Gelatinasas como marcadores de consumo crónico de alcohol: un estudio piloto en Uruguay / Gelatinases as markers of chronic alcohol consumption: a pilot study in Uruguay / Gelatinasas como marcadores de consumo crônico de álcool: um estúdio piloto em Uruguai

El consumo crónico de alcohol en Uruguay es un problema creciente, sin embargo, las determinaciones de biomarcadores consensuados no se realizan sistemáticamente ni se investigan otros marcadores potenciales. Para validar la hipótesis de que las metaloproteinasas de matriz con actividad gelatinasa son biomarcadores de consumo crónico de alcohol, se evaluaron muestras de sangre de 100 alcohólicos que comenzaron a atenderse en la Unidad de Trastornos Relacionados con el Alcohol y de 50 donantes sanos no alcohólicos. Las muestras de alcohólicos presentaron actividad de gelatinasas que triplicaron la de los controles y aumentos pequeños pero significativos en los niveles de γ-glutamil transferasa, aspartato-aminotransferasa y volumen corpuscular medio. Los valores de transferrina deficiente en carbohidratos fueron menores en alcohólicos que en controles. Estos resultados permiten proponer a las gelatinasas como los indicadores más sensibles del consumo sostenido de alcohol en la población analizada, ya que las enzimas hepáticas y el volumen corpuscular medio muestran una tendencia acorde con la literatura pero no alcanzaron valores asociados a la patología. Dado que la transferrina deficiente en carbohidratos es considerada el biomarcador indirecto más sensible y específico de consumo crónico de alcohol, los valores menores obtenidos en alcohólicos respecto de controles sugieren problemas metodológicos que podrían subsanarse aplicando otras técnicas de medida o por la presencia de interferencias que deben ser identificadas. Finalmente, estos hallazgos justifican una extensión de este trabajo piloto, así como estudios adicionales centrados en la participación de las metaloproteinasas de matriz con actividad gelatinasa en las cascadas de daño asociadas al consumo crónico de alcohol.

Chronic alcohol consumption in Uruguay is a growing problem, however, determinations of consensual biomarker are not performed systematically neither potential markers are explored. To validate the hypothesis that matrix metalloproteinases with gelatinase activity are biomarkers of chronic alcohol consumption, blood samples of 100 alcoholics that began medical treatment at the Unidad de Trastornos Relacionados con el Alcohol and 50 healthy non-alcoholic donors were evaluated. Alcoholic samples showed gelatinase activity that tripled that of controls and small but significant increases in levels of γ-glutamyl transferase, aspartate-aminotransferase and mean cellular volume. Carbohydrate deficient transferrin values were lower in alcoholics than in controls. These results allow proposing gelatinases as the most sensitive indicators of sustained alcohol consumption in the population analyzed since hepatic enzymes and mean cellular volume showed a tendency consistent with the literature but did not reach values associated with the pathology. Since carbohydrate-deficient transferrin is considered the most sensitive and specific indirect biomarker of chronic alcohol consumption, lower values in alcoholics related to controls suggest methodological problems that could be solved by applying other measurement techniques or by the presence of yet unknown interferences. Finally, these findings justify an extension of this pilot work, as well as additional studies focused on the participation of matrix metalloproteinases with gelatinase activity in the cascades of damage associated with chronic alcohol consumption.

O consumo crônico de álcool no Uruguai é um problema crescente, no entanto, as determinações consensuais de biomarcadores não são realizadas sistematicamente ou os potenciais marcadores são explorados. Para validar a hipótese de que as metaloproteinases de matriz com atividade gelatinase são biomarcadores do consumo crônico de álcool, foram avaliadas amostras de sangue cd 100 alcoólatras que começaram a ser tratadas na Unidad de Trastornos Relacionados con el Alcohol e 50 doadores não-alcoólatras saudáveis. As amostras alcoólicas apresentaram atividade de gelatinase que triplicou a dos controles e pequenos más significativos aumentos nos níveis de γ-glutamil transferase, aspartato-aminotransferase e volume médio celular. Os valores de transferrina deficientes em carboidratos foram menores nos alcoolistas que nos controles. Esses resultados permitem que as gelatinases sejam propostas como os indicadores mais sensíveis do consumo sustentado de álcool na população analisada, uma vez que as enzimas hepáticas e o volume celular médio apresentam uma tendência consistente com a literatura, mas não alcançaram valores associados à patologia. Como a transferrina deficiente em carboidratos é considerada o biomarcador indireto mais sensível e específico do consumo crônico de álcool, os valores mais baixos em alcoólatras do que em controles sugerem problemas metodológicos que poderiam ser sanados pela aplicação de outras técnicas de mensuração pela presença de interferências que deben ser identificadas. Finalmente, esses achados justificam uma extensão deste trabalho piloto, bem como estudos adicionais voltados para a participação de metaloproteinases de matriz com atividade de gelatinase nas cascatas de danos associados ao consumo crônico de álcool.

