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1.
Expert Rev Respir Med ; 18(5): 269-281, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38962827

RESUMO

INTRODUCTION: Cystic fibrosis (CF)-associated liver disease can significantly affect the quality of life and survival of people with CF. The hepatobiliary manifestations in CF are various, with focal/multilobular biliary cirrhosis more common in children and porto-sinusoidal vascular disease (PSVD) in young adults. Portal hypertensive complications, particularly bleeding from esophagogastric varices and hypersplenism are common, while liver failure is rarer and mainly linked to biliary disease. AREAS COVERED: This review explores current therapeutic options for CF-associated liver disease, presenting ongoing studies and new insights into parthenogenesis for potential future therapies. EXPERT OPINION: Monitoring for signs of portal hypertension is essential. Limited evidence supports ursodeoxycholic acid (UDCA) efficacy in halting CF liver disease progression. The effect of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on liver outcomes lacks definitive data, since patients with CF-related liver disease were excluded from trials due to potential hepatotoxicity. A proposed approach involves using UDCA and modulators in early stages, along with anti-inflammatory agents, with further therapeutic strategies awaiting randomized trials. Prevention of portal hypertensive bleeding includes endoscopic sclerotherapy or ligation of esophageal varices. Nonselective beta-blockers may also prevent bleeding and could be cautiously implemented. Other non-etiological treatments require investigation.


Assuntos
Fibrose Cística , Hipertensão Portal , Humanos , Hipertensão Portal/fisiopatologia , Hipertensão Portal/tratamento farmacológico , Hipertensão Portal/etiologia , Fibrose Cística/complicações , Fibrose Cística/fisiopatologia , Fibrose Cística/tratamento farmacológico , Ácido Ursodesoxicólico/uso terapêutico , Hepatopatias/fisiopatologia , Hepatopatias/terapia , Hepatopatias/tratamento farmacológico , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/terapia , Varizes Esofágicas e Gástricas/fisiopatologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Qualidade de Vida , Progressão da Doença
2.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(6): 656-659, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38991968

RESUMO

Infection is a common medical problem at present. Different pathogens can lead to different infections. Severe infections can ultimately lead to sepsis, resulting in multiple organ dysfunction and the high mortality of patients. Therefore, studying the occurrence and development of severe infections is essential to improve the survival rate of patients. More and more studies have revealed the important role of connection between intestine and liver in infectious diseases. The maintenance of intestinal mechanical barrier and biological barrier function and the regulation of intestinal flora metabolites can reduce infectious liver injury. Bile acids are important metabolites in the liver, which can inhibit the progression of certain infectious intestinal injuries and promote intestinal damage caused by certain pathogens. In this article, the mechanism of action of the intestinal-liver axis in infection was reviewed to find a new target for the treatment of clinical infection.


Assuntos
Intestinos , Fígado , Humanos , Fígado/metabolismo , Ácidos e Sais Biliares/metabolismo , Hepatopatias/metabolismo , Hepatopatias/etiologia , Mucosa Intestinal/metabolismo , Microbioma Gastrointestinal
3.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(6): 660-663, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38991969

RESUMO

Sepsis-associated liver injury (SALI) is a common complication of sepsis, which is characterized by systemic immune disorders induced by sepsis leading to liver damage. Currently, there are no effective treatments for SALI, which is related to its complex pathophysiological mechanisms. In recent years, the disorder of intestinal environment after sepsis has been considered as an important factor for SALI, but the specific molecular mechanism of the above process is still unclear. This article will review the pathological role and molecular mechanisms between intestinal environmental disturbance and SALI, aiming to analyze the potential research direction of SALI and identify potential therapeutic targets for its treatment.


