Drug-Induced Acute-on-Chronic Liver Failure: Challenges and Future Directions.

Drug-induced liver injury (DILI) is a global problem related to prescription and over-the-counter medications as well as herbal and dietary supplements. It can lead to liver failure with the risk of death and need for liver transplantation. Acute-on-chronic liver failure (ACLF) may be precipitated by DILI and is associated with a high risk of mortality. This review addresses the challenges in defining the diagnostic criteria of drug-induced ACLF (DI-ACLF). The studies characterizing DI-ACLF and its outcomes are summarized, highlighting geographic differences in underlying liver disease and implicated agents, as are future directions in the field.

Hepatitis aguda por virus E. Presentación de dos casos con evolución clínica diferente / Acute hepatitis due to E virus. Presentation of two cases with different clinical evolution

RESUMEN El virus de la hepatitis E tiene una amplia distribución a nivel mundial. Se presentaron dos casos clínicos en la provincia de Matanzas, con diagnóstico confirmado de hepatitis E mediante la determinación del ARN viral en heces fecales congeladas; a pesar de proceder de áreas de salud distantes, coincidieron en el mismo período de tiempo. El primero de ellos, una gestante asintomática diagnosticada fortuitamente a partir de elevación de enzimas hepáticas de citolisis. Evolucionó satisfactoriamente sin repercusión en su bienestar materno, trasmisión fetal, ni complicaciones perinatales. El segundo, una paciente portadora de síndrome metabólico, con evolución tórpida de su cuadro infeccioso viral, que la llevó a la insuficiencia hepática y a la muerte. Con estos casos se reflejó el amplio espectro de esta enfermedad en cuanto a formas clínicas de presentación y evolución. Se demostró que pueden ocurrir complicaciones en cualquier grupo poblacional, de ahí la importancia de considerarla en el diagnóstico diferencial de las enfermedades infecciosas hepáticas (AU).

ABSTRACT Hepatitis E virus is widely distributed around the world. Two clinical cases occurring in the province of Matanzas were presented, both with diagnosis of E hepatitis confirmed through viral RNA determination in frozen stool; although patients came from faraway health areas, they coincided in the same time period. The first patient, a pregnant asymptomatic woman, was incidentally diagnosed due to an increase of cytolysis liver enzymes. Her evolution was satisfactory without repercussion on maternal wellbeing, fetal transmission, nor perinatal complications. The second patient, a metabolic syndrome carrier, had torpid evolution of a viral infectious disease leading her to liver failure and death. These cases highlighted the wide range of this disease according to its clinical forms of presentation and evolution. It was showed that complications may occur in any population group, in consequence it is important to consider this disease when making the differential diagnosis of liver infectious diseases (AU).

Efectos protectores de la Ozonoterapia en el daño renal y hepático en la Diabetes Mellitus Tipo 2 / Protective effects of Ozone therapy on Diabetes Mellitus type 2 renal and hepatic damage

La Diabetes Mellitus tipo 2 cursa con grandes complicaciones graves como lo son la insuficiencia renal crónica, la hepatopatía, la neuropatía diabética y la enfermedad cerebrovascular relacionadas con una disfunción metabólica que conlleva a un estado de inflamación crónica en estos pacientes. Con el objetivo de evaluar la influencia de la ozonoterapia rectal como terapia complementaria en pacientes con diabetes Mellitus Tipo 2, se realizó un ensayo observacional en 38 pacientes con Diabetes Mellitus tipo 2. Los pacientes fueron distribuidos aleatoriamente en dos grupos, el primer grupo recibió tratamiento convencional (Metformina, Glibenclamida y vitaminas del complejo B) y ozonoterapia rectal y al segundo (Convencional) se le prescribió solamente tratamiento convencional. Se realizaron determinaciones en sangre de glicemia, hemoglobina glicosilada, LDL-colesterol, VLDL-colesterol y triglicéridos, además se les midió marcadores de daño hepático, de daño renal y la escala DNA-4 de dolor neuropático, al inicio y al finalizar las 20 sesiones de ozonoterapia rectal. El grupo de pacientes que recibió ozonoterapia rectal más el tratamiento convencional mostrό disminución significativa (p 0,05) los valores de glicemia, hemoglobina glicosilada, VLDL-colesterol, triglicérido, LDL ­colesterol con respecto al grupo con tratamiento convencional. La ozonoterapia rectal, redujo significativa los marcadores de daño hepático y renal al igual que la escala de dolor DN4, con respecto al grupo que solamente recibió tratamiento convencional. La aplicación complementaria de Ozonoterapia rectal mostró un efecto protector sobre la función metabólica, hepática y renal en pacientes portadores de Diabetes Mellitus tipo 2, además mostró un cierto carácter analgésico mediante la reducción del dolor en dicha enfermedad.