Hepatitis sifilítica: reporte de una serie de casos / Syphilitic hepatitis: report of three cases

Liver involvement occurs in 0.2 to 3% of patients with syphilis. We report three patients with liver involvement in syphilis. A 52-year-old male presenting with erythema and malaise. Laboratory showed a gamma glutamyl transpeptidase (GGT) of 853 u/l, alkaline phosphatases of 1,010 U/L and VDRL was positive. Treatment with penicillin resolved the skin problem and normalized liver enzymes. A HIV positive 30-year-old male in peritoneal dialysis presenting with itching, malaise and markedly elevated GGT and alkaline phosphatases. VDRL was positive. He was treated with penicillin with remission of symptoms and enzyme normalization. A 43-year-old male presenting with erythema, malaise, arthralgias and elevated GGT and alkaline phosphatases. VDRL was positive and treatment with penicillin reverted symptoms and laboratory abnormalities.

The application of Compont gel in chronic obstructive jaundice rats model

Abstract Purpose: To establish a new rat model, the pathogenesis of which is closer to the clinical occurrence of chronic obstructive jaundice with liver fibrosis. Methods: 90 SD rats were randomly divided into 3 groups. Group A common bile duct ligation, group B common bile duct injection compont and group C injection saline. The serum of three groups was extracted, and the liver function was detected by ELISA. HE staining, Masson staining and immunohistochemistry were used to detect liver pathology. Results: Group B showed a fluctuant development of jaundice, obstructive degree reached a peak at 2 weeks, and decreased from 3 weeks. HA, LA and PCIII were significantly higher than control group. 3 weeks after surgery, liver tissue fibrosis occurred in group B, and a wide range of fiber spacing was formed at 5 weeks. Immunohistochemistry showed that hepatic stellate cells were more active than the control group. Conclusion: Intra-biliary injection of Compont gel is different from the classic obstructive jaundice animal model caused by classic bile duct ligation, which can provide an ideal rat model of chronic obstructive jaundice with liver fibrosis.

Alterations in the lipid profiles and circulating liver enzymes in individuals infected by Schistosoma mansoni

Abstract INTRODUCTION Portal hypertension and periportal fibrosis commonly occur in severe Schistosoma mansoni infection. Changes in lipid profile and elevated levels of circulating liver enzymes have also been described in infected individuals. The present study sought to assess the alterations in laboratory parameters associated with liver disorder in individuals infected by S. mansoni who visited a private routine laboratory service. Levels of circulating liver enzymes (gamma-glutamyl transferase [γ-GT], aspartate transaminase [AST], alanine transaminase [ALT], and alkaline phosphatase [ALP]) and a lipid panel (total cholesterol [COL], high-density lipoprotein [HDL], low-density lipoprotein [LDL], very low-density lipoprotein [VLDL], and triglycerides [TRI]) were evaluated in both infected and non-infected individuals and relative risk was used to measure associations. METHODS Data were collected for analysis from a total of 1,078 cases identified in 379,600 individuals who submitted samples to the Datalab Laboratory (Salvador, Bahia) between 2004 and 2008. RESULTS S. mansoni infection led to increased circulating levels of γ-GT in both women and men, AST (women), and ALP (men). S. mansoni infection was a protective factor against increased levels of TRI, CHO, and VLDL for individuals aged 19 years or older. The results of our analysis indicate that alterations in lipid metabolism and circulating liver enzymes in asymptomatic S. mansoni-infected individuals might be attributed to eggs lodged in the hepatic sinusoids. CONCLUSIONS Parasitological testing for S. mansoni should be indicated in endemic areas when this pattern of alterations is detected.

Hepatitis isquémica fulminante inducida por disfunción cardiaca severa: reporte de caso / Fulminating ischemic hepatitis induced by severe cardiac dysfunction: case report

La hepatitis isquémica es una entidad infrecuente en la práctica clínica diaria con una prevalencia de 0,16 a 0,5% entre los pacientes admitidos en unidad de cuidados críticos, asociado a una mortalidad aproximada en el 60% de los casos. Esta hepatopatía se caracteriza por un incremento rápido y marcado (más de 20 veces el valor normal) del nivel de transaminasas secundario a una hipoperfusión hepática severa y persistente ocasionada por múltiples etiologías, que puede ser transitoria de identificarse y tratar la causa desencadenante oportunamente. A continuación presentamos el caso de un paciente adulto mayor con un cuadro clínico, epidemiológico y bioquímico compatible con hepatitis isquémica secundario a disfunción cardiaca severa.

Ischemic Hepatitis is an uncommon entity in daily clinical practice with a prevalence of 0.16 to 0.5% among patients admitted to a critical care unit, associated with an approximate 60% mortality rate. This liver disease is characterized by a rapid and marked increase (more than 20 times the normal value) of the level of transaminases secondary to a severe and persistent hepatic hypoperfusion caused by multiple etiologies, which may be transient when the triggering cause is timely identified and appropiately treated. The case of an elderly adult patient with a clinical, epidemiological and biochemical profile compatible with ischemic hepatitis secondary to severe cardiac dysfunction is presented below.

