Hepatotoxicidad por fármacos / Drug-induced hepatotoxicity

El daño hepático causado por medicamentos, drogas de abuso o remedios medicamentosos (productos de herboristería, etc.) se está convirtiendo en un importante problema de salud pública que afecta a los pacientes, médicos, industria farmacéutica y agencias reguladoras. El daño hepático inducido por drogas es la causa más común de muerte por fallo hepático agudo y representa alrededor del 10% de casos de fallo hepático agudo a nivel mundial. La hepatotoxicidad por medicamentos es la principal reacción adversa implicada en el abandono del desarrollo de futuros medicamentos en la fase preclínica o clínica, denegación de registros por parte de las agencias reguladoras, y retirada del mercado o restricciones de uso después de ser registrado. La mayor parte de la información se obtiene de los datos referidos a las agencias reguladoras a través del sistema de notificación voluntaria (tarjeta amarilla) y por la información aparecida en las revistas médicas, pero esto probablemente es sólo la “punta del iceberg”. El reconocimiento y diagnóstico de la hepatotoxicidad es a menudo difícil y largo en el tiempo, debido a la necesidad de excluir numerosas causas alternativas de daño hepático (AU)

Liver injury caused by medicines, recreational drugs, or non-standardized medical remedies (such as herbal products) is becoming a serious public health problem that affects patients, physicians, the pharmaceutical industry, and government regulators. Drug induced liver injury is the most common cause of death from acute liver failure and accounts for approximately 10% of cases of acute liver failure worldwide. Hepatotoxicity is the most frequent adverse drug event leading to abandonment of otherwise promising new drug candidates during the preclinical or clinical development stage, failure of drugs to obtain marketing authorisation approval by the regulatory agencies, and recall or restriction of prescription drugs after initial approval. The bulk of information is derived from the cases reported to the regulatory agencies by the spontaneous reporting system (yellow card) and those published in medical journals, but this is very probably only “the tip of the iceberg”. The recognition and diagnosis of hepatotoxicity are often difficult and delayed due to the need to exclude more common competing causes of liver injury (AU)

Sobre el Caso Clínico: Toxicidad neurológica por alteraciones hepáticas de medicamentos / No disponible

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Actividad hepatoprotectora del extracto acuoso seco de Boerhavia erecta L(tostón) en ratas / Hepatoprotective action of dry aqueous extract from Boerhavia erecta L (toston) in rats

INTRODUCCIÓN: estudios in vitro con extracto acuoso de partes aéreas secas de Boerhavia erecta L. y la línea celular de hepatoma humano PLC/PRF/5, mostraron supresión en la formación de antígeno de superficie de hepatitis B (HbsAg) en células hepáticas y actividad inhibitoria del antígeno en suero humano contaminado con antígeno de superficie de hepatitis B. OBJETIVOS: determinar el efecto hepatoprotector in vivo del extracto acuoso de B. erecta. MÉTODOS: se utilizaron ratas Wistar machos tratadas con dosis de 250 y 500 mg de extracto seco/kg durante 5 d por vía intragástrica, con inducción de daño hepático el ultimo día, con 1 mL/kg de una mezcla 1:1 de tetracloruro de carbono y aceite de oliva; transcurridas 24 h se extrajo sangre para las determinaciones de actividad enzimática de alanino aminotransferasa y la eutanasia de los animales para el estudio histológico del hígado. RESULTADOS: el extracto ocasionó una disminución significativa en los valores de actividad enzimática de alanino aminotransferasa del suero de ratas tratadas y una protección de 100 por ciento del parénquima de los animales tratados con la dosis de 500 mg/kg de peso corporal de extracto de B. erecta. CONCLUSIONES: se demostró el efecto hepatoprotector in vivo del extracto acuoso de B. erecta frente al daño inducido por tetracloruro de carbono(AU)

