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1.
Nat Commun ; 12(1): 5954, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642329

RESUMO

Leptomeningeal disease (LMD) is a common complication from solid tumor malignancies with a poor prognosis and limited treatment options. We present a single arm Phase II study of 18 patients with LMD receiving combined ipilimumab and nivolumab until progression or unacceptable toxicity (NCT02939300). The primary end point is overall survival at 3 months (OS3). Secondary end points include toxicity, cumulative time-to-progression at 3 months, and progression-free survival. A Simon two-stage design is used to compare a null hypothesis OS3 of 18% against an alternative of 44%. Median follow up based on patients still alive is 8.0 months (range: 0.5 to 15.9 months). The study has met its primary endpoint as 8 of 18 (OS3 0.44; 90% CI: 0.24 to 0.66) patients are alive at three months. One third of patients have experienced one (or more) grade-3 or higher adverse events. Two patients have discontinued protocol treatment due to unacceptable toxicity (hepatitis and colitis, respectively). The most frequent adverse events include fatigue (N = 7), nausea (N = 6), fever (N = 6), anorexia (N = 6) and rash (N = 6). Combined ipilimumab and nivolumab has an acceptable safety profile and demonstrates promising activity in LMD patients. Larger, multicenter clinical trials are needed to validate these results.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas/tratamento farmacológico , Ipilimumab/administração & dosagem , Carcinomatose Meníngea/tratamento farmacológico , Neoplasias Meníngeas/tratamento farmacológico , Nivolumabe/administração & dosagem , Adulto , Idoso , Anorexia/induzido quimicamente , Anorexia/mortalidade , Anorexia/patologia , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Colite/induzido quimicamente , Colite/mortalidade , Colite/patologia , Exantema/induzido quimicamente , Exantema/mortalidade , Exantema/patologia , Fadiga/induzido quimicamente , Fadiga/mortalidade , Fadiga/patologia , Feminino , Febre/induzido quimicamente , Febre/mortalidade , Febre/patologia , Hepatite/etiologia , Hepatite/mortalidade , Hepatite/patologia , Humanos , Ipilimumab/efeitos adversos , Masculino , Carcinomatose Meníngea/mortalidade , Carcinomatose Meníngea/patologia , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/patologia , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/mortalidade , Náusea/patologia , Nivolumabe/efeitos adversos , Análise de Sobrevida
2.
BMJ Case Rep ; 14(9)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479894

RESUMO

An 81-year-old woman with no history of immunocompromise presented with 2 days of upper abdominal pain associated with nausea. On arrival, her physical examination was unremarkable apart from mild epigastric and right hypochondriac tenderness, and laboratory investigations were unremarkable apart from mild thrombocytopenia and transaminitis. A CT scan performed on the day of admission revealed a tiny 0.3 cm stone in the common bile duct, with no upstream dilatation. On day 2 of admission, she developed a vesicular rash and with acutely worsening transaminitis. She deteriorated rapidly and demised from complications of acute liver failure within the next 24 hours. The diagnosis of varicella was confirmed with antibody testing. Fulminant varicella hepatitis is an extremely rare and lethal condition with only a handful of reported cases in the current literature. We aim to share our clinical experience and summarise the salient points from existing case reports.


Assuntos
Varicela , Hepatite , Dor Abdominal/etiologia , Idoso de 80 Anos ou mais , Ducto Colédoco , Feminino , Hepatite/diagnóstico , Hepatite/etiologia , Herpesvirus Humano 3 , Humanos
3.
BMC Pediatr ; 21(1): 345, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34399711

RESUMO

BACKGROUND: Drug-induced aseptic meningitis is a rare, but challenging diagnosis, most commonly reported with nonsteoroidal anti-inflammatory drugs (NSAIDs) and antibiotics. Trimethoprim/sulfamethoxazole (TMP/SMX) is a sulfonamide that is widely used in clinical practice for the treatment and prophylaxis of various infections. The most common side effects associated with TMP/SMX are generally mild and self-limited, but serious side effects have been reported, including liver injury and aseptic meningitis. CASE PRESENTATION: We report a 2,5 year old Dutch girl with both drug-induced aseptic meningitis and drug-induced liver injury while using TMP/SMX prophylaxis. Ursodeoxycholic acid was started because of cholestatic injury. After cessation of TMP/SMX, full convalescence was reached within weeks. CONCLUSIONS: This is the first report of a young patient with both aseptic meningitis and drug-induced liver injury caused by TMP/SMX. Drug-induced aseptic meningitis and cholestatic hepatitis constitute a considerable diagnostic challenge to clinicians. In addition to a thorough evaluation for infectious causes, clinicians should be aware of drug-induced aseptic meningitis and cholestatic hepatitis.