New index for the diagnosis of liver fibrosis in Schistosomiasis mansoni / Novo índice biológico para o diagnóstico da fibrose hepática na Esquistossomose mansoni

ABSTRACT BACKGROUND Periportal fibrosis is the major pathological consequence of the Schistosoma mansoni infection. OBJECTIVE To evaluate the accuracy of serum markers and to construct an index to assess fibrosis. METHODS Patients (n=116) with schistosomiasis were evaluated by ultrasound scan and measurements of serum levels of aminotransferases, γ-glutamyl transferase, alkaline phosphatase, hyaluronic acid, cytokines and platelets. Ultrasound images were used to evaluate the fibrosis using Niamey's classification and identified 19 patients without periportal fibrosis (patterns A and B), 48 with mild to moderate fibrosis (C and D) and 49 with advanced fibrosis (E and F). RESULTS Using multivariate analysis, a model was created, which involved alkaline phosphatase and platelets and could separate patients with different patterns of fibrosis. This index showed a better performance in separating patients without fibrosis from with advanced periportal fibrosis. The biological index showed an area under the ROC curve of 1.000. Using values below the lowest or above the highest cut-off point, the presence or absence of advanced fibrosis could be predicted in all patients. CONCLUSION The index constructed can be used to separate patients with different patterns of periportal fibrosis, specially to predict advanced fibrosis in schistosomiasis patients.

RESUMO CONTEXTO A fibrose periportal é a maior consequência patológica da infecção pelo Schistosoma mansoni. OBJETIVO Avaliar a acurácia de marcadores séricos e construir um índice para avaliar a fibrose. MÉTODOS Pacientes (n=116) com esquistossomose foram avaliados pela ultrassonografia e dosados os níveis de aminotransferases, γ-glutamil transferase, fosfatase alcalina, ácido hialurônico, citocinas e plaquetas. Imagens de ultrasom foram utilizadas para avaliar a fibrose através de classificação de Niamey e identificados 19 pacientes sem fibrose periportal (padrão A e B), 48 com fibrose média a moderada (C e D) e 49 com fibrose avançada (E e F). RESULTADOS Através de análise multivariada, um modelo foi criado, que envolveu a fosfatase alcalina e plaquetas e conseguiu separar pacientes com diferentes padrões de fibrose periportal. Este índice mostrou um melhor desempenho em separar pacientes sem fibrose dos pacientes com fibrose avançada. O índice biológico mostrou uma área sob a curva ROC de 1,000. Usando valores infereiores e acima do ponto de corte, a presença ou ausência de fibrose avançada pode ser prevista em todos os pacientes. CONCLUSÃO O índice construído pode ser usado para separar os pacientes com diferentes padrões de fibrose periportal, especialmente para prever fibrose avançada em pacientes com esquistossomose.

Candesartan, rather than losartan, improves motor dysfunction in thioacetamide-induced chronic liver failure in rats

Minimal hepatic encephalopathy is more common than the acute syndrome. Losartan, the first angiotensin-II receptor blocker (ARB), and candesartan, another widely-used ARB, have protected against developing fibrogenesis, but there is no clear data about their curative antifibrotic effects. The current study was designed to examine their effects in an already-established model of hepatic fibrosis and also their effects on the associated motor dysfunction. Low-grade chronic liver failure (CLF) was induced in 3-month old Sprague-Dawley male rats using thioacetamide (TAA, 50 mg·kg−1·day−1) intraperitoneally for 2 weeks. The TAA-CLF rats were randomly divided into five groups (n=8) treated orally for 14 days (mg·kg−1·day−1) as follows: TAA (distilled water), losartan (5 and 10 mg/kg), and candesartan (0.1 and 0.3 mg/kg). Rats were tested for rotarod and open-field tests. Serum and hepatic biochemical markers, and hepatic histopathological changes were evaluated by H&E and Masson's staining. The TAA-CLF rats showed significant increases of hepatic malondialdehyde, hepatic expression of tumor necrosis factor-α (TNF-α), and serum ammonia, alanine aminotransferase, γ-glutamyl transferase, TNF-α, and malondialdehyde levels as well as significant decreases of hepatic and serum glutathione levels. All treatments significantly reversed these changes. The histopathological changes were moderate in losartan-5 and candesartan-0.1 groups and mild in losartan-10 and candesartan-0.3 groups. Only candesartan significantly improved TAA-induced motor dysfunction. In conclusion, therapeutic antifibrotic effects of losartan and candesartan in thioacetamide-induced hepatic fibrosis in rats are possibly through angiotensin-II receptor blocking, antioxidant, and anti-inflammatory activities. Improved motor dysfunction by candesartan could be attributed to better brain penetration and slower "off-rate" from angiotensin-II receptors. Clinical trials are recommended.

Elevated gamma glutamyl transferase levels are associated with the location of acute pulmonary embolism. Cross-sectional evaluation in hospital setting / Níveis elevados de gama glutamil transferase estão associados com a localização de embolia pulmonar aguda. Estudo transversal em ambiente hospitalar

