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Background & aims: This study aims to assess the incidence and characteristics of all cancers, hepatocellular carcinoma (HCC), and extrahepatic cancers in patients with cirrhosis of various etiologies. Methods: Prospective cohort study in patients with cirrhosis but no cancer, followed every 6-9 months through the HCC early detection program. Cancer incidence was compared with Spanish population data to calculate standardized incidence ratios (SIR), and cumulative incidence was calculated separately for cancer and competing events. Longitudinal outcomes were assessed with multivariate Fine-Gray and Cox regression models. Results: A total of 215 patients (68.4% male, median age 61 years) were included. Cirrhotic etiology was alcohol (38%), hepatitis B or C virus infection (36%), alcohol plus hepatitis B or C virus infection (9%), and other causes (17%). Sixty percent were current or former smokers. Thirty-nine cancers were observed (56% liver cancer), while 3.3 were expected (SIR 11.7; 95% confidence interval [CI] 8.6-16.1). Ten (4.6%) patients were censored for liver transplantation and 34 (15.8%) for death, constituting relevant competing risks. Smoking was significantly associated with overall cancer incidence (smokers: subdistribution hazard ratio [SHR] 3.14, 95% CI 1.33-7.38; former smokers: SHR 2.54, 95% CI 1.08-5.98). In the multivariable regression analysis, viral etiology, Child-Pugh score (B or C versus A), and smoking were associated with liver cancer, and smoking with extrahepatic cancer. Conclusions: Patients with cirrhosis have an 11-fold risk of cancer compared to the general population. Risk is increased in liver and non-liver cancers. Active surveillance of any type of cancer and smoking cessation interventions are needed in these patients.
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BACKGROUND: Treatment with non-selective beta-blockers (NSBB) has been associated with anti-inflammatory and anti-cancer effects in patients with cirrhosis. This study aims to analyze the impact of chronic NSBB treatment on immune activation and disease progression in stable outpatients with cirrhosis. METHODS: In this prospective follow-up of 150 patients with cirrhosis, 39 received treatment with NSBB. Blood samples were taken every 6-9 months, and immune and adrenergic variables were measured. Mixed linear models were used to assess the effect of NSBB on these variables over time. Multivariate Cox regression was used to study associations with adverse clinical events (hepatocellular carcinoma, death, or liver transplant). RESULTS: Median follow-up was 1635 days. NSBB treatment was associated with significantly lower levels of IL-6 (ß - 4.7; 95% confidence interval [CI] -6.9, -2.6) throughout the study. During follow-up, 11 patients developed hepatocellular carcinoma, 32 died, and 4 underwent liver transplant. Patients with higher concentrations of IL-10, IL-6 and IFN-γ developed more clinical events. Event-free survival was significantly better in patients treated with NSBB (hazard ratio 0.36, 95% CI 0.18, 0.71) in a multivariate Cox regression adjusted for Child-Pugh-Score, esophageal varices, and platelets. CONCLUSION: Chronic treatment with NSBB in patients with stable cirrhosis gives rise to a different state of immune activation, characterized by lower concentrations of IL-6 over time, and it is associated with a reduced risk of adverse event (death, hepatocellular carcinoma, or transplant), after controlling for disease severity.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Estudios Prospectivos , Estudios Longitudinales , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/inducido químicamente , Interleucina-6 , Antagonistas Adrenérgicos beta/uso terapéutico , Cirrosis Hepática/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/inducido químicamenteRESUMEN
A method to obtain tetrahydroisoquinolines (THIQs) fused to tetrahydrofuran rings from aminosugar derivatives has been developed. The procedure relies on a key deprotection of benzyl ethers followed by a double-cyclization sequence, using FeCl3 as the sole reagent. This tandem reaction affords the construction of novel fused polycyclic heterocycles with total stereochemical control.