Assuntos
Anti-Infecciosos , Colestase , Hepatite , Meningite Asséptica , Pré-Escolar , Colestase/induzido quimicamente , Colestase/diagnóstico , Feminino , Hepatite/diagnóstico , Hepatite/etiologia , Humanos , Meningite Asséptica/induzido quimicamente , Meningite Asséptica/diagnóstico , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos
4.
Zhonghua Gan Zang Bing Za Zhi ; 29(7): 705-710, 2021 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-34371544

RESUMO

Ischemic hepatitis is inflammation caused by necrosis of liver cells due to ischemia and hypoxia caused by low cardiac output or septic shock. It is often complicated by heart failure or severe septic shock. One of the pathogenesis of ischemic hepatitis is hepatocyte injury caused by ischemia and hypoxia, which results in damage-associated molecular patterns (DAMPs) release and binding to membrane receptors such as toll like receptors (TLRs) to cause inflammatory reactions.The other is when the ischemic liver is reperfused, hepatocyte mitochondrias will produce a large amount of ROS causing ischemia reperfusion injury. These two mechanisms and related molecular pathways are elaborated in this paper.


Assuntos
Hepatite , Traumatismo por Reperfusão , Hepatite/etiologia , Hepatócitos , Humanos , Isquemia , Fígado
6.
J Coll Physicians Surg Pak ; 31(7): S125-S126, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34271811

RESUMO

Coronavirus disease 2019 (COVID-19) initially emerged in Wuhan, China, in December 2019, and now it has been declared a pandemic by the World Health Organization. COVID-19 commonly presents with respiratory manifestations like fever, cough, body aches, and shortness of breath. Neurological, myocardial, renal and gastrointestinal complications secondary to SARS-CoV-2 infection have been reported in the literature. Gastrointestinal symptoms reported with COVID-19 are mostly nausea, vomiting, and diarrhea. COVID-19 can rarely present with acute hepatitis. Here, we report a case of a 45-year male who presented with signs and symptoms of acute hepatitis secondary to SARS-CoV-2 infection. Key Words: SARS-CoV-2, COVID-19, Acute hepatitis.


Assuntos
COVID-19 , Hepatite , China , Hepatite/diagnóstico , Hepatite/etiologia , Humanos , Masculino , Pandemias , SARS-CoV-2
7.
Front Immunol ; 12: 679509, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305911

RESUMO

Group 2 innate lymphoid cells (ILC2s) are tissue resident in the lung and activated by inhaled allergens via epithelial-derived alarmins including IL-33. Activated ILC2s proliferate, produce IL-5 and IL-13, and induce eosinophilic inflammation. Here, we report that intranasal IL-33 or the protease allergen papain administration resulted in increased numbers of ILC2s not only in the lung but also in peripheral blood and liver. Analyses of IL-33 treated parabiosis mice showed that the increase in lung ILC2s was due to proliferation of lung resident ILC2s, whereas the increase in liver ILC2s was due to the migration of activated lung ILC2s. Lung-derived ILC2s induced eosinophilic hepatitis and expression of fibrosis-related genes. Intranasal IL-33 pre-treatment also attenuated concanavalin A-induced acute hepatitis and cirrhosis. These results suggest that activated lung resident ILC2s emigrate from the lung, circulate, settle in the liver and promote type 2 inflammation and attenuate type 1 inflammation.


