Lysosomal acid lipase deficiency in Brazilian children: a case series / Deficiência de lipase ácida lisossomal em crianças brasileiras: casuística

Abstract Objective: To describe the demographic, clinical, laboratory and molecular characteristics of patients with lysosomal acid lipase deficiency. Methods: A retrospective review of the medical records of children with the disease. Results: Seven children with lysosomal acid lipase deficiency (5 male; 2 female); 6 were mixed race, and 1 was black. The mean ages at the first onset of symptoms and at diagnosis were 5.0 years (4 months to 9 years) and 6.9 years (3-10 years), respectively. Symptom manifestations at onset were: 3 patients had abdominal pain, one had bone/joint pain due to rickets, and 1 had chronic diarrhea and respiratory insufficiency due to interstitial pneumonitis. One was asymptomatic, and clinical suspicion arose due to hepatomegaly. Six patients had hepatomegaly, and none had splenomegaly. Two patients were siblings. Enzymatic assay and molecular analysis confirmed the diagnoses. Genetic analysis revealed a rare pathogenic variant (p.L89P) in three patients, described only once in medical literature and never described in Brazil. None of those patients were related to each other. Lysosomal acid lipase deficiency was previously described as an autosomal recessive disease, but three patients were heterozygous and undoubtedly had the disease (low enzyme activity, suggestive lab findings and clinical symptoms). Conclusion: This case series supports that lysosomal acid lipase deficiency can present with highly heterogeneous signs and symptoms among patients, but it should be considered in children presenting with gastrointestinal symptoms associated with dyslipidemia. We describe a rare variant in three non-related patients that may suggest a Brazilian genotype for lysosomal acid lipase deficiency.

Resumo: Objetivo: Descrever as características demográficas, clínicas, laboratoriais e moleculares de pacientes com deficiência de lipase ácida lisossomal. Métodos: Análise retrospectiva dos prontuários médicos de crianças com a deficiência de lipase ácida lisossomal. Resultados: Sete crianças com deficiência de lipase ácida lisossomal (5 M:2F); seis eram pardas e uma negra. As faixas etárias no início dos sintomas e no diagnóstico foram 5 anos (4 meses a 9 anos) e 6,9 anos (3 a 10 anos), respectivamente. As manifestações dos sintomas no início foram as que seguem: três pacientes apresentaram dor abdominal, um apresentou dor nos ossos/articulações devido a raquitismo e um apresentou diarreia crônica e insuficiência respiratória devido à pneumonite intersticial. Os outros não apresentaram sintomas e a suspeita clínica surgiu devido à hepatomegalia. Seis pacientes apresentaram hepatomegalia e um apresentou esplenomegalia. Dois pacientes eram irmãos. O ensaio enzimético e a análise molecular confirmaram os diagnósticos. A análise genética revelou uma variante patogênica rara (p.L89P) em três pacientes, descrita uma única vez na literatura médica e nunca descrita no Brasil. Nenhum desses pacientes tinha parentesco com os outros. A deficiência de lipase ácida lisossomal foi anteriormente descrita como uma doença recessiva autossômica, porém três pacientes eram heterozigotos e, sem dúvida, apresentaram a doença (atividade enzimática baixa, achados laboratoriais sugestivos e sintomas clínicos). Conclusão: Esta casuística afirma que a deficiência de lipase ácida lisossomal pode se manifestar com sinais e sintomas altamente heterogêneos entre os pacientes, porém deve ser considerada em crianças que apresentam sintomas gastrointestinais associados à dislipidemia. Descrevemos uma variante rara em três pacientes não relacionados que pode sugerir um genótipo brasileiro para deficiência de lipase ácida lisossomal.

Yellow fever: profile of cases and factors associated with death in a hospital in the State of Rio de Janeiro, 2017-2018 / Febre amarela: perfil dos casos e fatores associados ao óbito em hospital referência no estado do Rio de Janeiro, 2017-2018

ABSTRACT OBJECTIVE Describe the clinical and epidemiological profile of confirmed cases of yellow fever whose patients were hospitalized in a general hospital for infectious diseases in the State of Rio de Janeiro, Brazil, from March 11, 2017 to June 15, 2018, during a recent outbreak and factors associated with death. METHODS This is a retrospective observational study with analysis of secondary databases of local epidemiological surveillance system, and complementary data collection from epidemiological investigation records and clinical records. Study variables included demographic, epidemiological, clinical, and laboratory data. A descriptive statistical analysis and a bivariate and multivariate analysis by logistic regression were performed to analyze factors associated with death. RESULTS Fifty-two patients diagnosed with yellow fever were hospitalized, 86.5% male patients, median age 49.5 years, 40.4% rural workers. The most frequent signs and symptoms were fever (90.4%), jaundice (86.5%), nausea and/or vomiting (69.2%), changes in renal excretion (53.8%), bleeding (50%), and abdominal pain (48.1%), with comorbidity in 38.5% of all cases. The lethality rate was 40.4%. Factors significantly associated with a higher chance of death in the bivariate analysis were: bleeding, changes in renal excretion, and maximum values of direct bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine. In the multivariate analysis by logistic regression, only changes in renal excretion and ALT remained significant predictors of higher chance of death. A threshold effect was also observed for AST. The cutoff points identified as high risk for death were ALT > 4,000 U/L and AST > 6,000 U/L. CONCLUSIONS This study contributed to the knowledge on the profile of confirmed cases of high severity yellow fever. The main factors associated with death were changes in renal excretion and elevated serum transaminases, especially ALT. High lethality emphasizes the need for early diagnosis and treatment, and the importance of increasing vaccination coverage.

