RESUMEN
La enfermedad de células falciformes (ECF) o anemia drepanocítica, es el trastorno hereditario más frecuente en los glóbulos rojos, y la enfermedad con más complicaciones en diferentes órganos, lo que provoca múltiples presentaciones de una misma enfermedad., se hace revisión literatura sobre ECF y colestasis intrahepática drepanocítica, y se describe un caso presentado en el Hospital General y de Especialidades Nuestra Señora de la Altagracia de Higüey Republica Dominicana en el año 2022. Es un varón de 24 años, con diagnóstico de ECF, que se complicó con una colestasis intrahepática drepanocítica muy severa que se manejó con hemodiálisis. El objetivo de publicar este caso es revisar la información respecto a la incidencia y la morbimortalidad de esta complicación, teniendo en cuenta que fue tratado por un equipo multidisciplinario usando la hemodiálisis como alternativa terapéutica(AU)
Sickle cell disease (SCD) or sickle cell anemia is the most common hereditary disorder in red blood cells, and the disease with the most complications in different organs, which causes multiple presentations of the same disease. Literature review on SCD is made and sickle cell intrahepatic cholestasis,and a case presented at the Hospital General y de Especialidades Nuestra Señora de la Altagracia de Higüey in the Dominican Republic in 2022 is described. Very severe sickle cell intrahepatic disease that was managed with hemodialysis. The purpose of publishing this case is to review the information regarding the incidence and morbidity and mortality of this complication,taking into account that it was treated by a multidisciplinary team using hemodialysis as a therapeutic alternative(AU)
Asunto(s)
Humanos , Masculino , Adulto , Colestasis/complicaciones , Colestasis Intrahepática/fisiopatología , Anemia de Células Falciformes , Diálisis Renal , Eritrocitos , Insuficiencia RenalRESUMEN
Chronic liver diseases are a group of pathologies affecting the liver with high prevalence worldwide. Among them, cholestatic chronic liver diseases (CCLD) are characterized by alterations in liver function and increased plasma bile acids. Secondary to liver disease, under cholestasis, is developed sarcopenia, a skeletal muscle dysfunction with decreased muscle mass, strength, and physical function. CCL5/RANTES is a chemokine involved in the immune and inflammatory response. Indeed, CCL5 is a myokine because it is produced by skeletal muscle. Several studies show that bile acids induce CCL5/RANTES expression in liver cells. However, it is unknown if the expression of CCL5/RANTES is changed in the skeletal muscle of mice with cholestatic liver disease. We used a murine model of cholestasis-induced sarcopenia by intake of hepatotoxin 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC diet), in which we detected the mRNA levels for ccl5. We determined that mice fed the DDC diet presented high levels of serum bile acids and developed typical features of sarcopenia. Under these conditions, we detected the ccl5 gene expression in diaphragm muscle showing elevated mRNA levels compared to mice fed with a standard diet (chow diet). Our results collectively suggest an increased ccl5 gene expression in the diaphragm muscle concomitantly with elevated serum bile acids and the development of sarcopenia.