Diabetes Mellitus Type 2 presents with major serious complications such as chronic kidney failure, liver disease, diabetic neuropathy, cerebrovascular disease created by metabolic dysfunction that leads to a state of chronic inflammation in these patients. With the objective of evaluating the influence of rectal ozone therapy as complementary therapy in patients with Type 2 diabetes Mellitus. 38 patients suffering Diabetes Mellitus Type 2 were selected and randomly divided into two groups. The first group (Ozone) received conventional treatment plus rectal ozone therapy and the second (Conventional) only received conventional treatment. Blood glucose, glycosylated hemoglobin, LDL-cholesterol, VLDL-cholesterol and triglycerides were measured in blood, markers of liver and kidney damage and the DNA-4 scale of neuropathic pain were measured at the beginning and at end of treatments with rectal ozone therapy. The group of patients who received rectal ozone therapy plus conventional treatment showed a significant decrease in glycemic, glycated hemoglobin, VLDL-cholesterol, triglyceride, LDL-cholesterol values compared to the group with conventional treatment. It reflected significant improvement in the liver and kidney damage markers as well as the levels of the DNA.-4 pain scale, compared to the group that only received conventional treatment. The complementary application of rectal ozone therapy showed a protective effect on metabolic, liver and kidney function in patients with Type 2 Diabetes Mellitus, and also showed a certain analgesic character by reducing pain in said disease.

Guarana (Paullinia cupana) consumption improves hepatic and renal parameters in alloxan-induced diabetic rats.

INTRODUCTION: Objective: this study aims to evaluate the protective action of the guarana compound on the biochemical profile of alloxan-induced diabetes in rats. Method: twenty-eight male Wistar Furth rats were divided into four groups of seven animals each: the control group (CG) was fed a standard diet; the guarana group (GG) was fed a standard diet supplemented with guarana; the diabetic group (DG) included alloxan-induced diabetic rats fed a standard diet; and the diabetic guarana group (DGG) included alloxan-induced diabetic rats fed a standard diet supplemented with guarana. Induction was performed by intraperitoneal injection of alloxan 150 mg/kg. Results: LDL (CG: 24.64 ± 2,59; GG: 38.93 ± 7.19; DG: 14.9 ± 3.96; DGG: 20.8 ± 4.04 mg/dL); HDL (CG: 14.8 ± 4.86; GG: 13 ± 1.41; DG: 22.5 ± 7.81; DGG: 30.66 ± 9.02 mg/dL); ALT (CG: 31.8 ± 4.81; GG: 22.16 ± 1.83; DG: 38 ± 1.4; DGG: 26.83 ± 2.13 U/L); AST (CG: 101.8 ± 5.07; GG: 117.5 ± 9.73; DG: 183.6 ± 4.21; DGG: 116.16 ± 12 U/L); urea (CG: 51.4 ± 5.03; GG: 42.5 ± 8.24; DG: 129.16 ± 31.72; DGG: 150.5 ± 36.02 mg/dL); creatinine (CG: 0.6 ± 0.12; GG: 0.53 ± 0.05; DG: 0.78 ± 0.11; DGG: 0.61 ± 0.07 mg/dL). Conclusions: consumption of guarana (Paullinia cupana) by male Wistar Furth rats with alloxan induced diabetes without treatment had a beneficial effect on hepatic and renal function parameters, and raises the possibility of being used as supportive therapy in the treatment of diabetes.

