Tuberculose e infecção VIH/SIDA : uma análise comparativa em Portugal continental no biénio 2008-2009

RESUMO - Introdução: Actualmente 11,3 milhões de indivíduos estão co-infectados pela Tuberculose/Vírus Imunodeficiência Humana (TB/VIH), uma das principais causas de incapacidade e morte no mundo. É determinada pela exposição dos indivíduos aos factores de risco e condições/determinantes sociais de saúde. Várias são as medidas criadas a nível nacional e internacional na luta contra TB e a infecção VIH. Objectivo: Caracterizar e comparar os casos de TB entre os indivíduos não infectados com VIH e os infectados com VIH, considerando as características sócio-demográficas, o tratamento, patologias associadas e factores de risco. Método: Estudo descritivo, quantitativo e observacional. A informação foi obtida a partir da base de dados do Sistema Nacional de Vigilância Epidemiológica da Tuberculose dos casos de TB notificados entre 1 de Janeiro de 2008 a 31 de Dezembro de 2009. Para tratamento e análise estatística (descritiva e inferencial) o programa usado foi o SPSS versão 18,0. Resultados: 12,8% dos indivíduos estavam co-infectados com TB/VIH e 87,2% não estavam co-infectados. A presença de VIH nos casos de tuberculose apresenta evidência de relação com quase todas variáveis em estudo (p<0,00) excepto a presença de insuficiência renal (p<0,307). Apresentam maior probalidade de risco da co-infecção TB/VIH os homens, a faixa etária [35;44[, os estrangeiros, os desempregados, estar em retratamento e fumar. Os indivíduos com Doença Hepática (OR= 5,238; IC95%: 3,706;7,403; ORA = 3,104; IC95%: 2,164;4,454), patologias associadas (OR=13,199; IC95%: 11,246; 15,491; ORA=21,348; IC95%:17,569; 25,940) e factores de risco (OR=3,237; IC95%: 2,968; 3,531; ORA=2,644; IC95%: 2,414; 2,985) tem maior probalidade da co-infecção TB/VIH. O ajustamento para o sexo e a idade interferiu em todas variáveis em estudo. Conclusão: Os homens, da faixa etária [35;44 [, desempregados, estrangeiros, em retratamento, fumadores apresentam maior probalidade de risco de estar co-infectado com TB/VIH.

A clinico-pathological study of 163 untreated cases of chronic hepatitis C

We performed a clinico-pathological study of 163 untreated cases of chronic hepatitis C. Eighty five percent of the patients were clinically asymptomatic and their physical examinations sbowed unremarkable or minimal changes at the time of the liver biopsy Liver function tests tended to present slight abnormalities, involving mild elevations of the activity of the aminotransferases and gamma-glutamil transferase levels. In spite of these mild abnormalities advanced chronic liver disease ivas histologically detected in eighty nine percent of the patients, mainly showing chronic active hepatitis. The most characteristic histological finding ivas an interlobular bile duct damage which correlated with the presence of tymphoid aggregates in the portal tracts and with the development of fibrosis.

Very low prevalence of hepatitis C virus infection in rural communities of northeastern Brazil with a high prevalence of schistosomiasis mansoni

The association of hepatitis C virus infection and the hepatosplenic form of schistosomiasis mansoni has been claimed to result in the concomitant evolution of the two pathologies, with a poor prognosis due to aggravated liver disease. Recently, however, some authors have begun to reject the hypothesis of a higher susceptibility of hepatosplenic schistosomal patients to HCV. The aim of the present transverse study carried out between July and August 1990 was to determine the possible association between SM and HCV markers in residents of Catolândia, Bahia State. Anti-HCV markers were assayed by ELISA-II and RIBA-II in serum samples obtained from 1,228 residents (85.8%). The anti-HCV antibody (ELISA-II) was positive in six (0.5%) individuals, eight (0.6%) cases were inconclusive and 1,214 (98.9%) were negative. However, only in one ELISA-positive serum sample (0.08%) were antibodies confirmed by RIBA-II, while two other samples assayed by RIBA-II were indeterminate. These three patients presented the hepatointestinal form of SM during the follow-up period (1976 to 1996). In conclusion, no association was observed between HCV and SM in the endemic area studied, especially among patients with the hepatosplenic form of the disease.