INTRODUCTION: several in vitro studies of the aqueous extract from Boerhavia erecta L. and the human hepatome cell line PLC/PRF/5 showed suppression in the formation of hepatitis B surface antigen (HbsAg) and the inhibitory action of the antigen present in human serum contaminated with hepatitis B surface antigen. OBJECTIVES: to determine the in vivo hepatoprotective effect of the aqueous extract from B. erecta. METHODS: male Wistar rats were treated with 250 and 500mg of dry extract per kg intragastrically for 5 days, with induced hepatic damage on the last day, using 1 ml/kg of a 1:1 mixture of carbon tetrachloride and olive oil; after 24 hours, blood samples were taken to determine enzymatic activity of alanine-aminotransferase and for the euthanasia of the rats in order to perform the histological study of their livers. RESULTS: the extract caused significant reduction in the enzymatic activity of alanine-aminotransferase from treated rat sera and provided complete protection to the parenchyma of those animals which were administered 500 mg/kg dose. CONCLUSIONS: the in vivo hepatoprotective effect of B. erecta aqueous extract was shown against carbon tetrachloride-induced damage(AU)

Hepatitis tóxica por escitalopram / No disponible

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Changes in liver-related hospital admissions and hospital mortality among HIV-infected patients (1998 to 2005)

La hepatopatía ha aumentado como causa de ingreso y muerte intrahospitalaria en pacientes infectados por el virus de la inmunodeficiencia humana (VIH) tras la aparición de la terapia antirretroviral de gran actividad (TARGA). Un mejor manejo clínico de la hepatopatía podría ayudar a disminuir su incidencia. En nuestro centro, los ingresos por hepatopatía aumentaron del 2,9% en 1998-1999 al 11,3% en 2004-2005 (p = 0,001). Las muertes intrahospitalarias debidas a hepatopatía aumentaron del 2,7% en 1998-1999 al 26% en el período 2002-2003 (p = 0,02) y disminuyeron al 22% en 2004-2005. Si bien el número de ingresos por hepatopatía en pacientes infectados por el VIH todavía sigue aumentando, parece que la mortalidad intrahospitalaria ha sufrido un cambio desde 2003 (AU)

Liver-related disease has increased as a cause of hospitalization and in-hospital death in HIV-infected patients since the introduction of highly active antiretroviral therapy (HAART). Better clinical management of these diseases may contribute to decreasing their incidence. Admissions due to liver-related disease in HIV-infected patients in our institution increased from 2.9% in 1998-1999 to 11.3% in 2004-2005 (P = 0.001). In-hospital deaths due to this cause increased from 2.7%in 1998-1999 to 26% in 2002-2003 (P = 0.02), with a subsequent decrease to 22% in 2004-2005. Hospitalization of HIV-infected patients for liver-related disease continues to increase, whereas the rate of in-hospital deaths from this cause appears to have changed since 2003 (AU)

Efeitos indesejáveis dos hipolipemiantes: condutas na prática clínica: [revisão] / Adverse effects of hypolipemic drugs: how to treat in clinical practice: [review]

Os fármacos hipolipemiantes, apesar de diminuírem a morbimortalidade por doença coronariana, não são destituídos de efeitos indesejáveis. Estes freqüentemente são transitórios, mas podem ocorrer alterações clínicas e laboratoriais que exigem especial atenção e diferentes condutas. Neste artigo, os autores relatam fundamentalmente como proceder diante do comprometimento muscular e hepático, considerados efeitos adversos mais relevantes dos hipolipemiantes. De modo sucinto, apontam os demais efeitos e a respectiva conduta.

Hypolipemic drugs improve coronary morbidity and mortality and appear to be safe; nevertheless appropriate monitoring is recommended. Adverse effects are reported that are frequently transitory. Severe adverse effects are infrequent, but clinicians must correctly screen them; symptoms and laboratory changes must be carefully interpreted. Often they call for special treatment and replacement of the hypolipemic drugs in use. This article emphasizes how to treat dyslipidemia if skeletal muscle and liver involvement are present. Briefly other adverse effects are also reported.

