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1.
Adv Kidney Dis Health ; 31(2): 139-146, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38649218

RESUMEN

Hyponatremia is common in patients with liver disease and is associated with increased mortality, morbidity, and a reduced quality of life. In liver transplantation, the inclusion of hyponatremia in organ allocation scores has reduced waitlist mortality. Portal hypertension and the resulting lowering of the effective arterial blood volume are important pathogenetic factors, but in most patients with liver disease, hyponatremia is multifactorial. Treatment requires a multifaceted approach that tries to reduce electrolyte-free water intake, restore urinary dilution, and increase nonelectrolyte solute excretion. Albumin therapy for hyponatremia is a peculiarity of advanced liver disease. Its use appears to be increasing, while the vaptans are currently only given in selected cases. Osmotic demyelination is a special concern in patients with liver disease. Serial checks of serum sodium concentrations and urine volume monitoring are mandatory.


Asunto(s)
Hiponatremia , Hepatopatías , Hiponatremia/terapia , Hiponatremia/etiología , Hiponatremia/diagnóstico , Humanos , Hepatopatías/complicaciones , Hepatopatías/sangre , Trasplante de Hígado , Sodio/sangre , Sodio/orina , Hipertensión Portal/terapia , Hipertensión Portal/complicaciones , Albúminas/metabolismo , Albúminas/uso terapéutico
2.
Int Ophthalmol ; 44(1): 177, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622271

RESUMEN

PURPOSE: This review examined existing literature to determine various ocular manifestations of liver pathologies, with a focus on metabolic deficiencies as well as viral and immune liver conditions. METHODS: Recent data were compiled from PubMed from 2000 to 2020 using keywords that were relevant to the assessed pathologies. Ocular presentations of several liver pathologies were researched and then summarized in a comprehensive form. RESULTS: Several ocular manifestations of liver disease were related to vitamin A deficiency, as liver disease is associated with impaired vitamin A homeostasis. Alcoholic liver cirrhosis can result in vitamin A deficiency, presenting with Bitot spots, xerosis, and corneal necrosis. Congenital liver diseases such as mucopolysaccharidoses and peroxisomal disorders are also linked with ocular signs. Viral causes of liver disease have associations with conditions like retinal vasculitis, keratoconjunctivitis sicca, retinopathies, Mooren's ulcer, and Sjogren's syndrome. Autoimmune hepatitis has been linked to peripheral ulcerative keratitis and uveitis. CONCLUSIONS: Building strong associations between ocular and liver pathology will allow for early detection of such conditions, leading to the early implementation of management strategies. While this review outlines several of the existing connections between hepatic and ophthalmic disease, further research is needed in the area in order to strengthen these associations.


Asunto(s)
Úlcera de la Córnea , Síndromes de Ojo Seco , Queratoconjuntivitis Seca , Hepatopatías , Vasculitis Retiniana , Síndrome de Sjögren , Deficiencia de Vitamina A , Humanos , Deficiencia de Vitamina A/complicaciones , Queratoconjuntivitis Seca/etiología , Úlcera de la Córnea/diagnóstico , Síndrome de Sjögren/complicaciones , Síndromes de Ojo Seco/complicaciones , Hepatopatías/etiología , Hepatopatías/complicaciones , Vasculitis Retiniana/complicaciones
4.
Pediatr Surg Int ; 40(1): 97, 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38581576

RESUMEN

PURPOSE: The effect of different types of lipid emulsion may guide therapy of patients with intestinal failure (IF) to limit morbidity such as intestinal failure-associated liver disease (IFALD). METHODS: A retrospective chart review of pediatric patients with IF who received soybean oil lipid emulsion (SL) or mixed oil lipid emulsion (ML) was performed. Data over 1 year were collected. RESULTS: Forty-five patients received SL and 34 received ML. There were no differences in the incidence (82 versus 74%, P = 0.35) or resolution (86 versus 92%, P = 0.5) of IFALD between the cohorts. The median dose of ML was higher compared to SL (2 versus 1 g/kg/day, P < 0.001). If resolved, IFALD resolved rapidly in the ML cohort compared to the SL cohort (67 versus 37 days, P = 0.01). Weight gain was higher in the ML compared to the SL cohort at resolution of IFALD or 1 year from diagnosis of IF (P = 0.009). CONCLUSION: The administration of ML did not alter the incidence or resolution of IFALD compared to SL in pediatric IF. There was rapid resolution of IFALD and enhanced weight gain in the ML cohort compared to SL in pediatric IF.