RESUMO OBJETIVO Descrever o perfil clínico-epidemiológico dos casos confirmados de febre amarela internados em hospital geral de referência para doenças infecciosas no estado do Rio de Janeiro, Brasil, de 11 de março de 2017 a 15 de junho de 2018, durante recente surto e fatores associados ao óbito. MÉTODOS Estudo observacional retrospectivo, com análise de bases de dados secundários da vigilância epidemiológica local e coleta complementar de dados nas fichas de investigação epidemiológica e prontuários clínicos. As variáveis analisadas incluíram dados demográficos, epidemiológicos, clínicos e laboratoriais. Foi conduzida análise estatística descritiva bivariada e múltipla por regressão logística para estudo de fatores associados ao óbito. RESULTADOS Foram internados 52 casos confirmados, 86,5% deles homens, com mediana de idade de 49,5 anos e 40,4% trabalhadores rurais. Os sinais e sintomas mais frequentes foram: febre (90,4%), icterícia (86,5%), náuseas e/ou vômitos (69,2%), alterações de excreção renal (53,8%), hemorragias (50%) e dor abdominal (48,1%), com comorbidade em 38,5% dos casos. A letalidade foi de 40,4%. Os fatores associados significativamente à maior chance de óbito na análise bivariada foram: hemorragia, alterações de excreção renal e valores máximos de bilirrubina direta, aspartato aminotransferase (AST), alanina aminotransferase (ALT), ureia e creatinina. Na análise múltipla por regressão logística, apenas alterações de excreção renal e ALT permaneceram como preditores significativos de maior chance de óbito. Observou-se ainda efeito limítrofe para AST. Os pontos de corte identificados como de alto risco para óbito foram ALT > 4.000 U/L e AST > 6.000 U/L. CONCLUSÕES O estudo contribuiu para o conhecimento do perfil de casos confirmados de febre amarela com gravidade alta. Os principais fatores associados ao óbito foram a alteração da excreção renal e a elevação sérica de transaminases, sobretudo a ALT. A letalidade elevada reforça a necessidade de diagnóstico e tratamento precoces, e a importância do incremento da cobertura vacinal.

Accuracy of transient elastography-FibroScan®, acoustic radiation force impulse (ARFI) imaging, the enhanced liver fibrosis (ELF) test, APRI, and the FIB-4 index compared with liver biopsy in patients with chronic hepatitis C

OBJECTIVES: Although liver biopsy is the gold standard for determining the degree of liver fibrosis, issues regarding its invasiveness and the small amount of liver tissue evaluated can limit its applicability and interpretation in clinical practice. Non-invasive evaluation methods for liver fibrosis can address some of these limitations. The aim of this study was to evaluate the accuracy of transient elastography-FibroScan®, acoustic radiation force impulse (ARFI), enhanced liver fibrosis (ELF), the aspartate aminotransferase-to-platelet ratio index (APRI), and the FIB-4 index compared with liver biopsy in hepatitis C. METHODS: We evaluated chronic hepatitis C patients who were followed at the Division of Clinical Gastroenterology and Hepatology, Hospital das Clínicas, Department of Gastroenterology of University of São Paulo School of Medicine, São Paulo, Brazil, and who underwent liver biopsy. The accuracy of each method was determined by a receiver operating characteristic (ROC) curve analysis, and fibrosis was classified as significant fibrosis (≥F2), advanced fibrosis (≥F3), or cirrhosis (F4). The Obuchowski method was also used to determine the diagnostic accuracy of each method at the various stages of fibrosis. In total, 107 FibroScan®, 51 ARFI, 68 ELF, 106 APRI, and 106 FIB-4 analyses were performed. RESULTS: A total of 107 patients were included in the study. The areas under the ROC curve (AUROCs) according to fibrosis degree were as follows: significant fibrosis (≥F2): FibroScan®: 0.83, FIB-4: 0.76, ELF: 0.70, APRI: 0.69, and ARFI: 0.67; advanced fibrosis (≥F3): FibroScan®: 0.85, ELF: 0.82, FIB-4: 0.77, ARFI: 0.74, and APRI: 0.71; and cirrhosis (F4): APRI: 1, FIB-4: 1, FibroScan®: 0.99, ARFI: 0.96, and ELF: 0.94. The accuracies of transient elastography, ARFI, ELF, APRI and FIB-4 determined by the Obuchowski method were F0-F1: 0.81, 0.78, 0.44, 0.72 and 0.67, respectively; F1-F2: 0.73, 0.53, 0.62, 0.60, and 0.68, respectively; F2-F3: 0.70, 0.64, 0.77, 0.60, and 0.67, respectively; and F3-F4: 0.98, 0.96, 0.82, 1, and 1, respectively. CONCLUSION: Transient elastography remained the most effective method for evaluating all degrees of fibrosis. The accuracy of all methodologies was best at F4.