INTRODUCCIÓN: Objetivo: este estudio tiene el objetivo de evaluar la posible acción protectora de este compuesto sobre el perfil bioquímico de ratas con diabetes inducida por aloxano. Material y métodos: veintiocho ratas macho Wistar Furth se dividieron en cuatro grupos de siete animales cada uno: el grupo de control (CG) se alimentó con la dieta estándar; el grupo de guaraná (GG) se alimentó con la dieta estándar complementada con guaraná; el grupo diabético (DG) se formó con ratas con diabetes inducida por aloxano que se alimentaron con la dieta estándar; el grupo diabético con guaraná (DGG) se formó con ratas con diabetes inducida por aloxano que se alimentaron con la dieta estándar complementada con guaraná. La inducción se realizó através de una inyección intraperitoneal de aloxano en dosis de 150 mg/kg. Resultados: LDL (CG: 24,64 ± 2,59; GG: 38,93 ± 7,19; DG: 14,9 ± 3,96; DGG: 20,8 ± 4,04 mg/dl); HDL (CG: 14,8 ± 4,86; GG: 13 ± 1,41; DG: 22,5 ± 7,81; DGG: 30,66 ± 9,02 mg/dl); ALT (CG: 31,8 ± 4,81; GG: 22,16 ± 1,83; DG: 38 ± 1,4; DGG: 26,83 ± 2,13 U/L); AST (CG: 101,8 ± 5,07; GG: 117,5 ± 9,73; DG: 183,6 ± 4,21; DGG: 116,16 ± 12 U/L); urea (CG: 51,4 ± 5,03; GG: 42,5 ± 8,24; DG: 129,16 ± 31,72; DGG: 150,5 ± 36,02 mg/dl); creatinina (CG: 0,6 ± 0,12; GG: 0,53 ± 0,05; DG: 0,78 ± 0,11; DGG: 0,61 ± 0,07 mg/dl). Conclusión: el consumo de guaraná (Paullinia cupana) por ratas Wistar con diabetes inducida por aloxano y sin tratamiento actuó de forma beneficiosa sobre los parámetros hepáticos y de función renal, planteando la posibilidad de poder ser utilizado como terapia de soporte en el tratamiento de la diabetes.

Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation Patients With Impaired Liver Function: A Retrospective Cohort Study.

Background Patients with impaired liver function ( ILF ) were excluded from clinical trials that investigated non-vitamin K antagonist oral anticoagulants ( NOAC s) for stroke prevention in patients with atrial fibrillation. The aim of this study was to evaluate the efficacy and safety of NOAC s in atrial fibrillation patients with ILF . Methods and Results A cohort study based on electronic medical records was conducted from 2009 to 2016 at a multicenter healthcare provider in Taiwan and included 6451 anticoagulated atrial fibrillation patients (aged 76.7±7.0 years, 52.5% male). Patients were classified into 2 subgroups: patients with normal liver function (n=5818) and patients with ILF (n=633, 9.8%). Cox regression analysis was performed to investigate the risks of thromboembolism, bleeding, and death associated with use of NOAC s and warfarin in patients with normal liver function and ILF , respectively. In patients with normal liver function, compared with warfarin therapy (n=2928), NOAC therapy (n=4048) was associated with significantly lower risks of stroke or systemic embolism (adjusted hazard ratio: 0.75; 95% confidence interval, 0.65-0.88; P<0.001) and death (adjusted hazard ratio: 0.69; 95% confidence interval, 0.60-0.80; P<0.001) with no difference in major bleeding or gastrointestinal bleeding. In patients with ILF , compared with warfarin therapy (n=394), NOAC therapy (n=342) was associated with significantly lower risk of death (adjusted hazard ratio: 0.64; 95% confidence interval, 0.49-0.83; P<0.001), but no difference in stroke or systemic embolism, major bleeding, or gastrointestinal bleeding. Conclusions In atrial fibrillation patients with ILF , NOAC therapy and warfarin therapy were associated with similar risks of stroke or systemic embolism, major bleeding, and gastrointestinal bleeding.

Agrimonia eupatoria L. (Agrimony) Extract Alters Liver Health in Subjects with Elevated Alanine Transaminase Levels: A Controlled, Randomized, and Double-Blind Trial.