Avaliação dos efeitos colaterais da nevirapina em gestantes HIV positivo em Hospital Universitário do sul do Brasil / Evaluation of the adverse effects of nevirapine in HIV-infected pregnant women in a South Brazilian University Hospital

OBJETIVO: avaliar a freqüência de efeitos advesos com o uso da nevirapina e suas correlações em gestantes infectadas pelo vírus da imunodeficiência humana (HIV). MÉTODOS: estudo retrospectivo foi realizado entre janeiro de 2003 e dezembro de 2006, incluindo todas as mulheres que utilizaram nevirapina durante a gestação. Os critérios de exclusão foram: início da nevirapina antes da gestação; presença de enzimas hepáticas basais aumentadas e dados incompletos de bioquímica hepática no prontuário. Os parâmetros avaliados foram idade, duração de exposição à nevirapina, idade gestacional no início da medicação, semanas de seguimento, carga viral, contagem de CD4 e dosagens de transaminases. A incidência de efeitos adversos hepáticos e/ou cutâneos foi determinada e correlacionada com a contagem de CD4. As análises estatísticas foram realizadas utilizando o teste exato de Fisher e o teste t de Student quando apropriado. A significância estatística foi estabelecida quando p<"0,05. RESULTADOS: cento e cinqüenta e sete gestantes foram incluídas nos critérios estabelecidos. Trinta e uma mulheres (19,7 por cento) apresentaram toxicidade cutânea e/ou hepática. Rash cutâneo foi responsável por 77,4 por cento das toxicidades e anormalidade da função hepática por 22,6 por cento. Hepatotoxicidades graus 1, 2 e 3 foram observadas em 0,6, 2,5 e 1,3 por cento, respectivamente. Contagem de CD4, carga viral e dosagem de transaminases basais foram similares em gestantes com e sem reação induzida pela nevirapina. A contagem de CD4 média foi de 465,4 e 416,6 células/µL em mulheres com e sem efeitos colaterais, respectivamente (p=0,3). Todas as pacientes que apresentaram hepatotoxicidade apresentavam contagem de CD4 prévia ao tratamento superior a 250 células/µL. CONCLUSÕES: a incidência de eventos adversos com nevirapina em nosso estudo foi alta, mas a maioria deles foi cutâneo. Não houve correlação entre a alta contagem de CD4 e os eventos adversos quando se analisou conjuntamente as reações cutâneas e hepáticas; entretanto, a hepatotoxicidade ocorreu apenas em gestantes com contagem de CD4 > 250 células/µL.

PURPOSE: The aim of this article is to evaluate the use of nevirapine HIV-infected pregnant women in our service. METHODS: a retrospective study was performed between January 2003 and December 2006 analysing all women prescribed nevirapine in pregnancy. Exclusion criteria included: (1) women who started nevirapine before pregnancy, (2) patients with abnormal baseline liver enzymes, and (3) women with incomplete liver biochemistry data. Evaluated parameters included age, weeks of exposure to nevirapine, gestational age in the begginning of medication, weeks of follow-up, viral load, CD4 cells count and serum aminotransferase levels. The incidence of adverse hepatic and/or cutaneous effects was determined and correlated to the CD4 cells count. Statistical analysis were performed using Fisher’s exact test and t-Student test when appropriate, with a statistical significance level of p<0,05. RESULTS: one hundred fifty-seven women met the inclusion criteria. Thirty-one (19.7 percent) presented cutaneous and/or hepatic toxicity. Skin rash accounted for 77.4 percent of toxicities and liver function abnormalities were noted in 22.6 percent of women exhibiting toxicities. Grade 1, 2 and 3 hepatotoxicities were observed in 0.6, 2.5 and 1.3 percent, respectively. Baseline CD4 counts, viral loads and transaminases were similar in pregnant women with nevirapine adverse effects and those without reaction. Median absolute CD4 cell counts were 465.4 and 416.6 cells/µL in women with and without side effects, respectively (p=0.3). All patients who experienced hepatotoxicity had pretreatment CD4 counts superior to 250 cells/µL. CONCLUSIONS: The incidence of adverse events with nevirapine in our study was high, but most of them were cutaneous. There was no correlation between high CD4 counts and adverse events when analysing both cutaneous and hepatic reactions; nevertheless, hepatotoxicity occurred only in pregnant women with CD4 counts >250 cells/µL.

