator haplotype [aOR 4.97, 95% confidence interval (CI) 1.47-16.82, p = 0.01]. CONCLUSION These findings suggest that patients with TB diagnosis who present the NAT2*5B/*5B genotype should be properly identified and more carefully monitored until treatment outcome in order to prevent the occurrence of anti-tuberculosis DIH.

[Severe hepatitis caused by green tea intoxication in a child. Case report]. / Hepatitis grave producida por intoxicación con té verde en un niño. Presentación de un caso.

Herb-induced liver injury is a type of adverse drug reaction related to using herbal medicine, and now is a segment of druginduced liver injury. The use of herbal products has increased significantly, because it is generally regarded as safe and natural by the public. In the United States, the incidence reaches 9 % and, in the countries of Asia, 19-63 % of the total cases of druginduced liver injury. Green tea is obtained from the leaves of the Camellia sinensis. Freshly harvested leaves are stabilized by dry heating to inactivate the polyphenol enzyme and then dried quickly. Its consumption has increased in recent years and has been reported with hepatotoxic reactions. We present a case of severe hepatitis related to the consumption of green tea in a 2-year-old child.

El daño hepático inducido por hierbas es una reacción adversa relacionada con el uso de medicina herbaria, incluida en el grupo de daño hepático inducido por drogas. El uso terapéutico de hierbas medicinales es cada vez más frecuente por la creencia de que los productos naturales o hierbas son siempre seguros. En Estados Unidos, la incidencia de toxicidad alcanza un 9 % y, en países de Asia, un 19-63 % de los casos totales de daño hepático inducido por drogas. El té verde es obtenido de las hojas de la Camellia sinensis. Las hojas recién cosechadas son estabilizadas por calentamiento en seco para inactivar la enzima polifenol y luego se secan rápidamente. Su consumo ha aumentado en los últimos años, y se han documentado reacciones hepatotóxicas. Se presenta un caso de hepatitis aguda grave asociada al consumo de té verde en un niño de 2 años.

Drug induced liver damage in a universitary hospital / Lesão hepática induzida por drogas em um hospital universitário

Introdução: lesão hepática induzida por drogas (DILI) é responsável por um amplo espectro de lesão hepática. Clinicamente, esses eventos são apresentados de várias formas e, para alcançar um diagnóstico diferente, outras causas de lesões devem ser excluídas. Objetivo: identificar e caracterizar casos de hepatotoxicidade induzida por medicamentos, fitoterápicos e suplementos alimentares em Hospital Universitário no Brasil. Metodologia: estudo observacional, retrospectivo. Os dados foram coletados em prontuários do Hospital Universitário, entre agosto de 2009, em agosto de 2014. A causalidade das reações medicamentosas suspeitas foi avaliada pelo Conselho de Organizações Internacionais de Ciências Médicas (CIOMS). Resultados: foram selecionados 30 casos suspeitos, 50% do sexo feminino e média de 39 anos. As classes terapêuticas mais comuns foram: anti-infecciosos; agentes antineoplásicos; drogas do sistema nervoso central, esteroides anabolizantes e suplementos herbáceos e dietéticos (HDS). Lesão colestática ou mista foi observada em 73% desses casos; 60% eram altamente prováveis, de acordo com o CIOMS. Conclusão: DILI é causada por uma grande variedade de drogas, suplementos dietéticos e suplementos dietéticos. Anti-infecciosos e quimioterapia foram responsáveis por grande parte da resposta.

Background: drug Induced Liver Injury (DILI) is responsible for wide spectrum of liver injury. Clinically, these events are presented in various forms and for reaching a different diagnosis other injury causes must be excluded. Aim: identify and characterize cases of hepatotoxicity induced by drugs, herbal and dietary supplements in University Hospital in Brazil. Methodology: observational and retrospective study. Was collected in records of University Hospital, between August 2009 at August 2014. The causality of the drug reactions suspected were evaluated Council for International Organizations of Medical Sciences (CIOMS). Results: we selected 30 suspected cases, 50% was female and average was 39 years. the therapeutic classes most common was: anti-infectives; antineoplastic agents; central nervous system drugs, anabolic steroid and herbal and dietary supplements (HDS). Cholestatic or mixed injury was observed in 73% these cases; 60% were highly probable, according to CIOMS. Conclusion: DILI is caused by a wide variety of drugs, dietary supplements and dietary supplements. Anti-infectives and chemotherapy were responsible for much of the response.