Agrimonia eupatoria L. has been shown to protect against liver injury due to its lipid lowering and antioxidant activities. The aim of this research was to evaluate the effect of A. eupatoria L. aqueous extract (AEE) on 80 subjects with elevated alanine transaminase (ALT) levels in a randomized, double-blind, placebo-controlled, 8-week study. This trial was conducted between January 2013 and July 2013 at the Oriental Medical Hospital (Jecheon) of Semyung University. The trial included subjects aged 20 years or older who were diagnosed with mildly to moderately elevated ALT levels (between 45 and 135 IU/L). Subjects received two capsules of placebo or AEE twice a day for 8 weeks. Adverse events were recorded. Eighty subjects were randomized to placebo or AEE groups who had similar baseline characteristics. During the 8 weeks of treatment, 11 subjects were excluded from the analysis for protocol violation or consent withdrawal; efficacy of treatment was, therefore, evaluated in 69 subjects (placebo = 35, AEE = 34). The AEE group showed a significant reduction in ALT and serum triglyceride (TG) at 8 weeks compared with the placebo group (ALT P = .044, TG P = .020). Significant group and time interactions were found in ALT (P = .038), aspartate aminotransferase (P = .040), and TG (P = .010). Alkaline phosphatase, total bilirubin, and gamma-glutamyl transferase levels were not different between the two groups. There were no reported severe adverse events during this study, and total protein, albumin, blood urea nitrogen, creatine, and total cholesterol levels were normal in both groups. AEE consumption was safe and generally well tolerated without severe adverse events.

Dietary Supplementation with Virgin Coconut Oil Improves Lipid Profile and Hepatic Antioxidant Status and Has Potential Benefits on Cardiovascular Risk Indices in Normal Rats.

Research findings that suggest beneficial health effects of dietary supplementation with virgin coconut oil (VCO) are limited in the published literature. This study investigated the in vivo effects of a 5-week VCO-supplemented diet on lipid profile, hepatic antioxidant status, hepatorenal function, and cardiovascular risk indices in normal rats. Rats were randomly divided into 3 groups: 1 control and 2 treatment groups (10% and 15% VCO-supplemented diets) for 5 weeks. Serum and homogenate samples were used to analyze lipid profile, hepatorenal function markers, hepatic activities of antioxidant enzymes, and malondialdehyde level. Lipid profile of animals fed VCO diets showed significant reduction in total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) levels; high-density lipoprotein (HDL) level increased significantly (p < .05) compared to control; and there were beneficial effects on cardiovascular risk indices. The level of malondialdehyde (MDA), a lipid peroxidation marker, remarkably reduced and activities of hepatic antioxidant enzymes-superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)-were markedly increased in VCO diet-fed rats. The VCO diet significantly modulated creatinine, sodium (Na+), potassium (K+), chloride (Cl-), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) compared to control. The findings suggest a beneficial effect of VCO on lipid profile, renal status, hepatic antioxidant defense system, and cardiovascular risk indices in rats.

Inhibition of Toll-like receptor 4 ameliorates experimental postischemic injury in the cholestatic liver through inhibition of high-mobility group box protein b1 (HMGB1) signaling.

BACKGROUND: The objective of this study was to elucidate whether the inhibition of Toll-like receptor 4 attenuates liver injury ischemia/reperfusion in the cholestatic liver. METHOD: Rats were assigned into sham, bile duct ligation, sham ischemia/reperfusion (ischemia/reperfusion after laparotomy), and bile duct ligation ischemia/reperfusion (ischemia/reperfusion after bile duct ligation) groups. In some rats, TAK-242, an inhibitor of Toll-like receptor 4, was administered 15 minutes before ischemia/reperfusion. We measured intrahepatic Toll-like receptor 4 expression, serum hepatic marker expression, liver necrosis, gene expression of inflammation-associated factors, and serum high-mobility group box protein b1 levels. RESULTS: Intrahepatic Toll-like receptor 4 expression was significantly greater in the bile duct ligation group than in the sham group. Toll-like receptor 4 expression was further increased after ischemia/reperfusion in bile duct ligation ischemia/reperfusion groups. The levels of serum hepatic markers were significantly greater in both the sham ischemia/reperfusion and bile duct ligation ischemia/reperfusion groups than in the groups without ischemia/reperfusion. Liver necrosis was greater in the bile duct ligation group than in the sham group and was further increased in the bile duct ligation ischemia/reperfusion group. Genomic expression of inflammation-associated factors was also significantly greater in the bile duct ligation ischemia/reperfusion group than in the sham group. Serum high-mobility groups box protein b1 levels were greater in the bile duct ligation ischemia/reperfusion group than in the sham group (28.1 ng/ml versus 9.2 ng/ml, P = .011) and the bile duct ligation group (28.1 ng/ml versus 10.6 ng/ml, P = .017). These changes in the bile duct ligation ischemia/reperfusion group were significantly attenuated by preconditioning with TAK242. CONCLUSIONS: Toll-like receptor 4 inhibition has a potential to minimize severe injury after ischemia/reperfusion in the cholestatic liver through inhibition of high-mobility groups box protein b1.

