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1.
BMJ Case Rep ; 13(9)2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32878840

RESUMO

The COVID-19 outbreak has spread across the globe at an alarming rate. As the pandemic escalates, experience of COVID-19 in pregnant women is accumulating. We present a case of COVID-19 pneumonia in a 28-week pregnant woman with a known low lying placenta. The patient had deranged liver function tests at presentation, along with elevated bile acids. We discuss the differential diagnosis of these findings, and the possible mechanisms of hepatic injury in COVID-19. The low lying placenta in this patient meant that we had to carefully consider the application of recommendations for thromboprophylaxis in pregnant COVID-19 patients. With supportive management, this patient improved enough to be discharged, and has gone on to deliver a healthy neonate at term.


Assuntos
Colestase/diagnóstico , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Complicações Infecciosas na Gravidez/diagnóstico , Terceiro Trimestre da Gravidez , Adulto , Colestase/complicações , Infecções por Coronavirus/complicações , Feminino , Humanos , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Pandemias , Pneumonia Viral/complicações , Gravidez , Resultado da Gravidez
2.
PLoS One ; 15(4): e0232089, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32353060

RESUMO

BACKGROUND: We aimed to determine the optimal approach with endoscopic biliary drainage (EBD) and corticosteroid (CS) for the treatment of IgG4-related sclerosing cholangitis (ISC). METHODS: To evaluate the safety of EBD for treatment of biliary stricture caused by ISC, we assessed the risk of stent dislodgement and sought to determine the most appropriate time for stent removal. We also assessed the safety of treatment with CS alone for patients with obstructive jaundice, and the rate of and risk factors for biliary tract complications. RESULTS: Sixty-nine patients with ISC treated with CS were enrolled. Twenty-eight patients (40.6%) were treated with EBD for biliary stricture before CS initiation. Intentional stent removal was performed in thirteen (46.4%) after confirming CS-induced improvement. Eleven of thirteen patients (84.6%) underwent stent removal within 1 month after CS initiation and all their stent removals were safely carried out without early (within two weeks) recurrence of obstructive jaundice. Ten of twenty-eight patients (35.7%) experienced spontaneous stent dislodgement after CS initiation, and seven (70%) of them developed stent dislodgement two weeks to two months after CS initiation. Among forty-one patients treated with CS alone without EBD, 10 patients had obstructive jaundice at the time of CS initiation and all of them achieved clinical improvement without biliary tract infection. During the follow-up, three patients (4.3%), all of whom had undergone EBD, developed bile-duct stones, while none of those treated with CS alone developed bile-duct stones (p = 0.032). Long-term biliary stenting was a risk factor for bile-duct stones. CONCLUSIONS: Biliary stent removal should be carried out within 2 weeks after CS initiation if biliary stricture improves to prevent stent dislodgement. Obstructive jaundice can be treated safely with CS alone in patients without infection. Clinicians should be aware of the possibility of bile-duct stones in patients treated with EBD.


Assuntos
Procedimentos Cirúrgicos do Sistema Biliar/métodos , Colangite Esclerosante/terapia , Stents/efeitos adversos , Corticosteroides/uso terapêutico , Idoso , Ductos Biliares/cirurgia , Colangite/etiologia , Colangite Esclerosante/complicações , Colangite Esclerosante/cirurgia , Colestase/complicações , Constrição Patológica/complicações , Constrição Patológica/cirurgia , Remoção de Dispositivo/efeitos adversos , Drenagem/efeitos adversos , Feminino , Humanos , Imunoglobulina G , Icterícia Obstrutiva/tratamento farmacológico , Icterícia Obstrutiva/etiologia , Icterícia Obstrutiva/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Esfinterotomia Endoscópica/efeitos adversos
3.
Am J Pathol ; 190(3): 614-629, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31972159