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BACKGROUND & AIMS: Few studies have fully applied an enhanced recovery after surgery (ERAS) protocol to liver transplantation (LT). Our aim was to assess the effects of a comprehensive ERAS protocol in our cohort of low- and medium-risk LT patients. METHODS: The ERAS protocol included pre-, intra-, and post-operative steps. During the five-year study period, 181 LT were performed in our institution. Two cohorts were identified: low risk patients (n = 101) had a laboratory model for end-stage liver disease (MELD) score of 20 points or less at the time of LT, received a liver from a donor after brain death, and had a balance of risk score of 9 points or less; medium-risk patients (n = 15) had identical characteristics except for a higher MELD score (21-30 points). In addition, we analyzed the remaining patients (n = 65) who were transplanted over the same study period separately using the ERAS protocol. RESULTS: The low-risk cohort showed a low need for packed red blood cells transfusion (median: 0 units) and renal replacement therapy (1%), as well as a short length of stay both in the intensive care unit (13 h) and in the hospital (4 days); morbidity during one-year follow-up, and probability of surviving to one year (89.30%) and five years (76.99%) were in line with well-established reference data. Similar findings were observed in the medium-risk cohort. CONCLUSIONS: This single-center prospective observational cohort study provides evidence that ERAS is feasible and safe for low- and medium-risk LT.
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Recuperación Mejorada Después de la Cirugía , Trasplante de Hígado/efectos adversos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de RiesgoRESUMEN
Bacterial (bact)DNA is an immunogenic product that frequently translocates into the blood in cirrhosis. We evaluated bactDNA clearance in patients undergoing liver transplantation (LT) and its association with inflammation and clinically relevant complications. We prospectively included patients consecutively admitted for LT in a one-year follow-up study. We evaluated bactDNA before and during the first month after LT, quantifying cytokine response at 30 days. One hundred patients were included. BactDNA was present in the blood of twenty-six patients undergoing LT. Twenty-four of these showed bactDNA in the portal vein, matching peripheral blood-identified bactDNA in 18 cases. Thirty-four patients showed bactDNA in blood during the first month after LT. Median TNF-α and IL-6 levels one month after LT were significantly increased in patients with versus without bactDNA. Serum TNF-α at baseline was an independent risk factor for bactDNA translocation during the first month after LT in the multivariate analysis (Odds ratio (OR) 1.14 [1.04 to 1.29], P = 0.015). One-year readmission was independently associated with the presence of bactDNA during the first month after LT (Hazard ratio (HR) 2.75 [1.39 to 5.45], P = 0.004). The presence of bactDNA in the blood of LT recipients was not shown to have any impact on complications such as death, graft rejection, bacterial or CMV infections. The rate of bactDNA translocation persists during the first month after LT and contributes to sustained inflammation. This is associated with an increased rate of readmissions in the one-year clinical outcome after LT.
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Traslocación Bacteriana/fisiología , ADN Bacteriano/sangre , Interleucina-6/sangre , Trasplante de Hígado , Factor de Necrosis Tumoral alfa/sangre , Disbiosis/microbiología , Femenino , Microbioma Gastrointestinal/fisiología , Tracto Gastrointestinal/microbiología , Humanos , Inflamación/microbiología , Cirrosis Hepática/patología , Cirrosis Hepática/cirugía , Masculino , Persona de Mediana Edad , Vena Porta/microbiología , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND & AIMS: The use of non-selective beta-blockers has been associated with lower rates of infection and reduced infection-associated morbidity in patients with cirrhosis. However, it is unknown if these drugs modify the systemic inflammatory response to circulating bacterial DNA. METHODS: Sixty-three patients with cirrhosis were included during an episode of decompensation by ascites. Thirty of those patients were on beta-blockers. Blood samples were obtained after each patient had been in the supine position for at least 30 minutes in a quiet atmosphere. Bacterial DNA, serum cytokines, nitric oxide, and LPS were determined. Phagocytic and oxidative burst activities were determined in polymorphonuclear cells from the patients. RESULTS: The detection rate of bacterial DNA in the blood was the same (33%) for patients not treated and treated with non-selective beta-blockers. Patients naive to non-selective beta-blockers showed significantly higher serum levels of IL6, IFN-gamma and IL10 in response to the presence of bacterial DNA. Patients treated with non-selective beta-blockers showed higher basal inflammatory activity that did not change with the presence of bacterial DNA. Monocytes and granulocytes from patients treated with non-selective beta-blockers showed a significantly increased phagocytic capacity in the presence of bacterial DNA. CONCLUSIONS: In patients with cirrhosis, chronic treatment with beta-blockers is associated with a higher unstimulated production of serum cytokines and an increased phagocytic activity in the presence of bacterial DNA.