Neonatal Citrulline Supplementation and Later Exposure to a High Fructose Diet in Rats Born with a Low Birth Weight: A Preliminary Report.

A low birth weight (LBW) leads to a higher risk of metabolic syndrome in adulthood. Literature suggests that citrulline supplementation in adulthood prevents the effect of a high fructose diet on energy metabolism. Whether neonatal citrulline supplementation would alter early growth or energy metabolism in the long-term in rats with LBW is unknown. LBW pups born from dams fed a low (4%) protein diet, were nursed by normally-fed dams and received isonitrogenous supplements of either l-citrulline or l-alanine by gavage from the sixth day of life until weaning, and were subsequently exposed to 10%-fructose in drinking water from weaning to 90 days of age. The oral glucose tolerance was tested (OGTT) at 70 days of age, and rats were sacrificed at 90 days of age. Pre-weaning citrulline supplementation failed to alter the growth trajectory, OGTT, plasma triglycerides, or fat mass accretion in adulthood; yet, it was associated with increased liver triglycerides, decreased liver total cholesterol, and a distinct liver lipidomic profile that may result in a predisposition to liver disease. We conclude that pre-weaning supplementation with citrulline does not impact early growth, but might impact liver fat metabolism in adulthood upon exposure to a high fructose diet.

Parenteral fish oil and liver function tests in hospitalized adult patients receiving parenteral nutrition: A propensity score-matched analysis.

BACKGROUND & AIMS: Intravenous fat emulsions are associated with liver disease and there is some evidence that the administration of intravenous fish oil (FO) may be useful in reversing it. The aim of our study was to assess whether there are differences in the changes of liver function tests (LFTs) in hospitalized adult patients with parenteral nutrition (PN) with FO and vegetal lipids vs patients without FO. The secondary aim was to study the relationship between impaired LFT and FO. METHODS: This was a 4-year, propensity score-matched analysis including patients aged ≥18 years treated with PN for ≥10 days. The exclusion criteria were previous liver disease, biliary disorders or pancreatic cancer, and altered initial LFT values. Patients were classified into 2 groups: FO cohort (patients who received FO - in addition to vegetal oil - after the first week of PN) and the vegetal oil cohort (patients who received only vegetal oil). A propensity score matched cohort design was developed. Univariate analyses were used to study the changes in LFTs. To evaluate whether LFT alterations vary with FO administration, four stepwise multiple linear regression models were conducted. RESULTS: 52 patients were included, 52% men, median 66 (55-75) years and 69 kg (61.7-78.8), with 18.5 (14-31.8) days of PN treatment. Maximum FO supplementation was 23%. During the first week with PN (none of the groups receiving FO), gammaglutamyl transferase (GGT), alkaline phosphatase (AP) and total bilirubin (BIL) increased significantly. Comparing LFT values at seven days of PN with at the end of PN treatment, the univariate analysis showed a better response for the FO group. The group without FO showed a significant increase for GGT and AP. In multivariate models, the percentage of FO administered was associated with a decrease in GGT, B = -0.33 [CI 95% = -0.54/-0.12], in AP, B = -0.12 [CI 95% = -0.20/-0.03] and ALT, B = -0.12 [CI 95% = -0.21/-0.024]. CONCLUSIONS: Lipid composition plays a significant role in LFT alteration associated with PN, and FO intravenous lipid emulsions (ILEs) minimize disturbance of LFTs in hospitalized adult patients.