ABSTRACT CONTEXT AND OBJECTIVE: The location of embolism is associated with clinical findings and disease severity in cases of acute pulmonary embolism. The level of gamma-glutamyl transferase increases under oxidative stress-related conditions. In this study, we investigated whether gamma-glutamyl transferase levels could predict the location of pulmonary embolism. DESIGN AND SETTING: Hospital-based cross-sectional study at Cumhuriyet University, Sivas, Turkey. METHODS : 120 patients who were diagnosed with acute pulmonary embolism through computed tomography-assisted pulmonary angiography were evaluated. They were divided into two main groups (proximally and distally located), and subsequently into subgroups according to thrombus localization as follows: first group (thrombus in main pulmonary artery; n = 9); second group (thrombus in main pulmonary artery branches; n = 71); third group (thrombus in pulmonary artery segmental branches; n = 34); and fourth group (thrombus in pulmonary artery subsegmental branches; n = 8). RESULTS : Gamma-glutamyl transferase levels on admission, heart rate, oxygen saturation, right ventricular dilatation/hypokinesia, pulmonary artery systolic pressure and cardiopulmonary resuscitation requirement showed prognostic significance in univariate analysis. The multivariate logistic regression model showed that gamma-glutamyl transferase level on admission (odds ratio, OR = 1.044; 95% confidence interval, CI: 1.011-1.079; P = 0.009) and pulmonary artery systolic pressure (OR = 1.063; 95% CI: 1.005-1.124; P = 0.033) remained independently associated with proximally localized thrombus in pulmonary artery. CONCLUSIONS : The findings revealed a significant association between increased existing embolism load in the pulmonary artery and increased serum gamma-glutamyl transferase levels.

RESUMO CONTEXTO E OBJETIVO : A localização da embolia está associada com os resultados clínicos e a gravidade da doença do embolismo pulmonar agudo (EPA). O nível de gama-glutamil transferase (GGT) aumenta em condições relacionadas com estresse oxidativo. Investigou-se se os níveis de GGT podem prever a localização do EPA. TIPO DE ESTUDO E LOCAL : Estudo observacional transversal na Universidade Cumhuriyet, Sivas, Turquia. MÉTODOS : Avaliamos 120 pacientes diagnosticados com EPA após a realização de angiografia pulmonar assistida por tomografia computadorizada. Eles foram divididos em dois grupos principais (localização proximal e distal) e depois em subgrupos de acordo com a localização do trombo da seguinte forma: primeiro grupo (trombo na artéria pulmonar [AP] principal, n = 9); segundo (trombo no ramo da AP principal; n = 71); terceiro grupo (trombo na segmentar da AP; n = 34); quarto grupo (trombo na subsegmentar da AP; n = 8). RESULTADOS : Na análise univariada, os níveis de GGT tiveram significado prognóstico em relação à admissão, pulsação arterial, saturação de oxigênio, dilatação do ventrículo direito/hipocinesia, pressão sistólica da artéria pulmonar (PSAP) e necessidade de ressuscitação cardiopulmonar. O modelo de regressão logística multivariada demonstrou que o nível de GGT na admissão (razão de possibilidades, OR: 1,044; 95% intervalo de confiança, CI: 1,011-1,079; P = 0,009) e PSAP (OR: 1,063, 95% CI: 1,005-1,124; P = 0,033) permaneceram independentemente associados com trombo localizado proximalmente na AP. CONCLUSÕES : Os resultados demonstraram associação significativa entre aumento da carga existente de embolia da AP e aumento dos níveis séricos da GGT.

GAMMA GLUTAMYLTRANSFERASE IMPACT IN THERAPEUTIC RESPONSE OF CHRONIC HEPATITIS C: a systematic review of the literature / Impacto da gama glutamiltransferase na resposta terapêutica da hepatite C crônica: revisão sistemática da literatura

BackgroundThe standard treatment of chronic hepatitis C is the administration of pegylated interferon α2a or α2b in combination with ribavirin, but adverse effects can be observed, as well as the high cost of this therapy. Therefore, there is interest in understanding the predictors of sustained virologic response, as the gamma glutamyltransferase.ObjectiveTo evaluate the serum levels of gamma glutamyltransferase as a predictor of response to treatment with pegylated interferon α and ribavirin in chronic hepatitis C.MethodsThis is a systematic review of literature, conducted by consulting PUBMED, LILACS, MEDLINE, SCOPUS, Cochrane electronic databases, and active search of articles selected between January 2000 and April 2013.ResultsA total of 4,785 titles were iden tified. Out of those material, following inclusion and exclusion criteria, 273 abstracts were selected, by two independent researchers. After reading those texts, the reviewers consensually included ten studies for systematization and classification, according to the criteria of the Oxford Scale. 1B studies are predominant (prospective cohort study - six studies). Rapid virologic response and early virological response were considered as estimates for the sustained virological response. The frequency of virologic response was identified in three studies and early virological response in two, with a total of 392 and 413 patients, respectively; sustained virologic response was reported in nine articles corresponding to 3,787 patients (76.5 %).ConclusionGamma glutamyltransferase is a predictor of sustained virologic response in the treatment of chronic hepatitis C with pegylated interferon α2a or α2b associated with ribavirin.