RESUMO

Bacterial flagellin, recognized by cell surface of Toll-like receptor (TLR) 5, is a potent activator of many types of cells, leading to the activation of innate or adaptive immunity, which are pivotal in regulating fibrotic process. However, the exact role of TLR5 signaling in hepatic fibrogenesis remains unclear, and this study aims to elucidate its underlying mechanisms. Flagellin was injected to hepatotoxin- and cholestasis-induced liver fibrosis murine models. Flagellin-induced TLR5 activation significantly decreased the severity of liver fibrosis. Interestingly, the expression levels of IL-1 receptor antagonist (IL1RN) and interferon (IFN)ß markedly increased in fibrotic livers on flagellin treatment. Consistently, in vivo activation of TLR5 signaling markedly increased IFNß and IL1RN expression in the livers. Notably, flagellin injection significantly exacerbated the severity of liver fibrosis in IFN-α/ß receptor 1 (IFNAR1) knockout mice. Furthermore, hepatic expression of IL1RN in the fibrotic livers of IFNAR1 knockout mice was significantly lower than those of wild-type mice. In support of these findings, flagellin-mediated IL1RN production is not sufficient to alleviate the severity of hepatic fibroinflammatory responses in IFNAR1-deficient milieu. Finally, hepatic stellate cells treated with IL1RN had significantly decreased cellular activation and its associated fibrogenic responses. Collectively, manipulation of TLR5 signaling may be a promising therapeutic strategy for the treatment of liver fibrosis.


Assuntos
Colestase/complicações , Interferon beta/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Cirrose Hepática/fisiopatologia , Transdução de Sinais , Receptor 5 Toll-Like/metabolismo , Imunidade Adaptativa , Animais , Modelos Animais de Doenças , Progressão da Doença , Flagelina/administração & dosagem , Imunidade Inata , Interferon beta/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/etiologia , Cirrose Hepática/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptor de Interferon alfa e beta/genética , Receptor 5 Toll-Like/genética
4.
Oxid Med Cell Longev ; 2019: 6565283, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827690

RESUMO

Cholestatic liver injury, due to obstruction of the biliary tract or genetic defects, is often accompanied by progressive inflammation and liver fibrosis. Methane-rich saline (MRS) has anti-inflammatory properties. However, whether MRS can provide protective effect in cholestatic liver injury is still unclear. In this study, Sprague-Dawley rats received bile duct ligation (BDL) to generate a cholestatic model followed by MRS treatment (10 mL/kg, ip treatment) every 12 h after the operation to explore the potential protective mechanism of MRS in cholestatic liver injury. We found that MRS effectively improved liver function, alleviated liver pathological damage, and localized infiltration of inflammatory cells. MRS treatment decreased the expression of hepatic fibrosis-associated proteins to alleviate liver fibrosis. Furthermore, MRS treatment suppressed the TLR4/NF-κB pathway and further reduced the levels of proinflammatory factors. Downregulation of NF-κB subsequently reduced the NLRP3 expression to inhibit pyroptosis. Our data indicated that methane treatment prevented cholestatic liver injury via anti-inflammatory properties that involved the TLR4/NF-κB/NLRP3 signaling pathway.


Assuntos
Colestase/complicações , Inflamassomos/efeitos dos fármacos , Hepatopatias/prevenção & controle , Metano/farmacologia , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Cloreto de Sódio/farmacologia , Receptor 4 Toll-Like/metabolismo , Animais , Ductos Biliares , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/etiologia , Inflamação/patologia , Inflamação/prevenção & controle , Ligadura , Hepatopatias/etiologia , Hepatopatias/patologia , Masculino , NF-kappa B/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Receptor 4 Toll-Like/genética
6.
Diagn Interv Radiol ; 25(6): 465-470, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31650963

