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OBJECTIVE: Follow established management guidelines from the ACR and improve adherence to follow-up recommendations for incidental liver lesions (ILLs) for all patients undergoing CT abdomen and pelvis with contrast (CTAPw) examinations, with advocacy from a multidisciplinary care team. METHODS: A mandatory structured radiology reporting module was developed for use in CTAPw reports for ILL recommendations. Data from the electronic medical record describing patients with radiology-reported ILLs and their clinical risk diagnosis categories were tabulated in a queryable electronic database. A nurse co-ordinator initiated workflow to communicate the need for ILL follow-up MRI to ordering physicians and primary care providers. MRIs were ordered by the ILL team. An interactive process was undertaken with continuous review to improve identification of eligible patients and adherence to recommendations. RESULTS: During the initial launch phase from December 2020 to March 2021, 1,577 ILLs were detected on 20,667 CTAPw examinations, and for those with the characterize now recommendation, 36 of 114 (31.6%) received follow-up in 30 days. Between January 2021 and June 2022, 117,520 CTAPws were performed and 4,371 ILLs were detected. Using the ILL workflow, in the MRI now cohort, follow-up occurred within 30 days in 202 of 542 (36.2%) patients, and a total of 368 of 542 (67.9%) patients have completed their follow-up to date. DISCUSSION: Using a focused effort to close a gap in ILL care, adherence to follow-up recommendations improved over the long term, although there remains a gap in adherence to short-term interventions. A multidisciplinary approach, radiology reporting, and software solutions were leveraged to improve a complex process.
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Achados Incidentais , Neoplasias Hepáticas , Humanos , Fluxo de Trabalho , Seguimentos , Tomografia Computadorizada por Raios X , Neoplasias Hepáticas/diagnóstico por imagemRESUMO
Venous thromboembolism (VTE) occurs in 0.4% to 15.5% and bleeding occurs in 20% to 35% of patients after liver transplantation (LT). Balancing the risk of bleeding from therapeutic anticoagulation and risk of thrombosis in the postoperative period is challenging. Little evidence exists regarding the best treatment strategy for these patients. We hypothesized that a subset of LT patients who develop postoperative deep vein thromboses (DVTs) could be managed without therapeutic anticoagulation. We implemented a quality improvement (QI) initiative using a standardized Doppler ultrasound-based VTE risk stratification algorithm to guide parsimonious implementation of therapeutic anticoagulation with heparin drip. Methods: In a prospective management QI initiative for DVT management, we compared 87 LT historical patients (control group; January 2016-December 2017) to 182 LT patients (study group; January 2018-March 2021). We analyzed the rates of immediate therapeutic anticoagulation after DVT diagnosis within 14 d of LT, clinically significant bleeding, return to the operating room, readmission, pulmonary embolism, and death within 30 d of LT before and after the QI initiative. Results: Ten patients (11.5%) in the control group and 23 patients (12.6%; P = 0.9) in the study group developed DVTs after LT. Immediate therapeutic anticoagulation was used in 7 of 10 and 5 of 23 patients in the control and study groups, respectively (P = 0.024). The study group had lower odds of receiving immediate therapeutic anticoagulation after VTE (21.7% versus 70%; odds ratio = 0.12; 95% confidence interval, 0.019-0.587; P = 0.013) and a lower rate of postoperative bleeding (8.7% versus 40%; odds ratio = 0.14, 95% confidence interval, 0.02-0.91; P = 0.048). All other outcomes were similar. Conclusions: Implementing a risk-stratified VTE treatment algorithm for immediate post-LT patients appears to be safe and feasible. We observed a decrease in the use of therapeutic anticoagulation and a lower rate of postoperative bleeding without adverse impacts on early outcomes.
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UNLABELLED: Between March 2000 and July 2001, at least 99 persons acquired a hepatitis C virus genotype 3a (HCV-3a) infection in an oncology clinic. This nosocomial HCV outbreak provided an opportunity to examine the subsequent clinical course in a well-defined cohort. This was a retrospective/prospective observational study of the short-term significant health outcomes of a large, single-source, patient-to-patient HCV-3a outbreak. Outbreak patients or their legal representatives consenting to study were enrolled between September 2002 and December 2007. We measured history and physical examinations, medical records, HCV serology, HCV RNA and genotype, liver enzymes, histology, response to antiviral therapy, and liver-related morbidity and mortality. Sixty-four of the 99 known HCV-3a outbreak patients participated. During a 6-year period, six patients developed life-threatening complications from liver disease, three died, one received a liver transplant, and two were stable after esophageal variceal banding or diuretic therapy of ascites. Thirty-three patients underwent antiviral therapy, with 28 achieving a sustained viral remission. One patient acquired HCV-3a infection sexually from an outbreak patient and was successfully treated. Eleven study patients died of malignancy, including two that had achieved a sustained viral remission after antiviral therapy. CONCLUSION: Our patient cohort had a nosocomial source and an oncologic or hematologic comorbidity. Compared with previous HCV outcome studies, a patient-to-patient HCV outbreak in an oncology clinic exhibited significant morbidity and mortality. Attention is needed to the public health risk of nosocomial HCV transmission, emphasizing infection control, early diagnosis, and therapy.