Assuntos
Sepse , Humanos , Sepse/complicações , Sepse/etiologia , Sepse/fisiopatologia , Hepatopatias/etiologia , Intestinos/lesões , Animais , Microbioma Gastrointestinal
4.
Commun Biol ; 7(1): 849, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992061

RESUMO

Hereditary fructose intolerance (HFI) is a painful and potentially lethal genetic disease caused by a mutation in aldolase B resulting in accumulation of fructose-1-phosphate (F1P). No cure exists for HFI and treatment is limited to avoid exposure to fructose and sugar. Using aldolase B deficient mice, here we identify a yet unrecognized metabolic event activated in HFI and associated with the progression of the disease. Besides the accumulation of F1P, here we show that the activation of the purine degradation pathway is a common feature in aldolase B deficient mice exposed to fructose. The purine degradation pathway is a metabolic route initiated by adenosine monophosphate deaminase 2 (AMPD2) that regulates overall energy balance. We demonstrate that very low amounts of fructose are sufficient to activate AMPD2 in these mice via a phosphate trap. While blocking AMPD2 do not impact F1P accumulation and the risk of hypoglycemia, its deletion in hepatocytes markedly improves the metabolic dysregulation induced by fructose and corrects fat and glycogen storage while significantly increasing the voluntary tolerance of these mice to fructose. In summary, we provide evidence for a critical pathway activated in HFI that could be targeted to improve the metabolic consequences associated with fructose consumption.


Assuntos
AMP Desaminase , Intolerância à Frutose , Frutose-Bifosfato Aldolase , Frutose , Animais , Intolerância à Frutose/metabolismo , Intolerância à Frutose/genética , Camundongos , AMP Desaminase/genética , AMP Desaminase/metabolismo , Frutose-Bifosfato Aldolase/metabolismo , Frutose-Bifosfato Aldolase/genética , Frutose/metabolismo , Hepatopatias/metabolismo , Hepatopatias/etiologia , Hepatopatias/genética , Masculino , Camundongos Knockout , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Fígado/metabolismo , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Frutosefosfatos/metabolismo
5.
Pharmacol Res Perspect ; 12(4): e1213, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38993008

RESUMO

This phase 1, open-label, three-arm study (NCT05098054) compared the pharmacokinetics and safety of soticlestat (TAK-935) in participants with hepatic impairment. Participants aged ≥18 to <75 years had moderate (Child-Pugh B) or mild (Child-Pugh A) hepatic impairment or normal hepatic function (matched to hepatic-impaired participants by sex, age, and body mass index). Soticlestat was administered as a single oral 300 mg dose. Pharmacokinetic parameters of soticlestat and its metabolites TAK-935-G (M3) and M-I were assessed and compared by group. The incidence of treatment-emergent adverse events (TEAEs) and other safety parameters were also monitored. The pharmacokinetic analyses comprised 35 participants. Participants with moderate hepatic impairment had lower proportions of bound and higher proportions of unbound soticlestat than participants with mild hepatic impairment and normal hepatic function. Total plasma soticlestat pharmacokinetic parameters (maximum observed concentration [Cmax], area under the concentration-time curve from time 0 to time of last quantifiable concentration [AUClast], and AUC from time 0 to infinity [AUC∞]) were approximately 115%, 216%, and 199% higher with moderate and approximately 45%, 35%, and 30% higher with mild hepatic impairment, respectively, than healthy matched participants. Moderate hepatic impairment decreased the liver's ability to metabolize soticlestat to M-I; glucuronidation to M3 was also affected. Mild hepatic impairment resulted in a lower total plasma M-I exposure, but glucuronidation was unaffected. TEAEs were similar across study arms, mild, and no new safety findings were observed. A soticlestat dose reduction is required for individuals with moderate but not mild hepatic impairment.


Assuntos
Área Sob a Curva , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Fígado/metabolismo , Administração Oral , Hepatopatias/metabolismo , Adulto Jovem
6.
Am J Gastroenterol ; 119(7): 1235-1271, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38958301

RESUMO

Focal liver lesions (FLLs) have become an increasingly common finding on abdominal imaging, especially asymptomatic and incidental liver lesions. Gastroenterologists and hepatologists often see these patients in consultation and make recommendations for management of multiple types of liver lesions, including hepatocellular adenoma, focal nodular hyperplasia, hemangioma, and hepatic cystic lesions including polycystic liver disease. Malignancy is important to consider in the differential diagnosis of FLLs, and healthcare providers must be familiar with the diagnosis and management of FLLs. This American College of Gastroenterology practice guideline uses the best evidence available to make diagnosis and management recommendations for the most common FLLs.