RESUMO

PURPOSE: In patients with malignant biliary obstruction complicated by massive ascites, when endoscopy fails, safe routes for biliary decompression are needed as an alternative to percutaneous approach. We aimed to evaluate the safety and effectiveness of transjugular insertion of biliary stent (TIBS) in patients with malignant biliary obstruction complicated by massive ascites with or without coagulopathy. METHODS: From March 2012 to December 2017, a total of 12 consecutive patients with malignant biliary obstructions treated with TIBS were enrolled in this study. Five patients had jaundice and cholangitis, while seven had jaundice only. Clinical parameters including technical and clinical success rates and complications following TIBS were evaluated. Overall survival and stent occlusion-free survival were assessed using Kaplan-Meier analysis. RESULTS: The indications for transjugular approach were massive ascites with (n=2) or without (n=10) coagulopathy. TIBS was technically successful in 11 of 12 patients. Clinical success was defined as successful internal drainage and was achieved in eight patients. The mean serum bilirubin level was initially 13.9±6.3 mg/dL and decreased to 4.9±5.3 mg/dL within 1 month after stent placement (P = 0.037). Two patients had procedure-related complications (hemobilia). During the follow-up period (mean, 30 days; range, 1-146 days), all 12 patients died of disease progression. The median overall survival and stent occlusion-free survival times were 19 days (95% confidence interval [CI], 16-22 days) and 19 days (95% CI, 12-26 days), respectively. There was no stent dysfunction in the eight patients that had successful internal drainage. CONCLUSION: TIBS appears to be safe, technically feasible, and clinically effective for patients with malignant biliary obstruction complicated by massive ascites with or without coagulopathy.


Assuntos
Ascite/etiologia , Neoplasias dos Ductos Biliares/patologia , Colestase/complicações , Stents/efeitos adversos , Adulto , Idoso , Neoplasias dos Ductos Biliares/mortalidade , Sistema Biliar/patologia , Colangite/etiologia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
7.
Am J Physiol Gastrointest Liver Physiol ; 317(6): G773-G783, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31604030

RESUMO

The CXC chemokine receptor 2 (CXCR2) is critical for neutrophil recruitment and hepatocellular viability but has not been studied in the context of cholestatic liver injury following bile duct ligation (BDL). The present study sought to elucidate the cell-specific roles of CXCR2 on acute liver injury after BDL. Wild-type and CXCR2-/- mice were subjected BDL. CXCR2 chimeric mice were created to assess the cell-specific role of CXCR2 on liver injury after BDL. SB225002, a selective CXCR2 antagonist, was administrated intraperitoneally after BDL to investigate the potential of pharmacological inhibition. CXCR2-/- mice had significantly less liver injury than wild-type mice at 3 and 14 days after BDL. There was no difference in biliary fibrosis among groups. The chemokines CXCL1 and CXCL2 were induced around areas of necrosis and biliary structures, respectively, both areas where neutrophils accumulated after BDL. CXCR2-/- mice showed significantly less neutrophil accumulation in those injured areas. CXCR2Liver+/Myeloid+ and CXCR2Liver-/Myeloid- mice recapitulated the wild-type and CXCR2-knockout phenotypes, respectively. CXCR2Liver+/Myeloid+ mice suffered higher liver injury than CXCR2Liver+/Myeloid- and CXCR2Liver-/Myeloid+; however, only those chimeras with knockout of myeloid CXCR2 (CXCR2Liver+/Myeloid- and CXCR2Liver-/Myeloid-) showed reduction of neutrophil accumulation around areas of necrosis. Daily administration of SB225002 starting after 3 days of BDL reduced established liver injury at 6 days. In conclusion, neutrophil CXCR2 guides the cell to the site of injury, while CXCR2 on liver cells affects liver damage independent of neutrophil accumulation. CXCR2 appears to be a viable therapeutic target for cholestatic liver injury.NEW & NOTEWORTHY This study is the first to reveal cell-specific roles of the chemokine receptor CXCR2 in cholestatic liver injury caused by bile duct ligation. CXCR2 on neutrophils facilitates neutrophil recruitment to the liver, while CXCR2 on liver cells contributes to liver damage independent of neutrophils. CXCR2 may represent a viable therapeutic target for cholestatic liver injury.