Positive effects of Green Tea on hepatic dysfunction, lipid peroxidation and antioxidant defence depletion induced by cadmium

Cadmium (Cd) is a highly toxic environmental and industrial cumulative pollutant that affects many organs,especially the liver. The present study was designed to evaluate the antioxidant effect of green tea oncadmium-induced hepatic dysfunction and oxidative stress in rats. Adult male Wistar rats were administeredcadmium by injection of 20 ìmoles /kg bw/ every 3 days for six months. This study revealed significant (p <0.05) liver dysfunction, lipid peroxidation and a decline in antioxidant enzyme activities in the liver of cadmium-treated rats compared to control animals. Compared to control rats, the activities of lactate dehydrogenase (LDH), gammaglutamyl transferase (GGT), acid phosphatase (PAC), phosphatase alkaline (PAL), as well as bilirubin and thiobarbituric acid-reactive substances (TBARs), were significantly (p < 0.05)increased in Cd-treated rats. Moreover, antioxidant enzyme activities, such as superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase, were significantly (p < 0.05) decreased in the liver of cadmiumtreatedrats. The oral administration of 5% aqueous green tea extract, along with cadmium treatment for six months, caused a significant (p < 0.05) improvement in cadmium-induced toxicity by significantly decreasing(p < 0.05) the activities of enzymatic markers of liver dysfunction (LDH, GGT, PAC, PAL activities, as well as the bilirubin rate). Indeed, green tea extract significantly increased (p < 0.05) antioxidant enzymatic activities (SOD, Catalase, GPX) in rat liver, compared to those given cadmium alone. Thus, the oral administration of green tea, along with cadmium significantly (p < 0.05) improves cadmium-induced liverdysfunction and stress oxidant in rats’ liver.

Glycyrrhizin attenuates endotoxin- induced acute liver injury after partial hepatectomy in rats

Massive hepatectomy associated with infection induces liver dysfunction, or even multiple organ failure and death. Glycyrrhizin has been shown to exhibit anti-oxidant and anti-inflammatory activities. The aim of the present study was to investigate whether glycyrrhizin could attenuate endotoxin-induced acute liver injury after partial hepatectomy. Male Wistar rats (6 to 8 weeks old, weighing 200-250 g) were randomly assigned to three groups of 24 rats each: sham, saline and glycyrrhizin. Rats were injected intravenously with lipopolysaccharide (LPS) 24 h after 70 percent hepatectomy. Glycyrrhizin, pre-administered three times with 24 h intervals 48 h before hepatectomy, prolonged the survival of rats submitted to partial hepatectomy and LPS injection, compared with saline controls. Glycyrrhizin was shown to attenuate histological hepatic changes and significantly reduced serum levels of aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase, at all the indicated times (6 rats from each were sacrificed 1, 3, 6, and 9 h after LPS injection), compared with saline controls. Glycyrrhizin also significantly inhibited hepatocyte apoptosis by down-regulating the expression of caspase-3 and inhibiting the release of cytochrome C from mitochondria into the cytoplasm. The anti-inflammatory activity of glycyrrhizin may rely on the inhibition of release of tumor necrosis factor-a, myeloperoxidase activity, and translocation of nuclear factor-kappa B into the nuclei. Glycyrrhizin also up-regulated the expression of proliferating cell nuclear antigen, implying that it might be able to promote regeneration of livers harmed by LPS. In summary, glycyrrhizin may represent a potent drug protecting the liver against endotoxin-induced injury, especially after massive hepatectomy.