Nitric oxide levels are not changed in saliva of patients infected with hepatitis C virus

The aim of this investigation was to determine nitric oxide metabolite levels in saliva samples from hepatitis C virus-positive patients in an attempt to test the hypothesis if increased levels of nitric oxide metabolites correlates with the presence of HCV-RNA in saliva. Saliva of 39 HCV-positive patients and 13 HCV-negative patients, without clinical or laboratorial evidence of liver disease were tested for nitric oxide metabolites. HCV-RNA was detected in serum and saliva by a RT-PCR method and nitric oxide level was determined by evaluation of its stable degradation products, nitrate and nitrite. No differences were found between the concentration of nitrite in saliva from HCV patients and controls, in despite of the presence or not of HCV RNA in saliva. Patients with HCV and cirrhosis had higher concentrations of nitrite but not significantly different from the control group or the groups of anti-HCV patients without cirrhosis. Increased levels of nitrite were not detected in anti-HCV positive patients, an indirect indication that chronic sialoadenitis are infrequent in these patients or occurs with low intensity not sufficient to increase nitric oxide metabolite levels in saliva.

Treatment of American tegumentary leishmaniasis in special populations: a summary of evidence

We aimed to assess and synthesize the information available in the literature regarding the treatment of American tegumentary leishmaniasis in special populations. We searched MEDLINE (via PubMed), EMBASE, LILACS, SciELO, Scopus, Cochrane Library and mRCT databases to identify clinical trials and observational studies that assessed the pharmacological treatment of the following groups of patients: pregnant women, nursing mothers, children, the elderly, individuals with chronic diseases and individuals with suppressed immune systems. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. The available evidence suggests that the treatments of choice for each population or disease entity are as follows: nursing mothers and children (meglumine antimoniate or pentamidine), patients with renal disease (amphotericin B or miltefosine), patients with heart disease (amphotericin B, miltefosine or pentamidine), immunosuppressed patients (liposomal amphotericin), the elderly (meglumine antimoniate), pregnant women (amphotericin B) and patients with liver disease (no evidence available). The quality of evidence is low or very low for all groups. Accurate controlled studies are required to fill in the gaps in evidence for treatment in special populations. Post-marketing surveillance programs could also collect relevant information to guide treatment decision-making.

Impact of the IL-18 gene polymorphism in response to antiviral therapy in chronic HCV genotype 4 patients

^a Introduction Interleukin (IL)-18 is a well-known major proinflammatory cytokine with broad biological effects. The major immunomodulatory functions of IL-18 include enhancing T cell and natural killer cell cytotoxicity. Serum levels of this cytokine were shown to increase in chronic hepatitis C patients compared to non-infected healthy people. An association between IL-18 gene promoter polymorphisms and pegylated interferon (PEG-IFN) and ribavirin treatment outcomes has been reported for individuals with chronic hepatitis C virus genotype 1 (HCV-1). In this study, HCV genotype 4 (HCV-4) patients were assessed for IL-18 gene polymorphisms and treatment outcomes or severity of liver disease because data concerning the impact of IL-18 gene polymorphisms on patients with HCV-4 infections are limited. Methods This study included 123 chronic HCV-4 Egyptian patients and 123 apparently healthy volunteer blood donors who served as a control group. HCV genotyping was performed using the line probe assay. IL-18 genotyping was performed using the TaqMan Real-Time PCR method in all 246 patient and control samples. Results In our study, all patients had HCV-4. IL-18 gene single nucleotide polymorphism (SNP) (-607C/A) genotype distributions and allele frequencies did not differ between HCV patients and normal healthy subjects or between patient groups when compared according to the therapeutic response. Moreover, the presence of an IL-18 SNP was not associated with histological disease severity. We conclude that the presence of the IL-18 SNP rs1946518 does not affect the outcome of chronic HCV-4 treatment in Egyptian patients. Conclusions The IL-18 SNP rs1946518 does not affect response to treatment in chronic HCV-4 patients.