ContextoO tratamento padrão da hepatite C crônica consiste na administração de interferon peguilado α2a ou α2b associado à ribavirina. Contudo, podem ser observados efeitos adversos além do alto custo desta terapêutica. Por isso há interesse no conhecimento dos fatores preditivos de resposta virológica sustentada como a gama glutamiltransferase.ObjetivoAvaliar os níveis séricos da gama glutamiltransferase como fator preditivo de resposta terapêutica com interferon peguilado α e ribavirina na hepatite C crônica.MétodosTrata-se de uma revisão sistemática da literatura, conduzida através de consulta às bases eletrônicas de dados PUBMED, LILACS, MEDLINE, SCOPUS e COCHRANE, e busca ativa das referências dos artigos selecionados, no período de janeiro de 2000 a abril de 2013.ResultadosForam identificados 4.785 títulos. Destes, seguindo os critérios de inclusão e exclusão, foram selecionados 273 resumos para a leitura por dois pesquisadores independentes. Após a leitura dos artigos, na íntegra e em consenso, os revisores incluíram dez estudos, para sistematização e qualificação, segundo os critérios da Escala de Oxford. Predominaram os estudos 1B A (Coorte prospectivo - seis estudos), publicações da Alemanha. A frequência de resposta virológica rápida foi identificada em três estudos e resposta virológica precoce em dois estudos, com um total de 392 e 413 pacientes respectivamente; a resposta virológica sustentada foi registrada em nove artigos correspondendo a 3.787 pacientes (76,5%).ConclusãoO nível sérico da gama glutamiltransferase é um fator preditivo de resposta virológica sustentada no tratamento da hepatite C crônica com interferon peguilado α2a ou α2b associado à ribavirina.

Toll-like receptor 3 gene polymorphisms are not associated with the risk of hepatitis B and hepatitis C virus infection

INTRODUCTION: The present study investigated the prevalence of two single-nucleotide polymorphisms (SNPs) in the Toll-like receptor 3 (TLR3) gene in patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). METHODS: Samples collected from HCV (n = 74) and HBV (n = 35) carriers were subjected to quantitative real-time PCR (qPCR) to detect the presence of the SNPs rs5743305 and rs3775291 in TLR3 and to measure the following biomarkers: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), and prothrombin time (PT). A healthy control group was investigated and consisted of 299 HCV- and HBV-seronegative individuals. RESULTS: No significant differences in allele, genotype and haplotype frequencies were observed between the investigated groups, and no association was observed between the polymorphisms and histopathological results. Nevertheless, genotypes TA/AA (rs5743305) and GG (rs3775291) appear to be associated with higher levels of ALT (p<0.01), AST (p<0.05) and PT (p<0.05). In addition, genotypes TT (rs5743305; p<0.05) and GG (rs3775291; p<0.05) were associated with higher GGT levels. CONCLUSIONS: This genetic analysis revealed the absence of an association between the polymorphisms investigated and susceptibility to HBV and HCV infection; however, these polymorphisms might be associated with a greater degree of biliary damage during the course of HCV infection. .

Physical activity as a protective factor for development of non-alcoholic fatty liver in men / Atividade física como fator de proteção para o desenvolvimento de esteatose hepática não alcoólica em homens / Atividade física como fator de proteção para o desenvolvimento de esteatose hepática não alcoólica em homens

Objective To determine the impact of physical activity on the prevalence of fatty liver, metabolic and cardiovascular disease in adult men. Methods This study evaluated 1,399 men (40.7±8.18 years) with body mass index of 26.7kg/m2 (±3.4) who participated in the Protocol of Preventive Health Check-up at Hospital Israelita Albert Einstein from January to October 2011. We conducted tests of serum blood glucose, total cholesterol, LDL, HDL, triglycerides, reactive c-protein, aspartate transaminase, alanine transaminase and gamma-glutamyl transpeptidase. The statistical analysis comprised in the comparison of mean and standard deviation. The analysis of variance was based in two paths of two way ANOVA, Student’s t-test, Mann Whitney U test, Wald test and χ2. We considered a significance level at p<0.05 and correlation of univariate Poison with 95% confidence interval. Results Fatty liver was diagnosed in 37.0% of the sample. Triglyceride levels of active men with fatty liver were 148.2±77.6mg/dL while inactive men with fatty liver had 173.4±15.6mg/dL. The remaining serum levels were normal. Inactive individuals showed higher values than active. In addition, inactive individuals have 10.68 times higher risk of developing fatty liver compared with active. Conclusion Physical activity improves metabolic parameters such as triglycerides, weight control, HDL, which interfere in the development of fatty liver. Physically active individuals had lower fatty liver prevalence regardless of values of body composition and lipid profile, leading the conclusion that physical activity has a protective role against development of fatty liver. .

Objetivo Determinar o impacto do nível de atividade física na prevalência de esteatose hepática, perfil metabólico e comportamento cardiovascular em homens adultos. Métodos Foram avaliados 1.399 homens (40,7±8,18 anos) com índice massa corporal de 26,7kg/m2 (±3,4) pelo protocolo da Revisão Continuada de Saúde do Hospital Israelita Albert Einstein entre janeiro a outubro de 2011. Foram realizadas análise séricas de glicose sanguínea, colesterol total e séries, triglicerídeos, PCR, ALT, AST e Gama GT. A análise estatística utilizada consistiu na comparação de média e desvio padrão. A análise de variância de dois caminhos ANOVA two way, teste t de Student, teste U Mann Whitney, teste de Wald e teste χ2, sendo o nível de significância p<0,05 e correlação univariada de Poison, com intervalo de confiança de 95%. Resultados Os resultados demonstraram que 37,0% da amostra apresentou diagnóstico de esteatose hepática. Homens ativos com esteatose hepática apresentaram níveis de triglicerídeos de 148,2±77,6mg/dL enquanto os inativos com esteatose hepática apresentaram 173,4±15,6mg/dL. Os demais níveis séricos apresentaram-se dentro dos padrões considerados saudáveis, porém os inativos apresentaram todos os valores superiores, em relação aos ativos. Apontou-se que indivíduos inativos apresentam 10,68 vezes maior risco em desenvolver esteatose hepática em relação aos ativos. Conclusão A atividade física melhora os indicadores metabólicos, como triglicérides, controle de peso, HDL, que interferem no desenvolvimento de esteatose hepática, mostrando que indivíduos fisicamente ativos apresentaram menor prevalência de esteatose hepática independentemente dos valores de composição corporal e perfil lipídico, concluindo que a atividade física apresenta papel protetor no desenvolvimento de esteatose hepática. .