Assuntos
Movimento Celular/efeitos dos fármacos , Fígado , Neutrófilos/fisiologia , Compostos de Fenilureia/farmacologia , Receptores de Interleucina-8B , Animais , Inibição de Migração Celular , Quimiocina CXCL1/metabolismo , Quimiocina CXCL2/metabolismo , Colestase/complicações , Modelos Animais de Doenças , Infarto Hepático/tratamento farmacológico , Infarto Hepático/etiologia , Infarto Hepático/metabolismo , Fígado/metabolismo , Fígado/patologia , Camundongos , Necrose , Substâncias Protetoras/farmacologia , Receptores de Interleucina-8B/antagonistas & inibidores , Receptores de Interleucina-8B/metabolismo
8.
Int J Mol Sci ; 20(17)2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31455001

RESUMO

The purpose of this study was to investigate whether Ger-Gen-Chyn-Lian-Tang (GGCLT) suppresses oxidative stress, inflammation, and angiogenesis during experimental liver fibrosis through the hypoxia-inducible factor-1α (HIF-1α)-mediated pathway. Male C57BL/6 mice were randomly assigned to a sham-control or bile duct ligation (BDL) group with or without treatment with GGCLT at 30, 100, and 300 mg/kg. Plasma alanine aminotransferase (ALT) levels were analyzed using a diagnostic kit. Liver histopathology and hepatic status parameters were measured. Compared to control mice, the BDL mice exhibited an enlargement in liver HIF-1α levels, which was suppressed by 100 and 300 mg/kg GGCLT treatments (control: BDL: BDL + GGCLT-100: BDL + GGCLT-300 = 0.95 ± 0.07: 1.95 ± 0.12: 1.43 ± 0.05: 1.12 ± 0.10 fold; p < 0.05). GGCLT restrained the induction of hepatic hydroxyproline and malondialdehyde levels in the mice challenged with BDL, further increasing the hepatic glutathione levels. Furthermore, in response to increased hepatic inflammation and fibrogenesis, significant levels of ALT, nuclear factor kappa B, transforming growth factor-ß, α-smooth muscle actin, matrix metalloproteinase-2 (MMP-2), MMP-9, and procollagen-III were found in BDL mice, which were attenuated with GGCLT. In addition, GGCLT reduced the induction of angiogenesis in the liver after BDL by inhibiting vascular endothelial growth factor (VEGF) and VEGF receptors 1 and 2. In conclusion, the anti-liver fibrosis effect of GGCLT, which suppresses hepatic oxidative stress and angiogenesis, may be dependent on an HIF-1α-mediated pathway.


Assuntos
Colestase/complicações , Medicamentos de Ervas Chinesas/farmacologia , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Animais , Biomarcadores , Biópsia , Colestase/patologia , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Masculino , Camundongos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Resultado do Tratamento
9.
BMC Med Genet ; 20(1): 123, 2019 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-31296176

RESUMO

BACKGROUND: Niemann-Pick disease type C (NP-C) is an inherited neurodegenerative disease (1 per 100 000 newborns) caused by NPC proteins impairment that leads to unesterified cholesterol accumulation in late endosomal/lysosomal compartments. To date the NP-C diagnostics is usually based on cholesterol detection in fibroblasts using an invasive and time-consuming Filipin staining and we need more arguments to widely introduce oxysterols as a biomarkers in NP-C. METHODS: Insofar as NP-C represents about 8% of all infant cholestases, in this prospective observational study we tried to re-assess the specificity plasma oxysterol and chitotriosidase as a biochemical screening markers of NP-C in children with cholestasis syndrome of unknown origin. For 108 patients (aged from 2 weeks to 7 years) the levels of cholestane-3ß,5α,6ß-triol (C-triol) and chitotriosidase (ChT) were measured. For patients with elevated C-triol and/or ChT the NPC1 and NPC2 genes were Sanger-sequenced and 47 additional genes (from the custom liver damage panel) were NGS-sequenced. RESULTS: Increased C-triol level (> 50 ng/ml) was detected in 4 (of 108) infants with cholestasis syndrome of unknown origin, with following molecular genetic NP-C diagnosis for one patient. Plasma cholesterol significantly correlates with C-triol (p < 0.05). NGS of high C-triol infants identified three patients with mutations in JAG1 (Alagille syndrome) and ABCB11 (Byler disease) genes. Increased ChT activity was detected in 8 (of 108) patients with various aetiologies, including NP-C, Byler disease and biliary atresia. CONCLUSION: Combined analysis of ChT activity and C-triol levels is an effective method for identifying NP-C.