Assuntos
Adenoma de Células Hepáticas , Cistos , Hiperplasia Nodular Focal do Fígado , Hemangioma , Hepatopatias , Neoplasias Hepáticas , Humanos , Hiperplasia Nodular Focal do Fígado/diagnóstico , Hiperplasia Nodular Focal do Fígado/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/diagnóstico por imagem , Hepatopatias/diagnóstico , Hepatopatias/terapia , Hepatopatias/diagnóstico por imagem , Hepatopatias/patologia , Hemangioma/diagnóstico , Hemangioma/terapia , Hemangioma/patologia , Hemangioma/diagnóstico por imagem , Cistos/diagnóstico , Cistos/diagnóstico por imagem , Cistos/patologia , Adenoma de Células Hepáticas/diagnóstico , Adenoma de Células Hepáticas/patologia , Adenoma de Células Hepáticas/terapia , Adenoma de Células Hepáticas/diagnóstico por imagem , Diagnóstico Diferencial , Gastroenterologia/normas , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/diagnóstico por imagem
7.
Nutrients ; 16(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38999772

RESUMO

Coffee consumption is globally widespread and has become a lifestyle habit. This study investigated coffee consumption and liver-related survival in a large cohort of 455,870 individuals with UK biobank, categorized into without steatosis, metabolic dysfunction-associated steatotic liver disease (MASLD), and MASLD and increased alcohol intake (MetALD). Inverse probability of treatment weighting (IPTW) adjusted for confounding variables was used, followed by Kaplan-Meier analysis. Moderate coffee consumption (1-2 cups per day) was associated with lower all-cause mortality across the entire cohort, without the steatosis, MASLD (p < 0.0001), and MetALD cohorts (p = 0.0047 for pre-IPTW, p = 0.027 for post-IPTW). Before IPTW adjustment, consuming one or more cups of coffee per day appeared to significantly reduce liver-related mortality in the overall (p = 0.015) and MASLD cohorts (p = 0.011). However, post-IPTW application, no significant differences in liver-related mortality were observed between the coffee intake groups (p = 0.778, 0.319, 0.564, 0.238 for each group). While increased coffee consumption initially seemed to reduce liver-related mortality, after IPTW adjustment, only all-cause mortality significantly decreased (p < 0.0001 and p = 0.027). These findings suggest that previous studies might have overestimated the favorable effect of coffee intake on chronic liver disease due to confounding factors.


Assuntos
Café , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos de Coortes , Idoso , Hepatopatias/mortalidade , Adulto , Reino Unido/epidemiologia , Fatores de Risco , Estimativa de Kaplan-Meier
8.
Int J Mol Sci ; 25(13)2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38999981

RESUMO

The interferon regulatory factors (IRFs) family comprises 11 members that are involved in various biological processes such as antiviral defense, cell proliferation regulation, differentiation, and apoptosis. Recent studies have highlighted the roles of IRF1-9 in a range of liver diseases, including hepatic ischemia-reperfusion injury (IRI), alcohol-induced liver injury, Con A-induced liver injury, nonalcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC). IRF1 is involved in the progression of hepatic IRI through signaling pathways such as PIAS1/NFATc1/HDAC1/IRF1/p38 MAPK and IRF1/JNK. The regulation of downstream IL-12, IL-15, p21, p38, HMGB1, JNK, Beclin1, ß-catenin, caspase 3, caspase 8, IFN-γ, IFN-ß and other genes are involved in the progression of hepatic IRI, and in the development of HCC through the regulation of PD-L1, IL-6, IL-8, CXCL1, CXCL10, and CXCR3. In addition, IRF3-PPP2R1B and IRF4-FSTL1-DIP2A/CD14 pathways are involved in the development of NAFLD. Other members of the IRF family also play moderately important functions in different liver diseases. Therefore, given the significance of IRFs in liver diseases and the lack of a comprehensive compilation of their molecular mechanisms in different liver diseases, this review is dedicated to exploring the molecular mechanisms of IRFs in various liver diseases.