Assuntos
Hepatite/etiologia , Hipersensibilidade/etiologia , Imunidade Inata , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Pneumonia/etiologia , Animais , Biomarcadores , Citocinas/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Expressão Gênica , Hepatite/metabolismo , Hepatite/patologia , Hipersensibilidade/metabolismo , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Knockout , Pneumonia/metabolismo , Pneumonia/patologia , Eosinofilia Pulmonar/etiologia , Eosinofilia Pulmonar/metabolismo , Eosinofilia Pulmonar/patologia
8.
Life Sci ; 277: 119618, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34004252

RESUMO

AIMS: The current study aims to investigate the role of the key effector cytokines produced by CD4+T cells in the pathogenesis of Con A-induced liver injury in mice and testing whether etanercept can be repurposed to differentially regulate these cytokines. MAIN METHODS: Four groups of mice were used: group I: control group, group II: mice received 15 mg/kg Con A i.v, group III: mice received 15 mg/kg etanercept i.p, group IV: mice received both Con A and etanercept as described. Hepatic injury and necroinflammation were assessed. Infiltration of CD4+ T cells and neutrophils were evaluated. Hepatic levels of TNF-α, IL-4, IL-10, and MDA were assigned and expression of NF-κB as well. KEY FINDINGS: A significant decrease in ALT, AST, and LDH levels occurred when etanercept was injected before Con A. Hepatic necrosis and infiltration of CD4+ T cells and neutrophils were reduced by etanercept. Levels of TNF-α, IL-4, and MDA were significantly decreased in group IV compared to group II while that of IL-10 was increased. Also, number of NF-κB positive cells was significantly low in group IV. SIGNIFICANCE: The study elucidates an interplay between the two effector cytokines of CD4+ T cells, TNF-α and IL-4, and their key role in Con A-induced liver injury. Additionally, our results showed that etanercept could be repurposed to differentially regulate effector cytokines produced by CD4+ T cells. Not only TNF-α, but also IL-4 signaling pathways, through which it exerts immunomodulatory, anti-inflammatory, and anti-oxidant effects leading to attenuation of Con A-induced liver injury.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Concanavalina A/toxicidade , Citocinas/metabolismo , Etanercepte/farmacologia , Hepatite/tratamento farmacológico , Imunossupressores/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Hepatite/etiologia , Hepatite/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mitógenos/toxicidade , Transdução de Sinais
9.
Phytomedicine ; 87: 153586, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34044253

RESUMO

BACKGROUND: Chemical liver injury is one of the main causes of acute liver failure and death. To date, however, treatment strategies for acute liver injury have been limited. Therefore, there is an urgent need to find new therapeutic targets and effective drugs. NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome is a complex of multiple proteins that has been shown to induce cell death under inflammatory and stress pathologic conditions and is thought to provide new targets for the treatment of a variety of diseases. PURPOSE: The purpose of this study was to investigate whether luteolin has a protective effect on the liver and further elucidate whether it is realized through the thioredoxin interacting protein (TXNIP)-NLRP3 axis. STUDY DESIGN: Acute hepatic injury in mice caused by intraperitoneal injection of lipopolysaccharide (LPS) was treated with or without luteolin. METHODS: Male C57BL/6 mice and mouse primary hepatocytes were selected. TXNIP protein knockdown was achieved by siRNA, qPCR and Western blot were performed to explore the mechanism of luteolin in alleviating acute liver injury. RESULTS: The results indicated that luteolin had a markedly protective effect on acute liver injury induced by LPS in mice by inhibiting the TXNIP-NLRP3 axis. Luteolin inhibits NLRP3 inflammasome activation by suppressing TXNIP, apoptosis associated speck-like protein containing a CARD domain (ASC), caspase-1, interleukin-1ß (IL-1ß) and IL-18 to reduce liver injury. In addition, luteolin inhibits LPS-induced liver inflammation by inhibiting the production of inflammation-related gene tumor necrosis factor-α (TNF-α), IL-10, and IL-6. What's more, luteolin alleviated LPS-induced hepatocyte injury by inhibiting oxidative stress and regulating MDA, SOD, and GSH levels. However, the protective effect of luteolin on acute LPS-induced liver injury in mice was blocked by si-TXNIP in vitro. CONCLUSIONS: These combined data showed that luteolin may alleviate LPS-induced liver injury through the TXNIP-NLPR3 axis, providing new therapeutic targets and therapeutic drugs for subsequent studies.