El zumo de Tahitian Noni® no es hepatotóxico / No disponible

No disponible

Réplica. El zumo de Tahitian Noni® no es hepatotóxico: nuestros comentarios / No disponible

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Análise morfológica dos fígados e rins no binômio materno-fetal após tratamento de ratas prenhes com Ritonavir durante toda a prenhez / Morphological analysis of liver and kidneys of pregnant rats and their fetuses upon chronic Ritonavir administration

OBJETIVO: avaliar os efeitos da administração crônica de três diferentes doses de Ritonavir nos fígados e rins de ratas prenhes e seus conceptos do ponto de vista morfológico. MÉTODOS: Quarenta ratas albinas EPM-1 Wistar, prenhes, foram aleatoriamente divididas em quatro grupos: Contr (controle do veículo) e três grupos experimentais, Exp20, Exp60 e Exp180, que receberam, respectivamente, 20, 60 e 180 mg/kg por dia de Ritonavir por via oral. A droga e o veículo (propilenoglicol) foram administrados por gavagem, desde o primeiro até o 20º dia da prenhez. No último dia do experimento, todos os animais foram anestesiados e sacrificados. Em seguida, fragmentos dos fígados e rins maternos e fetais foram coletados e preparados para análise em microscopia de luz. RESULTADOS: não observamos nenhuma alteração morfológica nas vísceras estudadas nos Grupos Contr e Exp20. No Grupo Exp60, encontramos, no fígado materno, hepatócitos com sinais de atrofia e de apoptose (eosinofilia citoplasmática e núcleos picnóticos) e vasodilatação marcante dos capilares sinusóides (congestão). No rim materno, encontramos áreas eosinofílicas e núcleos hipercromáticos na parede dos túbulos contorcidos proximais. O fígado e rins maternos do Grupo Exp180 tiveram alterações morfológicas mais intensas do que no Grupo Exp60. Não observamos alterações histomorfológicas nos fígados e rins fetais em todos os grupos, o que pode ser decorrente da ação protetora da glicoproteína P. CONCLUSÕES: nossos resultados mostram que a administração de Ritonavir a ratas prenhes causou alterações morfológicas nos fígados e rins maternos em doses mais altas que a convencional. Já a ausência de anormalidades nos órgãos fetais pode ser explicada pelo papel protetor da glicoproteína P.

PURPOSE: to evaluate the effect of the chronic administration of three different doses of Ritonavir in the liver and kidneys of pregnant albino rats and their concepts from a morphological standpoint. METHODS: forty pregnant albino EPM-1 Wistar rats were randomly divided into four groups: Contr (vehicle control), and three experimental groups, Exp20, Exp60, Exp180, which received daily 20, 60 or 180 mg/kg of Ritonavir, respectively. The drug and the vehicle (propyleneglycol) were orally administered by gavage, from the first up to the 20th day of pregnancy. At the last experimental day, all the animals were sacrificed under deep anesthesia, and fragments from the maternal and fetal liver and kidneys were taken and prepared for histological analysis by light microscope. RESULTS: no morphological changes were identified in Exp20 and control group. In the Exp60 group, we found hepatocytes with signs of atrophy and apoptosis (eosinophilic cytoplasm and picnotic nuclei) and marked sinusoid capillary vasodilation (congestion). The proximal convoluted tubules of maternal kidneys and liver showed eosinophilic areas and hyperchromatic nuclei, as well as signs of vasodilation. The maternal kidneys and livers of the Exp180 rats presented more prominent morphological changes than the ones of Exp60. Regarding the fetal organs, no histomorphological abnormalities were observed in all the groups. CONCLUSIONS: our results show that the administration of Ritonavir to pregnant rats, in higher than conventional doses causes morphological changes in the maternal liver and kidneys. On the other hand, the lack of abnormalities in the fetal organs may be due to the protective role of glycoprotein P.

Hepatotoxicidad relacionada con el consumo de productos adelgazantes a base de plantas / Hepatotoxicity asociated with the consumption of herbal slimming products

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Alfuzosin-induced Acute Liver Injury / 대한간학회지

We describe a 56-year-old man who developed an acute liver injury after taking alfuzosin for 1 month to control his newly diagnosed benign prostatic hypertrophy (BPH). There was no history of alcohol consumption or the taking herbal or traditional remedies. Viral causes, autoimmune hepatitis, and biliary tree obstruction were excluded. Other rare causes of hepatitis such as hemochromatosis, primary biliary cirrhosis and Wilson's disease were also absent in this patient. His liver test results began to improve after discontinuing the alfuzosin. Two weeks later, alfuzosin was administered again because the patient complained of dysuria. After 10 days of alfuzosin reuse, his liver test results worsened. Five months later after the complete discontinuation of the drug, his liver test results had returned to normal. This clinical sequence suggests that alfuzosin caused his acute liver injury.