A New Paradigm in Gallstones Diseases and Marked Elevation of Transaminases: An Observational Study

ABSTRACT Background. In clinical practice, it is assumed that a severe rise in transaminases is caused by ischemic, viral or toxic hepatitis. Nevertheless, cases of biliary obstruction have increasingly been associated with significant hypertransaminemia. With this study, we sought to determine the true etiology of marked rise in transaminases levels, in the context of an emergency department. Material and methods. We retrospectively identified all patients admitted to the emergency unit at Centro Hospitalar e Universitário de Coimbra between 1st January 2010 and 31st December 2010, displaying an increase of at least one of the transaminases by more than 15 times. All patient records were analyzed in order to determine the cause of hypertransaminemia. Results. We analyzed 273 patients - 146 males, mean age 65.1 ± 19.4 years. The most frequently etiology found for marked hypertransaminemia was pancreaticobiliary acute disease (n = 142;39.4%), mostly lithiasic (n = 113;79.6%), followed by malignancy (n = 74;20.6%), ischemic hepatitis (n = 61;17.0%), acute primary hepatocellular disease (n = 50;13.9%) and muscle damage (n = 23;6.4%). We were not able to determine a diagnosis for 10 cases. There were 27 cases of recurrence in the lithiasic pancreaticobiliary pathology group. Recurrence was more frequent in the group of patients who had not been submitted to early cholecystectomy after the first episode of biliary obstruction (p = 0.014). The etiology of hypertransaminemia varied according to age, cholestasis and glutamic-pyruvic transaminase values. Conclusion. Pancreaticobiliary lithiasis is the main cause of marked hypertransaminemia. Hence, it must be considered when dealing with such situations. Not performing cholecystectomy early on, after the first episode of biliary obstruction, may lead to recurrence.

A New Paradigm in Gallstones Diseases and Marked Elevation of Transaminases: An Observational Study.

BACKGROUND: In clinical practice, it is assumed that a severe rise in transaminases is caused by ischemic, viral or toxic hepatitis. Nevertheless, cases of biliary obstruction have increasingly been associated with significant hypertransaminemia. With this study, we sought to determine the true etiology of marked rise in transaminases levels, in the context of an emergency department. MATERIAL AND METHODS: We retrospectively identified all patients admitted to the emergency unit at Centro Hospitalar e Universitário de Coimbra between 1st January 2010 and 31st December 2010, displaying an increase of at least one of the transaminases by more than 15 times. All patient records were analyzed in order to determine the cause of hypertransaminemia. RESULTS: We analyzed 273 patients - 146 males, mean age 65.1 ± 19.4 years. The most frequently etiology found for marked hypertransaminemia was pancreaticobiliary acute disease (n = 142;39.4%), mostly lithiasic (n = 113;79.6%), followed by malignancy (n = 74;20.6%), ischemic hepatitis (n = 61;17.0%), acute primary hepatocellular disease (n = 50;13.9%) and muscle damage (n = 23;6.4%). We were not able to determine a diagnosis for 10 cases. There were 27 cases of recurrence in the lithiasic pancreaticobiliary pathology group. Recurrence was more frequent in the group of patients who had not been submitted to early cholecystectomy after the first episode of biliary obstruction (p = 0.014). The etiology of hypertransaminemia varied according to age, cholestasis and glutamic-pyruvic transaminase values. CONCLUSION: Pancreaticobiliary lithiasis is the main cause of marked hypertransaminemia. Hence, it must be considered when dealing with such situations. Not performing cholecystectomy early on, after the first episode of biliary obstruction, may lead to recurrence.

Acute aflatoxicosis in swines in Northeastern Brazil / Aflatoxicose aguda em suínos no Nordeste do Brasil

Background: Aflatoxins are hepatotoxic mycotoxins derived from the secondary metabolism of toxigenic fungi belonging to the genus Aspergillus, especially A. flavus and A. parasiticus. Aflatoxin B1 is the most important metabolite, because of its deleterious effect mainly to the liver, especially for its carcinogenic, mutagenic and haemorrhagic properties, and usually is detected in higher concentrations in contaminated substrates. This paper reports the epidemiological, clinical, pathological and toxicological aspects of an outbreak of acute aflatoxicosis in pigs raised in Northeastern Brazil. Case: The cases occurred in a complete cycle farm, in the city of Mossoró, Rio Grande do Norte, Northeastern Brazil, in pigs ingesting low quality (moldy) corn being produced and processed on the farm. Sixty (73.1%) out of 82 two to five-months old pigs were clinicaly affected and 54 (65.8%) died. All animals showed fever, weight loss, tachycardia, tachypnea, lethargy, muscle tremors, muscle weakness and diarrhea. The clinical course ranged from five to 48 hours. Adult pigs were not affected. At necropsies, generalized jaundice, ascites, hydropericardium, petechial hemorrhages in the mesentery, subcutaneous edema and mesocolon were observed. The liver was yellow-orange with reddish diffuse multifocal areas, enlarged and extremely friable. Histologically there was swelling of hepatocytes [...]