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Infecção Hospitalar/complicações , Surtos de Doenças , Hepatite C/complicações , Fígado/patologia , Neoplasias/complicações , RNA Viral/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Antivirais/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/mortalidade , Infecção Hospitalar/virologia , Feminino , Genótipo , Hepatite C/tratamento farmacológico , Hepatite C/genética , Hepatite C/mortalidade , Anticorpos Anti-Hepatite C/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Nebraska/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: In the United States, 5% of adult liver transplant recipients receive a graft donation after circulatory determination of death (DCDD). Concerns for ischemic cholangiopathy (IC), a disease of diffuse intrahepatic stricturing limits broader DCDD use. Single-center reports demonstrate large variation in outcomes. METHODS: Retrospective deidentified data collected between 2005 and 2013 were entered electronically by 10 centers via a Research Electronic Data Capture database. Our primary outcome was development of intrahepatic biliary strictures consistent with IC. RESULTS: Within 6 months post-DCDD transplant, 162 (21.8%) patients developed a biliary stricture, of which 88 (11.8%) exhibited intrahepatic structuring consistent with IC. Unadjusted 6-month IC rate among the 10 centers varied significantly (P = 0.006) from 6.3% to 25.9%. The only factor associated with increased risk of IC within 6 months was Roux-en-Y hepaticojejunostomy (vs duct-to-duct) (odds ratio, 3.06; 95% confidence interval, 1.52-6.16; P = 0.002). Graft failure by 6 months was more than 3 times higher for DCDD recipients with IC (odds ratio for IC, 3.36; 95% confidence interval, 1.95-5.79). CONCLUSIONS: This first report of the large combined experience with DCDD from the Improving DCDD Outcomes in Liver Transplant consortium demonstrates significant differences in IC among centers, the importance of biliary strictures as a risk factor for graft failure, and does not validate other risk factors for IC found in smaller studies.
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Doenças dos Ductos Biliares/etiologia , Ductos Biliares Intra-Hepáticos/irrigação sanguínea , Seleção do Doador/métodos , Isquemia/etiologia , Transplante de Fígado/métodos , Complicações Pós-Operatórias/etiologia , Doadores de Tecidos , Adulto , Idoso , Causas de Morte , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Fatores de Risco , Estados UnidosRESUMO
Cholestasis of sepsis is a form of hepatocellular cholestasis that occurs as a result of sepsis. Usually, prior to the development of cholestasis, the manifestations of sepsis dominate the clinical picture. The occurrence of cholestasis is without direct bacterial involvement of the biliary system and appears to be mediated systemically by pro-inflammatory cytokines. These cytokines are released in response to the vigorous inflammatory reaction mediated by endotoxinaemia and bacterial wall lipopolysaccharides. The principal cytokines involved are the pro-inflammatory tumour necrosis factor-alpha (TNF-alpha), interleukin (IL) 1-beta and IL-6. Interplay between these cytokines and a series of hepatocyte membrane transporters appears to result in the cholestasis. Management principles focus upon the control of sepsis.
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Colestase Intra-Hepática/etiologia , Colestase Intra-Hepática/fisiopatologia , Estado Terminal , Sepse/complicações , Sepse/fisiopatologia , Colestase Intra-Hepática/terapia , Humanos , Padrões de Prática Médica , Sepse/terapiaRESUMO
The retinoid-related orphan receptors (RORs) were postulated to have functions in tissue development and circadian rhythm. In this study, we revealed a novel function of RORα (NR1F1) and RORγ (NR1F3) in regulating the human hydroxysteroid sulfotransferase (SULT2A1), a phase II conjugating enzyme known to sulfonate bile acids, hydroxysteroid dehydroepiandrosterone, and related androgens. A combination of promoter reporter gene assay and EMSA and chromatin immunoprecipitation (ChIP) assays showed that both RORα and RORγ transactivated the SULT2A1 gene promoter through their binding to a ROR response element found in the SULT2A1 gene promoter. Interestingly, this ROR response element overlaps with a previously reported constitutive androstane receptor response element on the same promoter. Down-regulation of RORα and/or RORγ by small interfering RNA inhibited the expression of endogenous SULT2A1. In primary human hepatocytes and human livers, we found a positive correlation between the expression of SULT2A1 and RORs, which further supported the regulation of SULT2A1 by RORs. We also found that the expression of RORα and RORγ was impaired in several liver disease conditions, such as steatosis/steatohepatitis, fibrosis, and hepatocellular carcinoma. The positive regulation of human SULT2A1 by RORs is opposite to the negative regulation of Sult2a1 by RORs in rodents. In summary, our results established SULT2A1 as a novel ROR target gene. The expression of RORs is a potential predictor for the expression of SULT2A1 as well as disease conditions.
