Obesity-dependent metabolic signatures associated with nonalcoholic fatty liver disease progression.

Our understanding of the mechanisms by which nonalcoholic fatty liver disease (NAFLD) progresses from simple steatosis to steatohepatitis (NASH) is still very limited. Despite the growing number of studies linking the disease with altered serum metabolite levels, an obstacle to the development of metabolome-based NAFLD predictors has been the lack of large cohort data from biopsy-proven patients matched for key metabolic features such as obesity. We studied 467 biopsied individuals with normal liver histology (n=90) or diagnosed with NAFLD (steatosis, n=246; NASH, n=131), randomly divided into estimation (80% of all patients) and validation (20% of all patients) groups. Qualitative determinations of 540 serum metabolite variables were performed using ultraperformance liquid chromatography coupled to mass spectrometry (UPLC-MS). The metabolic profile was dependent on patient body-mass index (BMI), suggesting that the NAFLD pathogenesis mechanism may be quite different depending on an individual's level of obesity. A BMI-stratified multivariate model based on the NAFLD serum metabolic profile was used to separate patients with and without NASH. The area under the receiver operating characteristic curve was 0.87 in the estimation and 0.85 in the validation group. The cutoff (0.54) corresponding to maximum average diagnostic accuracy (0.82) predicted NASH with a sensitivity of 0.71 and a specificity of 0.92 (negative/positive predictive values=0.82/0.84). The present data, indicating that a BMI-dependent serum metabolic profile may be able to reliably distinguish NASH from steatosis patients, have significant implications for the development of NASH biomarkers and potential novel targets for therapeutic intervention.

A pilot trial of fenofibrate for the treatment of non-alcoholic fatty liver disease.

BACKGROUND: Dyslipidaemia and insulin resistance are two important risk factors for non-alcoholic fatty liver disease. Both factors can improve with fenofibrate. AIMS: To evaluate the effect of fenofibrate on the clinical, analytical and histological evolution of patients with non-alcoholic fatty liver disease. SUBJECTS AND METHODS: Sixteen consecutive patients with biopsy-confirmed non-alcoholic fatty liver disease were treated with 200mg/day of fenofibrate for 48 weeks. A clinical and biochemical follow-up was done every 3 months. A new liver biopsy was performed in all patients at the end of therapy. RESULTS: All patients completed 48 weeks of therapy with fenofibrate, without adverse events. At the end of the study, a significant decrease in triglyceride, glucose, alkaline phosphatase and gamma-glutamyl transpeptidase and an increase of apolipoprotein A1 levels were found. Insulin levels and insulin resistance showed a trend to decrease. Moreover, a reduction in the proportion of patients with abnormal aminotransferase levels (>45IU/L) was observed (alanine aminotransferase: 93.7% vs. 62.5%, p=0.02; aspartate aminotransferase: 50% vs. 18.7%, p=0.02). The body mass index did not show any significant change, but the proportion of patients with metabolic syndrome decreased significantly (43.7% vs. 18.7%, p=0.04). A control biopsy after treatment revealed a decrease in the grade of hepatocellular ballooning degeneration (p=0.03), but the grade of steatosis, lobular inflammation, fibrosis or non-alcoholic fatty liver disease activity score did not change significantly. CONCLUSIONS: In patients with non-alcoholic fatty liver disease, treatment with fenofibrate is safe and improves metabolic syndrome, glucose and liver tests. However, its effects on liver histology are minimal.

Ascitis y síndrome constitucional en una mujer de 70 años / Clinicopathological Conference Ascites and constitutional síndrome in a 70-year-old woman

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Dolor abdominal agudo con radiografía de tórax patológica / Acute abdominal pain with pathological chest X-ray

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[Epstein-Barr virus infection and acute cholestatic hepatitis]. / Infección por el virus de Epstein-Barr y hepatitis aguda colestásica.

Epstein-Barr virus (EBV) is a herpesvirus whose only reservoir host is the human. It is transmitted by oropharyngeal secretions. Primary EBV infection is usually asymptomatic, but sometimes it causes infectious mononucleosis with fever, lymphadenopathies, splenomegaly and pharyngitis. Acute infection is diagnosed by serology (heterophile or specific antibodies). Immunofluorescence and molecular biologic techniques may be used to demonstrate the presence of EBV in biopsy specimens. Mild and transient elevations of serum aminotransferases are common, thus liver biopsy is usually not necessary to confirm the diagnosis. Severe cholestasis is rare (5%). We describe a patient with cholestatic hepatitis and acute EBV infection with atypical lymphocytes and positive anti-VCA IgM. The patient had taken drugs (ibuprofen, paracetamol and valerian). The bad evolution of the patient, the history of exposure to drugs, and the few cases of cholestatic hepatitis due to EBV infection reported, led us to consider liver biopsy. Molecular biologic techniques confirmed the presence of EBV in liver tissue however histologic features did not exclude the toxic aetiology or the concomitant effect of drugs and EBV infection.