Asunto(s)
Enfermedades Intestinales , Insuficiencia Intestinal , Hepatopatías , Fallo Hepático , Humanos , Niño , Emulsiones Grasas Intravenosas/uso terapéutico , Nutrición Parenteral , Estudios Retrospectivos , Enfermedades Intestinales/tratamiento farmacológico , Hepatopatías/complicaciones , Fallo Hepático/complicaciones , Aceite de Soja/uso terapéutico , Aumento de Peso , Aceites de Pescado
5.
Thromb Res ; 237: 71-78, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38552497

RESUMEN

BACKGROUND AND AIMS: The effects of direct oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (NVAF) and liver disease remain poorly understood. Our multinational cohort study assessed the effectiveness and safety of DOACs in this high-risk population. METHODS: We assembled two population-based cohorts in United Kingdom and in Québec of NVAF patients with liver disease initiating DOACs or vitamin K antagonists (VKAs) between 2011 and 2020. Using an as-treated exposure definition, we compared DOACs to VKAs and apixaban to rivaroxaban. After inverse probability of treatment weighting, Cox proportional hazards models estimated site-specific hazard ratios (HRs) and 95 % confidence intervals (CIs) of ischemic stroke and major bleeding. Site-specific estimates were pooled using random-effects models. Analyses were repeated among NVAF patients with cirrhosis. RESULTS: There were 11,881 NVAF patients with liver disease (2683 with cirrhosis). Among those, 8815 initiated DOACs (4414 apixaban, 2497 rivaroxaban) and 3696 VKAs. The HRs (95 % CIs) for DOACs compared to VKAs were 1.01 (0.76-1.34) for ischemic stroke and 0.87 (0.77-0.99) for major bleeding. Results were consistent among patients with cirrhosis. The HRs (95 % CIs) for apixaban compared to rivaroxaban were 0.85 (0.60-1.20) for ischemic stroke and 0.80 (0.68-0.95) for major bleeding. This decreased bleeding risk was not observed among patients with cirrhosis (HR, 1.01; 95 % CI 0.72-1.43). CONCLUSIONS: Among NVAF patients with liver disease, DOACs were as effective and slightly safer than VKAs, and apixaban was as effective but safer than rivaroxaban. The safety benefit with apixaban was not present among patients with cirrhosis.


Asunto(s)
Fibrilación Atrial , Hepatopatías , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Femenino , Masculino , Anciano , Estudios de Cohortes , Administración Oral , Hepatopatías/complicaciones , Hepatopatías/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Persona de Mediana Edad , Hemorragia/inducido químicamente , Rivaroxabán/uso terapéutico , Rivaroxabán/efectos adversos , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Piridonas/uso terapéutico , Piridonas/efectos adversos , Pirazoles/uso terapéutico , Pirazoles/efectos adversos , Anciano de 80 o más Años
6.
Front Immunol ; 15: 1330536, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38545104

RESUMEN

Introduction: Alcohol-related liver disease (ARLD) accounts for over one third of all deaths from liver conditions, and mortality from alcohol-related liver disease has increased nearly five-fold over the last 30 years. Severe alcohol-related hepatitis almost always occurs in patients with a background of chronic liver disease with extensive fibrosis or cirrhosis, can precipitate 'acute on chronic' liver failure and has a high short-term mortality. Patients with alcohol-related liver disease have impaired immune responses, and increased susceptibility to infections, thus prompt diagnosis of infection and careful patient management is required. The identification of early and non-invasive diagnostic and prognostic biomarkers in ARLD remains an unresolved challenge. Easily calculated predictors of infection and mortality are required for use in patients who often exhibit variable symptoms and disease severity and may not always present in a specialized gastroenterology unit. Methods: We have used a simple haematological analyser to rapidly measure circulating myeloid cell parameters across the ARLD spectrum. Results and Discussion: We demonstrate for the first time that immature granulocyte (IG) counts correlate with markers of disease severity, and our data suggests that elevated counts are associated with increased short-term mortality and risk of infection. Other myeloid populations such as eosinophils and basophils also show promise. Thus IG count has the potential to serve alongside established markers such as neutrophil: lymphocyte ratio as a simply calculated predictor of mortality and risk of infectious complications in patients with alcohol-related hepatitis. This would allow identification of patients who may require more intensive management.