A New Paradigm in Gallstones Diseases and Marked Elevation of Transaminases: An Observational Study

ABSTRACT Background. In clinical practice, it is assumed that a severe rise in transaminases is caused by ischemic, viral or toxic hepatitis. Nevertheless, cases of biliary obstruction have increasingly been associated with significant hypertransaminemia. With this study, we sought to determine the true etiology of marked rise in transaminases levels, in the context of an emergency department. Material and methods. We retrospectively identified all patients admitted to the emergency unit at Centro Hospitalar e Universitário de Coimbra between 1st January 2010 and 31st December 2010, displaying an increase of at least one of the transaminases by more than 15 times. All patient records were analyzed in order to determine the cause of hypertransaminemia. Results. We analyzed 273 patients - 146 males, mean age 65.1 ± 19.4 years. The most frequently etiology found for marked hypertransaminemia was pancreaticobiliary acute disease (n = 142;39.4%), mostly lithiasic (n = 113;79.6%), followed by malignancy (n = 74;20.6%), ischemic hepatitis (n = 61;17.0%), acute primary hepatocellular disease (n = 50;13.9%) and muscle damage (n = 23;6.4%). We were not able to determine a diagnosis for 10 cases. There were 27 cases of recurrence in the lithiasic pancreaticobiliary pathology group. Recurrence was more frequent in the group of patients who had not been submitted to early cholecystectomy after the first episode of biliary obstruction (p = 0.014). The etiology of hypertransaminemia varied according to age, cholestasis and glutamic-pyruvic transaminase values. Conclusion. Pancreaticobiliary lithiasis is the main cause of marked hypertransaminemia. Hence, it must be considered when dealing with such situations. Not performing cholecystectomy early on, after the first episode of biliary obstruction, may lead to recurrence.

Obesity, Serum Resistin and Leptin Levels Linked to Coronary Artery Disease / Obesidade, Soro Resistina e Níveis de Leptina Ligados à Doença Arterial Coronariana

Abstract Background: Clinical studies have demonstrated that adipocytokines play an important role in developing atherosclerotic cardiovascular diseases. Objective: The aim of study was to evaluate the relationship between serum resistin and leptin levels with obesity and coronary artery disease (CAD). Methods: In a cross-sectional study, we assessed the levels of serum resistin and leptin, C-reactive protein (CRP), lipid profile and cardiac enzyme tests (AST, CPK, LDH, CK-MB) in 40 CAD patients compared to 40 healthy controls. Anthropometric measurements including weight and height for calculating of body mass index (BMI), and waist circumference (WC) were performed for evaluation of obesity. Results: CAD patients had increased levels of leptin and CRP, (p < 0.001), cholesterol (p < 0.05), triglyceride (p < 0.01), and WC (p < 0.05) compared to healthy controls. There was no statistical difference between CAD and control subjects for resistin (p = 0.058). In a multiple regression analysis, only an association between serum leptin with BMI (β = 0.480, p < 0.05) and WC (β = 1.386, p < 0.05) was found. Conclusions: The findings suggest that leptin is a better marker of fat mass value than resistin and may be considered an independent risk factor for cardiac disorders that is largely dependent on obesity. However, further prospective studies are needed to confirm these results.

Resumo Fundamento: Estudos clínicos demonstraram que adipocitocinas têm papel importante no desenvolvimento de doenças cardiovasculares ateroscleróticas. Objetivo: Avaliar a relação entre níveis de leptina e resistina em soro com obesidade e doença arterial coronariana (DAC). Métodos: Em estudo transversal, avaliamos os níveis de resistina e leptina em soro, proteína C-reativa (CPR), perfil lipídico e testes de enzimas cardíacas (AST, CPK, LDH, CK-MB) em quarenta pacientes com DAC comparados a 40 controles saudáveis. Para avaliação de obesidade, foram feitas as medições antropométricas, incluindo peso e altura para o cálculo do índice de massa corporal (IMC) e circunferência da cintura (CC). Resultados: Pacientes com DAC apresentaram aumento nos níveis de leptina e CPR, (p < 0,001), colesterol (p < 0,05), triglicérides (p < 0,01) e CC (p < 0,05) em comparação aos controles. Não houve diferença significativa entre DAC e controles com relação à resistina (p = 0,058). Na análise de regressão múltipla, foi encontrada apenas uma associação entre leptina em soro ao IMC (β = 0,480, p < 0,05) e CC (β = 1,386, p < 0,05). Conclusões: Os achados sugerem que a leptina é melhor marcadora de valor de massa gorda do que a resistina, e pode ser considerada um fator de risco, dependente da obesidade, independente para distúrbios cardíacos. Contudo, outros estudos prospectivos serão necessários para a confirmação desses resultados.

Evaluation of clinical signs, parasitemia, hematologic and biochemical changes in cattle experimentally infected with Trypanosoma vivax / Avaliação dos sinais clínicos, parasitemia e alterações hematológicas e bioquímicas de bovinos experimentalmente infectados peloTrypanosoma vivax

Abstract Infections by Trypanosoma vivax cause great losses to livestock in Africa and Central and South Americas. Outbreaks due this parasite have been occurred with increasing frequency in Brazil. Knowledge of changes caused byT. vivax during the course of this disease can be of great diagnostic value. Thus, clinical signs, parasitemia, hematologic and biochemical changes of cattle experimentally infected by this hemoparasite were evaluated. Two distinct phases were verified during the infection – an acute phase where circulating parasites were seen and then a chronic phase where fluctuations in parasitemia were detected including aparasitemic periods. A constant reduction in erythrocytes, hemoglobin and packed cell volume (PVC) were observed. White blood cells (WBC) showed pronounced changes such as severe neutropenia and lymphopenia during the acute phase of the illness. Decreases in cholesterol, albumin, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and increases in glucose, globulin, protein, and alkaline phosphatase (ALP) were observed. The “Lins” isolate of T. vivax showed pathogenicity for cattle, and intense parasitemia was detected in the early stages of infection. Circulating parasites were detected for about two months. The most evident laboratory abnormalities were found in WBC parameters, including thrombocytopenia.