Assuntos
Fatores Reguladores de Interferon , Hepatopatias , Humanos , Hepatopatias/metabolismo , Hepatopatias/patologia , Hepatopatias/genética , Animais , Fatores Reguladores de Interferon/metabolismo , Fatores Reguladores de Interferon/genética , Transdução de Sinais
9.
World J Gastroenterol ; 30(22): 2920-2922, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38947285

RESUMO

Percutaneous ultrasound has been a longstanding method in the diagnostics and interventional procedures of liver diseases. In some countries, its use is restricted to radiologists, limiting access for other clinicians, such as gastroenterologists. Endoscopic ultrasound, as a novel technique, plays a crucial role in diagnosis and treatment of digestive diseases. However, its use is sometimes recommended for conditions where no clear advantage over percutaneous ultrasound exists, leaving the impression that clinicians sometimes resort to an endoscopic approach due to the unavailability of percutaneous options.


Assuntos
Endossonografia , Hepatopatias , Humanos , Endossonografia/métodos , Hepatopatias/diagnóstico por imagem , Hepatopatias/terapia , Fígado/diagnóstico por imagem , Fígado/patologia , Ultrassonografia de Intervenção/métodos
10.
Clin Transl Sci ; 17(7): e13872, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38949489

RESUMO

Physiological determinants of drug dosing (PDODD) are a promising approach for precision dosing. This study investigates the alterations of PDODD in diseases and evaluates a variational autoencoder (VAE) artificial intelligence model for PDODD. The PDODD panel contained 20 biomarkers, and 13 renal, hepatic, diabetes, and cardiac disease status variables. Demographic characteristics, anthropometric measurements (body weight, body surface area, waist circumference), blood (plasma volume, albumin), renal (creatinine, glomerular filtration rate, urine flow, and urine albumin to creatinine ratio), and hepatic (R-value, hepatic steatosis index, drug-induced liver injury index), blood cell (systemic inflammation index, red cell, lymphocyte, neutrophils, and platelet counts) biomarkers, and medical questionnaire responses from the National Health and Nutrition Examination Survey (NHANES) were included. The tabular VAE (TVAE) generative model was implemented with the Synthetic Data Vault Python library. The joint distributions of the generated data vs. test data were compared using graphical univariate, bivariate, and multidimensional projection methods and distribution proximity measures. The PDODD biomarkers related to disease progression were altered as expected in renal, hepatic, diabetes, and cardiac diseases. The continuous PDODD panel variables generated by the TVAE satisfactorily approximated the distribution in the test data. The TVAE-generated distributions of some discrete variables deviated from the test data distribution. The age distribution of TVAE-generated continuous variables was similar to the test data. The TVAE algorithm demonstrated potential as an AI model for continuous PDODD and could be useful for generating virtual populations for clinical trial simulations.


Assuntos
Biomarcadores , Cardiopatias , Nefropatias , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores/sangue , Adulto , Hepatopatias/sangue , Hepatopatias/diagnóstico , Hepatopatias/metabolismo , Idoso , Doenças Metabólicas/diagnóstico , Inteligência Artificial , Inquéritos Nutricionais , Cálculos da Dosagem de Medicamento , Modelos Biológicos
11.
12.
BMJ Case Rep ; 17(7)2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38960424

RESUMO

In this article we report the case of a man with congenital liver disease who later developed psychotic illness and was diagnosed with schizophrenia. We illustrate how decompensation in liver function was associated with the exacerbation of psychotic symptoms. We discuss differential diagnostic challenges, and the possible overlapping neuropathology in these two conditions that may converge on glutamate/N-methyl-D-aspartate dysfunction. This patient's case underscores the need for further research to elucidate the possible underlying mechanisms linking congenital liver disease and psychosis.