Asunto(s)
Hepatitis Alcohólica , Hepatopatías , Humanos , Pronóstico , Hepatopatías/complicaciones , Cirrosis Hepática/complicaciones , Recuento de Leucocitos
7.
Cir Cir ; 92(1): 131-136, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38537242

RESUMEN

Patients with chronic liver disease of any etiology who become infected with SARS-CoV-2 have been found to have a higher risk of mortality compared to those patients who do not have chronic liver disease. A literature review was conducted in the relationship between COVID 19 and preexistence of liver disease. The proportion of COVID-19 patients with abnormal liver function on admission ranged from 40 % to 75 % and the proportion with liver injury was close to 30%. Current studies show an important association between preexisting liver disease and COVID-19. The presence of cirrhosis is now an independent predictor of severity for COVID-19 and prolonged hospitalization in this group of patients. Patients with cirrhosis have a higher mortality rate, and this rate rises with increasing severity.


Pacientes con enfermedad hepática crónica de cualquier etiología que se infectan con SARS-CoV-2 tienen un mayor riesgo de mortalidad en comparación con aquellos pacientes que no tienen enfermedad hepática crónica. Se llevó a cabo una revisión de la literatura en relación a lo publicado de COVID 19 y enfermedad hepática pre-existente. La proporción de pacientes con COVID-19 con función hepática anormal al ingreso osciló entre el 40 % y el 75 % y la proporción con daño hepático fue cercana al 30 %. Los estudios actuales muestran una asociación importante entre la enfermedad hepática preexistente y la COVID-19. La presencia de cirrosis es ahora un predictor independiente de gravedad para COVID-19 y hospitalización prolongada en este grupo de pacientes. Los pacientes con cirrosis tienen una mayor tasa de mortalidad y esta tasa se incrementa con el aumento de la gravedad de la enfermedad hepática.


Asunto(s)
COVID-19 , Hepatopatías , Humanos , COVID-19/complicaciones , SARS-CoV-2 , Cirrosis Hepática/complicaciones , Hepatopatías/complicaciones
8.
Korean J Gastroenterol ; 83(3): 123-126, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38522856

RESUMEN

Donor lymphocyte infusion (DLI) is performed to augment an anti-tumor immune response or ensure donor stem cells remain engrafted following allogeneic stem cell transplantation but may induce graft-versus-host disease (GVHD) involving skin, intestine, and liver. Although hepatic involvement of GVHD can manifest as mild to severe hepatitis, few reports have mentioned acute severe liver dysfunction with encephalopathy. We experienced a case of acute severe liver dysfunction with semicoma after DLI in a patient with relapsed multiple myeloma following allogeneic stem cell transplantation, in whom chronic viral hepatitis B had been suppressed by antiviral treatment. The patient recovered after high-dose glucocorticoid administration based on an assessment of hepatic GVHD. Clinicians should be aware of the possibility of this catastrophic hepatic complication after DLI in hematologic disorders.


Asunto(s)
Enfermedad Injerto contra Huésped , Hepatopatías , Mieloma Múltiple , Humanos , Mieloma Múltiple/terapia , Trasplante Homólogo/efectos adversos , Recurrencia Local de Neoplasia , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/etiología , Linfocitos , Hepatopatías/complicaciones
9.
Clin Liver Dis ; 28(2): 253-263, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38548437

RESUMEN

Hepatic encephalopathy (HE) can occur as a complication of chronic liver disease as well as acute liver failure. HE is associated with significantly increased morbidity and worse patient outcomes. The clinical manifestation of HE ranges from early less-severe presentations that may only be accurately detected on dedicated psychomotor diagnostic testing to overt alterations in cognition and mental status to the most severe form of coma. Greater awareness of the clinical manifestations of HE across the spectrum of symptom severity is critical for early identification and timely initiation of appropriate therapy to improve patient outcomes.