Enfermedad grasa del hígado no alcohólica. Desde la resistencia a la insulina a la disfunción mitocondrial / Non-alcoholic fatty liver disease. From insulin resistance to mitochondrial dysfunction

La enfermedad grasa del hígado no alcohólica representa unconjunto de lesiones hepáticas similares a las que produce el alcoholque se aparecen en personas que no consumen alcohol de formaabusiva. Cuando las lesiones consisten en degeneración grasae hidrópica, inflamación y, eventualmente, fibrosis se habla de esteatohepatitisno alcohólica (EHNA). No se conoce con exactitudla patogenia de estas lesiones, pero en la mayoría de los casos seasocian a la resistencia a la insulina. Consecuencia de esta, se producela lipólisis del tejido adiposo abdominal y la llegada excesivade ácidos grasos al hígado. Esto, junto con un trastorno para laexportación de los triglicéridos en forma de VLDL, determina laformación de un hígado graso. El componente inflamatorio y degenerativohepatocelular de la EHNA se atribuye al estrés oxidativo.En la génesis de este interviene la pérdida de actividad de lacadena respiratoria mitocondrial. Esto puede ser originado por elTNF-alfa, la inducción de la iNOS, la formación de peroxinitrito y lanitración en tirosina de las enzimas de esa cadena. Consecuenciasdel estrés oxidativo son: peroxidación de los lípidos de las membranascelulares, activación de las células estrelladas del hígado, fibrosishepática, inflamación crónica y apoptosis

Non-alcoholic fatty liver disease represents a set of liver lesionssimilar to those induced by alcohol that develop in individuals withno alcohol abuse. When lesions consist of fatty and hydropic degeneration,inflammation, and eventually fibrosis, the condition isdesignated non-alcoholic steatohepatitis (NASH). The pathogenesisof these lesions is not clearly understood, but they are associatedwith insulin resistance in most cases. As a result, abdominal fattissue lipolysis and excessive fatty acid uptake by the liver occur.This, together with a disturbance of triglyceride export as VLDL,results in fatty liver development. Both the inflammatory and hepatocellulardegenerative components of NASH are attributed tooxidative stress. Mitochondrial respiratory chain loss of activityplays a critical role in the genesis of latter stress. This may be initiatedby an increase in the hepatic TNF-alpha, iNOS induction, peroxynitriteformation, tyrosine nitration and inactivation of enzymesmaking up this chain. Consequences of oxidative stress include:lipid peroxidation in cell membranes, stellate cell activation in theliver, liver fibrosis, chronic inflammation, and apoptosis

Infección por el virus de Epstein-Barr y hepatitis aguda colestásica / Epstein-Barr virus infection and cholestatic hepatitis

El virus de Epstein-Barr (VEB) es un herpesvirus cuyo único huésped es el hombre, al que infecta por vía orofaríngea. La primoinfección generalmente es asintomática o cursa como una mononucleosis infecciosa que se caracteriza por fiebre, adenopatías, esplenomegalia y amigdalitis. El diagnóstico de la infección aguda suele ser serológico (anticuerpos heterófilos o específicos para el VEB), aunque el virus también puede detectarse en los tejidos mediante inmunohistoquímica o por técnicas de biología molecular. Habitualmente la infección por el VEB produce una alteración leve y autolimitada de las transaminasas (AST y ALT), por lo que no suele precisarse una biopsia hepática, y solo en el 5% causa una hepatitis aguda colestásica (HAC). Presentamos a un paciente con una HAC e infección aguda por el VEB, con linfocitos atípicos en sangre periférica y anticuerpos IgM contra la cápside VCA, que había tomado tóxicos (ibuprofeno, paracetamol y valeriana). La evolución tórpida del cuadro, la relación cronológica con la exposición a fármacos y los escasos casos publicados de HAC atribuidos al VEB, recomendaron realizar una biopsia hepática. Aunque el estudio de biología molecular en el tejido hepático resultó positivo para el VEB, los hallazgos morfológicos no permitieron excluir el origen tóxico ni la posible interacción entre fármacos y el propio virus en la etiología del cuadro