Assuntos
Proteínas de Transporte/antagonistas & inibidores , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Inflamassomos/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Luteolina/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Tiorredoxinas/antagonistas & inibidores , Animais , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Morte Celular/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Hepatite/tratamento farmacológico , Hepatite/etiologia , Hepatite/patologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Inflamassomos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Tiorredoxinas/genética , Tiorredoxinas/metabolismo
11.
Nat Metab ; 3(5): 604-617, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34002097

RESUMO

Non-alcoholic fatty liver disease (NAFLD), the most prevalent liver pathology worldwide, is intimately linked with obesity and type 2 diabetes. Liver inflammation is a hallmark of NAFLD and is thought to contribute to tissue fibrosis and disease pathogenesis. Uncoupling protein 1 (UCP1) is exclusively expressed in brown and beige adipocytes, and has been extensively studied for its capacity to elevate thermogenesis and reverse obesity. Here we identify an endocrine pathway regulated by UCP1 that antagonizes liver inflammation and pathology, independent of effects on obesity. We show that, without UCP1, brown and beige fat exhibit a diminished capacity to clear succinate from the circulation. Moreover, UCP1KO mice exhibit elevated extracellular succinate in liver tissue that drives inflammation through ligation of its cognate receptor succinate receptor 1 (SUCNR1) in liver-resident stellate cell and macrophage populations. Conversely, increasing brown and beige adipocyte content in mice antagonizes SUCNR1-dependent inflammatory signalling in the liver. We show that this UCP1-succinate-SUCNR1 axis is necessary to regulate liver immune cell infiltration and pathology, and systemic glucose intolerance in an obesogenic environment. As such, the therapeutic use of brown and beige adipocytes and UCP1 extends beyond thermogenesis and may be leveraged to antagonize NAFLD and SUCNR1-dependent liver inflammation.


Assuntos
Suscetibilidade a Doenças , Hepatite/etiologia , Hepatite/metabolismo , Ácido Succínico/metabolismo , Proteína Desacopladora 1/genética , Tecido Adiposo Bege/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Espaço Extracelular/metabolismo , Glucose/metabolismo , Intolerância à Glucose/metabolismo , Hepatite/patologia , Humanos , Redes e Vias Metabólicas , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Proteína Desacopladora 1/metabolismo
12.
Front Immunol ; 12: 680855, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054870

RESUMO

Clearance of red blood cells and hemoproteins is a key metabolic function of macrophages during hemolytic disorders and following tissue injury. Through this archetypical phagocytic function, heme is detoxified and iron is recycled to support erythropoiesis. Reciprocal interaction of heme metabolism and inflammatory macrophage functions may modify disease outcomes in a broad range of clinical conditions. We hypothesized that acute hemolysis and heme induce acute anti-inflammatory signals in liver macrophages. Using a macrophage-driven model of sterile liver inflammation, we showed that phenylhydrazine (PHZ)-mediated acute erythrophagocytosis blocked the anti-CD40 antibody-induced pathway of macrophage activation. This process attenuated the inflammatory cytokine release syndrome and necrotizing hepatitis induced by anti-CD40 antibody treatment of mice. We further established that administration of heme-albumin complexes specifically delivered heme to liver macrophages and replicated the anti-inflammatory effect of hemolysis. The anti-inflammatory heme-signal was induced in macrophages by an increased intracellular concentration of the porphyrin independently of iron. Overall, our work suggests that induction of heme-signaling strongly suppresses inflammatory macrophage function, providing protection against sterile liver inflammation.