Asunto(s)
Encefalopatía Hepática , Hepatopatías , Humanos , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/etiología , Encefalopatía Hepática/terapia , Cirrosis Hepática/complicaciones , Índice de Severidad de la Enfermedad , Hepatopatías/complicaciones , Cognición
10.
Alcohol Alcohol ; 59(2)2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38469882

RESUMEN

AIMS: Chronic alcohol consumption is well known to cause peripheral neuropathy, affecting both small and large nerve fibers. The aim of this study was to correlate biochemical and neurophysiological findings and investigate possible biomarkers and risk factors for pathogenetic mechanisms of neuropathy in patients diagnosed with alcohol use disorder (AUD). METHODS: Ninety patients diagnosed with AUD were enrolled in this prospective study over a period of 3 years. Serum biochemical parameters, as well as thiamine blood levels, were determined upon admission. Every subject was assessed by clinical neurological examination, followed by Nerve Conduction Studies, Quantitative Sensory Testing, and Sympathetic Skin Response. Fifty age and gender-matched patients without a diagnosis of AUD were used as the control group. RESULTS: Peripheral neuropathy was diagnosed in 54 patients (60%). Among them, pure large fiber neuropathy was found in 18 patients, pure small fiber neuropathy in 12 patients, and both large and small fiber neuropathy was diagnosed in 24 patients. Elevated liver enzymes and fasting glucose levels upon admission were significantly correlated with neuropathy. Lower blood thiamine levels (than reference) were found in seven patients and were not correlated with neuropathy. CONCLUSIONS: Our study suggests that alcohol-related liver dysfunction and hyperglycemia may contribute as risk factors of peripheral neuropathy in patients diagnosed with AUD, while blood thiamine levels do not correlate with neuropathy. Moreover, we suggest that liver enzymes and the De Ritis ratio could be potentially used as biomarkers for the incidence and severity of alcohol-related neuropathy.


Asunto(s)
Alcoholismo , Hepatopatías , Enfermedades del Sistema Nervioso Periférico , Neuropatía de Fibras Pequeñas , Humanos , Tiamina , Alcoholismo/complicaciones , Alcoholismo/diagnóstico , Neuropatía de Fibras Pequeñas/complicaciones , Estudios Prospectivos , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades del Sistema Nervioso Periférico/patología , Consumo de Bebidas Alcohólicas/efectos adversos , Hepatopatías/complicaciones , Biomarcadores , Ayuno , Glucosa
11.
BMJ Open ; 14(3): e081926, 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38479735

RESUMEN

OBJECTIVES: HFE haemochromatosis genetic variants have an uncertain clinical penetrance, especially to older ages and in undiagnosed groups. We estimated p.C282Y and p.H63D variant cumulative incidence of multiple clinical outcomes in a large community cohort. DESIGN: Prospective cohort study. SETTING: 22 assessment centres across England, Scotland, and Wales in the UK Biobank (2006-2010). PARTICIPANTS: 451 270 participants genetically similar to the 1000 Genomes European reference population, with a mean of 13.3-year follow-up through hospital inpatient, cancer registries and death certificate data. MAIN OUTCOME MEASURES: Cox proportional HRs of incident clinical outcomes and mortality in those with HFE p.C282Y/p.H63D mutations compared with those with no variants, stratified by sex and adjusted for age, assessment centre and genetic stratification. Cumulative incidences were estimated from age 40 years to 80 years. RESULTS: 12.1% of p.C282Y+/+ males had baseline (mean age 57 years) haemochromatosis diagnoses, with a cumulative incidence of 56.4% at age 80 years. 33.1% died vs 25.4% without HFE variants (HR 1.29, 95% CI: 1.12 to 1.48, p=4.7×10-4); 27.9% vs 17.1% had joint replacements, 20.3% vs 8.3% had liver disease, and there were excess delirium, dementia, and Parkinson's disease but not depression. Associations, including excess mortality, were similar in the group undiagnosed with haemochromatosis. 3.4% of women with p.C282Y+/+ had baseline haemochromatosis diagnoses, with a cumulative incidence of 40.5% at age 80 years. There were excess incident liver disease (8.9% vs 6.8%; HR 1.62, 95% CI: 1.27 to 2.05, p=7.8×10-5), joint replacements and delirium, with similar results in the undiagnosed. p.C282Y/p.H63D and p.H63D+/+ men or women had no statistically significant excess fatigue or depression at baseline and no excess incident outcomes. CONCLUSIONS: Male and female p.C282Y homozygotes experienced greater excess morbidity than previously documented, including those undiagnosed with haemochromatosis in the community. As haemochromatosis diagnosis rates were low at baseline despite treatment being considered effective, trials of screening to identify people with p.C282Y homozygosity early appear justified.