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Antagonistas Adrenérgicos beta/uso terapéutico , ADN Bacteriano/sangre , Hipertensión Portal/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Cirrosis Hepática/fisiopatología , Estallido Respiratorio/efectos de los fármacos , Antagonistas Adrenérgicos beta/efectos adversos , Anciano , Ascitis/microbiología , Líquido Ascítico/microbiología , Traslocación Bacteriana/efectos de los fármacos , Citocinas/sangre , Femenino , Humanos , Hipertensión Portal/complicaciones , Modelos Lineales , Masculino , Persona de Mediana Edad , Monocitos/efectos de los fármacos , Análisis Multivariante , Neutrófilos/efectos de los fármacos , Óxido Nítrico/sangre , Estudios ProspectivosRESUMEN
The present study was designed to investigate the functional status of ß2 adrenoceptors (ß2AR) in two models of chronic inflammatory disease: liver cirrhosis (LC) and osteoarthritis (OA). The ß2AR gene contains three single nucleotide polymorphisms at amino acid positions 16, 27 and 164. The aim of the present study was to investigate the potential influence of lymphocyte ß2AR receptor functionality and genotype in LC and OA patients. Blood samples from cirrhotic patients (n=52, hepatic venous pressure gradient 13±4 mmHg, CHILD 7±2 and MELD 11±4 scores), OA patients (n=30, 84% KellgrenLawrence severity 4 grade, 14% knee replacement joint) and healthy volunteers as control group (n=26) were analyzed. Peripheral blood mononuclear cells (PBMC) were isolated from whole blood and basal and isoproterenol induced adenylate cyclase activity (isoproterenol stimulus from 109 to 104 mM), and ß2AR allelic variants (rs1042713, rs1042714, rs1800888) were determined. ß2AR functionality was decreased in the two different models of chronic inflammatory disease studied, OA (50% vs. control) and LC (85% vs. control). In these patients, the strength of the ß2AR response to adrenergic stimulation was very limited. Adrenergic modulation of PBMC function through the ß2AR stimulus is decreased in chronic inflammatory processes including LC and OA, suggesting that the adrenergic system may be important in the development of these processes.
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Genotipo , Cirrosis Hepática/etiología , Cirrosis Hepática/metabolismo , Osteoartritis/etiología , Osteoartritis/metabolismo , Receptores Adrenérgicos beta 2/genética , Receptores Adrenérgicos beta 2/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Animales , Biomarcadores , Estudios de Casos y Controles , Enfermedad Crónica , AMP Cíclico/metabolismo , Modelos Animales de Enfermedad , Femenino , Regulación de la Expresión Génica , Humanos , Leucocitos Mononucleares/metabolismo , Cirrosis Hepática/diagnóstico , Masculino , Persona de Mediana Edad , Osteoartritis/diagnósticoRESUMEN
BACKGROUND: To analyse the clinical, epidemiological, microbiological and prognostic differences of pyogenic liver abscess (PLA) in older (≥ 65 years of age) versus younger patients (< 65 years). METHODS: Multicentre, retrospective cohort study in all patients with PLA admitted to two Spanish hospitals from January 2000 to January 2014. Cases were divided into two age groups (< 65 years and ≥65 years) for comparison of clinical, epidemiological and microbiological characteristics as well as treatment. RESULTS: Of 98 patients analysed, 40 patients were younger than 65, and 58 were aged 65 or older. Significant associations in the older group were found with female sex (adjusted odds ratio [ORa] 9.0; 95% CI 1.4, 56), non-cryptogenic origin (ORa 14.5; 95% CI 1.6, 129), absence of chronic liver disease (ORa 14; 95% CI 1.3, 155), Escherichia coli infection (ORa 7.7; 95% CI 1.03, 58), and incidence of complications (ORa 2.3; 95% CI 1.04, 5.4). Mortality was 8.2% overall, although all deaths occurred in the older group (8/58; 13.8%) (p = 0.02). DISCUSSION: Our results are in consonance with other published studies. Older patients with PLA tend to present more anomalies in the biliary tract (Kai et. al, World J Gastroenterol 18: 2948-295, 2012, Rahimian et. al, Clin Infect Dis 39:1654-9, 2004, Seeto, Medicine (Baltimore) 75:99-113, 1996, Kao et.al, Aliment Pharmacol Ther 36:467-76, 2012, Lai et. al, Gastroenterology 146:129-37, 2014), while younger patients are more often male and present more commonly with previous liver disease (especially related to alcohol) and cryptogenic PLA. CONCLUSION: In patients aged 65 or older, PLA was more common in women and in those with a history of biliary disease, and E. coli was the most frequent bacterium. Mortality was also higher in the older group.