Controversias sobre el rastreo de los niveles séricos de vitamina D y su suplementación / Controversies about serum vitamin D levels screening and its supplementation

Si bien los niveles bajos de vitamina D se han asociado con varios resultados de interés en salud, aún resulta motivo de controversia qué significa un nivel bajo, cual es la utilidad de su suplementación y cuales son sus potenciales efectos adversos. En ese contexto, se realizó en el Servicio de Medicina Familiar y Comunitaria del Hospital Italiano un taller de discusión denominado "Actividad ECCO" (Evidencia Científica en la Clínica Cotidiana) en la que fueron presentados los resulta-dos de estudios identificados que hubieran comparado el uso de vitamina D (con o sin suplementación de calcio) ver-sus placebo, con el objetivo de discutir cuál es la evidencia actual para el rastreo de deficiencia de vitamina D y para, eventualmente, recomendar o no su suplementación. Este artículo resume la evidencia identificada y las conclusiones consensuadas en dicha actividad. (AU)

Although low levels of vitamin D have been associated with several health outcomes, it is controversial what a low level means, the usefulness of its supplementation and its potential adverse effects. In this context, a workshop called "ECCO Activity" (Scientific Evidence in the Daily Clinic) was held in the Family and Community Medicine Division of Hospital Italiano de Buenos Aires, where the results of identified studies that compared the use of vitamin D (with or without calcium supplementation) versus placebo, with the aim of discussing what is the current evidence for screening of vitamin D deficiency and to, eventually, recommend or not its supplementation. This article summarizes the identified evidence and the agreed conclusions in that activity. (AU)

Effects of Myrtus communis extract treatment in bile duct ligated rats.

BACKGROUND: The aim of our study was to investigate the antifibrotic and antioxidant effects of Myrtus communis subsp. communis (MC) extract against liver injury and fibrosis occurring in rats with biliary obstruction. MATERIALS AND METHODS: The rats were randomized into four groups (n = 8). Control group (C), MC-administrated group (MC), the bile duct ligation (BDL), and BDL + MC groups. MC was administered at a dose of 50 mg/kg a day orally for 28 days. In blood samples, total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase levels, tumor necrosis factor-α, and interleukin-1ß measurement were measured. Oxidative injury was examined by measuring luminol and lucigenin chemiluminescence, malondialdehyde and glutathione levels, superoxide dismutase and myeloperoxidase activities. Transforming growth factor-beta and hydroxyproline levels were measured for analyzing fibrosis. The hepatic injury was also analyzed microscopically. RESULTS: Plasma total bilirubin, direct bilirubin, alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, and interleukin-1ß levels were found significantly high in the BDL group, while these values significantly decreased in the BDL group treated with MC. On the other hand, the glutathione and superoxide dismutase values significantly decreased in the BDL group compared to the control group but increased markedly in BDL + MC group compared to the BDL group. Malondialdehyde levels, myeloperoxidase activity, tissue luminol, lucigenin, transforming growth factor-beta, and hydroxyproline levels when compared with the control group increased dramatically in the BDL group and reduced the MC + BDL group. CONCLUSIONS: Our results suggest that MC protects the liver tissues against oxidative damage following BDL via its radical scavenging and antioxidant activities, which appear to involve the inhibition of tissue neutrophil infiltration.

Construction of local gene network for revealing different liver function of rats fed deep-fried oil with or without resistant starch.

To study the mechanism underlying the liver damage induced by deep-fried oil (DO) consumption and the beneficial effects from resistant starch (RS) supplement, differential gene expression and pathway network were analyzed based on RNA sequencing data from rats. The up/down regulated genes and corresponding signaling pathways were used to construct a novel local gene network (LGN). The topology of the network showed characteristics of small-world network, with some pathways demonstrating a high degree. Some changes in genes led to a larger probability occurrence of disease or infection with DO intake. More importantly, the main pathways were found to be almost the same between the two LGNs (30 pathways overlapped in total 48) with gene expression profile. This finding may indicate that RS supplement in DO-containing diet may mainly regulate the genes that related to DO damage, and RS in the diet may provide direct signals to the liver cells and modulate its effect through a network involving complex gene regulatory events. It is the first attempt to reveal the mechanism of the attenuation of liver dysfunction from RS supplement in the DO-containing diet using differential gene expression and pathway network.