Resumo Infecções pelo Trypanosoma vivax causam grandes prejuízos à pecuária na África e Américas Central e do Sul. Surtos devido a este protozoário têm ocorrido com frequência cada vez maior no Brasil. O conhecimento das alterações provocadas pelo T. vivax durante a evolução desta enfermidade podem ser de grande valia para o auxílio no diagnóstico. Para tanto foram estudados os sinais clínicos, parasitemia, alterações hematológicas e bioquímicas em bovinos experimentalmente infectados por este hemoparasito. Foram verificadas duas fases distintas durante a infecção, uma aguda onde parasitos circulantes foram vistos durante todo o período, e posteriormente uma crônica, onde foram detectadas flutuações na parasitemia, com períodos aparasitêmicos. Foi verificada constante diminuição da contagem global de eritrócitos, teor de hemoglobina e volume globular (VG). O leucograma revelou leucopenia por neutropenia e linfopenia durante a fase aguda da enfermidade. Foram observados diminuição do colesterol, albumina, aspartato aminotransferase (AST), lactato desidrogenase (LDH) e aumento da glicose, globulinas, proteínas e fosfatase alcalina (FA). O isolado “Lins” de T. vivax apresentou patogenicidade para bovinos, verificando-se parasitemia intensa nos estágios iniciais da infecção, sendo detectados parasitas circulantes por aproximadamente dois meses. As alterações laboratoriais mais evidentes foram encontradas nos parâmetros do leucograma, ainda destacando-se um quadro de trombocitopenia.

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. .

Assessment of immunological changes in Epstein-Barr virus co-infection in Egyptian chronic HCV patients

Epstein-Barr virus (EBV) plays a major role in liver pathology. Similar to other members of the herpesvirus family, EBV establishes a persistent infection in more than 90% of adults. The aim of this study was to evaluate the impact of EBV and chronic hepatitis C co-infection (HCV) on biochemical and immunological responses in patients. The study was conducted in 62 patients and 33 apparently healthy controls. Patients were divided into three groups: group I, consisting of 31 patients with chronic hepatitis C infection (CHC), group II, consisting of eight patients with EBV infection and without HCV infection and group III, consisting of 23 patients with EBV and chronic HCV. The percentage of CD3+ cells, helper CD4+ cells and CD19+ B-cells was measured by flow cytometry. Human interferon-γ (IFN-γ) and interleukin (IL)-15 levels were measured by an ELISA. The levels of liver alanine aminotransferase and aspartate aminotransferase enzymes were higher in EBV/HCV patients compared to that in EBV and HCV mono-infected patients. EBV/HCV patients had significantly reduced percentages of CD3+ and CD4+ cells compared to EBV patients. Serum IFN-γ levels were significantly reduced in EBV/HCV patients (3.86 pg/mL) compared to CHC patients (6.76 pg/mL) and normal controls (4.69 pg/mL). A significant increase in serum IL-15 levels was observed in EBV/HCV patients (67.7 pg/mL) compared to EBV patients (29.3 pg/mL). Taken together, these observations suggest that HCV and EBV co-infection can potentiate immune response dampening in patients.

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. .

Liver enzymes in patients with chronic kidney disease undergoing peritoneal dialysis and hemodialysis

OBJECTIVE: The present study was designed to analyze the serum levels of aspartate and alanine aminotransferases, gamma-glutamyl transferase, and the hematocrit in patients with chronic kidney disease who were undergoing peritoneal dialysis or hemodialysis. PATIENTS AND METHODS: Twenty patients on peritoneal dialysis and 40 on hemodialysis were assessed, and the patients were matched according to the length of time that they had been on dialysis. Blood samples were collected (both before and after the session for those on hemodialysis) to measure the enzymes and the hematocrit. RESULTS: In the samples from the patients who were undergoing peritoneal dialysis, the aspartate and alanine aminotransferase levels were slightly higher compared with the samples collected from the patients before the hemodialysis session and slightly lower compared with the samples collected after the hemodialysis session. The levels of gamma-glutamyl transferase in the hemodialysis patients were slightly higher than the levels in the patients who were undergoing peritoneal dialysis. In addition, the levels of aminotransferases and gamma-glutamyl transferase that were collected before the hemodialysis session were significantly lower than the values collected after the session. The hematocrit levels were significantly lower in the patients who were on peritoneal dialysis compared with the patients on hemodialysis (both before and after the hemodialysis session), and the levels were also significantly lower before hemodialysis compared with after hemodialysis. CONCLUSION: The aminotransferase levels in the patients who were undergoing peritoneal dialysis were slightly higher compared with the samples collected before the hemodialysis session, whereas the aminotransferase levels were slightly lower compared with the samples collected after the session. The hematocrits and the aminotransferase and gamma-glutamyl transferase levels of the samples collected after the hemodialysis session were significantly higher than the samples collected before the session. Taken together, the present data suggest that hemodilution could alter the serum levels of liver enzymes.