Asunto(s)
Delirio , Hemocromatosis , Hepatopatías , Adulto , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Bancos de Muestras Biológicas , Delirio/complicaciones , Genotipo , Hemocromatosis/diagnóstico , Hemocromatosis/epidemiología , Hemocromatosis/genética , Proteína de la Hemocromatosis/genética , Antígenos de Histocompatibilidad Clase I/genética , Homocigoto , Hepatopatías/complicaciones , Mutación , Estudios Prospectivos , Biobanco del Reino Unido , Anciano
12.
Rev Med Virol ; 34(2): e2523, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38512106

RESUMEN

COVID-19 is not only associated with substantial acute liver and kidney injuries, but also with an elevated risk of post-acute sequelae involving the kidney and liver system. We aimed to investigate whether COVID-19 exposure increases the long-term risk of kidney and liver disease, and what are the magnitudes of these associations. We searched PubMed, Embase, Web of Science, ClinicalTrials.gov, and the Living Overview of the Evidence COVID-19 Repository for cohort studies estimating the association between COVID-19 and kidney and liver outcomes. Random-effects meta-analyses were performed to combine the results of the included studies. We assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Fifteen cohort studies with more than 32 million participants were included in the systematic review COVID-19 was associated with a 35% greater risk of kidney diseases (10 more per 1000 persons; low certainty evidence) and 54% greater risk of liver disease (3 more per 1000 persons; low certainty evidence). The absolute increases due to COVID-19 for acute kidney injury, chronic kidney disease, and liver test abnormality were 3, 8, and 3 per 1000 persons, respectively. Subgroup analyses found no differences between different type of kidney and liver diseases. The findings provide further evidence for the association between COVID-19 and incident kidney and liver conditions. The absolute magnitude of the effect of COVID-19 on kidney and liver outcomes was, however, relatively small.


Asunto(s)
Lesión Renal Aguda , COVID-19 , Hepatopatías , Humanos , COVID-19/complicaciones , Riñón , Hepatopatías/complicaciones , Hepatopatías/epidemiología , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología
13.
Medicine (Baltimore) ; 103(13): e37705, 2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38552039

RESUMEN

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) is commonly used in gastroenterology wards for both diagnostic and therapeutic purposes. It doesn't however come free of complications. As a matter of fact, complications are reported in up to 10% of patients undergoing ERCP. PATIENT CONCERNS: In this article, we report the case of a patient who underwent ERCP and sphincterotomy for choledocholithiasis. Twenty-four hours after the procedure, the patient developed sudden sharp abdominal pain and dropped her hemoglobin levels. DIAGNOSIS: An emergent gastroscopy was done and it ruled out bleeding from the sphincterotomy. Computed tomography of the abdomen showed a large hepatic subcapsular hematoma. INTERVENTIONS: Blood was urgently transfused and the patient was transferred to the intensive care unit for monitoring. OUTCOMES: The patient's condition quickly deteriorated despite extensive resuscitative measures, and eventually passed away on day 4 post ERCP. LESSONS: Hepatic subcapsular hematoma is a very rare but fatal complication after ERCP and should be ruled out in patients who underwent the procedure and develop sudden abdominal pain with hemodynamic and laboratory instability.


Asunto(s)
Coledocolitiasis , Hepatopatías , Humanos , Femenino , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Hepatopatías/complicaciones , Coledocolitiasis/complicaciones , Hematoma/complicaciones , Hemorragia Gastrointestinal/etiología , Dolor Abdominal/etiología
14.
Clin Nutr ; 43(4): 909-914, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38394971

RESUMEN

Albumin is a relatively small molecule with a radius of 7.5 nm and a molecular weight of 65 kDa. It is the most abundant protein in plasma, accounting for 60-75% of its oncotic pressure. Its concentration in plasma is merely one static measurement reflecting a dynamic and complex system of albumin physiology, and is the net result of several different processes, one or more of which may become deranged by disease or its treatment. It is also unsurprising that hypoalbuminaemia has proved to be an indicator of morbidity and mortality risk since the underlying conditions which cause it, including protein energy malnutrition, crystalloid overload, inflammation, and liver dysfunction are themselves risk factors. In some cases, its underlying cause may require treatment but mostly it is just a parameter to be monitored and used as one measure of clinical progress or deterioration. While malnutrition, associated with a low protein intake, may be a contributory cause of hypoalbuminaemia, in the absence of inflammation and/or dilution with crystalloid its development in response to malnutrition alone is slow compared with the rapid change caused by inflammatory redistribution or dilution with crystalloids. Other significant causes include liver dysfunction and serous losses. These causal factors may occur singly or in combination in any particular case. Treatment is that of the underlying causes and associated conditions such as a low plasma volume, not of hypoalbuminaemia per se.