The Influence of Alcoholic Liver Disease on Serum PIVKA-II Levels in Patients without Hepatocellular Carcinoma

BACKGROUND/AIMS: Prothrombin induced by vitamin K deficiency or antagonist II (PIVKA-II) is a widely used diagnostic marker for hepatocellular carcinoma (HCC). We evaluated the correlation between alcoholic liver disease (ALD) and serum PIVKA-II levels in chronic liver disease (CLD) patients. METHODS: We retrospectively reviewed the medical records of 2,528 CLD patients without HCC. Among these patients, 76 exhibited serum high PIVKA-II levels of >125 mAU/mL (group 1). We categorized 76 control patients matched by age, sex, and the presence of liver cirrhosis from the remaining patients who were negative for serum PIVKA-II (group 2). RESULTS: Group 1 revealed increased antibiotic usage (23.7% vs 2.6%, p<0.001) and incidence of ALD (60.5% vs 14.5%, p<0.001) as well as elevated aspartate aminotransferase (52.5 IU/L vs 30.5 IU/L, p=0.025) and gamma glutamyl transpeptidase (67.5 IU/L vs 36.5 IU/L, p=0.005) levels compared with group 2. Further, group 1 was significantly associated with a worse Child-Pugh class than group 2. In the multivariate analysis, ALD (odds ratio [OR], 7.151; p<0.001) and antibiotic usage (OR, 5.846; p<0.001) were significantly associated with positive PIVKA-II levels. CONCLUSIONS: Our study suggests that ALD and antibiotics usage may be confounding factors when interpreting high serum PIVKA-II levels in patients without HCC. Therefore, serum PIVKA-II levels in patients with ALD or in patients administered antibiotics should be interpreted with caution.

The Influence of Alcoholic Liver Disease on Serum PIVKA-II Levels in Patients without Hepatocellular Carcinoma

BACKGROUND/AIMS: Prothrombin induced by vitamin K deficiency or antagonist II (PIVKA-II) is a widely used diagnostic marker for hepatocellular carcinoma (HCC). We evaluated the correlation between alcoholic liver disease (ALD) and serum PIVKA-II levels in chronic liver disease (CLD) patients. METHODS: We retrospectively reviewed the medical records of 2,528 CLD patients without HCC. Among these patients, 76 exhibited serum high PIVKA-II levels of >125 mAU/mL (group 1). We categorized 76 control patients matched by age, sex, and the presence of liver cirrhosis from the remaining patients who were negative for serum PIVKA-II (group 2). RESULTS: Group 1 revealed increased antibiotic usage (23.7% vs 2.6%, p<0.001) and incidence of ALD (60.5% vs 14.5%, p<0.001) as well as elevated aspartate aminotransferase (52.5 IU/L vs 30.5 IU/L, p=0.025) and gamma glutamyl transpeptidase (67.5 IU/L vs 36.5 IU/L, p=0.005) levels compared with group 2. Further, group 1 was significantly associated with a worse Child-Pugh class than group 2. In the multivariate analysis, ALD (odds ratio [OR], 7.151; p<0.001) and antibiotic usage (OR, 5.846; p<0.001) were significantly associated with positive PIVKA-II levels. CONCLUSIONS: Our study suggests that ALD and antibiotics usage may be confounding factors when interpreting high serum PIVKA-II levels in patients without HCC. Therefore, serum PIVKA-II levels in patients with ALD or in patients administered antibiotics should be interpreted with caution.

Physical Activity- and Alcohol-dependent Association Between Air Pollution Exposure and Elevated Liver Enzyme Levels: An Elderly Panel Study / 예방의학회지

OBJECTIVES: The deleterious effects of air pollution on various health outcomes have been demonstrated. However, few studies have examined the effects of air pollution on liver enzyme levels. METHODS: Blood samples were drawn up to three times between 2008 and 2010 from 545 elderly individuals who regularly visited a community welfare center in Seoul, Korea. Data regarding ambient air pollutants (particulate matter < or =2.5 mum [PM2.5], nitrogen dioxide [NO2], ozone [O3], carbon monoxide, and sulfur dioxide) from monitoring stations were used to estimate air pollution exposure. The effects of the air pollutants on the concentrations of three liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and gamma-glutamyltranspeptidase [gamma-GTP)]) were evaluated using generalized additive and linear mixed models. RESULTS: Interquartile range increases in the concentrations of the pollutants showed significant associations of PM2.5 with AST (3.0% increase, p=0.0052), ALT (3.2% increase, p=0.0313), and gamma-GTP (5.0% increase, p=0.0051) levels; NO2 with AST (3.5% increase, p=0.0060) and ALT (3.8% increase, p=0.0179) levels; and O3 with gamma-GTP (5.3% increase, p=0.0324) levels. Significant modification of these effects by exercise and alcohol consumption was found (p for interaction <0.05). The effects of air pollutants were greater in non-exercisers and heavy drinkers. CONCLUSIONS: Short-term exposure to air pollutants such as PM2.5, NO2, and O3 is associated with increased liver enzyme levels in the elderly. These adverse effects can be reduced by exercising regularly and abstinence from alcohol.