Assuntos
Colestase/complicações , Hexosaminidases/sangue , Doença de Niemann-Pick Tipo C/diagnóstico , Doença de Niemann-Pick Tipo C/genética , Oxisteróis/sangue , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/genética , Síndrome de Alagille/genética , Aminoacil-tRNA Sintetases/genética , Atresia Biliar/genética , Biomarcadores/sangue , Proteínas de Transporte/genética , Criança , Pré-Escolar , Colestase Intra-Hepática/genética , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Glicoproteínas/genética , Hexosaminidases/metabolismo , Humanos , Lactente , Recém-Nascido , Proteína Jagged-1/genética , Fígado , Masculino , Glicoproteínas de Membrana/genética , Mutação , Doenças Neurodegenerativas , Oxisteróis/metabolismo , Estudos Prospectivos , Sensibilidade e Especificidade
10.
Transplant Proc ; 51(6): 1939-1945, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303414

RESUMO

AIMS: Our aim was to review the rate of biliary duct stones (BDS) after liver transplantation (LT), risk factors, and treatments, and to identify predictive factors for their onset. METHODS: LTs performed in our center from 2004 to 2014 were studied. Risk factors for the onset of BDS were identified using univariable Cox's proportional hazards models. RESULTS: Three hundred and sixty-four grafts with 317 duct-to-duct end-to-end biliary anastomosis on a T-tube and 47 hepaticojejunal anastomosis (HJ) were analyzed. BDS were identified in 13 of 364 (3.5%) grafts, including 10 duct-to-duct end-to-end biliary anastomosis on a T-tube grafts (3.2%) and 3 HJ grafts (6.4%). Predictive factors for BDS were biliary strictures (hazard ratio [HR] 9.94; 95% confidence interval [95% CI] 3.25-30.4), bilirubin (HR 1.04; 95% CI 1.01-1.06, for 1 unit increase), Model for End-Stage Liver Disease score (HR 1.07; 95% CI 1.01-1.14, for 1 unit increase), surgery time (HR 1.04; 95% CI 1.01-1.08, for 10-minute increase), hepatocellular disease (HR 8.3; 95% CI 1.09-64.0), hepatic artery thrombosis (HR 6.71; 95% CI 1.47-30.6), and retransplantation (HR 3.69; 95% CI 1.02-13.43). Among 51 grafts (14%) with biliary strictures, female sex was identified as a risk factor for BDS (HR 5.19; 95% CI 1.29-20.98). Multimodality treatment of BDS was often successful but open surgery was still needed in 23% of them. One-, 5-, and 10-year graft survival was not influenced by the onset of BDS. CONCLUSION: Main predictive factor for BDS in liver grafts is biliary stricture. Recipient's age and body mass index failed to show any statistical importance. In grafts with biliary strictures, female sex is the main risk factor for BDS. In the absence of biliary strictures, hepatic artery thrombosis lead to an increase in the risk of BDS. Multimodality treatment of BDS is often successful. BDS do not influence outcome.