Asunto(s)
Hipoalbuminemia , Hepatopatías , Desnutrición , Humanos , Hipoalbuminemia/etiología , Relevancia Clínica , Albúminas , Inflamación/complicaciones , Desnutrición/complicaciones , Soluciones Cristaloides , Hepatopatías/complicaciones
15.
JCI Insight ; 9(6)2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38358827

RESUMEN

Mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene lead to CF, a life-threating autosomal recessive genetic disease. While recently approved Trikafta dramatically ameliorates CF lung diseases, there is still a lack of effective medicine to treat CF-associated liver disease (CFLD). To address this medical need, we used a recently established CF rabbit model to test whether sotagliflozin, a sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor drug that is approved to treat diabetes, can be repurposed to treat CFLD. Sotagliflozin treatment led to systemic benefits to CF rabbits, evidenced by increased appetite and weight gain as well as prolonged lifespan. For CF liver-related phenotypes, the animals benefited from normalized blood chemistry and bile acid parameters. Furthermore, sotagliflozin alleviated nonalcoholic steatohepatitis-like phenotypes, including liver fibrosis. Intriguingly, sotagliflozin treatment markedly reduced the otherwise elevated endoplasmic reticulum stress responses in the liver and other affected organs of CF rabbits. In summary, our work demonstrates that sotagliflozin attenuates liver disorders in CF rabbits and suggests sotagliflozin as a potential drug to treat CFLD.


Asunto(s)
Fibrosis Quística , Hepatopatías , Animales , Conejos , Fibrosis Quística/complicaciones , Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/genética , Hepatopatías/complicaciones , Glicósidos , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/complicaciones
16.
Sci Rep ; 14(1): 4240, 2024 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-38378873

RESUMEN

Patients with intestinal failure who receive long-term parenteral nutrition (PN) often develop intestinal failure-associated liver disease (IFALD). Although there are identified risk factors, the early pathogenesis is poorly understood and treatment options are limited. Here, we perform a transcriptomic analysis of liver tissue in a large animal IFALD model to generate mechanistic insights and identify therapeutic targets. Preterm Yorkshire piglets were provided PN or bottle-fed with sow-milk replacer for 14 days. Compared to bottle-fed controls, piglets receiving PN developed biochemical cholestasis by day of life 15 (total bilirubin 0.2 vs. 2.9 mg/dL, P = 0.01). RNA-Seq of liver tissue was performed. Ingenuity Pathway Analysis identified 747 differentially expressed genes (343 upregulated and 404 downregulated) with an adjusted P < 0.05 and a fold-change of > |1|. Enriched canonical pathways were identified, demonstrating broad activation of inflammatory pathways and inhibition of cell cycle progression. Potential therapeutics including infliximab, glucocorticoids, statins, and obeticholic acid were identified as predicted upstream master regulators that may reverse the PN-induced gene dysregulation. The early driver of IFALD in neonates may be inflammation with an immature liver; identified therapeutics that target the inflammatory response in the liver should be investigated as potential treatments.


Asunto(s)
Enfermedades Intestinales , Insuficiencia Intestinal , Hepatopatías , Fallo Hepático , Animales , Humanos , Femenino , Porcinos , Hepatopatías/genética , Hepatopatías/complicaciones , Enfermedades Intestinales/genética , Enfermedades Intestinales/complicaciones , Fallo Hepático/complicaciones , Inflamación/genética , Inflamación/complicaciones
18.
Rev Invest Clin ; 76(1): 18-28, 2024 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-38262366