Asunto(s)
Colestasis , Hepatopatías , Sarcopenia , Ratones , Animales , Sarcopenia/patología , Diafragma/metabolismo , Diafragma/patología , Regulación hacia Arriba , Quimiocina CCL5/metabolismo , Colestasis/complicaciones , Colestasis/metabolismo , Colestasis/patología , Hígado/metabolismo , Ácidos y Sales Biliares , Hepatopatías/metabolismo , Expresión Génica , Ratones Endogámicos C57BLRESUMEN
Introduction: Autoimmune hepatitis (AIH) is a chronic liver disease with a relevant inflammatory component and an unknown etiology. Evidence for clinical characteristics and risk factors in large cohorts of patients with acute AIH (AAIH) is lacking. We clinically characterized patients with AAIH, the prevalence of a combined adverse outcome (death or liver transplantation (LT)), and its risk factors. Methods: A retrospective study of adult patients diagnosed with AAIH at three centers (Santiago, Chile; 2000-2018) was conducted. Clinical and laboratory characteristics were obtained. A liver biopsy was performed for all patients. Descriptive statistics and logistic regression models were used. Results: A total of 126 patients were admitted; 77% were female, 33 (26.2%) had a severe presentation, and 14 (11.1%) had a fulminant presentation. Overall, 24 patients (19.0%) lacked typical autoantibodies, and 26.2% had immunoglobulin G levels in the normal range. The most frequent histological findings were plasma cells (86.5%), interface hepatitis (81.7%), and chronic hepatitis (81.0%). Rosettes were uncommon (35.6%). Advanced fibrosis was present in 27% of patients. Combined adverse outcomes occurred in 7.9% of cases, all fulminant with histological cholestasis. Alkaline phosphatase, bilirubin, and prothrombin less than 50% were independent risk factors for in-hospital death or LT (p value <0.05). Although corticosteroid treatment was associated with better outcomes (OR 0.095, p value = 0.013), more severe patients were less likely to receive this therapy. Discussion. In this large cohort of patients with AAIH, clinical characteristics differ from those reported in patients with chronic AIH. Fulminant hepatitis, histological cholestasis, alkaline phosphatase, bilirubin, and prothrombin were associated with death/LT.
Asunto(s)
Colestasis , Hepatitis Autoinmune , Corticoesteroides/uso terapéutico , Adulto , Fosfatasa Alcalina , Autoanticuerpos , Bilirrubina , Colestasis/complicaciones , Femenino , Hepatitis Autoinmune/diagnóstico , Mortalidad Hospitalaria , Humanos , Inmunoglobulina G/uso terapéutico , Hígado/patología , Masculino , Protrombina/uso terapéutico , Estudios RetrospectivosRESUMEN
To relate omphalocele and biliary atresia and investigate possible embryological correlations that justify the simultaneous occurrence. A female preterm newborn diagnosed as omphalocele; cesarean delivery, weight 2,500g, 46 XX karyotype. Initially, the newborn remained fasting and on parenteral nutrition, and enteral diet was introduced later, with good acceptance. On the 12th day of life, the newborn presented direct hyperbilirubinemia, increased levels of liver enzymes and fecal acholia, with a presumptive diagnosis of biliary atresia. However, the ultrasound was inconclusive, due to anatomical changes resulting from omphalocele. A surgical approach was chosen on the 37th day of life aiming to confirm diagnosis of biliary atresia and to repair omphalocele. During the surgical procedure, structural alterations compatible with biliary atresia were observed, later confirmed by pathological examination; a hepatoportoenterostomy was performed and the omphalocele was corrected. She evolved well in the postoperative period, with a decrease in direct bilirubin and liver enzymes, as well as resolution of fecal acholia, and was discharged in good clinical condition. This is a bizarre and extremely rare association, but the prognosis may be good when an early diagnosis is made and surgery performed, besides support and clinical management to prevent complications in the perioperative period. Although the pathogenesis of the diseases has not been fully defined yet, there is, to date, no direct relation between them. The association between omphalocele and biliary atresia is extremely uncommon, with only two published cases.
Asunto(s)
Atresia Biliar , Colestasis , Hernia Umbilical , Atresia Biliar/complicaciones , Atresia Biliar/diagnóstico , Atresia Biliar/cirugía , Bilirrubina , Colestasis/complicaciones , Femenino , Hernia Umbilical/complicaciones , Hernia Umbilical/diagnóstico por imagen , Hernia Umbilical/cirugía , Humanos , Lactante , Recién Nacido , Nutrición Parenteral , EmbarazoRESUMEN
In this cross-sectional study, serum matrix metalloproteinase-7 levels were significantly lower in infants with jaundice and parenteral nutrition-associated liver disease compared with those with confirmed biliary atresia. Serum metalloproteinase-7 may aid in excluding biliary atresia and thus may minimize invasive testing in infants with a history of parenteral nutrition.