Assuntos
Ductos Biliares/cirurgia , Cálculos Biliares/etiologia , Jejuno/cirurgia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/etiologia , Adolescente , Adulto , Anastomose Cirúrgica/efeitos adversos , Morte Encefálica , Colestase/complicações , Feminino , Cálculos Biliares/terapia , Sobrevivência de Enxerto , Humanos , Hepatopatias/complicações , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/terapia , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
11.
Dis Model Mech ; 12(7)2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31262748

RESUMO

Insulin receptor substrate 2 (IRS2) is a key downstream mediator of insulin and insulin-like growth factor 1 (IGF1) signalling pathways and plays a major role in liver metabolism. The aim of this study was to investigate whether IRS2 had an impact on the hepatic fibrotic process associated with cholestatic injury. Bile duct ligation (BDL) was performed in wild-type (WT) and Irs2-deficient (IRS2KO) female mice. Histological and biochemical analyses, together with fibrogenic and inflammatory responses were evaluated in livers from mice at 3, 7 and 28 days following BDL. We also explored whether activation of human hepatic stellate cells (HSCs) induced by IGF1 was modulated by IRS2. IRS2KO mice displayed reduced disruption of liver histology, such hepatocyte damage and excess deposition of extracellular matrix components, compared with WT mice at 3 and 7 days post-BDL. However, no histological differences between genotypes were found at 28 days post-BDL. The less pro-inflammatory profile of bile acids accumulated in the gallbladder of IRS2KO mice after BDL corresponded with the reduced expression of pro-inflammatory markers in these mice. Stable silencing of IRS2 or inhibition of ERK1/2 reduced the activation of human LX2 cells and also reduced induction of MMP9 upon IGF1 stimulation. Furthermore, hepatic MMP9 expression was strongly induced after BDL in WT mice, but only a slight increase was found in mice lacking IRS2. Our results have unravelled the signalling pathway mediated by IGF1R-IRS2-ERK1/2-MMP9 as a key axis in regulating HSC activation, which might be therapeutically relevant for targeting liver fibrosis.


Assuntos
Colestase/complicações , Proteínas Substratos do Receptor de Insulina/genética , Cirrose Hepática/genética , Animais , Ductos Biliares/patologia , Linhagem Celular , Colestase/patologia , Feminino , Células Estreladas do Fígado/patologia , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Camundongos , Camundongos Knockout , Transdução de Sinais
15.
Gastrointest. endosc ; 89(6): [1075­1105], June 2019.
Artigo em Inglês | BIGG | ID: biblio-1094991

RESUMO

Each year choledocholithiasis results in biliary obstruction, cholangitis, and pancreatitis in a significant number of patients. The primary treatment, ERCP, is minimally invasive but associated with adverse events in 6% to 15%. This American Society for Gastrointestinal Endoscopy (ASGE) Standard of Practice (SOP) Guideline provides evidence-based recommendations for the endoscopic evaluation and treatment of choledocholithiasis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to rigorously review and synthesize the contemporary literature regarding the following topics: EUS versus MRCP for diagnosis, the role of early ERCP in gallstone pancreatitis, endoscopic papillary dilation after sphincterotomy versus sphincterotomy alone for large bile duct stones, and impact of ERCP-guided intraductal therapy for large and difficult choledocholithiasis. Comprehensive systematic reviews were also performed to assess the following: same-admission cholecystectomy for gallstone pancreatitis, clinical predictors of choledocholithiasis, optimal timing of ERCP vis-à-vis cholecystectomy, management of Mirizzi syndrome and hepatolithiasis, and biliary stent therapy for choledocholithiasis. Core clinical questions were derived using an iterative process by the ASGE SOP Committee. This body developed all recommendations founded on the certainty of the evidence, balance of risks and harms, consideration of stakeholder preferences, resource utilization, and cost-effectiveness.


Assuntos
Humanos , Coledocolitíase/complicações , Coledocolitíase/diagnóstico , Endoscopia/enfermagem , Endoscopia/instrumentação , Endoscopia/métodos , Pancreatite/complicações , Colestase/complicações
16.
Proc Natl Acad Sci U S A ; 116(21): 10525-10530, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31068464