Acute aflatoxicosis in swines in Northeastern Brazil / Aflatoxicose aguda em suínos no Nordeste do Brasil

Background: Aflatoxins are hepatotoxic mycotoxins derived from the secondary metabolism of toxigenic fungi belonging to the genus Aspergillus, especially A. flavus and A. parasiticus. Aflatoxin B1 is the most important metabolite, because of its deleterious effect mainly to the liver, especially for its carcinogenic, mutagenic and haemorrhagic properties, and usually is detected in higher concentrations in contaminated substrates. This paper reports the epidemiological, clinical, pathological and toxicological aspects of an outbreak of acute aflatoxicosis in pigs raised in Northeastern Brazil. Case: The cases occurred in a complete cycle farm, in the city of Mossoró, Rio Grande do Norte, Northeastern Brazil, in pigs ingesting low quality (moldy) corn being produced and processed on the farm. Sixty (73.1%) out of 82 two to five-months old pigs were clinicaly affected and 54 (65.8%) died. All animals showed fever, weight loss, tachycardia, tachypnea, lethargy, muscle tremors, muscle weakness and diarrhea. The clinical course ranged from five to 48 hours. Adult pigs were not affected. At necropsies, generalized jaundice, ascites, hydropericardium, petechial hemorrhages in the mesentery, subcutaneous edema and mesocolon were observed. The liver was yellow-orange with reddish diffuse multifocal areas, enlarged and extremely friable. Histologically there was swelling of hepatocytes [...](AU)

Intoxicación por fósforo blanco en pediatría / White phosphorus poisoning in pediatrics

La intoxicación por fósforo blanco es una patología que es frecuente en festividades navideñas y de fin de año debido al uso de la pólvora recreativa como las martinicas, elementos de fácil acceso para los niños, principalmente lactantes y preescolares, los cuales sin medir consecuencias se convierten en víctimas de intoxicaciones al llevarse estos elementos a la boca y en ocasiones ingerirlos. En esta revisión se describe el caso de una menor intoxicada al ingerir fósforo blanco, con el objetivo de dar a conocer los efectos de este tóxico y advertir a los adultos a cargo acerca de la letalidad de esta patología, con el propósito de derivar a partir de esta revisión políticas encaminadas principalmente hacia prevención del evento. Se describe el caso de una niña de 2 años de edad que ingiere cuatro martinicas, presentando todos los efectos nocivos que ocasiona este tóxico a nivel hepático; la paciente recibió medidas iniciales las cuales fueron insuficientes por lo que tuvo que ser llevada a la unidad de cuidados intensivos con evolución favorable que hasta el momento no ha requerido transplante.

White phosphorus’ poisoning is a frequent pathology during holydays and New Year’s Eve. Fire works such as “martinicas”, are accessible for children – especially toddlers and preschoolers – who can have poisoning when they bring these elements to their mouths and ingest them, by accident. This work describes the case of a minor who was poisoned when she ingested white phosphorus. Our purpose is to show white phosphorus’ toxic effects and warn adults about this lethal pathology, in order to create policies directed towards its prevention. A two years old girl ingested four “martinicas”, presenting with hepatotoxicity. The patient needed an ntensive care unit admission with a favorable outcome and without requiring liver transplant.

Lesões viscerais em dois casos fatais consequentes ao manuseio de agrotóxicos / Visceral lesions in 2 fatal cases due to the handling of agrotoxic products

São apresentados dois casos de pacientes com lesões viscerais do fígado e rins consequentes ao manuseio inadequado de um agrotóxico, o dicloreto de paraquat 1,1'-dimetil-4,4'-dipiridilio dicloreto (Gramoxone) e chamam a atenção para um tipo especial de hepatite tóxica; descrevem o tipo de lesão hepática Q sua topografia intralobular, assim como lesões graves nos túbulos renais, com formação de sais de cálcio. São feitas considerações sobre as vias de absorção do tóxico e das áreas de predileção de atuação dentro do lóbulo hepático, assim como sobre o diagnóstico diferencial com outros tipos de hepatite tóxica (AU).