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Hepatopatias/metabolismo , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Sulfotransferases/genética , Animais , Sequência de Bases , Receptor Constitutivo de Androstano , Indução Enzimática , Feminino , Genes Reporter , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Fígado/patologia , Luciferases/biossíntese , Luciferases/genética , Masculino , Camundongos , Cultura Primária de Células , Regiões Promotoras Genéticas , Ligação Proteica , Receptores Citoplasmáticos e Nucleares/metabolismo , Elementos de Resposta , Sulfotransferases/metabolismoRESUMO
AIMS: The nuclear receptor liver X receptor-α (LXRα) stimulates lipogenesis, leading to steatosis. Nuclear factor erythroid-2-related factor-2 (Nrf2) contributes to cellular defense mechanism by upregulating antioxidant genes, and may protect the liver from injury inflicted by fat accumulation. However, whether Nrf2 affects LXRα activity is unknown. This study investigated the inhibitory role of Nrf2 in hepatic LXRα activity and the molecular basis. RESULTS: A deficiency of Nrf2 enhanced the ability of LXRα agonist to promote hepatic steatosis, as mediated by lipogenic gene induction. In hepatocytes, Nrf2 overexpression repressed gene transactivation by LXR-binding site activation. Consistently, treatment of mice with sulforaphane (an Nrf2 activator) suppressed T0901317-induced lipogenesis, as confirmed by the experiments using hepatocytes. Nrf2 activation promoted deacetylation of farnesoid X receptor (FXR) by competing for p300, leading to FXR-dependent induction of small heterodimer partner (SHP), which was responsible for the repression of LXRα-dependent gene transcription. In human steatotic samples, the transcript levels of LXRα and SREBP-1 inversely correlated with those of Nrf2, FXR, and SHP. INNOVATION: Our findings offer the mechanism to explain how decrease in Nrf2 activity in hepatic steatosis could contribute to the progression of NAFLD, providing the use of Nrf2 as a molecular biomarker to diagnose NAFLD. As certain antioxidants have the abilities to activate Nrf2, clinicians might utilize the activators of Nrf2 as a new therapeutic approach to prevent and/or treat NAFLD. CONCLUSION: Nrf2 activation inhibits LXRα activity and LXRα-dependent liver steatosis by competing with FXR for p300, causing FXR activation and FXR-mediated SHP induction. Our findings provide important information on a strategy to prevent and/or treat steatosis.
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Acetilesterase/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Receptores Nucleares Órfãos/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Acetilesterase/genética , Animais , Western Blotting , Imunoprecipitação da Cromatina , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/metabolismo , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Hidrocarbonetos Fluorados/farmacologia , Imunoprecipitação , Isotiocianatos , Lipogênese/efeitos dos fármacos , Lipogênese/genética , Receptores X do Fígado , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 2 Relacionado a NF-E2/genética , Receptores Nucleares Órfãos/agonistas , Ligação Proteica/efeitos dos fármacos , Reação em Cadeia da Polimerase em Tempo Real , Receptores Citoplasmáticos e Nucleares/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Sulfonamidas/farmacologia , Sulfóxidos , Tiocianatos/farmacologiaRESUMO
The syndrome of multiple intestinal atresia with immunodeficiency is a rare, invariably fatal congenital disorder. At 16 months of age, a child with this syndrome underwent liver-small bowel transplantation from a 1-of-6 HLA-matched donor. He acquired full enteral tolerance and normal liver function and has never shown evidence of allograft rejection. After mild graft-versus-host disease developed, studies revealed that more than 99% of his CD3(+) lymphocytes and 50% of his CD19(+) lymphocytes were of donor origin, whereas granulocytes and monocytes remained of recipient origin. He synthesizes polyclonal immunoglobulin G (IgG), IgA, and IgM and has developed antibodies to cytomegalovirus (CMV) and parainfluenza 3. His T lymphocytes are predominately CD3(+)CD4(-)CD8(-) with T-cell receptor gammadelta heterodimers and CD3(+)CD4(-)CD8(+) with CD8alphaalpha homodimers, populations consistent with an intraepithelial lymphocyte phenotypic profile. We postulate that he has engrafted a donor intestine-derived immune system and is incapable of rejecting his engrafted organs.