Assuntos
Transtornos Psicóticos , Humanos , Masculino , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/etiologia , Diagnóstico Diferencial , Esquizofrenia/complicações , Adulto , Antipsicóticos/uso terapêutico , Hepatopatias/diagnóstico , Hepatopatias/complicações
13.
Ethiop J Health Sci ; 34(1): 85-100, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38957334

RESUMO

Background: Coronaviruses (CoVs) belong to the RNA viruses family. The viruses in this family are known to cause mild respiratory disease in humans. The origin of the novel SARS-COV2 virus that caused the coronavirus-19 disease (COVID-19) is the Wuhan city in China from where it disseminated to cause a global pandemic. Although lungs are the predominant target organ for Coronavirus Disease-19 (COVID-19), since its outbreak, the disease is known to affect heart, blood vessels, kidney, intestine, liver and brain. This review aimed to summarize the catastrophic impacts of Coronavirus disease-19 on heart and liver along with its mechanisms of pathogenesis. Methods: The information used in this review was obtained from relevant articles published on PubMed, Google Scholar, Google, WHO website, CDC and other sources. Key searching statements and phrases related to COVID-19 were used to retrieve information. Original research articles, review papers, research letters and case reports were used as a source of information. Results: Besides causing severe lung injury, COVID-19 has also been reported to affect and cause dysfunction of many other organs. COVID-19 infection can affect people by downregulating membrane-bound active angiotensin-converting enzyme (ACE). People who have deficient ACE2 expression are more vulnerable to COVID-19 infection. The patients' pre-existing co-morbidities are major risk factors that predispose individuals to severe COVID-19. Conclusion: The disease severity and its broad spectrum phenotype is a result of combined direct and indirect pathogenic factors. Therefore, protocols that harmonize many therapeutic preferences should be the best alternatives to de-escalate the disease and obviate deaths caused as a result of multiple organ damage and dysfunction induced by the disease.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/complicações , COVID-19/epidemiologia , Hepatopatias/etiologia , Hepatopatias/virologia , Cardiopatias/etiologia , Cardiopatias/virologia , Enzima de Conversão de Angiotensina 2/metabolismo , Fígado/patologia , Fígado/virologia
14.
Zhonghua Gan Zang Bing Za Zhi ; 32(6): 551-557, 2024 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-38964898

RESUMO

Objective: To investigate the clinical and genetic characteristics and predictive role of the severe liver disease phenotype in patients with hepatolenticular degeneration (HLD). Methods: Inpatients with HLD confirmed at Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine from January 1989 to December 2022 were selected as the research subjects. Clinical classification was performed according to the affected organs. Patients with liver disease phenotypes were classified into the liver disease group and further divided into the severe liver disease group and the ordinary liver disease group. The clinical characteristics and genetic variations were compared in each group of patients. The predictive indicators of patients with severe liver disease were analyzed by multiple regression. Statistical analysis was performed using the t-test, Mann-Whitney U test, or χ(2) test according to different data. Results: Of the 159 HLD cases, 142 were in the liver disease group (34 in the severe liver disease group and 108 in the ordinary liver disease group), and 17 were in the encephalopathy group. The median age of onset was statistically significantly different between the liver disease group and the encephalopathy group [12.6 (7.0, 13.3) years versus 16.9 (11.0, 21.5) years, P<0.01]. 156 ATP7B gene mutation sites were found in 83 cases with genetic testing results, of which 54 cases carried the p.Arg778Leu gene mutation (allele frequency 46.2%). Compared with patients with other types of gene mutations (n=65), patients with homozygous p.Arg778Leu mutations (n=18) had lower blood ceruloplasmin and albumin levels, a higher prognostic index, Child-Pugh score, an international normalized ratio, and prothrombin time (P<0.05). Hemolytic anemia, corneal K-F ring, homozygous p.Arg778Leu mutation, and multiple laboratory indexes in the severe liver disease group were statistically significantly different from those in the ordinary liver disease group (P<0.05). Multivariate logistic regression analysis showed that the predictive factors for severe liver disease were homozygous p.Arg778Leu mutation, total bilirubin, and bile acids (ORs=16.512, 1.022, 1.021, 95% CI: 1.204-226.425, 1.005-1.039, and 1.006-1.037, respectively, P<0.05). The drawn ROC curve demonstrated a cutoff value of 0.215 3, an AUC of 0.953 2, and sensitivity and specificity of 90.91% and 92.42%, respectively. Conclusion: Liver disease phenotypes are common in HLD patients and have an early onset. Total bilirubin, bile acids, and the homozygous p.Arg778Leu mutation of ATP7B is related to the severity of liver disease in HLD patients, which aids in predicting the occurrence and risk of severe liver disease.