Analysis of 83 consecutive liver transplants performed at a tertiary care reference hospital in the interior of the state of Sao Paulo / Analise de 83 transplantes hepáticos consecutivos realizados em hospital universitário de referência terciária do interior do estado de São Paulo

PURPOSE: To analyze pre-, intra- and immediate postoperative parameters of patients submitted to liver transplantation. METHODS: Eighty-three consecutive orthotopic liver transplants performed from January 2009 to July 2011 were analyzed. The patients were divided into 2 groups: A, survivors (MELD between 9 and 60) and B, non-survivors (MELD between 14 and 40), with 30.6 percent of group A patients being CHILD C, 51℅ CHILD B and 18,4℅ CHILD A. In group B ,32.1℅ of the patients were CHILD C, 42,9℅ CHILD B, and 25℅ CHILD A. All orthotopic liver transplantations were performed using the piggyback technique without a portacaval shunt. Systemic arterial pressure and serum ALT and AST levels were determined preoperatively and 5, 60 and 1440 minutes after arterial graft revascularization. Serum ALT and AST profiles were evaluated for seven days after surgery. RESULTS: Systemic arterial blood pressure levels, time of hot and hypothermic ischemia and time of graft implant were statistically similar for the two groups (p>0.05). Serum levels (U/L) of ALT and AST at the 5, 60 and 1440 minute time points after arterial revascularization of the graft were also similar for the two groups studied, as also were the serum ALT and AST profiles. CONCLUSIONS: No statistically significant difference in any of the parameters studied was detected between the two groups. Under the conditions of the present study and on the basis of the parameters evaluated, no direct relation was detected between the intraoperative period and the type of patient outcome in the two groups studied.

OBJETIVO: Analisar parâmetros do pré, intra e pós-operatório imediato de pacientes submetidos ao transplante de fígado. MÉTODOS: Foram analisados 83 transplantes ortotópicos de fígado realizados consecutivamente no período janeiro de 2009 a julho de 2011. Os pacientes foram dividos em dois grupos: A, survivors (MELD entre 16 e 60), e B, non-survivors (MELD entre 14 e 40) sendo que 30,6℅ dos pacientes do grupo A eram CHILD C, 51℅ CHILD B e 18,4℅ CHILD A. No grupo B, 32,1℅ dos pacientes eram CHILD C, 42,9℅ CHILD B, e 25℅ CHILD A. Todos os transplantes ortotópicos de fígado foram feitos com a técnica de piggyback sem "shunt" porto cava. Foram analisados os valores de pressão arterial sistêmica e os níveis séricos de ALT e AST, no pré-operatório, 5, 60 e 1440 minutos após revascularização arterial do enxerto. Avaliaram-se os perfis séricos da ALT e AST durante sete dias de pós-operatorio. RESULTADOS: Verificou-se que em ambos os grupos, os níveis de pressão arterial sistêmica, os tempos de isquemia normotérmica, hipotérmica e de implante do enxerto foram estatisticamente semelhantes (p>0,05). Os níveis séricos (U/L) de ALT e AST nos tempos de 5, 60 e 1440 minutos após a revascularização arterial do enxerto também foram semelhantes nos grupos estudados. Os perfis séricos da ALT e AST foram semelhantes nos dois grupos estudados. CONCLUSÕES: Não se verificou diferença estatisticamente significante entre todos os parâmetros estudados, em ambos os grupos. Nas condições do presente estudo, não se verificou relação direta do intra-operatório com o tipo de evolução (outcome) dos pacientes nos dois grupos estudados.

Clinical and laboratory findings in patients with dengue associated with hepatopathy / Achados clínicos e laboratoriais em pacientes com dengue associada à hepatopatia

INTRODUCTION: Hepatic disorders caused by dengue infection may progress to severe manifestations, including mortality and morbidity. Cytokines are involved in it, such as the migration inhibitory factor of macrophages (MIF), tumor necrosis factor (TNF), natural killer cells (NK), B lymphocytes, and macrophages. METHODS: This study was carried out from January to April 2007 at a public hospital from the Federal University of Mato Grosso do Sul, Campo Grande, Brazil. Sixty-eight patients were studied concerning hepatic alterations, with 56 reported having classic dengue, 6 with hemorrhagic dengue grade I, and 6 with hemorrhagic dengue grade II. RESULTS: Among the 56 with classic dengue, 83.3 percent had aspartate aminotransferase (AST) alterations, and 69.6 percent had altered alanine aminotransferase (ALT). For those with hemorrhagic dengue grade I, 100 percent had AST alterations, and 83.3 percent had altered ALT. All the patients with hemorrhagic dengue grade II had AST and ALT alterations. AST variations reached 22.0 and 907.0, with an average value of 164.6. For ALT, we found variations between 25.0 and 867.0, with an average value of 166.07. There had been statistical significance between dengue clinical shapes and hepatic function markers. CONCLUSIONS: We conclude that the infection was predominant in adults, females, and in those with low income and education. The liver enzymes were of larger amount in hemorrhagic dengue, but there was weak statistical evidence of the clinical manifestations and transaminases. Major signs and clinical symptoms were fever, headache, myalgia, arthralgia, weakness, severe pain behind the eyes, and rashes.