Asunto(s)
Atresia Biliar , Colestasis , Hepatopatías , Atresia Biliar/complicaciones , Colestasis/complicaciones , Estudios Transversales , Humanos , Lactante , Hígado , Hepatopatías/complicaciones , Metaloproteinasa 7 de la Matriz , Nutrición Parenteral/efectos adversosRESUMEN
This review is focused on updating knowledge about cholestatic pruritus. It summarizes clinical-epidemiological characteristics, pathophysiology, diagnostic approach, and evidence-based therapeutic recommendations regarding this form of pruritus. Pruritus is a frequent symptom that accompanies several liver diseases, particularly cholestatic ones. The symptom may be mild and tolerable, but it can also dramatically reduce the quality of life. Although the exact pathophysiology of this form of pruritus remains unclear, current evidence supports a mixed origin. It is extremely important for dermatologists to have knowledge about cholestatic pruritus since they are usually the first physicians to be sought by the patient when they experience the symptom. In the absence of specific dermatological alterations, cholestasis must always be considered as a possible cause of pruritus. In addition to allowing an adequate diagnosis, a better pathophysiological understanding of hepatic pruritus provides the identification of new therapeutic targets and, consequently, optimization of the approach in patients with this condition.
Asunto(s)
Colestasis , Calidad de Vida , Colestasis/complicaciones , Humanos , Prurito/diagnóstico , Prurito/tratamiento farmacológico , Prurito/etiologíaRESUMEN
During liver fibrogenesis, there is an imbalance between regeneration and wound healing. The current treatment is the withdrawal of the causing agent; thus, investigation of new and effective treatments is important. Studies have highlighted the action of chondroitin sulfate (CS) in different cells; thus, our aim was to analyze its effect on an experimental model of bile duct ligation (BDL). Adult Wistar rats were subjected to BDL and treated with CS for 7, 14, 21, or 28 days intraperitoneally. We performed histomorphometric analyses on Picrosirius-stained liver sections. Cell death was analyzed according to caspase-3 and cathepsin B activity and using a TUNEL assay. Regeneration was evaluated using PCNA immunohistochemistry. BDL led to increased collagen content with corresponding decreased liver parenchyma. CS treatment reduced total collagen and increased parenchyma content after 21 and 28 days. The treatment also promoted changes in the hepatic collagen type III/I ratio. Furthermore, it was observed that CS treatment reduced caspase-3 activity and the percentage of TUNEL-positive cells after 14 days and cathepsin B activity only after 28 days. The regeneration increased after 14, 21, and 28 days of CS treatment. In conclusion, our study showed a promising hepatoprotective action of CS in fibrogenesis induced by BDL.
Asunto(s)
Colestasis/complicaciones , Sulfatos de Condroitina/farmacología , Conducto Colédoco/cirugía , Hepatopatías/tratamiento farmacológico , Animales , Hepatopatías/etiología , Hepatopatías/metabolismo , Hepatopatías/patología , Masculino , Sustancias Protectoras/farmacología , Ratas , Ratas WistarRESUMEN
Cholestasis, which is impaired bile flow from the liver into the intestine, can be caused by cholangitis and/or bile duct obstruction. Cholangitis can arise from bacterial infections and cholelithiasis, however, immune-mediated cholangitis in primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) is characterized by a strong immune response targeting the biliary epithelial cells (BECs). Persistent biliary inflammation further represents a risk for biliary neoplasia, cholangiocarcinoma (CCA) by driving chronic cellular stress in the BECs. Currently, immune-mediated cholangitis is considered a Th1-Th17-dominant disease, however, the presence of Th2-related mast cells (MCs) in tissue samples from PBC, PSC and CCA patients has been described, showing that these MCs are active players in these diseases. Here, we reviewed and discussed experimental and clinical data supporting a pro-fibrotic role for MCs in immune-mediated cholangitis as well as their participation in supporting tumor growth acting as angiogenesis promoters. Thus, although MCs have classically been identified as downstream effectors of Th2 responses in allergies and parasitic infections, evidence suggests that these MCs are relevant players in biliary inflammation and neoplasia. The availability of strategies to prevent MCs' activation represents a therapeutic opportunity in biliary diseases.
Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Colangitis Esclerosante , Colangitis , Colestasis , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patología , Colangiocarcinoma/patología , Colangitis/complicaciones , Colangitis Esclerosante/patología , Colestasis/complicaciones , Humanos , Inflamación/complicaciones , Mastocitos/patologíaRESUMEN
Targeted therapies with MAPK inhibitors have proven to modulate the clinical manifestations of patients with Langerhans cell histiocytosis (LCH). We explored the presence of BRAFV600E mutation in our cohort of patients with LCH and cholestasis, sclerosing cholangitis, or liver fibrosis that presented resistance to chemotherapy. The BRAFV600E mutation was detected either in the diagnosis (skin and bone) or liver biopsy in our cohort of 13 patients. Thus, we observed a high incidence of BRAFV600E mutation in 100% either in diagnostic biopsy (skin and bone) or liver biopsy in patients with progressive liver disease, sequela, or liver transplant requirement.
Asunto(s)
Colangitis Esclerosante , Colestasis , Histiocitosis de Células de Langerhans , Proteínas Proto-Oncogénicas B-raf/genética , Colangitis Esclerosante/complicaciones , Colangitis Esclerosante/epidemiología , Colangitis Esclerosante/genética , Colestasis/complicaciones , Colestasis/genética , Histiocitosis de Células de Langerhans/epidemiología , Histiocitosis de Células de Langerhans/etiología , Histiocitosis de Células de Langerhans/genética , Humanos , Cirrosis Hepática , Mutación , PrevalenciaRESUMEN
BACKGROUND: Pruritus is a major health-related quality-of-life burden in progressive familial intrahepatic cholestasis (PFIC) and other childhood cholestatic liver diseases. Several nontransplant surgical techniques were developed in an attempt to ameliorate symptoms and slow disease progression. Very few case-series have been published on a particular intervention, ileal exclusion (IE), which has been considered to be inferior to the other approaches. METHODS: We conducted a single-center retrospective chart-review case-series of patients submitted to IE as the first-line surgical treatment at our institution from 1995 to 2018. The primary goal was pruritus relief, followed by survival with the native liver and improvement in biochemical parameters. RESULTS: Eleven patients were submitted to IE, with a mean follow-up of 60â¯months. Complete resolution or significant reduction of pruritus was obtained in 72.7% (nâ¯=â¯8) of patients. One patient (9.1%) had a major postoperative complication that required surgery. No other morbidities were reported. Two cases progressed to end-stage liver disease (ESLD) within the short-term and one year after surgery. CONCLUSIONS: This case series study shows that IE provided excellent results in pruritus control and permitted survival with the native liver. We believe IE is a safe procedure, with few associated morbidities, and should be considered more often as primary surgical treatment for PFIC and other cholestasis. LEVEL OF EVIDENCE: IV.