Molecular characterization of Torque teno virus and SEN virus co-infection with HIV in patients from Southern Iran

Introduction Torque teno virus (TTV) and SEN virus are circular single-stranded DNA viruses that cause blood-borne infections. The SEN virus (SEN-V) was originally detected in the serum of an injection drug user infected with human immunodeficiency virus (HIV). Recently TTV was discovered as a potential causative agent of non-A-E hepatitis. The aim of this study was to investigate the prevalence of the SEN-V-D/H and TTV in HIV patients and healthy blood donors in Iran. Methods One hundred and fifty HIV patients with a mean age of 50.46 ± 18.46 years and 150 healthy blood donors with a mean age of 48.16 ± 13.73 years were included in this study. TTV and SEN-V were detected by the PCR and were quantitatively assayed by competitive PCR (nested and semi-nested PCR). Restriction fragment length polymorphisms (RFLPs) were used to determine the heterogeneity of TTV. Results TTV and SEN-V were detected 96 (64%) and 84 (56%) of 150 HIV patients respectively. These rates were 34% (n=51) and 37.33% (n=56) in healthy blood donors (significant, p<0.05). PCR detected SEN-V/TTV DNA from 32 of the healthy blood donors (21.33%), while 65 (43.33%) of HIV patients were positive for SEN-V/TTV DNA. Of 150 HIV patients, 32.66% and 23.33% were positive for SEN-V-H and SEN-V-D, respectively and 18.66% (n=28) were co-infected with SEN-V-D/H. Conclusions The prevalence of SEN-VD/H and TTV is higher in HIV patients than in healthy blood donors in Southern Iran. Our results suggest that TTV and SEN-V might play a role in the development of liver disease in patients with immunodeficiency diseases.

Clinical and epidemiological profile of female blood donors with positive serology for viral hepatitis B

ABSTRACTINTRODUCTION:Since women are frequently the minority among blood donors worldwide, studies evaluating this population usually reflect male features. We assessed the features of female blood donors with positive serology for HBV and compared them with those of men.METHODS The study comprised consecutive blood donors referred to a specialized liver disease center to be evaluated due to HBsAg- and/or anti-HBc-positive tests.RESULTS: The study encompassed 1,273 individuals, 219 (17.2%) of whom were referred due to positive HBsAg test and 1,054 (82.8%) due to reactive anti-HBc test. Subjects' mean age was 36.8±10.9 years, and 28.7% were women. Female blood donors referred for positive HBsAg screening tests demonstrated higher prevalence of healthcare workers (9.3% vs 2.5%) and lower prevalence of sexual risk behaviors (15.1% vs 41.1%) and alcohol abuse (1.9% vs 19.8%) compared to men. Women had lower ALT (0.6 vs 0.8×ULN), AST (0.6 vs 0.8×ULN), direct bilirubin (0.2 vs 0.3mg/dL), and alkaline phosphatase (0.5 vs 0.6×ULN) levels and higher platelet count (223,380±50,293 vs 195,020±53,060/mm3). Women also had a higher prevalence of false-positive results (29.6% vs 17.0%). No differences were observed with respect to liver biopsies. Female blood donors referenced for reactive anti-HBc screening tests presented similar clinical, epidemiological, and biochemical characteristics to those reported for positive HBsAg screening tests and similarly had a higher prevalence of false-reactive results.CONCLUSIONS: Compared to men, female blood donors with positive HBsAg and/or anti-HBc screening tests demonstrated higher prevalence of professional risk and false-positive results and reduced alteration of liver chemistry.

Primary biliary cirrhosis and myopathy: an uncommon association

Primary biliary cirrhosis (PBC) is a cholestatic liver disease, which is characterized by a chronic inflammatory destruction of intrahepatic bile ducts. It is a rare disorder whose precise etiology is still to be elucidated. Even though the liver is the principal target of PBC, other organ systems also might be affected. Muscular involvement has rarely been described in this disease, and in the majority of cases, muscular weakness has been interpreted as polymyositis. We report the case of a 48-year-old woman suffering from classic PBC, in association with a myopathy whose histological features are distinct from the cases reported before. We also performed a MEDLINE research for PBC and concomitant muscular diseases.