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Infecciones por Escherichia coli/diagnóstico por imagen , Infecciones por Escherichia coli/epidemiología , Escherichia coli , Absceso Piógeno Hepático/diagnóstico por imagen , Absceso Piógeno Hepático/epidemiología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVE: Currently, there are not many data on the evolution of nodular regenerative hyperplasia (NRH) associated or not with underlying diseases and in particular that associated with common variable inmunodeficiency (CVID). Twenty cases of NRH are presented, and the differences between the cases associated with CVID and those related to other diseases are analysed. METHODS: Retrospective and descriptive study over a period of 14 years. RESULTS: Twelve out of the 20 patients were men; the median age was 51 years. CVID was the main illness associated with NRH. In patients with CVID and NRH, gastrointestinal haemorrhage was more common, all the patients had high gamma glutamyl transferase and alkaline phosphatase and none had altered albumin and bilirubin levels compared to the patients without CVID. On follow-up, 50% of patients with CVID (2/4) had died compared to 33.3% (5/15) without CVID. CONCLUSIONS: NRH in patients with CVID seems to have more biochemical data of anicteric cholestasis and portal hypertension and could be associated with lower survival.
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Inmunodeficiencia Variable Común/complicaciones , Hipertensión Portal/etiología , Enfermedades Inflamatorias del Intestino/complicaciones , Regeneración Hepática , Hígado/patología , Adulto , Anciano , Comorbilidad , Várices Esofágicas y Gástricas/etiología , Femenino , Hemorragia Gastrointestinal/etiología , Humanos , Hiperplasia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Chronic pancreatitis (CP) is a relatively uncommon, complex and highly heterogeneous disease. There is no clear pattern applicable to the initial stages of CP, which hampers its early diagnosis. Some of the complications of CP, especially chronic pain, can be difficult to manage. There is wide variation in the diagnosis and treatment of CP and its complications among centers and health professionals. The Spanish Pancreatic Club has developed a consensus document on the management of CP. Two coordinators chose a multidisciplinary panel of 24 experts in this disease. A list of questions was drawn up. Each question was reviewed by two experts. These questions were then used to produce a draft, which was discussed in a face-to-face meeting with all the participants. The first part of the consensus document focusses on the diagnosis of CP and its complications.
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Pancreatitis Crónica/diagnóstico , HumanosRESUMEN
A series of carbasugars were prepared and their conformational properties studied by means of NMR spectroscopy. The results were compared to those previously found for O-, S-, and C-ß-glycoside analogs. While the rotational populations of the hydroxymethyl group in O-, S-, and C-glycosides are known to depend on the structural nature of their aglycon, in carbasugars it proved to be independent of the pseudo-aglycon. This result confirms that endocyclic oxygen is necessary for the observed relationship between the structure of the aglycon and the rotational populations of the hydroxymethyl group, and indicates that the stereoelectronic exo-anomeric effect is mainly responsible for such conformational dependence.