Attenuation of copaiba oil in hepatic damage in rats

PURPOSE: To investigate the copaiba oil on the hepatic damage induced by acetaminophen, comparing against corn oil. METHODS: Fifty four rats were distributed into nine study groups (N=6): control group, that didn't receive the acetaminophen; Acetaminophen Group, that only received the acetaminophen; Prophylactic Copaiba Group 1, that received copaiba oil two hours before the acetaminophen; Prophylactic Copaiba Group 7, that received copaiba oil seven days, once by day, before the acetaminophen; Therapy Copaiba Group, that received the copaiba oil two hours after the acetaminophen, the corn's groups were similar than copaiba oil groups; and N-Acetyl-Cysteine Group, that received the N-Acetyl-Cysteine two hours after the acetaminophen. Euthanasia was performed after 24 hours. The serum levels transaminases, bilirubin and canalicular enzymes were analyzed. RESULTS: The prophylactic copaiba group 7, therapy copaiba group and N-Acetyl-Cysteine Group showed amounts of AST and ALT similar to the control group; and the prophylactic copaiba group 1 and corn's groups showed similar levels to the acetaminophen group. There was no significant difference between the groups regarding the amount of alkaline phosphatase and ɤ GT (p>0.05). The therapy copaiba group showed the highest levels of total bilirubin and was statistically different from the other groups (p<0.01). CONCLUSIONS: Copaiba oil administered prophylactically for seven days and therapeutically 2 hours after the acetaminophen acute intoxication offered a potential hepato protection against paracetamol-induced hepatic damage, normalizing the biochemical parameters similarly to N-Acetyl-Cysteine, and the treatment with corn oil shows no effect on the liver damage. .

Coronary artery plaque burden and calcium scores in healthy men adhering to long-term wine drinking or alcohol abstinence

Observational studies suggest there are clinical benefits to moderate red wine (RW) consumption. However, the effects on coronary vasculature and overall lifestyle are unclear. We investigated whether a lifestyle of regular long-term RW consumption is associated with changes in coronary plaque burden, calcium score, carotid intima/media thickness, endothelial function, and metabolic variables, compared with alcohol abstinence. Healthy volunteers were evaluated by coronary computed tomography angiography (CTA) as well as carotid and brachial artery ultrasound. Nutritional status, psychological status, and metabolic variables were assessed. The study included 101 drinkers [aged 58.9±7.3 years (means±SD)], from wine brotherhoods, and 104 abstainers, from Anglican, Evangelical and Catholic churches both in the city of São Paulo, Brazil. No significant differences in demographics were noted. Lesion prevalence per patient assessed by coronary CTA and classified as absent (0), 1-25, 26-49, and ≥50% stenosis was similar between groups. When analyzed by individual arteries, i.e., left anterior descending, circumflex, and right coronary, prevalence was also not different. On the other hand, calcium scores were higher among drinkers than abstainers (144.4±362.2 vs 122.0±370.3; P<0.01). However, drinkers reported less history of diabetes and exercised more. RW drinkers consumed 2127.9±387.7 kcal/day while abstainers consumed 1836.0±305.0 (P<0.0001). HDL cholesterol was significantly higher among drinkers compared to abstainers (46.9±10.9 vs 39.5±9.0 mg/dL; P<0.001), while fasting plasma glucose was lower (97.6±18.2 vs 118.4±29.6 mg/dL; P<0.02). Liver enzymes were normal in both groups. In conclusion, long-term wine drinkers displayed a similar plaque burden but greater calcium score than abstainers, despite a more atherogenic diet, and the mechanisms for the increased calcium scores in the former remain speculative.

Effect of treatment with sitagliptin on somatosensory-evoked potentials and metabolic control in patients with type 2 diabetes mellitus / Efeito do tratamento com sitagliptina sobre os potenciais evocados somatossensoriais e controle metabólico de pacientes com diabetes melito tipo 2

Objective: To evaluate the effect of sitagliptin on somatosensory-evoked potentials (SEPs) and metabolic control in patients with type 2 diabetes mellitus without clinical diabetic neuropathy. Materials and methods: Interventional, prospective, and open study. Patients with less than six months from the diagnosis were included. Examinations of SEPs and laboratory tests at fasting and after food stimulation were performed before and after three months of treatment with sitagliptin (100 mg/day). Results: There was a reduction in the mean levels of HbA1c (P < 0.0001), fasting glucose (P = 0.001), total cholesterol (P = 0.019), and ALT (P = 0.022). An increase in active GLP-1 was found at the end of the study (P = 0.0025). Several SEPs showed statistically significant differences when analyzed before and after treatment with sitagliptin. Conclusion: The results give a glimpse of the possible use of sitagliptin in the treatment of some neurodegenerative conditions of the peripheral nervous system, in addition to its already established role in glycemic control. .