Déficit de vitamina D en la enfermedad hepática crónica, análisis clínico epidemiológico y tras aporte vitamínico / Vitamin D deficiency in chronic liver disease, clinical-epidemiological analysis and report after vitamin d supplementation

INTRODUCCIÓN: La vitamina D (VD) participa en multitud de funciones extraesqueléticas en el organismo y cada vez es más importante su relación con las enfermedades hepáticas crónicas (EHC). OBJETIVOS: Analizar la prevalencia de déficit o insuficiencia de VD en los pacientes con EHC de nuestra área. Evaluar si el aporte de VD influye en la concentración sérica y se asocia a mejoría de la función hepática. MATERIAL Y MÉTODOS: Realizamos un estudio en 2 fases. En el primer tiempo se analizaron características clínico-epidemiológicas de 94 pacientes con EHC; en un segundo tiempo, se administraron diferentes dosis de calcifediol (25-OH-VD) a aquellos pacientes con déficit (<20ng/mL) e insuficiencia (20-30ng/mL) de VD. Se determinaron concentraciones plasmáticas, variables analíticas y de función hepática (Child-Pugh y MELD) al finalizar el tratamiento y se compararon con los datos basales. RESULTADOS: El 87% de los pacientes tenían concentraciones deficitarias o insuficientes de VD, con una media de 18,8ng/mL, siendo menor en los cirróticos (15,9ng/mL) (p = 0,002) y en la etiología por alcohol. Igualmente la concentración sérica de VD era inversamente proporcionales al grado de función hepática: Child A (16,52ng/mL) vs. C (7,75ng/mL). Tras el aporte con VD, se consiguió normalizar los niveles en el 94% de los pacientes, mejorar significativamente la cifra de plaquetas, de albúmina (p < 0,05) y el grado funcional valorado por la escala de Child-Pugh (p < 0,05). CONCLUSIÓN: Dada la alta prevalencia de déficit o insuficiencia de VD debería plantearse la necesidad de cribado en la población con EHC. El aporte de VD podría ser seguro y eficaz

INTRODUCTION: Vitamin D (VD) is known to have multiple extra-skeletal health functions. There is emerging interest in exploring the relationship between vitamin D and chronic liver disease (CLD). OBJECTIVES: To determine the prevalence of VD deficiency in patients with CLD in our setting and to assess whether VD supplementation influences plasma levels and is associated with improved liver function. MATERIAL AND METHODS: We conducted a study in 2 phases. First, we analysed clinical and epidemiological characteristics in 94 patients with CLD; second, different doses of calcifediol (25-OH-VD) were administered to patients with VD deficiency (<20ng/mL) and insufficiency (20-30ng/mL). Plasma concentrations and liver function (Child-Pugh and MELD) at the end of treatment were compared with baseline data. RESULTS: Deficient or insufficient VD levels were found in 87% of the patients, with an average concentration of 18.8ng/mL. Levels were lower in patients with cirrhosis (15.9ng/mL) (P=.002) and in alcoholic liver disease. VD levels were inversely proportional to the degree of liver function: Child A (16.52ng/mL) vs C (7.75ng/mL). After VD supplementation, optimal serum levels were achieved in 94% of patients and significant improvements were observed in platelet count, albumin levels (P<.05) and functional status assessed by the Child-Pugh scale (P<.05). CONCLUSION: Given the high prevalence of VD deficiency or insufficiency, the need for screening should be considered in the population with CLD. VD supplementation could be safe and effective

Lipid emulsions in the treatment and prevention of parenteral nutrition-associated liver disease in infants and children.

Long-term parenteral nutrition (PN) carries the risk of progressive liver disease in infants with intestinal failure. Although PN-associated liver disease (PNALD) is multifactorial in etiology, components of soybean oil lipid emulsions have been implicated in the disease's pathogenesis. Historically, infants with PNALD who were unable to wean from PN to full enteral feeding developed cirrhosis and end-stage liver disease, which require liver transplantation to survive. Over the past 2 decades, novel strategies for the management of parenteral lipids have improved morbidity and mortality from PNALD in infants with intestinal failure. Current strategies for the treatment of PNALD include restricting the dose of parenteral soybean oil lipid emulsion and/or replacing the soybean oil with a parenteral fish-oil lipid emulsion or emulsions of mixed-lipid sources. The purpose of this report is to review published data that evaluate these strategies in parenteral lipid management for the treatment and prevention of PNALD.

Mercuric chloride induced hepatotoxic and hematologic changes in rats: The protective effects of sodium selenite and vitamin E.