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Carba-azúcares/química , Glicósidos/química , Oxígeno/química , Carba-azúcares/síntesis química , Conformación de Carbohidratos , Glicósidos/síntesis química , Espectroscopía de Resonancia Magnética , SolucionesRESUMEN
OBJECTIVE: The objective of this study was to determine the prevalence and genotype distribution of chronic hepatitis C virus (HCV) infection in a penitentiary population. The secondary objective was to describe histological findings in liver of the biopsied population, and identify risk factors associated with liver fibrosis and inflammatory activity. METHODS: Among 800 inmates, 730 accepted HCV antibody screening and PCR confirmation. Sociodemographic, behavioral, and incarceration-related variables were analyzed. Liver biopsy was offered to individuals with chronic HCV infection. Advanced liver disease was defined as fibrosis 3 and/or an inflammatory activity index score 8). RESULTS: HCV antibodies were found in 279 inmates. PCR confirmed HCV infection in 250 inmates, yielding a prevalence of 34.2% (95% confidence interval [CI]: 30.8-37.8). Intravenous drug use was independently associated with HCV infection, odds ratio (OR) 51.7 (95% CI: 31-86). Genotypes were 1a 32.9%, 3 29.7%, 1b 18.4% and 4 17.1%. Fifty-one liver biopsies were performed; advanced liver disease was found in 7 patients (13.7%) based on fibrosis and in 31 patients (60.7%) based on the inflammatory activity index. High AST and ALT levels were associated with advanced liver disease established on both fibrosis and inflammatory activity (P<.05). Lengthy intravenous drug use was associated with inflammatory activity (P=.02; OR 1.2; 95% CI: 1.03-1.7). CONCLUSIONS: Persistent HCV infection is highly prevalent among prison inmates and is associated with intravenous drug abuse. HCV genotype diversity is higher in prison inmates than in the general population. Higher transaminase levels are associated with advanced liver disease.
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Hepatitis C Crónica/epidemiología , Cirrosis Hepática/epidemiología , Prisioneros/estadística & datos numéricos , Adulto , Árabes/estadística & datos numéricos , Biopsia , Comorbilidad , Europa (Continente)/etnología , Femenino , Infecciones por VIH/epidemiología , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/patología , Humanos , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , Pruebas de Función Hepática , Masculino , Reacción en Cadena de la Polimerasa , ARN Viral/sangre , Romaní/estadística & datos numéricos , Estudios Seroepidemiológicos , Índice de Severidad de la Enfermedad , España/epidemiología , Abuso de Sustancias por Vía Intravenosa/epidemiología , Adulto JovenRESUMEN
UNLABELLED: We tested the hypothesis that the presence of bacterial DNA (bactDNA) in ascitic fluid and serum is associated with decreased survival in patients with cirrhosis. In a prospective, multicenter study, we analyzed the clinical evolution of 156 patients with cirrhosis and ascites (first or recurrence) with lower than 250 polymorphonuclear cells (PMN)/muL, negative ascites bacteriological culture, and absence of other bacterial infections being admitted for evaluation of large-volume paracentesis, according to the presence of bactDNA at admission. Survival, causes of death, and successive hospital admissions were determined during a 12-month follow-up period. BactDNA was detected in 48 patients. The most prevalent identified bactDNA corresponded to Escherichia coli (n = 32/48 patients, 66.6%). Patients were followed for 12 months after inclusion and in this period 34 patients died: 16 of 108 (15%) bactDNA negative versus 18 of 48 (38%) bactDNA positive (P = 0.003). The most frequent cause of death was acute-on-chronic liver failure in both groups (7/16 and 9/18 in patients without or with bactDNA, respectively), although more prevalent in the first month of follow-up in patients with presence of bactDNA (0 versus 4/7). When considering patients with model for end-stage liver disease (MELD) score less than 15, mortality was significantly higher in those with presence of bactDNA. Spontaneous bacterial peritonitis developed similarly in patients with or without bactDNA at admission. CONCLUSION: The presence of bactDNA in a patient with cirrhosis during an ascitic episode is an indicator of poor prognosis. This fact may be related to the development of acute-on-chronic liver failure at short term and does not predict the development of spontaneous bacterial peritonitis.