Objetivo: Avaliar o efeito da sitagliptina nos potenciais evocados somatossensoriais (PESS) e controle metabólico de pacientes com diabetes melito tipo 2, sem neuropatia diabética. Materiais e métodos: Estudo de intervenção, prospectivo e aberto. Os pacientes com menos de seis meses de diagnóstico foram incluídos. Exames dos PESS e testes laboratoriais em jejum e após a estimulação com alimentos foram realizados antes e depois de três meses de tratamento com sitagliptina (100 mg/dia). Resultados: Houve redução nos níveis médios de HbA1c (P < 0,0001), glicemia de jejum (P = 0,001), colesterol total (P = 0,019) e ALT (P = 0,022). Verificou-se aumento de GLP-1 ativo (P = 0,0025). Vários PESS mostraram diferenças estatisticamente significativas quando os valores foram analisados antes e após o tratamento com sitagliptina. Conclusão: Os resultados vislumbram a possível utilização de sitagliptina no tratamento de algumas condições neurodegenerativas do sistema nervoso periférico, em adição ao seu papel no controle glicêmico. .

Liver enzymes serum levels in patients with chronic kidney disease on hemodialysis: a comprehensive review

We reviewed the literature regarding the serum levels of the enzymes aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase in patients with chronic kidney disease on hemodialysis with and without viral hepatitis. Original articles published up to January 2013 on adult patients with chronic kidney disease on hemodialysis were selected. These articles contained the words “transaminases” “aspartate aminotransferase” “alanine aminotransferase” “gamma glutamyl transferase,” “liver enzymes”, AND “dialysis” OR “hemodialysis”. A total of 823 articles were retrieved. After applying the inclusion and exclusion criteria, 49 articles were selected. The patients with chronic kidney disease on hemodialysis had reduced serum levels of aminotransferases due to hemodilution, lower pyridoxine levels, or elevated homocysteine levels. The chronic kidney disease patients on hemodialysis infected with the hepatitis C virus also had lower aminotransferase levels compared with the infected patients without chronic kidney disease. This reduction is in part due to decreased viremia caused by the dialysis method, the production of a hepatocyte growth factor and endogenous interferon-α, and lymphocyte activation, which decreases viral action on hepatocytes. Few studies were retrieved on gamma-glutamyl transferase serum levels; those found reported that there were no differences between the patients with or without chronic kidney disease. The serum aminotransferase levels were lower in the patients with chronic kidney disease on hemodialysis (with or without viral hepatitis) than in the patients with normal renal function; this reduction has a multifactorial origin.

Association between histological findings, aminotransferase levels and viral genotype in chronic hepatitis C infection

Introduction: The genomic heterogeneity of hepatitis C virus (HCV) influences liver disorders. This study aimed to determine the prevalence of HCV genotypes and to investigate the influence of these genotypes on disease progression. Methods: Blood samples and liver biopsies were collected from HCV-seropositive patients for serological analysis, biochemical marker measurements, HCV genotyping and histopathological evaluation. Results: Hepatitis C virus-ribonucleic acid (HCV-RNA) was detected in 107 patients (90.6% with genotype 1 and 9.4% with genotype 3). Patients infected with genotype 1 exhibited higher mean necroinflammatory activity and fibrosis. Conclusions: HCV genotype 1 was the most prevalent and was associated with greater liver dysfunction. .

Gender Differences in the Association between Serum gamma-Glutamyltransferase and Blood Pressure Change: A Prospective Community-Based Cohort Study

We evaluated the gender differences in the relation of baseline serum gamma-glutamyltransferase (GGT) levels to blood pressure (BP) change during 4 yr. 4,025 normotensive subjects (1,945 men and 2,080 women) who aged 40-69 yr at baseline participated in the Ansung-Ansan cohort of the Korean Genome Epidemiology Study were included. The associations of GGT with baseline BP or 4-yr change of BP were evaluated. GGT levels were associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) at baseline after adjusting for age, body mass index (BMI), HDL-cholesterol, triglyceride, C-reactive protein (CRP), current smoking status and alcohol intake (SBP, beta=1.28, P<0.001; DBP, beta=1.41, P<0.001). GGT levels were also associated with 4-yr change in BP after adjusting for age, BMI, HDL-cholesterol, triglyceride, CRP, current smoking status, alcohol intake and SBP (SBP, beta=1.08, P=0.001; DBP, beta=0.64, P=0.003). This association was statistically significant in men (SBP, beta=1.82, P<0.001; DBP, beta=1.05, P=0.001), but not in women (SBP, beta=0.38, P=0.466; DBP, beta=-0.37, P=0.304). Remarkably, this association between GGT and BP was significant in men at 40-49 yr of age. In summary, we found positive associations between GGT levels at baseline and the change of BP. The relation of GGT level and the change of BP was only significant in men, not in women, which warrants further studies to elucidate the biologic mechanisms.