Generalized Pustular Psoriasis and Hepatic Dysfunction Associated with Oral Terbinafine Therapy

We report a case of 61-yr-old man with stable psoriasis who progressively developed generalized pustular eruption, erythroderma, fever, and hepatic dysfunction following oral terbinafine. Skin biopsy was compatible with pustular psoriasis. After discontinuation of terbinafine and initiating topical corticosteroid and calcipotriol combination with narrow band ultraviolet B therapy, patient's condition slowly improved until complete remission was reached 2 weeks later. The diagnosis of generalized pustular psoriasis (GPP) induced by oral terbinafine was made. To our knowledge, this is the first report of GPP accompanied by hepatic dysfunction associated with oral terbinafine therapy.

The Survey for the Actual Condition of Drug Medication and Development of Health Care Cost Associated with Toxic Liver Injury in Korean; A Multicenter Study for the Detection and the Development of Nationwide Reporting System of Toxic Liver Injury / 대한간학회지

BACKGROUNDS/AIMS: In Korea, interests in health and health care costs have been increased along with the increase of mean survival rate and income level. The aim of this study is to investigate the actual condition of drug medication and burden of health care cost. METHODS: A total of 1,434 subjects in four tertiary medical centers were enrolled in this study. The questionnaires were obtained between March 2005 and September 2005. Based on this information, the actual condition of drug medication and health care cost were analyzed. RESULTS: The mean age of the subjects was 55.0+/-11.4 years (16-87 years). The male and female ratio was 1.74:1. The subjects with drug medication except for doctor's prescription are presently 26.6% and were 40.9% in the past. Traditional medicine (39.6%) and health food (29.9%) are more frequently used than herbal medicine (5.8%) and medical supplies (4.2%) now. In the past, herbal medicine (14.6%) was more frequently used compared with the present. The side effects of drug medication were developed in 90 subjects (7.5%). The total mean health care costs were 895,000 won/year, the herbal medicine, 834,000 won/year, the health food, 950,000 won/year, and the traditional medicine, 324,000 won/year. CONCLUSIONS: In this study, the subjects with other drug medications without doctor's prescription were as high as ever. The frequency of the use of the herbal medicine was decreased. However, the frequency for the use of the health food and traditional medicine have relatively increased. The side effects and additional large amounts of health care costs were occurred.

Expression of G1 Cell Cycle Regulators in Rat Liver upon Repeated Exposure to Thioacetamide / 대한간학회지

BACKGROUND/AIMS: Eukaryotic cell cycle is regulated by signal transduction pathways mediated by complexes of cyclin dependent kinases (CDKs) and their partner cyclins, or by interaction with CDK inhibitors. Thioacetamide (TA) is a weak hepatocarcinogen causing several types of liver damage in a dose dependent manner and ultimately producing malignant transformation. We investigated alterations of expression of cell cycle regulators in the rat liver, involved in G1 entry and progression during TA administration. METHODS: We studied expression patterns of cyclin D1, CDK4, CDK6, p21(CIP1) and p16(INK4a) during daily intraperitoneal injection of low dose TA (50 mg/kg) till 7 day. We used western blot and immunohistochemistry for detection. RESULTS: Expression of cyclin D1, CDK4, CDK6 and p21(CIP1) increased from 6 hour and peaked at 2, 3 day, then decreased next 2 days, and re-increased at 6 day. Cytoplasmo-nuclear translocation of cyclin D1 and p21(CIP1) was evident within 1 day and prominent at 2 and 7 day. Expression of p16(INK4a) increased immediately after TA treatment and remarkably increased from 3 day and progressed till 7 day, showing cytoplasmic location, suggestive of inactive form. Most of in situ immunoreactions occurred at the centrilobular hepatocytes. Concomitant nuclear translocation of p21(CIP1) and cyclin D1, different with p16(INK4a) suggests that p21(CIP1) might be a transporter for nuclear translocation rather than cell cycle inhibitor. CONCLUSIONS: Daily administration of low dose TA makes cell cycle open and G1 progress, possibly due to cyclin D1, CDK4 and CDK 6, their transporter p21(CIP1), and inactive p16(INK4a), which occur at quiescent hepatocytes, not stem cells.