Evolução, a curto prazo, do perfil do estado de nutrição no transplante hepático, em adultos : contributo para otimização da abordagem clínica e nutricional

RESUMO:Contexto: A avaliação do estado de nutrição do doente com indicação para transplante hepático (TH) deve ser abrangente, considerando o amplo espetro de situações clínicas e metabólicas. As alterações metabólicas relacionadas com a doença hepática podem limitar a aplicação de métodos de avaliação nutricional, subestimando a desnutrição. Após o TH, é expectável a reversão dos distúrbios metabólicos da doença hepática, pela melhoria da função do fígado. No entanto, algumas complicações metabólicas podem surgir após o TH, relacionadas com a má-nutrição, a desnervação hepática e o uso prolongado de imunossupressão, comprometendo os resultados clínicos a longo-prazo. A medição longitudinal e confiável do metabolismo energético e dos compartimentos corporais após o TH, avaliada em conjunto com fatores influentes no estado de nutrição, pode identificar precocemente situações de risco e otimizar e individualizar estratégias clínicas e nutricionais com vantagens no prognóstico. Objetivo: Avaliar longitudinalmente, a curto prazo, o estado de nutrição após o TH em doentes com insuficiência hepática por doença crónica e identificar os fatores, para além da cirurgia, que determinam diferentes evoluções do metabolismo energético e da composição corporal. Métodos: Foi estudada uma coorte de indivíduos com indicação para TH por doença hepática crónica, admitidos consecutivamente para TH ortotópico eletivo, durante 2 anos. Foram programados 3 momentos de avaliação: na última consulta pré-TH (T0), logo que adquirida autonomia respiratória e funcional após o TH (T1) e um mês após o TH (T2). Nesses momentos, foram medidos no mesmo dia: o suprimento nutricional por recordatório das últimas 24 horas, o estado de nutrição por Avaliação Subjetiva Global (ASG), o gasto energético em repouso (GER) por calorimetria indireta, a antropometria, a composição corporal por bioimpedância elétrica tetrapolar multifrequências e a força muscular por dinamometria de preensão palmar. O índice de massa magra (IMM) e a massa celular corporal (MCC) foram usados como indicadores do músculo esquelético e a percentagem de massa gorda (%MG) e o índice de massa gorda (IMG) como indicadores de adiposidade. O GER foi comparado com o estimado pelas fórmulas de Harris-Benedict para classificação do estado metabólico em:hipermetabolismo (GER medido >120% do GER estimado), normometabolismo (GER medido entre 80 e 120% do GER estimado) e hipometabolismo (GER medido <80% do GER estimado). Foi utilizada análise multivariável: por regressão logística, para identificar variáveis associadas à possibilidade (odds ratio – OR) de pertencer a cada grupo metabólico pré-TH; por regressão linear múltipla, para identificar variáveis associadas à variação dos compartimentos corporais no período pós-TH; e por modelos de efeitos mistos generalizados, para identificar variáveis associadas à evolução do GER e dos compartimentos corporais entre o período pré- e pós-TH. Resultados: Foram incluídos 56 indivíduos com idade, média (DP), 53,7 (8,5) anos, 87,5% do sexo masculino, 23,2% com doença hepática crónica de etiologia etanólica. Após o TH, em 60,7% indivíduos foi administrado regime imunossupressor baseado no tacrolimus. Os indivíduos foram avaliados [mediana (AIQ)] 90,5 (P25: 44,2; P75: 134,5) dias antes do TH (T0), 9,0 (P25: 7,0; P75: 12,0) dias após o TH (T1) e 36,0 (P25: 31,0; P75: 43,0) dias após o TH (T2). Após o TH houve melhoria significativa do estado de nutrição, com diminuição da prevalência de desnutrição classificada pela ASG (37,5% em T0, 16,1% em T2, p<0,001). Antes do TH, 41,1% dos indivíduos eram normometabólicos, 37,5% hipometabólicos e 21,4% hipermetabólicos. A possibilidade de pertencer a cada grupo metabólico pré-TH associou-se à: idade (OR=0,899, p=0,010) e desnutrição pela ASG (OR=5,038, p=0,015) para o grupo normometabólico; e índice de massa magra (IMM, OR=1,264, p=0,049) e etiologia viral da doença hepática (OR=8,297, p=0,019) para o grupo hipermetabólico. Não se obteve modelo múltiplo para o grupo de hipometabólico pré-TH, mas foram identificadas associações univariáveis com a história de toxicodependência (OR=0,282, p=0,047) e com a sarcopénia pré- TH (OR=8,000, p=0,040). Após o TH, houve normalização significativa e progressiva do estado metabólico, indicada pelo aumento da prevalência de normometabolismo (41,1% em T0, 57,1% em T2, p=0,040). Foram identificados diferentes perfis de evolução do GER após o TH, estratificado pelo estado metabólico pré-TH: no grupo hipometabólico pré-TH, o GER (Kcal) aumentou significativa e progressivamente (1030,6 em T0; 1436,1 em T1, p=0,001; 1659,2 em T2, p<0,001); no grupo hipermetabólico pré-TH o GER diminuiu significativa e progressivamente (2097,1 em T0; 1662,5 em T1, p=0,024; 1493,0 em T2, p<0.001); no grupo normometabólico não houve variações significativas. Os perfis de evolução do GER associaram-se com: peso corporal (β=9,6, p<0,001) e suprimento energético (β=13,6, p=0,005) na amostra total; com peso corporal (β=7,1, p=0,018) e contributo energético dos lípidos (β=18,9, p=0,003) no grupo hipometabólico pré-TH; e com peso corporal (β=14,1, p<0,001) e desnutrição pela ASG (β=-171,0, p=0,007) no grupo normometabólico pré-TH.Houve redução transitória dos compartimentos corporais entre T0 e T1, mas a maioria destes recuperou para valores semelhantes aos pré-TH. As exceções foram a água extracelular, que diminuiu entre T0 e T2 (média 18,2 L e 17,8 L, p=0,042), a massa gorda (média 25,1 Kg e 21,7 Kg, p<0,001) e o IMG (média 10,6 Kg.m-2 e 9,3 Kg.m-2, p<0,001) que diminuíram entre T1 e T2. Relativamente à evolução dos indicadores de músculo esquelético e adiposidade ao longo do estudo: a evolução do IMM associou-se com força de preensão palmar (β=0,06, p<0,001), creatininémia (β=2,28, p<0,001) e número total de fármacos administrados (β=-0,21, p<0,001); a evolução da MCC associou-se com força de preensão palmar (β=0,16, p<0,001), creatininémia (β=4,17, p=0,008) e número total de fármacos administrados (β=-0,46, p<0,001); a evolução da %MG associou-se com força de preensão palmar (β=-0,11, p=0,028), história de toxicodependência (β=-5,75, p=0,024), creatininémia (β=-5,91, p=0,004) e suprimento proteico (β=-0,06, p=0,001); a evolução do IMG associou-se com história de toxicodependência (β=- 2,64, p=0,019), creatininémia (β=-2,86, p<0,001) e suprimento proteico (β=-0,02, p<0,001). A variação relativa (%Δ) desses compartimentos corporais entre T1 e T2 indicou o impacto da terapêutica imunossupressora na composição corporal: o regime baseado na ciclosporina associou-se positivamente com a %Δ do IMM (β=23,76, p<0,001) e %Δ da MCC (β=26,58, p<0,001) e negativamente com a %Δ MG (β=-25,64, p<0,001) e %Δ do IMG (β=-25,62, p<0,001), relativamente ao regime baseado no tacrolimus. Os esteróides não influenciaram a evolução do GER nem com a dos compartimentos corporais. Conclusões: O estado de nutrição, avaliado por ASG, melhorou significativamente após o TH, traduzida pela diminuição da prevalência de desnutrição. O normometabolismo pré-TH foi prevalente e associou-se à menor idade e à desnutrição pré- TH. O hipometabolismo pré-TH associou-se à história de toxicodependência e à sarcopénia pré-TH. O hipermetabolismo pré-TH associou-se ao maior IMM e à etiologia viral da doença hepática. Após o TH, houve normalização progressiva do estado metabólico. Foram identificados três perfis de evolução do GER, associando-se com: peso corporal e suprimento energético na amostra total; peso corporal e contributo energético dos lípidos no grupo hipometabólico pré- TH; e peso corporal e desnutrição pela ASG no grupo normometabólico pré-TH. Foram identificados diferentes perfis de evolução da composição corporal após TH. A evolução do músculo esquelético associou-se positivamente com a força de preensão palmar e a creatininémia e negativamente com o número total de fármacos administrados. A evolução da adiposidade (%MG e IMG) associou-se inversamente com a história de toxicodependência, a creatininémia e o suprimento proteico; adicionalmente, a %MG associou-se inversamente com a força de preensão palmar. O regime baseado na ciclosporina associou-se independentemente com diminuição da adiposidade e aumento do músculo esquelético, comparativamente ao regime baseado no tacrolimus.