Epstein-Barr virus (EBV) is a herpesvirus whose only reservoir host is the human. It is transmitted by oropharyngeal secretions. Primary EBV infection is usually asymptomatic, but sometimes it causes infectious mononucleosis with fever, lymphadenopathies, splenomegaly and pharyngitis. Acute infection is diagnosed by serology (heterophile or specific antibodies). Immunofluorescence and molecular biologic techniques may be used to demonstrate the presence of EBV in biopsy specimens. Mild and transient elevations of serum aminotransferases are common, thus liver biopsy is usually not necessary to confirm the diagnosis. Severe cholestasis is rare (5%). We describe a patient with cholestatic hepatitis and acute EBV infection with atypical lymphocytes and positive anti-VCA IgM. The patient had taken drugs (ibuprofen, paracetamol and valerian). The bad evolution of the patient, the history of exposure to drugs, and the few cases of cholestatic hepatitis due to EBV infection reported, led us to consider liver biopsy. Molecular biologic techniques confirmed the presence of EBV in liver tissue however histologic features did not exclude the toxic aetiology or the concomitant effect of drugs and EBV infection

Peritonitis neumocócica espontánea en un cirrótico sin foco respiratorio / Spontaneous pneumococcal peritonitis in a cirrhotic patient without respiratory focus

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Non-alcoholic fatty liver disease. From insulin resistance to mitochondrial dysfunction.

Non-alcoholic fatty liver disease represents a set of liver lesions similar to those induced by alcohol that develop in individuals with no alcohol abuse. When lesions consist of fatty and hydropic degeneration, inflammation, and eventually fibrosis, the condition is designated non-alcoholic steatohepatitis (NASH). The pathogenesis of these lesions is not clearly understood, but they are associated with insulin resistance in most cases. As a result, abdominal fat tissue lipolysis and excessive fatty acid uptake by the liver occur. This, together with a disturbance of triglyceride export as VLDL, results in fatty liver development. Both the inflammatory and hepatocellular degenerative components of NASH are attributed to oxidative stress. Mitochondrial respiratory chain loss of activity plays a critical role in the genesis of latter stress. This may be initiated by an increase in the hepatic TNFalpha, iNOS induction, peroxynitrite formation, tyrosine nitration and inactivation of enzymes making up this chain. Consequences of oxidative stress include: lipid peroxidation in cell membranes, stellate cell activation in the liver, liver fibrosis, chronic inflammation, and apoptosis.

Mujer joven con colestasis y ductopenia / No disponible

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Poliposis de glándulas fúndicas: dos situaciones clínicas diferentes para una sola clase de pólipos / Fundic gland polyposis: two clinical settings for only one type of polyps

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[Electrolytic disturbances and colonoscopy: bowel lavage solutions, age and procedure].

INTRODUCTION: Colonoscopy and bowel preparation cause a number of serum electrolytes changes. AIMS: To determine the prevalence of these changes in patients who underwent colonoscopy and to identify risk factors for these effects. PATIENTS AND METHODS: Forty five patients undergoing colonoscopy were assessed prospectively. They have been previously randomized to receive either sodium phosphate (NaP) or polyethylene glycol (PEG) as preparation. Serum levels of sodium and potassium were analyzed before colonoscopy, immediately after the end of colonoscopy, and 1 hour thereafter. Serum calcium and phosphorus levels were measured just before colonoscopy. RESULTS: Twenty five patients (55.5%) received PEG and 17 (37.7%) NaP. Three patients (6.6%) did not follow the recommended bowel preparation instructions and were excluded from the study. Five patients (11%) developed hyponatremia, of whom, in 4 cases (8.8%), it occurred after the procedure. Thirteen patients (28.8%) developed hypokalemia, of whom it occurred after the end of the procedure in seven (15.5%). There was a non-significant trend to decreased serum potassium levels 1 hour after colonoscopy in patients prepared with NaP (63.6 vs 36.4%). The multivariate analysis showed that low potassium levels were independently associated with age and NaP preparation. Hypocalcemia was observed in 2 patients (4%) and hypophosphatemia in 8 (18%). Hyperphosphatemia was found in 8 cases (18%). Non-significant increases in phosphorus levels were observed in the NaP group. CONCLUSIONS: Temporal sequences of the development of serum electrolyte disturbances suggest that colonoscopy itself might play a role in the pathogenesis of these changes. Preparation for colonoscopy with NaP and the age of patients are risk factors for the development of hypokalemia.