INTRODUÇÃO: Afecções hepáticas causadas pela infecção da dengue podem evoluir para quadro grave, incluindo mortalidade e morbidade. O mecanismo de lesão do fígado está relacionado com a exacerbação da resposta imune. As citocinas estão envolvidas nele como fator inibidor da migração de macrófagos (MIF), fator de necrose tumoral (TNF), células natural killer (NK), B linfócitos e macrófagos. MÉTODOS: Este estudo foi realizado em um hospital público da Universidade Federal do Mato Grosso do Sul. As alterações hepáticas pelo dengue podem evoluir com quadros graves e potencialmente letais. Foram avaliados exames de 68 pacientes atendidos e confirmados com dengue, onde 56 foram classificados como dengue clássico, seis, como dengue hemorrágico grau I e seis como dengue hemorrágico grau II. RESULTADOS: Do dengue clássico, 83,3 por cento tiveram alterações de aspartato aminotransferase (AST) e 69,6 por cento alterações para alanino aminotransferase (ALT). No dengue hemorrágico grau I, AST elevou-se 100 por cento e para ALT 83,3 por cento. No dengue hemorrágico grau II observou-se 100 por cento de alterações tanto para AST, quanto para ALT. A variação de AST ficou entre 22,0 e 907,0 com média de 164,6. A alanino aminotransferase variou entre 25,0 e 867,0 com média de 166,07. Houve significância entre formas clínicas do dengue e marcadores de função hepática. CONCLUSÕES: Conclui-se que a infecção predominou em adultos do sexo feminino, de baixa renda e escolaridade. As enzimas hepáticas elevam-se mais no dengue hemorrágico, fraca evidência estatística entre as manifestações clínicas e as transaminases. Os mais prevalentes sinais/sintomas clínicos foram febre, cefaléia, mialgia, artralgia, fraqueza, dor retrorbitária e exantema.

Successful rituximab therapy in refractory autoimmune hepatitis and Evans syndrome / Tratamiento exitoso de hepatitis autoinmune y síndrome de Evans con rituximab

A 44-year-old woman was found to have elevated aminotransferases, twice the upper limit of normal. Liver biopsy demonstrated a mixed inflammatory process suggestive of both primary biliary cirrhosis and autoimmune hepatitis (AIH). Prednisone and azathioprine were started, with normalization of aminotransferases. Six months later, she returned with worsening pruritus and re-evaluation demonstrated probable reactivation of AIH with acute elevation of liver injury tests. Repeat liver biopsy was suggestive of a flare of AIH which did not respond to prednisone, azathioprine, or mycophenolate mofetil. One month later the patient was hospitalized for sudden onset of anemia and thrombocytopenia, suggestive of autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura consistent with Evans syndrome. Rituximab was initiated and mycophenolate mofetil discontinued. After one infusion of rituximab, liver injury tests significantly improved. Within four weeks of rituximab infusion (4 doses) the patient's Evans syndrome completely resolved with normal hemoglobin and platelet levels; aminotransferases also significantly improved to less than twice the upper limit of normal.

Biochemical liver function after partial hepatic resection with or without partial hepatic vascular exclusion / Função bioquímica do fígado após ressecção hepática parcial com ou sem exclusão vascular hepática parcial

PURPOSE: The aim of the present study was to assess the advantages and disadvantages of liver vascular partial exclusion (LVPE) (liver dysfunction due to ischemia) during liver resection in patients submitted to partial hepatectomy. METHODS: A total of 114 patients were submitted to partial hepatectomy (minor versus major resections) with LPVE being used in 57 of them but not in the remaining 57. Patient age ranged from 35 to 73 years and 57 percent were women. Mitochondrial function was assessed 30 minutes after liver resection in the remnant liver and serum aminotransferases were determined before surgery and for seven days postoperatively. LPVE time ranged from 30 to 60 minutes. Data were analyzed statistically by the Student T test (5 percent level of significance). RESULTS: Mitochondrial function was similar in the minor and major liver resections. The maximum postoperative aminotransferase peak was similar in the groups with and without LPVE. CONCLUSION: LPVE did not induce mitochondrial changes in hepatic tissue in either type of surgery, and aminotransferase levels were similar for patients with and without LPVE. Thus, the results show that LPVE is a safe procedure that does not induce the significant changes typical of ischemia and reperfusion in the liver remnant.

OBJETIVO: Avaliar as vantagens e desvantagens da oclusão vascular parcial do fígado durante ressecções hepáticas parciais. MÉTODOS: Cento e quatorze pacientes foram submetidos a hepatectomia parcial(ressecção maior versus ressecção menor) com liver partial vascular exclusion (LPVE) sendo utilizada em 57 deles. A idade dos pacientes variou entre 35 e 73 anos e 57 por cento deles eram mulheres. A função mitocondrial foi avaliada por método polarografico avaliada 30 minutos após a ressecção hepática no fígado remanescente, e o perfil das aminotransferase foi determinado antes da cirurgia e durante sete dias de pós-operatório. A EVPH variou de 30 a 60 minutos. Dados foram analisados estatisticamente pelo teste T Student (nível de significância de 5 por cento). RESULTADOS: Nas ressecções hepáticas maiores e menores, a função mitocondrial do fígado remanescente foi semelhante dos dois grupos. O pico máximo de aminotransferases ocorreu as 24 horas de pós-operatório e o perfil enzimático de ALT e AST foi semelhante nos grupos estudados ( minor vs major hepatectomy.) CONCLUSÃO: A EVPH não induziu alterações mitocondriais no tecido hepático em qualquer tipo de cirurgia, e os níveis de aminotransferases foram similares para pacientes hepatectomizados com e sem LPVE.Assim a LPVE foi um procedimento seguro que não induziu alterações significativas típicos de isquemia e reperfusão no fígado remanescente.