Assuntos
Degeneração Hepatolenticular , Fenótipo , Humanos , Degeneração Hepatolenticular/genética , Degeneração Hepatolenticular/diagnóstico , Masculino , Feminino , Adolescente , Adulto Jovem , Criança , Mutação , Adulto , Hepatopatias/genética , Hepatopatias/diagnóstico , Pessoa de Meia-Idade
15.
Zhonghua Gan Zang Bing Za Zhi ; 32(6): 572-576, 2024 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-38964902

RESUMO

Liver biopsy is an important means of clinical diagnosis and treatment of liver diseases, but it is not easily accepted by patients because of its invasiveness. The most commonly employed liver biopsy approaches are percutaneous or transjugular. Endoscopic ultrasound-guided liver biopsy (EUS-LB), a newly emerging transjugular technique, has been widely studied and applied in recent years, but its application in China is less common. The EUS-LB has the advantages of high safety and comfort, simultaneous sampling of both liver lobes, and adequate sampling volume; however, it also has the disadvantages of high requirements for hardware, operators, and cost. This article reviews the clinical application of EUS-LB in accordance with pertinent research findings from recent years and discusses its advantages, disadvantages, and implementation feasibility.


Assuntos
Endossonografia , Fígado , Humanos , Fígado/patologia , Fígado/diagnóstico por imagem , Endossonografia/métodos , Hepatopatias/patologia , Hepatopatias/diagnóstico por imagem , Hepatopatias/diagnóstico
17.
BMC Pediatr ; 24(1): 444, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987716

RESUMO

Trichohepatoenteric syndrome (THES), also known as phenotypic diarrhea or syndromic diarrhea, is a rare autosomal recessive genetic disorder caused by mutations in SKIC2 (THES-type 2) or SKIC3 (THES-type 1) and is characterized by early onset diarrhea, woolly brittle hair, facial dysmorphic features and liver disease. We report the case of a 24-month-old girl who presented with chronic diarrhea since the neonatal period along with intrauterine growth restriction (IUGR), developmental delay, dysmorphic features, congenital heart defects, liver disease, and recurrent infections. The diagnosis was made through whole-exome sequencing analysis, which detected a homozygous variant (c.4070del, p.Pro1357Leufs*10) in the SKIC3 gene. The patient required parenteral nutrition and was hospitalized for the first 10 months of life and then discharged on PN after showing improvement. She remained stable on PN after discharge despite a few admissions for central line infections. Recent follow-up at the age of 2 years revealed that she was stable on long-term parenteral nutrition and that she had advanced chronic liver disease.


Assuntos
Diarreia , Doenças do Cabelo , Homozigoto , Humanos , Feminino , Diarreia/genética , Doenças do Cabelo/genética , Doenças do Cabelo/diagnóstico , Pré-Escolar , Diarreia Infantil/genética , Mutação , Nutrição Parenteral , Hepatopatias/genética , Hepatopatias/diagnóstico , Sequenciamento do Exoma , Retardo do Crescimento Fetal/genética , DNA Helicases , Fácies
18.
World J Gastroenterol ; 30(22): 2866-2880, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38947288

RESUMO

Coronavirus disease 2019 (COVID-19), caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome, multiple organ failure, and death. Despite extensive studies on the pathogenicity of SARS-CoV-2, its impact on the hepatobiliary system remains unclear. While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels, the exact source of this damage is not fully understood. Proposed mechanisms for injury include direct cytotoxicity, collateral damage from inflammation, drug-induced liver injury, and ischemia/hypoxia. However, evidence often relies on blood tests with liver enzyme abnormalities. In this comprehensive review, we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients, drawing from liver biopsies, complete autopsies, and in vitro liver analyses. We present evidence of the direct impact of SARS-CoV-2 on the liver, substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes, including mitochondrial swelling, endoplasmic reticulum dilatation, and hepatocyte apoptosis. Additionally, we describe the diverse liver pathology observed during COVID-19 infection, encompassing necrosis, steatosis, cholestasis, and lobular inflammation. We also discuss the emergence of long-term complications, notably COVID-19-related secondary sclerosing cholangitis. Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.