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Líquido Ascítico/microbiología , ADN Bacteriano/sangre , Cirrosis Hepática/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Ascitis/epidemiología , Ascitis/microbiología , Escherichia coli/genética , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Estimación de Kaplan-Meier , Cirrosis Hepática/metabolismo , Cirrosis Hepática/mortalidad , Fallo Hepático/epidemiología , Fallo Hepático/microbiología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neutrófilos/microbiología , Peritonitis/epidemiología , Peritonitis/microbiología , Pronóstico , Estudios Prospectivos , Factores de RiesgoRESUMEN
BACKGROUND/AIMS: Extrapyramidal signs have been described in cirrhosis and there is little information about their clinical significance. The aims of this study have been to investigate the relationship between extrapyramidal signs and cognitive impairment, and what is their influence on quality of life. METHODS: 46 patients with cirrhosis were evaluated for cognitive impairment with psychometric tests (Trail-Making Test part A, Grooved-Pegboard, Block-Design, Oral Symbol Digit and Stroop Test) and cognitive evoked potentials (P300). Extrapyramidal signs were evaluated using the UPDRS scale. Health-related quality of life (HRQL) was measured using SF-36 scale and the Chronic Liver Disease Questionnaire (CLDQ). RESULTS: Twenty-two patients had extrapyramidal signs, and these patients scored worse in all psychometric tests, except Block-Design. Patients with extrapyramidal signs also showed a longer P300 latency. Moreover, patients with extrapyramidal signs had the worst score in all the HRQL scales used. A multivariate analysis disclosed that the only variable showing an independent relationship to the mental component summary of SF-36 and with CLDQ was UPDRS score. CONCLUSIONS: We have found a clear relationship between the presence of extrapyramidal signs and cognitive impairment. Moreover, patients with extrapyramidal signs have worse scores in quality of life scales.
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Enfermedades de los Ganglios Basales/diagnóstico , Enfermedades de los Ganglios Basales/etiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Calidad de Vida , Enfermedades de los Ganglios Basales/psicología , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/psicología , Potenciales Relacionados con Evento P300 , Femenino , Humanos , Cirrosis Hepática/psicología , Masculino , Persona de Mediana Edad , PsicometríaRESUMEN
Bacterial translocation is currently considered the main pathogenic mechanism leading to spontaneous bacterial peritonitis in patients with advanced cirrhosis and ascites. However, to the authors' knowledge there is no information regarding the characteristics of this process in humans. The goals of the current study were to pursue partially identified bacterial DNA in blood (what the authors consider molecular evidence of bacterial translocation) through its relative quantification in a 72-hour study period by using real-time polymerase chain reaction (PCR). A consecutive series of 17 patients with advanced cirrhosis and culture-negative, nonneutrocytic ascites were studied. Therapeutic paracentesis was performed at the time of admission, and blood samples were obtained at baseline and every 8 hours in a 3-day period. Bacterial DNA was detected by a PCR-based method, relatively quantified by real-time PCR, and identified by automated nucleotide sequencing. Seven of 17 patients demonstrated the simultaneous presence of bacterial DNA in blood and ascitic fluid at the time of admission. After therapeutic paracentesis was performed, bacterial DNA persisted in the blood for a minimum of 24 hours, and was reported to last as long as 72 hours in some patients. In addition, different patterns of bacterial DNA appearance and clearance from the blood were identified. The nucleotide sequencing process demonstrated that bacteria detected in the first sample were identical to those noted in subsequent detections over time. In conclusion, bacterial translocation is a single-species, dynamic process that appears to develop in a subgroup of patients with advanced cirrhosis.