RESUMEN

Background: Iron overload is frequent in patients with chronic liver disease, associated with shorter survival after liver transplantation in patients with hereditary hemochromatosis. Its effect on patients without hereditary hemochromatosis is unclear. The aim of the study was to study the clinical impact of iron overload in patients who underwent liver transplantation at an academic tertiary referral center. Methods: We performed a retrospective cohort study including all patients without hereditary hemochromatosis who underwent liver transplantation from 2015 to 2017 at an academic tertiary referral center in Mexico City. Explant liver biopsies were reprocessed to obtain the histochemical hepatic iron index, considering a score ≥ 0.15 as iron overload. Baseline characteristics were compared between patients with and without iron overload. Survival was estimated using the Kaplan-Meier method, compared with the log-rank test and the Cox proportional hazards model. Results: Of 105 patients included, 45% had iron overload. Viral and metabolic etiologies, alcohol consumption, and obesity were more frequent in patients with iron overload than in those without iron overload (43% vs. 21%, 32% vs. 22%, p = 0.011; 34% vs. 9%, p = 0.001; and 32% vs. 12%, p = 0.013, respectively). Eight patients died within 90 days after liver transplantation (one with iron overload). Complication rate was higher in patients with iron overload versus those without iron overload (223 vs. 93 events/100 personmonths; median time to any complication of 2 vs. 3 days, p = 0.043), without differences in complication type. Fatality rate was lower in patients with iron overload versus those without iron overload (0.7 vs. 4.5 deaths/100 person-months, p = 0.055). Conclusion: Detecting iron overload might identify patients at risk of early complications after liver transplantation. Further studies are required to understand the role of iron overload in survival.


Asunto(s)
Hemocromatosis , Sobrecarga de Hierro , Hepatopatías , Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Hemocromatosis/complicaciones , Hemocromatosis/epidemiología , Hemocromatosis/patología , Estudios Retrospectivos , Sobrecarga de Hierro/etiología , Sobrecarga de Hierro/complicaciones , Hepatopatías/complicaciones , Hepatopatías/metabolismo , Hepatopatías/patología , Hígado/metabolismo
19.
Curr Opin Gastroenterol ; 40(2): 77-84, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38190383

RESUMEN

PURPOSE OF REVIEW: Primary sclerosing cholangitis is a chronic cholestatic liver disease for which no pharmacological treatment options are available. It is an immune-mediated disease and macrophages have been implicated in disease pathogenesis. However, which specific macrophage populations contribute to disease, and how we can apply this as therapeutic strategy is still unclear. RECENT FINDINGS: Recent studies have shown that fibrous tissue is characterized by osteopontin-positive macrophages, including in patients with primary sclerosing cholangitis. Experimental models indicate that intracellular osteopontin in macrophages confers protection, while secreted osteopontin contributes to disease. Serum osteopontin is increased in different liver diseases, including primary sclerosing cholangitis, and might thus serve as therapeutic target. SUMMARY: Although several studies report on the role of osteopontin in liver disease, only a minority of the studies have focused on isoform-specific functions, and the importance of the cellular source of secreted osteopontin. Future studies investigating these aspects, and how this can be translated to therapies for primary sclerosing cholangitis, and other chronic liver diseases, are required.


Asunto(s)
Colangitis Esclerosante , Osteopontina , Humanos , Colangitis Esclerosante/terapia , Hepatopatías/complicaciones , Macrófagos
20.
Expert Rev Gastroenterol Hepatol ; 18(1-3): 5-12, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38236640

RESUMEN

The effectiveness and risks of anticoagulant therapy in cirrhotic patients with non-symptomatic portal vein thrombosis (PVT) remain unclear. We conducted a multicenter, Zelen-designed randomized controlled trial to determine the effectiveness of warfarin in cirrhotic patients with non-symptomatic PVT during a one-year follow-up. In brief, 64 patients were 1:1 randomly divided into the anticoagulation group or the untreated group. The probability of recanalization was significantly higher in the anticoagulation group than those untreated in both ITT analysis (71.9% vs 34.4%, p = 0.004) and PP analysis (76.7% vs 32.4%, p < 0.001). Anticoagulation treatment was the independent predictor of recanalization (HR 2.776, 95%CI 1.307-5.893, p = 0.008). The risk of bleeding events and mortality were not significantly different. A significantly higher incidence of ascites aggravation was observed in the untreated group (3.3% vs 26.5%, p = 0.015). In conclusion, warfarin was proved to be an effective and safe as an anticoagulation therapy for treating non-symptomatic PVT in cirrhotic patients.


Asunto(s)
Hepatopatías , Trombosis de la Vena , Humanos , Warfarina/efectos adversos , Anticoagulantes/efectos adversos , Vena Porta , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/tratamiento farmacológico , Hepatopatías/complicaciones , Resultado del Tratamiento
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