Posible hepatotoxicidad del rizoma de cimicífuga / No disponible

El uso de preparados de rizoma de cimicífuga se ha extendido en los últimos años, por su eficacia en el tratamiento de los síntomas asociados al climaterio. El hallazgo reciente de indicios sobre su posible toxicidad hepática, aunque con una frecuencia de aparición rara, ha llevado a las agencias de medicamentos a efectuar recomendaciones tanto a los pacientes como a los profesionales de la salud sobre la utilización de los mismos. De los más de 40 casos evaluados por la EMEA, sólamente cuatro muestran una secuencia temporal compatible con la administración del producto, aunque en ninguno de ellos se ha podido establecer con certeza una relación de causalidad. La evaluación se ha visto dificultada por la falta de una adecuada información médica, así como sobre la composición y la calidad de los preparados y sobre su forma de utilización (especialmente en productos no registrados), datos necesarios para establecer la posible relación con un determinado tipo de preparado, su dosificación, duración del tratamiento, o incluso si la causa se encuentra en una adulteración o falsificación

The use of black cohosh preparations has increased in the last years due to its efficacy for the treatment of climacteric symptoms. The recent reports of its possible hepatotoxicity, even considered rare, lead the medical agencies to make recommendations for patients as well as for health professionals on their use. Among more than 40 cases assessed by EMEA, only 4 showed a temporal sequence compatible with the use of the investigated product, although in none of them could be established a causality relationship with an entire certainty. The assessment has been difficulted by the lack of appropriate medical information, as well as on the composition and quality of the concerned products (especially for unlicensed ones), data that are needed for the establishment of a possible relationship with a specific type of preparation, its dose, the duration of the treatment, or even if any adulteration or falsification was involved

Coinfección por VIH/VHC y hepatotoxicidad: Perfi l hepático de los no análogos de nucleósidos / No disponible

La coinfección por el VHC es un importante factor de riesgo para el desarrollo de hepatotoxicidad inducida por los antirretrovirales, la cual constituye uno de los efectos adversos más comunes y uno de los principales motivos para la suspensión de éstos. Aunque casi todos los fármacos de este grupo terapéutico pueden resultar lesivos para el hígado, ritonavir (a dosis plenas) y nevirapinason los que con mayor frecuencia se asocian con esta circunstancia. Así, entre los no-análogos denucleósidos en concreto, diversos estudios han puesto de manifiesto una menor incidencia de hepatotoxicidad con efavirenz que con nevirapina, hecho que también se ha objetivado en el subgrupo de pacientes que han desarrollado cirrosis hepática. Respecto al impacto de los antirretrovirales sobre la progresión de la fibrosis hepática inducida por el VHC, sin duda otro aspecto muy importante de la coinfección por VIH/VHC, se ha observado que los inhibidores de la proteasa ejercen un efecto protector antela misma, el cual, aunque de menor intensidad, presenta también efavirenz, pero no nevirapina (AU)

HCV coinfection is an important risk factor for antiretroviral-associated hepatotoxicity, which is one of the most common adverse events of antiretroviral therapy and one of the main causes for its discontinuation. Although almost all drugs of this therapeutic group could be harmful for the liver, ritonavir (in therapeutic doses) and nevirapine are those which most frequently are associated with hepatotoxicity. Specifically, among non-nucleoside analogues, several studies have revealed a smaller hepatotoxicityi ncidence with efavirenz rather than with nevirapine. This fact has been also observed in patients who developed hepatic cirrhosis. Regarding antiretroviral ‘impact over progression of HCV-induced hepaticfibrosis, another very important aspect of HIV/HCV coinfection, it has been reported that protease inhibitors have a protector effect over that progression. Efavirenz also presents this positive effect, but this one is not so intense. However, nevirapine doesn’t have it (AU)