RESUMO

Patients suffering from cholestasis, the slowing or stoppage of bile flow, commonly report experiencing an intense, chronic itch. Numerous pruritogens are up-regulated in cholestatic patient sera, including bile acids (BAs). Acute injection of BAs results in itch in both mice and humans, and BA-modulating therapy is effective in controlling patient itch. Here, we present evidence that human sensory neuron-expressed Mas-related G protein-coupled receptor X4 (MRGPRX4), an orphan member of the Mrgpr family of GPCRs, is a BA receptor. Using Ca2+ imaging, we determined that pathophysiologically relevant levels of numerous BAs activated MRGPRX4. No mouse Mrgpr orthologs were activated by BAs. To assess the in vivo relevance of BA activation of MRGPRX4, we generated a humanized mouse with targeted expression of MRGPRX4 in itch-encoding sensory neurons. BAs activated MRGPRX4+ sensory neurons at higher levels compared with WT neurons. Compared with control animals, MRGPRX4+ mice scratched more upon acute injection of BAs and in a model of cholestatic itch. Overall, these data suggest that targeting MRGPRX4 is a promising strategy for alleviating cholestatic itch.


Assuntos
Ácidos e Sais Biliares/metabolismo , Colestase/complicações , Prurido/etiologia , Receptores Acoplados a Proteínas-G/metabolismo , Células Receptoras Sensoriais/metabolismo , Animais , Colestase/metabolismo , Humanos , Camundongos , Prurido/metabolismo
17.
J Am Acad Dermatol ; 81(6): 1371-1378, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31009666

RESUMO

Patients suffering from cholestasis often report experiencing a debilitating, unrelenting itch. In contrast to conditions, such as urticaria, in which histamine primarily drives itch (pruritus), cholestatic pruritus is multifactorial and more difficult to treat. Existing therapies are not always effective and have undesirable adverse effect profiles. Here, we conducted a systematic literature review to evaluate conventional treatment strategy, current pathophysiologic understanding, and the role of new therapies in the context of cholestatic pruritus. We discuss novel findings implicating bile acids, lysophosphatidic acid, and bilirubin as potential important mediators of cholestatic itch. New therapies that aim to remove or modulate pruritogens have been supported in observational cohort studies and randomized controlled trials. Although these new therapies show promise, further research is needed to confirm the pathophysiology of cholestatic pruritus so that targeted therapy can be developed.


Assuntos
Colestase/complicações , Prurido/etiologia , Prurido/terapia , Humanos
18.
Rev Recent Clin Trials ; 14(3): 217-223, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30919782

RESUMO

BACKGROUND: Pruritus is one of the most common and disabling symptoms of liver disease such as Primary Sclerosing Cholangitis and Primary Biliary Cholangitis. Cholestyramine, rifampin, opioid antagonists, antihistaminic agents and SSRIs are used for the management of pruritus. Due to rifampin drug interactions as well as its serious side effects such as hepatotoxicity, clinicians are endeavoruing to find a safer and a more effective substitution. OBJECTIVE: The purpose of this study was to compare the efficacy and safety of sertraline with rifampin in the management of cholestatic pruritus. METHODS: In a single-blinded randomized clinical trial a total of 36 patients of PSC and PBC were divided into two equal groups, one group received 100 mg/day sertraline and the other group received rifampin 300 mg/day for 4 weeks. Visual analog scale was used to record pruritus severity at baseline and 4 weeks after drug intervention, also, ALT, AST, ALP and total bilirubin of all patients were measured at three different time points. RESULTS: Over the follow-up period, pruritus had relieved in both groups, but there was no significant differences between sertraline and rifampin in pruritus management (pvalue=0.740), also there was no significant difference between the two intervention strategies (A versus B) in total bilirubin level (pvalue=0.106). Moreover, the ALT, AST and ALP levels were found to be significantly different between the two groups (Pvalue˂0.01). CONCLUSION: There is no difference between sertraline and rifampin in pruritus improvement, but sertraline has less adverse effects on hepatobiliary enzyme levels, so it seems to be safer than rifampin.


Assuntos
Antibacterianos/uso terapêutico , Colestase/complicações , Prurido/tratamento farmacológico , Rifampina/uso terapêutico , Inibidores de Captação de Serotonina/uso terapêutico , Sertralina/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prurido/etiologia , Método Simples-Cego , Resultado do Tratamento
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