Asunto(s)
Procedimientos Quirúrgicos del Sistema Biliar , Colestasis Intrahepática , Íleon/cirugía , Prurito , Niño , Colestasis/complicaciones , Colestasis/cirugía , Colestasis Intrahepática/complicaciones , Colestasis Intrahepática/cirugía , Humanos , Prurito/etiología , Prurito/cirugía , Estudios RetrospectivosAsunto(s)
Colestasis/diagnóstico , Enfermedad de Gilbert/diagnóstico , Hiperbilirrubinemia/etiología , Ictericia/etiología , Cirrosis Hepática/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Bilirrubina/metabolismo , Colestasis/complicaciones , Diagnóstico Diferencial , Enfermedad de Gilbert/complicaciones , Humanos , Ictericia Obstructiva/etiología , Cirrosis Hepática/complicaciones , Pruebas de Función Hepática , Enfermedad del Hígado Graso no Alcohólico/complicacionesRESUMEN
OBJECTIVE: To assess the diagnostic and prognostic usefulness of the serum matrix metallopeptidase-7 (MMP-7) level for biliary atresia in infants with cholestasis after hepatoportoenterostomy. STUDY DESIGN: We enrolled 100 infants with cholestasis (age, 43.56 ± 1.97 days; 62 males) with a direct bilirubin level of >1 mg/dL, of whom 36 (36%) were diagnosed with biliary atresisa. The MMP-7 levels in serum samples collected during the cholestasis workup and 6 months after hepatoportoenterostomy were assessed by enzyme-linked immunosorbent assay. We quantified liver fibrosis by Picro Sirius red staining of collagen in specimens from the 81 infants with cholestasis. RESULTS: Infants with biliary atresisa had a significantly higher serum MMP-7 level than that of non-biliary atresisa infants with cholestasis of equivalent age (P < .0001). Receiver operating characteristic analysis showed that a serum MMP-7 level of >1.43 ng/mL was predictive of biliary atresisa in infants with cholestasis (diagnostic accuracy, 88%). There was a positive correlation between the serum MMP-7 level and the severity of liver fibrosis (P = .0002). Survival analysis showed that the frequency of liver transplantation was significantly higher in infants with biliary atresisa with a serum MMP-7 level of >10.30 ng/mL compared with a serum MMP-7 level of ≤10.30 ng/mL after hepatoportoenterostomy (hazard ratio, 4.22; P = .02). CONCLUSIONS: The serum MMP-7 level, which reflects the severity of liver fibrosis and can be determined noninvasively, may facilitate the diagnosis of biliary atresisa among infants with cholestasis. Moreover, the serum MMP-7 level after hepatoportoenterostomy is associated with a need for liver transplantation in infants with biliary atresisa.
Asunto(s)
Atresia Biliar/diagnóstico , Atresia Biliar/enzimología , Colestasis/complicaciones , Cirrosis Hepática/etiología , Metaloproteinasa 7 de la Matriz/sangre , Portoenterostomía Hepática/efectos adversos , Atresia Biliar/cirugía , Colestasis/enzimología , Estudios de Cohortes , Femenino , Humanos , Lactante , Trasplante de Hígado , Masculino , Valor Predictivo de las Pruebas , Curva ROCRESUMEN
Bone marrow cells (BMC) migrate to the injured liver after transplantation, contributing to regeneration through multiple pathways, but mechanisms involved are unclear. This work aimed to study BMC migration, characterize cytokine profile, cell populations and proliferation in mice with liver fibrosis transplanted with GFP+ BMC. Confocal microscopy analysis showed GFP+ BMC near regions expressing HGF and SDF-1 in the fibrotic liver. Impaired liver cell proliferation in fibrotic groups was restored after BMC transplantation. Regarding total cell populations, there was a significant reduction in CD68+ cells and increased Ly6G+ cells in transplanted fibrotic group. BMC contributed to the total populations of CD144, CD11b and Ly6G cells in the fibrotic liver, related to an increment of anti-fibrotic cytokines (IL-10, IL-13, IFN-γ and HGF) and reduction of pro-inflammatory cytokines (IL-17A and IL-6). Therefore, HGF and SDF-1 may represent important chemoattractants for transplanted BMC in the injured liver, where these cells can give rise to populations of extrahepatic macrophages, neutrophils and endothelial progenitor cells that can interact synergistically with other liver cells towards the modulation of an anti-fibrotic cytokine profile promoting the onset of liver regeneration.