Chronic hepatitis virus infection in patients with multiple myeloma: clinical characteristics and outcomes

OBJECTIVES: Cytotoxic agents and steroids are used to treat lymphoid malignancies, but these compounds may exacerbate chronic viral hepatitis. For patients with multiple myeloma, the impact of preexisting hepatitis virus infection is unclear. The aim of this study is to explore the characteristics and outcomes of myeloma patients with chronic hepatitis virus infection. METHODS: From 2003 to 2008, 155 myeloma patients were examined to determine their chronic hepatitis virus infection statuses using serologic tests for the hepatitis B (HBV) and C viruses (HCV). Clinical parameters and outcome variables were retrieved via a medical chart review. RESULTS: The estimated prevalences of chronic HBV and HCV infections were 11.0 percent (n = 17) and 9.0 percent (n = 14), respectively. The characteristics of patients who were hepatitis virus carriers and those who were not were similar. However, carrier patients had a higher prevalence of conventional cytogenetic abnormalities (64.3 percent vs. 25.0 percent). The cumulative incidences of grade 3-4 elevation of the level of alanine transaminase, 30.0 percent vs. 12.0 percent, and hyperbilirubinemia, 20.0 percent vs. 1.6 percent, were higher in carriers as well. In a Kaplan-Meier analysis, carrier patients had worse overall survival (median: 16.0 vs. 42.4 months). The prognostic value of carrier status was not statistically significant in the multivariate analysis, but an age of more than 65 years old, the presence of cytogenetic abnormalities, a beta-2-microglobulin level of more than 3.5 mg/L, and a serum creatinine level of more than 2 mg/ dL were independent factors associated with poor prognosis. CONCLUSION: Myeloma patients with chronic hepatitis virus infections might be a distinct subgroup, and close monitoring of hepatic adverse events should be mandatory.

Alteración de pruebas hepáticas en pacientes chilenos con enfermedades hepáticas agudas y crónicas / Liver enzyme alteration in Chilean patients with acute and chronic liver diseases

Background: Liver function tests are a useful tool in clinical practice to identify patterns that are characteristic of liver enzyme alterations associated to liver diseases. Objective: To perform a descriptive analysis of liver enzyme abnormalities among Chilean population affected by chronic or acute liver diseases, compared with international reports. Material and Methods: Prospective study with > 18 year-old patients who were under medical care in the Hepatology department at the Clinic of the Pontificia Universidad Católica and at Posta Central hospital, between 2005- 2009. All of them had at least one evaluation of liver function test during this period. Results: 348 patients were evaluated: 49 non-alcoholic steatohepatitis (NASH), 28 primary biliary cirrhosis (PBC), 74 autoimmune hepatitis (AIH), 10 hemochromatosis, 147 chronic hepatitis C (HCV), 5 chronic hepatitis B (HBC) and 34 severe alcoholic hepatitis. Piruvic and Oxaloacetic Aminotransferase levels were: NASH 89.9 and 62.7 IU/L, PBC 105.5 and 96 IU/L; AIH 412 and 360IU/L; Hemochromatosis 106 and 75.9 IU/L, HCV 178 and 166 IU/L, HVB 337.2 and 89.6 IU/L, and in alcoholic hepatitis, 67 and 168 IU/L. Levels of alkaline phosphatase in PBC were 518 IU/L, with a maximum level of 2206. Conclusions: This study describes the transaminase abnormalities in a subgroup of patients with known hepatic disease. Future studies will be useful to determine if there are substantial differences between the Chilean population compared to other populations.

Antecedentes: El estudio de la bioquímica hepática es una herramienta útil en la práctica clínica para identificar ciertos patrones que orientan a determinadas patologías. Objetivos: Realizar un análisis descriptivo en población chilena del comportamiento de las pruebas hepáticas en pacientes en pacientes con enfermedades hepáticas agudas y crónicas frecuentes y compararlas con lo reportado en literatura internacional. Material y Método: Estudio prospectivo realizado en pacientes mayores de 18 años en control en los centros de gastroenterología de la Pontificia Universidad Católica y la Posta Central, entre los años 2005 y 2009. Se realizaron análisis de pruebas hepáticas completas en al menos una ocasión. Resultados: Se evalúan 348 pacientes que se desglosan según patología en 49 esteatohepatitis no alcohólica (EHNA), 28 cirrosis biliar primaria (CBP), 74 hepatitis autoinmune (HAI), 10 hemocromatosis, 147 hepatitis crónica C (HVC), 5 hepatitis crónica B (HVB) Y 34 hepatitis alcohólica grave. Los niveles de aminotransferasas pirúvica (SGPT) y oxaloacética (SGOT) promedio fueron: EHNA 89,9 y 62,7 UI/L, CBP 105,5 y 96 UI/L; HAI 412 y 360 UI/L; Hemocromatosis 106 y 75,9 UI/L, HCV 178 y 166 UI/L, HVB 337,2 y 89,6 UI/L y en hepatitis OH 67 y 168 UI/L. Los niveles de Fosfatasas Alcalinas en CBP promedio fueron 518 UI/L, con máximo 2.206. Conclusiones: Se describen las alteraciones de transaminasas en un subgrupo de pacientes portadores de patología hepática conocida. Estudios futuros permitirán determinar si existen diferencias sustanciales en población chilena con respecto a lo descrito en otras poblaciones.