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Ascitis/microbiología , Traslocación Bacteriana , ADN Bacteriano/sangre , Cirrosis Hepática/complicaciones , Peritonitis/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Citrobacter freundii/genética , Infecciones por Enterobacteriaceae/complicaciones , Infecciones por Enterobacteriaceae/diagnóstico , Escherichia coli/genética , Infecciones por Escherichia coli/complicaciones , Infecciones por Escherichia coli/diagnóstico , Femenino , Humanos , Infecciones por Klebsiella/complicaciones , Infecciones por Klebsiella/diagnóstico , Klebsiella pneumoniae/genética , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND/AIMS: The dysfunction of the intestinal barrier is a factor that has been related to bacterial translocation from lumen to extra-intestinal sites and consequently to the development of spontaneous bacterial peritonitis. The aim of this study was to investigate if the alterations of the intestinal barrier in cirrhosis are related with the degree of liver failure and associated with other clinical complications. METHODOLOGY: Intestinal permeability was assessed by means of the lactulose/mannitol test in 79 cirrhotic and 25 controls subjects. They received 10 g of lactulose and 5 g of mannitol. Lactulose and mannitol were measured in a five-hour urinary volume. RESULTS: Lactulose/mannitol ratio was significantly higher in cirrhotic patients than in controls (p = 0.03). This was more evident in end-stage cirrhosis. Patients with ascites, or encephalopathy showed a statistically significant increase in lactulose/mannitol ratio when compared to patients without these complications. CONCLUSIONS: The increased intestinal permeability is related to the progression of the liver disease and is more relevant with overt clinical complications. This is due to an increased absorption of lactulose. However, as liver disease progresses, mannitol absorption is progressively reduced, probably due to a reduced surface of absorption, and these events are more relevant in patients with overt clinical complications.
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Intestinos/fisiopatología , Cirrosis Hepática/fisiopatología , Progresión de la Enfermedad , Femenino , Fármacos Gastrointestinales , Humanos , Lactulosa , Masculino , Persona de Mediana Edad , Peritonitis/fisiopatologíaRESUMEN
The intramolecular attack of a hydroxy group on an exo-biscobalthexacarbonyl propargylic cation provides cyclic ethers with six- to nine-membered rings. The scope and limitations of the methodology are described. The reaction is stereoselective when additional stereocenters are present, providing iterative methodology to access ladder-like cyclic ethers.
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The current pathogenic theory of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis and ascites suggests that repeated episodes of bacterial translocation (BT) from intestinal lumen to mesenteric lymph nodes followed by systemic seeding are the key steps for the final development of infectious events. However, most of the episodes of systemic bacterial circulation remain undetected. Therefore, we investigated the hypothetical presence of bacteria in blood and/or ascitic fluid (AF) from patients with cirrhosis and sterile (culture negative) AF by means of bacterial DNA (bactDNA) detection and identification. Twenty-eight consecutively admitted patients with cirrhosis and presence of AF were included in the study. BactDNA was detected using a polymerase chain reaction (PCR)-based method. The corresponding bacteria were identified by nucleotide sequencing of purified PCR products. BactDNA was detected simultaneously in blood and AF in 9 patients (32.1%). DNA sequencing allowed the identification of Escherichia coli (n = 7) and Staphylococcus aureus (n = 2). In all cases, the similarity between the sequence found in AF and blood indicated that the bactDNA present in both locations originated from a single clone (single translocation event). Child-Pugh score and basic hemodynamic, clinical, endoscopic, and biochemical characteristics were similar among patients with or without the presence of bactDNA. In conclusion, we have detected bactDNA in serum and AF in 32% of all patients studied, and this likely represents single clone episodes of translocation and systemic seeding. E. coli is the most frequently identified bacteria.