Asunto(s)
Células de la Médula Ósea/citología , Trasplante de Médula Ósea , Comunicación Celular , Colestasis/terapia , Citocinas/metabolismo , Hepatocitos/metabolismo , Cirrosis Hepática/terapia , Animales , Movimiento Celular , Proliferación Celular , Quimiocina CXCL12/metabolismo , Colestasis/complicaciones , Colestasis/genética , Colestasis/patología , Colágeno/metabolismo , Citocinas/genética , Técnica del Anticuerpo Fluorescente , Regulación de la Expresión Génica , Proteínas Fluorescentes Verdes/metabolismo , Factor de Crecimiento de Hepatocito/metabolismo , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/genética , Cirrosis Hepática/patología , Masculino , Ratones Endogámicos C57BL , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Pruritus represents one of the main clinical complaints in medical practice, and leads to significant impairment of life quality and some discomfort. Although the knowledge of its main primary and secondary etiologies is well-established in Internal Medicine, especially in Hepatology, its pathophysiological basis and specific therapeutic-directed approaches are still very complex and need a proper systematization for comprehension. This review aims to present the main current themes regarding the main clinical, pathophysiological, therapeutical and management aspects of cholestasis-associated pruritus. METHODS: The authors performed a wide review of practical clinical guidelines, review articles and original articles from manuscripts published and indexed in PubMed. CONCLUSIONS: Pruritus in cholestasis represents a complex symptom in clinical practice and can be secondary to different pathophysiological mechanisms; its early recognition allows a proper therapeutic approach in most cases.
O prurido representa uma das principais queixas clínicas na prática médica e origina importante comprometimento da qualidade de vida, além de desconforto. Apesar de suas principais etiologias primárias e secundárias serem de conhecimento bem estabelecido na Clínica Médica, em especial na Hepatologia, suas bases fisiopatológicas e os princípios da terapêutica específica direcionada são bastante complexos e necessitam uma sistematização adequada para sua compreensão apropriada. Esta revisão objetiva abordar os principais temas atuais referentes às bases clínicas, fisiopatológicas, terapêuticas e de manejo do prurido relacionados à colestase. Os autores realizaram ampla revisão em diretrizes clínicas práticas, artigos de revisão e publicações originais de artigos publicados e indexados na base PubMed. O prurido na colestase representa um sintoma complexo na prática clínica e pode decorrer de diferentes mecanismos fisiopatológicos secundários. Seu reconhecimento precoce possibilita a abordagem terapêutica apropriada na maioria dos casos.
Asunto(s)
Humanos , Antipruriginosos/uso terapéutico , Colestasis/complicaciones , Prurito/etiología , Prurito/terapia , Piel/inervación , Neuralgia/fisiopatologíaRESUMEN
Polycystic liver disease is an autosomal dominant disorder commonly associated with autosomal dominant polycystic kidney disease. It is a rare disease that usually occurs asymptomatically in 85% of cases and diagnosis is incidentally. We present the case of 57 years old woman with progressive pruritus and jaundice secondary to stenosis of the common hepatic duct and common bile by liver cyst, rare presentation which only has been documented in case reports: Deepak, et al., Wittig, et al. and Howard, et al.1-3.
Asunto(s)
Colestasis/complicaciones , Quistes/complicaciones , Ictericia Obstructiva/etiología , Hepatopatías/complicaciones , Femenino , Conducto Hepático Común , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND: Biliary complications are important causes of morbidity and mortality in patients undergoing hepatic surgery. The aim of the study was to evaluate late liver alterations after a long period of choledochal clamping in Wistar rats. METHODS: Ten male Wistar rats, weighing 304 grams, anesthetized with sodium thiopental (25 mg/kg) and xylazine (10 mg/kg) intravenously, were distributed into 2 groups: the choledochal clamping group (CCG) and the operation sham group (OSG), with 5 animals each submitted to an abdominal incision. In the CCG, the choledochal was isolated, dissected, and clamped with a microvascular clamp for 40 minutes. After this occlusion time, the clamp was removed and the incision was closed. In the OSG the animals, under normal conditions, were submitted only to anesthesia and laparotomy for choledochal manipulation. In all animals, after the 31st day, a hepatic biopsy was carried out for histology and blood biochemical tests: total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase. The animals were euthanized under anesthesia. This research was approved by the Ethics Committee on Animal Use (CEUA, Unicamp, No. 2511-1). RESULTS: In the CCG, 100% of the animals showed bile duct dilatation, ductular proliferation, and portal inflammatory infiltrate; 60% showed regenerative nodule formation; and 80% had porta-porta septa and foci of necrosis, all of which were not found in the OSG. All CCG group biochemical tests had significant increases (P < .05) compared with OSG. CONCLUSIONS: Long-time choledochal clamping in Wistar rats caused hepatic dysfunction and biochemical and histological injuries with degrees of distortion to the hepatic architecture.