Mushroom poisoning: retrospective analysis of 294 cases

OBJECTIVE: The objective of this study was to present special clinical and laboratory features of 294 cases of mushroom poisoning. MATERIALS AND METHODS: In this retrospective study, 294 patients admitted to the Pediatric and Adult Emergency, Internal Medicine and ICU Departments of Cumhuriyet University Hospital were investigated. RESULTS: Of 294 patients between the ages of 3 and 72 (28.97 ± 19.32), 173 were female, 121 were male and 90 were under the age of 16 years. One hundred seventy-three patients (58.8 percent) had consumed the mushrooms in the early summer. The onset of mushroom toxicity symptoms was divided into early (within 6 h after ingestion) and delayed (6 h to 20 d). Two hundred eighty-eight patients (97.9 percent) and six (2.1 percent) patients had early and delayed toxicity symptoms, respectively. The onset of symptoms was within two hours for 101 patients (34.3 percent). The most common first-noticed symptoms were in the gastrointestinal system. The patients were discharged within one to ten days. Three patients suffering from poisoning caused by wild mushrooms died from fulminant hepatic failure. CONCLUSION: Education of the public about the consumption of mushrooms and education of health personnel working in health centers regarding early treatment and transfer to hospitals with appropriate facilities are important for decreasing the mortality.

An acqueous extract of Bidens pilosa L. protects liver from cholestatic disease: experimental study in young rats / Um extrato aquoso de Bidens pilosa L. protege o fígado da doença colestática: estudo experimental em ratos jovens

PURPOSE: To test the hepatoprotective effect of water extract from Bidens Pilosa L. (BPE) in cholestatic liver disease induced by ligature and resection of the common bile ducts (LRBD) in young rats. METHODS: We studied four groups of ten 21 days old (P21) Wistar rats, Group SW: sham operation and water; Group SD: sham operation and BPE (160 mg of fresh leaves/100 g of body weight/day); Group LW: LRBD and water and Group LD: LRBD and BPE daily. Pentobarbital sleeping time (PST) and serum activities of aspartate aminotransferase (AST) and of alanine aminotransferase (ALT) were determined after the sacrifice (P70). A Ruwart's score for hepatic fibrosis (RS) was given to each animal. Were employed two way ANOVA and the test of Tukey or a non-parametric test for multiple comparisons. RESULTS: There were statistically significant differences between LW and LD in the measurements of the PST ((means LW=390; LD=173), AST (means LW=8, LD=5), ALT (medians LW=2; LD=1) e RS (medians LW=2; LD=1). CONCLUSION: BPE could be used in the phytotherapy of the hepatic damage induced by chronic obstructive cholestasis, because protects liver function, decreases the rate of necrosis and liver fibrosis in cholestatic liver disease.

OBJETIVO: Testar o efeito hepatoprotetor do extrato aquoso de Bidens pilosa L. (EBP) na doença hepática induzida pela ligadura e ressecção do ducto biliar comum (LRDBC) em ratos jovens. MÉTODOS: Estudamos ratos Wistar com 21º. dia de vida (P21) divididos em quatro grupos de 10 animais, Grupo SA: operação simulada e água; Grupo SD: operação simulada e EBP (160mg de folhas frescas/100g de peso corporal/dia); Grupo LA: LRDBC e água e Grupo LD: LRDBC e EBP diariamente. O tempo de sono por pentobarbital (TSP), aspartato (AST) e alanina (ALT) aminotransferase foram determinadas após o sacrifício (P70). O Score de Ruwart (SR) para fibrose hepática foi atribuído para cada animal. Foi realizada análise de variância com dois fatores e pelo teste de Tukey para comparações múltiplas ou por teste não paramétrico. RESULTADOS: Houve diferença estatisticamente significativa entre LA e LD nas variáveis: TSP (médias LA=390; LD=173), AST (médias LA=8, LD=5), ALT (medianas LA=2; LD=1) e SR (medianas LA=2; LD=1). CONCLUSÃO: EBP poderá ser empregado na fitoterapia da doença hepática induzida pela colestase obstrutiva crônica, pois protege a função hepática, diminui a velocidade de necrose e a intensidade da fibrose hepática na obstrução biliar extra-hepática.

Analysis of GB virus C infection among HIV-HCV coinfected patients / Análise da infecção pelo vírus GB-C em pacientes com coinfecção VIH-VHC

The aim of this study was to evaluate the effect of GB virus C on laboratory markers and histological parameters among HIV-seropositive patients coinfected with HCV. Lower degrees of hepatic lesions were observed in the triple-infected patients, in comparison with HIV-HCV coinfected patients who were negative for GBV-C RNA.

O objetivo do estudo foi avaliar o efeito da infecção pelo vírus GB-C em marcadores laboratoriais e parâmetros histológicos em pacientes HIV soropositivos coinfectados com VHC. Menor grau de lesão hepática foi observado nos pacientes com tripla infecção em comparação aos pacientes coinfectados com VIH-VHC negativos para GBV-C RNA.