Assuntos
Anticorpos/imunologia , Antígenos CD40/antagonistas & inibidores , Antígenos CD40/imunologia , Hemólise/imunologia , Hepatite/etiologia , Albuminas/metabolismo , Animais , Anticorpos/efeitos adversos , Biópsia , Modelos Animais de Doenças , Suscetibilidade a Doenças , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Eritrócitos/patologia , Perfilação da Expressão Gênica , Heme/metabolismo , Hepatite/metabolismo , Hepatite/patologia , Ferro/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Fenil-Hidrazinas/efeitos adversos , Porfirinas/metabolismo , Ligação Proteica
13.
Viruses ; 13(5)2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33925701

RESUMO

Hepatitis viruses and liver-stage malaria are within the liver infections causing higher morbidity and mortality rates worldwide. The highly restricted tropism of the major human hepatotropic pathogens-namely, the human hepatitis B and C viruses and the Plasmodium falciparum and Plasmodium vivax parasites-has hampered the development of disease models. These models are crucial for uncovering the molecular mechanisms underlying the biology of infection and governing host-pathogen interaction, as well as for fostering drug development. Bioengineered cell models better recapitulate the human liver microenvironment and extend hepatocyte viability and phenotype in vitro, when compared with conventional two-dimensional cell models. In this article, we review the bioengineering tools employed in the development of hepatic cell models for studying infection, with an emphasis on 3D cell culture strategies, and discuss how those tools contributed to the level of recapitulation attained in the different model layouts. Examples of host-pathogen interactions uncovered by engineered liver models and their usefulness in drug development are also presented. Finally, we address the current bottlenecks, trends, and prospect toward cell models' reliability, robustness, and reproducibility.


Assuntos
Bioengenharia , Técnicas de Cultura de Células , Suscetibilidade a Doenças , Hepatite/etiologia , Hepatite/metabolismo , Hepatócitos/metabolismo , Animais , Bioengenharia/métodos , Modelos Animais de Doenças , Descoberta de Drogas , Hepatite/tratamento farmacológico , Hepatite/patologia , Hepatite Viral Humana/etiologia , Hepatite Viral Humana/metabolismo , Hepatite Viral Humana/patologia , Hepatócitos/parasitologia , Hepatócitos/virologia , Interações Hospedeiro-Patógeno , Humanos , Fígado/metabolismo , Fígado/parasitologia , Fígado/virologia , Hepatopatias Parasitárias/etiologia , Hepatopatias Parasitárias/metabolismo , Hepatopatias Parasitárias/patologia
14.
Biochem Biophys Res Commun ; 555: 54-60, 2021 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-33813276

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is the pathological manifestation of metabolic syndrome in liver. Its pathological changes may evolve from the initial simple steatosis to non-alcoholic steatohepatitis, liver fibrosis and even liver cancer. Numerous studies have proved that platelets play a vital role in liver disease and homeostasis. Particularly, anti-platelet therapy can reduce intrahepatic platelet aggregation and improve the inflammation of fatty liver. Previous study has also confirmed that SAA is a gene closely related to high-fat diet (HFD) induced obesity, and SAA1 can promote liver insulin resistance induced by Palmitate or HFD. Here, we found that SAA1 treated platelets presented increased sensitivity of platelet aggregation, enhanced activation and increased adhesion ability, and such function was partly dependent on Toll-Like Receptor (TLR) 2 signaling. In addition, blocking SAA1 expression in vivo not only inhibited platelet aggregation in the liver tissues of NAFLD mice, but also alleviated the inflammation of fatty liver. In conclusion, our findings identify that HFD-induced hepatic overexpressed SAA1 aggravates fatty liver inflammation by promoting intrahepatic platelet aggregation, these results also imply that SAA1 may serve as a potential target for ameliorating NAFLD.


Assuntos
Hepatócitos/metabolismo , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Agregação Plaquetária/efeitos dos fármacos , Proteína Amiloide A Sérica/metabolismo , Animais , Adesão Celular/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Feminino , Hepatite/etiologia , Hepatócitos/patologia , Humanos , Camundongos Endogâmicos BALB C , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteína Amiloide A Sérica/genética , Proteína Amiloide A Sérica/farmacologia , Receptor 2 Toll-Like/metabolismo
15.
Molecules ; 26(9)2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33926126

RESUMO

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1ß in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.