Asunto(s)
Conductos Biliares/patología , Conductos Biliares/cirugía , Colestasis/complicaciones , Cirrosis Hepática/etiología , Animales , Bilirrubina , Constricción , Modelos Animales de Enfermedad , Pruebas de Función Hepática , Masculino , Ratas , Ratas WistarRESUMEN
PURPOSE: To determine the effect of grape-seed extract against ischemia/reperfusion injury in cholestatic liver. METHODS: Eighteen Wistar albino rats were divided into three groups. In control and study groups, cholestasis was provided by bile duct ligation. Seven days later, the rats were subjected to 30 min hepatic ischemia, followed by 60 min of reperfusion. Oral administration of 50 mg/kg/day grape-seed extract was started 15 days before bile duct ligation and continued to the second operation in the study group. Serum, plasma and liver samples were taken. Laboratory analysis, tissue gluthation, malondialdehyde, myeloperoxidase levels and histopathological examination were performed. RESULTS: Significant decrease in liver gluthation level and significant increase in malondialdehyde level and myeloperoxidase activity were observed after ischemia/reperfusion in cholestatic rats. Serum and plasma levels for laboratory analysis were also significantly higher in cholestatic I/R group. Hepatic necrosis and fibrosis were detected in histopathological examination. Oral grape-seed extract administiration reversed all these parameters and histopathological findings except serum bilirubin levels. CONCLUSION: Oral grape-seed extract treatment can improve liver functions and attenuate the inflammation and oxidative stress in cholestatic ischemia/reperfusion injury.
Asunto(s)
Antioxidantes/farmacología , Colestasis/complicaciones , Extracto de Semillas de Uva/farmacología , Daño por Reperfusión/prevención & control , Alanina Transaminasa/efectos de los fármacos , Alanina Transaminasa/metabolismo , Animales , Aspartato Aminotransferasas/efectos de los fármacos , Aspartato Aminotransferasas/metabolismo , Bilirrubina/metabolismo , Colestasis/metabolismo , Colestasis/patología , Modelos Animales de Enfermedad , Inflamación/metabolismo , Lactato Deshidrogenasas/efectos de los fármacos , Lactato Deshidrogenasas/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Daño por Reperfusión/metabolismoRESUMEN
Abstract Objective: To evaluate the nutritional status of children with persistent cholestasis and to compare the anthropometric indices between children with and without liver cirrhosis and children with and without jaundice. Methods: Children with persistent cholestasis, i.e. increased direct bilirrubin or changes in the canalicular enzyme gamma-glutamyl transferase (GGT), were included. The anthropometric measures were weight (W), height or length (H), arm circumference (AC), triceps skinfold thickness (TST), arm muscle circumference (AMC), and body mass index (BMI). Results: Ninety-one children with cholestasis, with current median age of 12 months, were evaluated. W/age (A) and H/A indices below −2 Z-scores were observed in 33% and 30.8% of patients, respectively. Concerning the W/H index and BMI, only 12% and 16% of patients, respectively, were below −2 Z-scores. Regarding AC, 43.8% of 89 evaluated patients had some depletion. Observing the TST, 64% of patients had depletion, and 71.1% of the 45 evaluated patients had some degree of depletion regarding the ACM index. Conclusion: Evaluation using weight in patients with chronic liver diseases may overestimate the nutritional status due to visceromegaly, subclinical edema, or ascites. Indices that correlate weight and height, such as W/H and BMI, may also not show depletion because of the chronic condition in which there are depletion of both weight and height. TST, AC, and ACM are parameters that better estimate nutritional status and should be part of the management of patients with liver diseases and cholestasis.