Assuntos
COVID-19 , Fígado , SARS-CoV-2 , Humanos , COVID-19/complicações , COVID-19/patologia , COVID-19/virologia , Fígado/patologia , Fígado/virologia , SARS-CoV-2/patogenicidade , Hepatopatias/patologia , Hepatopatias/virologia , Hepatopatias/etiologia , Hepatócitos/patologia , Hepatócitos/virologia
19.
Br J Gen Pract ; 74(suppl 1)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902105

RESUMO

BACKGROUND: Liver disease is common, but not part of routine chronic disease management in primary care. AIM: The aim of this study was to explore the challenges of implementing pathways of care for liver disease within existing highly protocolised structures in primary care. METHOD: Semi-structured interviews with 20 health professionals working in primary care. Interviews were informed by normalisation process theory (NPT) and boundary theory. Data were subject to thematic analysis. RESULTS: Three themes were identified relating to chronic disease work; definitions; need and worth, and roles. Participants identified that understanding and value of roles within chronic disease management were pre-defined by targets imposed on them as part of national incentives schemes. Structural boundaries constrained professional autonomy and the potential to influence this area of primary care management, including taking on new work. CONCLUSION: The inability to influence care decisions blurs occupational boundaries and goes to the core of what it means to be a professional. Unless liver disease sits within this target-based system, it is unlikely to become part of routine work in primary care.


Assuntos
Hepatopatias , Papel do Médico , Atenção Primária à Saúde , Pesquisa Qualitativa , Humanos , Hepatopatias/terapia , Atitude do Pessoal de Saúde , Entrevistas como Assunto , Doença Crônica/terapia , Masculino , Feminino , Gerenciamento Clínico , Clínicos Gerais/psicologia
20.
PLoS One ; 19(6): e0303151, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38870207

RESUMO

PURPOSE: To determine the incidence of newly diagnosed liver disorders (LD) up to 3.5-year post-acute COVID-19, and risk factors associated with new LD. METHODS: We analyzed 54,699 COVID-19 patients and 1,409,547 non-COVID-19 controls from March-11-2020 to Jan-03-2023. New liver disorders included abnormal liver function tests, advanced liver failure, alcohol and non-alcohol related liver disorders, and cirrhosis. Comparisons were made with ambulatory non-COVID-19 patients and patients hospitalized for other lower respiratory tract infections (LRTI). Demographics, comorbidities, laboratory data, incomes, insurance status, and unmet social needs were tabulated. The primary outcome was new LD at least two weeks following COVID-19 positive test. RESULTS: Incidence of new LD was not significantly different between COVID-19 and non-COVID-19 cohorts (incidence:1.99% vs 1.90% p>0.05, OR = 1.04[95%CI: 0.92,1.17], p = 0.53). COVID-19 patients with new LD were older, more likely to be Hispanic and had higher prevalence of diabetes, hypertension, chronic kidney disease, and obesity compared to patients without new LD. Hospitalized COVID-19 patients had no elevated risk of LD compared to hospitalized LRTI patients (2.90% vs 2.07%, p>0.05, OR = 1.29[0.98,1.69], p = 0.06). Among COVID-19 patients, those who developed LD had fewer patients with higher incomes (14.18% vs 18.35%, p<0.05) and more with lower incomes (21.72% vs 17.23%, p<0.01), more Medicare and less Medicaid insurance, and more patients with >3 unmet social needs (6.49% vs 2.98%, p<0.001) and fewer with no unmet social needs (76.19% vs 80.42%, p<0.001). CONCLUSIONS: Older age, Hispanic ethnicity, and obesity, but not COVID-19 status, posed increased risk for developing new LD. Lower socioeconomic status was associated with higher incidence of new LD.


Assuntos
COVID-19 , Hepatopatias , Humanos , COVID-19/epidemiologia , Masculino , Feminino , Fatores de Risco , Pessoa de Meia-Idade , Incidência , Idoso , Hepatopatias/epidemiologia , SARS-CoV-2/isolamento & purificação , Adulto , Cidade de Nova Iorque/epidemiologia , Comorbidade , Pandemias
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