This study focuses on investigating the possible protective effect of sodium selenite (Na2SeO3) and/or vitamin E against mercuric chloride (HgCl2)-induced hepatotoxicity in rat. Male rats were given HgCl2 (1 mg/kg body weight (bw)) and HgCl2 plus Na2SeO3 (0.25 mg/kg bw) and/or vitamin E (100 mg/kg bw) daily via gavage for 4 weeks. HgCl2-treated groups had significantly higher white blood cell and thrombocyte counts than the control group. Serum activities of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl-transferase, and lactate dehydrogenase significantly increased and serum levels of total protein, albumin, triglyceride, total cholesterol, and low-density lipoprotein cholesterol significantly decreased in the HgCl2-treated groups compared with control group. Malondialdehyde level significantly increased and superoxide dismutase, catalase, and glutathione peroxidase activities decreased in liver tissue of HgCl2-treated rats. Also, HgCl2 exposure resulted in histopathological changes. Supplementation of Na2SeO3 and/or vitamin E provided partial protection in hematological and biochemical parameters that were altered by HgCl2 As a result, Na2SeO3 and/or vitamin E significantly reduced HgCl2-induced hepatotoxicity, but not protected completely.

The safety of green tea extract supplementation in postmenopausal women at risk for breast cancer: results of the Minnesota Green Tea Trial.

Green tea is thought to provide health benefits, though adverse reactions to green tea extract (GTE) have been reported. We conducted a randomized, double-blind, placebo-controlled study of GTE on breast cancer biomarkers, including mammographic density, in which 1075 postmenopausal women were randomly assigned to consume GTE containing 843 mg (-)-epigallocatechin-3-gallate (EGCG) or placebo daily for one year. There were no significant differences in % of women with adverse events (AEs, 75.6% and 72.8% of the GTE group and placebo group, respectively) or serious AEs (2.2 % and 1.5% of GTE and placebo groups, respectively). Women on GTE reported significantly higher incidence of nausea (P < 0.001) and dermatologic AEs (P = 0.05) and significantly lower diarrhea incidence (P = 0.02). More women in the GTE group experienced an alanine aminotransferase (ALT) elevation compared with placebo group (n = 36, (6.7%) vs. n = 4, (0.7%); P < 0.001). There were no statistically significant differences between groups in frequencies of other AEs. Overall, AEs were mainly mild and transient, indicating that daily consumption of GTE containing 843 mg EGCG is generally well tolerated by a group of predominantly Caucasian postmenopausal women. However, 6.7% of GTE consumers experienced ALT elevations, with 1.3% experiencing ALT-related serious AEs.

Preservation of biochemical liver function with low-dose soy-based lipids in children with intestinal failure-associated liver disease.

OBJECTIVES: Intestinal failure-associated liver disease (IFALD) contributes to significant morbidity in pediatric patients with intestinal failure (IF); however, the use of parenteral nutrition (PN) with a fish oil-based intravenous (IV) emulsion (FO) has been associated with biochemical reversal of cholestasis and improved outcomes. Unfortunately, FO increases the complexity of care: because it can be administered only under Food and Drug Administration compassionate use protocols requiring special monitoring, it is not available as a 3-in-1 solution and is more expensive than comparable soy-based IV lipid emulsion (SO). Because of these pragmatic constraints, a series of patient families were switched to low-dose (1 g kg(-1) day(-1)) SO following biochemical resolution of cholestasis. The present study examines whether reversal of cholestasis and somatic growth are maintained following this transition. METHODS: The present study is a chart review of all children with IFALD who switched from FO to SO following resolution of cholestasis. Variables are presented as medians (interquartile ranges). Comparisons were performed using the Wilcoxon signed-rank test. RESULTS: Seven patients ages 25.9 (16.2-43.2) months were transitioned to SO following reversal of cholestasis using FO. At a median follow-up of 13.9 (4.3-50.1) months, there were no significant differences between pretransition and post-transition serum alanine and aspartate aminotransferases, direct bilirubin, and weight-for-age z scores. Because of recurrence of cholestasis, 1 patient was restarted on FO after 4 months on SO. CONCLUSIONS: Biochemical reversal of IFALD and growth were preserved after transition from FO to SO in 6 of 7 (86%) patients. Given the challenges associated with the use of FO, SO may be a viable alternative in select patients with home PN.