Resumo Objetivo: Avaliar a situação nutricional de crianças com colestase persistente e comparar os índices antropométricos entre crianças com e sem cirrose hepática e crianças com e sem icterícia. Métodos: Foram incluídas crianças com colestase persistente, ou seja, aumento da bilirrubina direta ou alterações na enzima canalicular, gamaglutamiltransferase (GGT). As medidas antropométricas foram peso, estatura ou altura, circunferência do braço (CB), espessura da prega cutânea do tríceps (TST), circunferência muscular do braço (CMB) e índice de massa corporal (IMC). Resultados: Foram avaliadas 91 crianças com colestase, com idade média de 12 meses; 33% e 30,8% dos pacientes apresentaram índices P/I e A/I com escore Z abaixo de –2, respectivamente. Com relação ao índice P/A e IMC, somente 12% e 16% dos pacientes, respectivamente, apresentaram escore Z abaixo de –2. Com relação à CB, 43,8% de 89 pacientes avaliados apresentaram alguma depleção. Observando a TST, 64% dos pacientes que apresentaram depleção, 71,1% dos 45 pacientes avaliados apresentaram algum grau de depleção com relação ao índice de CMB. Conclusão: A avaliação do peso em pacientes com doenças hepáticas crônicas poderá superestimar a situação nutricional devido a visceromegalia, edema subclínico ou ascite. Os índices que correlacionam peso e altura, como P/A e IMC, também podem não mostrar depleção devido à doença crônica em que há depleção tanto do peso quanto da altura. A TST, BC e CMB são parâmetros que estimam melhor a situação nutricional e devem fazer parte de gestão de pacientes com doenças hepáticas e colestase.
Asunto(s)
Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Trastornos de la Nutrición del Niño/fisiopatología , Colestasis/fisiopatología , Ictericia/fisiopatología , Cirrosis Hepática/fisiopatología , Grosor de los Pliegues Cutáneos , Estatura , Peso Corporal , Trastornos de la Nutrición del Niño/etiología , Índice de Masa Corporal , Evaluación Nutricional , Colestasis/complicaciones , Enfermedad Crónica , Ictericia/complicaciones , Cirrosis Hepática/complicacionesRESUMEN
ABSTRACT PURPOSE: To determine the effect of grape-seed extract against ischemia/reperfusion injury in cholestatic liver. METHODS: Eighteen Wistar albino rats were divided into three groups. In control and study groups, cholestasis was provided by bile duct ligation. Seven days later, the rats were subjected to 30 min hepatic ischemia, followed by 60 min of reperfusion. Oral administration of 50 mg/kg/day grape-seed extract was started 15 days before bile duct ligation and continued to the second operation in the study group. Serum, plasma and liver samples were taken. Laboratory analysis, tissue gluthation, malondialdehyde, myeloperoxidase levels and histopathological examination were performed. RESULTS: Significant decrease in liver gluthation level and significant increase in malondialdehyde level and myeloperoxidase activity were observed after ischemia/reperfusion in cholestatic rats. Serum and plasma levels for laboratory analysis were also significantly higher in cholestatic I/R group. Hepatic necrosis and fibrosis were detected in histopathological examination. Oral grape-seed extract administiration reversed all these parameters and histopathological findings except serum bilirubin levels. CONCLUSION: Oral grape-seed extract treatment can improve liver functions and attenuate the inflammation and oxidative stress in cholestatic ischemia/reperfusion injury.