Assuntos
Anti-Inflamatórios/farmacologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Fator de Transcrição AP-1/metabolismo , Animais , Anti-Inflamatórios/química , Linhagem Celular , Modelos Animais de Doenças , Hepatite/tratamento farmacológico , Hepatite/etiologia , Hepatite/metabolismo , Humanos , Masculino , Camundongos , Extratos Vegetais/química , Substâncias Protetoras/química , Células RAW 264.7
17.
Curr Oncol ; 28(1): 898-902, 2021 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-33617506

RESUMO

Immune checkpoint inhibitors (ICIs) have led to major therapeutic advances in the management of malignancy. Despite promising outcomes for some cancers, ICIs are linked to unique side-effects known as immune-related adverse events (IrAEs). These may affect a wide array of organ systems. In particular, ICI-induced hepatitis is diagnostically challenging given its variable natural history and clinical manifestations. The onset of ICI-induced hepatitis often occurs between 6 and 14 weeks after treatment initiation and rarely exhibits delayed presentations or manifests after treatment cessation. We present a case of very delayed-onset ICI-induced hepatitis, stressing the importance of long-term surveillance for immune-indued hepatitis in patients initiated on ICIs even long after treatment cessation.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hepatite , Neoplasias , Anticorpos Monoclonais Humanizados/efeitos adversos , Hepatite/diagnóstico , Hepatite/etiologia , Humanos
19.
Ugeskr Laeger ; 183(6)2021 02 08.
Artigo em Dinamarquês | MEDLINE | ID: mdl-33570026

RESUMO

Hepatotoxicity is a well-known side effect to isoniazid treatment with the risk of progression to liver failure. This case report describes a 39-year-old male, who received standard isoniazid treatment for latent TB infection (LTBI) and developed severe isoniazid-induced acute hepatitis. Liver transplantation was considered, but the patient slowly recovered with full hepatic regeneration. With increasing focus on treating LTBI in Denmark, routine follow-up including biochemical monitoring should be implemented for patients receiving LTBI treatment to prevent severe complications.


Assuntos
Hepatite , Tuberculose Latente , Adulto , Antituberculosos/efeitos adversos , Hepatite/tratamento farmacológico , Hepatite/etiologia , Humanos , Isoniazida/efeitos adversos , Tuberculose Latente/tratamento farmacológico , Masculino
20.
Hepatol Int ; 15(2): 510-519, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33634373

RESUMO

BACKGROUND: Checkpoint inhibitor-induced hepatitis is an immune-related adverse event of programmed cell death protein 1 (PD-1) inhibition, cytotoxic T-lymphocyte associated 4 (CTLA-4) inhibition or the combination of both. Aim of this study was to assess whether checkpoint inhibitor-induced hepatitis is related to liver metastasis and outcome in a real-world nationwide cohort. METHODS: Data from the prospective nationwide Dutch Melanoma Treatment Registry (DMTR) was used to analyze incidence, risk factors of checkpoint inhibitor-induced grade 3-4 hepatitis and outcome. RESULTS: 2561 advanced cutaneous melanoma patients received 3111 treatments with checkpoint inhibitors between May 2012 and January 2019. Severe hepatitis occurred in 30/1620 (1.8%) patients treated with PD-1 inhibitors, in 29/1105 (2.6%) patients treated with ipilimumab and in 80/386 (20.7%) patients treated with combination therapy. Patients with hepatitis had a similar prevalence of liver metastasis compared to patients without hepatitis (32% vs. 27%; p = 0.58 for PD-1 inhibitors; 42% vs. 29%; p = 0.16 for ipilimumab; 38% vs. 43%; p = 0.50 for combination therapy). There was no difference in median progression free and overall survival between patients with and without hepatitis (6.0 months vs. 5.4 months progression-free survival; p = 0.61; 17.0 vs. 16.2 months overall survival; p = 0.44). CONCLUSION: Incidence of hepatitis in a real-world cohort is 1.8% for PD-1 inhibitor, 2.6% for ipilimumab and 20.7% for combination therapy. Checkpoint inhibitor-induced hepatitis had no relation with liver metastasis and had no negative effect on the outcome.


Assuntos
Hepatite , Neoplasias Hepáticas , Melanoma , Neoplasias Cutâneas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Hepatite/epidemiologia , Hepatite/etiologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Melanoma/tratamento farmacológico , Nivolumabe/efeitos adversos , Estudos Prospectivos , Neoplasias Cutâneas/tratamento farmacológico
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