---------------------------ABSTRACT:Background: The assessment of nutritional status in patients undergoing liver transplantation (LTx) should be comprehensive, accounting for the wide spectrum of the clinical and metabolic conditions. The metabolic disturbances related to liver disease may limit the precision and accuracy of traditional nutritional assessment methods underestimating the undernourishment. After LTx, it is expected that many metabolic derangements improve with the recovery of liver function. However, some metabolic complications arising after LTx, related to nutritional status, hepatic denervation, and prolonged immunosuppression, may compromise the longterm outcome. A reliable longitudinal assessment of both energy metabolism and body compartments after LTx, combined with assessments of other factors potentially affecting the nutritional status, may enable a better interpretation on the relationship between the metabolic and the nutritional status. These reliable assessments may precociously identify nutritional risk conditions and optimize and customize clinical and nutritional strategies improving the prognosis. Objective: To assess longitudinally the nutritional status shortly after orthotopic LTx in patients with chronic liver disease, and identify factors, beyond surgery, determining different energy metabolism and body composition profiles.Methods: A cohort of consecutive patients who underwent LTx due to chronic liver disease was studied within a period of two years. The assessments were performed in three occasions: at the last visit before LTx (T0), after surgery as soon as respiratory and functional autonomy was established (T1), and approximately one month after surgery (T2). On each occasion all assessments were performed on the same day, and included: the dietary assessment by 24- hour dietary recall, nutritional status by the Subjective Global Assessment (SGA), the resting energy expenditure (REE) by indirect calorimetry, anthropometry, body composition by multifrequency bioelectrical impedance analysis, and muscle strength by handgrip strength. Both the lean mass index (LMI) and body cell mass (BCM) were used as surrogates of skeletal muscle, and both the percentage of fat mass (%FM) and fat mass index (FMI) of adiposity. The REE was predicted according to the Harris and Benedict equation. Hypermetabolism was defined as a measured REE more than 120% of the predicted value; normometabolism as a measured REE within 80-120% of the predicted value; and hypometabolism as a measured REE less than 80% of the predicted value. Multiple regression analysis was used: by logistic regression to identify variables associated with odds of belong each pre-LTx metabolic groups; by linear multiple regression analysis to identify variables associated with body compartments relative variations (%Δ) in the post-LTx period; and by mixed effects models to identify variables associated with the REE and body compartments profiles pre- and post-LTx. Results: Fifty six patients with a mean (SD) of 53.7 (8.5) years of age were included, 87.5% were men and 23.2% with alcoholic liver disease. After LTx 60.7% individuals were assigned to tacrolimus-based immunosuppressive regimen. The patients were assessed at a median time (inter-quartil range) of 90.5 (P25 44.2; P75 134.5) days before LTx (T0), at a median time of 9.0 (P25 7.0; P75 12.0) (T1) and 36 (P25 31.0; P75 43.0) (T2) days after LTx. After LTx the nutritional status significantly improved: the SGA-undernourishment decreased from 37.5% (T0) to 16.1% (T2) (p<0.001). Before LTx, 41.1% patients were normometabolic, 37.5% hypometabolic, and 21.4% hypermetabolic. The predictors of each pre-LTx metabolic group were: age (OR=0.899, p=0.010) and SGA-undernourishment (OR=5.038, p=0.015) for the normometabolic group; and LMI (OR=1.264, p=0.049) and viral etiology of liver disease (OR=8.297, p=0.019) for the hypermetabolic group. No multiple model was found for the pre-LTx hypometabolic group, but univariate association was found with history of drug addiction (OR=0.282, p=0.047) and pre- LTx sarcopenia (OR=8.000, p=0.040). After LTx a significant normalization of the metabolic status occurred, indicated by the increase in the prevalence of normometabolic patients (from T0: 41.1% to T2: 57.1%, p=0.040). Different REE profiles were found with REE stratified by preoperative metabolic status: in the hypometabolic group a significant progressive increase in mean REE (Kcal) was observed (T0: 1030.6; T1: 1436.1, p=0.001; T2: 1659.2, p<0.001); in the hypermetabolic group, a significant progressive decrease in mean REE (Kcal) was observed (T0: 2097.1; T1: 1662.5, p=0.024; T2: 1493.0, p<0.001); and in the normometabolic group, no significant differences were found. The REE profiles were associated with: body weight (β- estimate=9.6, p<0.001) and energy intake (β-estimate=13.6, p=0.005) in the whole sample; with body weight (β-estimate=7.1, p=0.018) and %TEV from lipids (β-estimate=18.9, p=0.003) in the hypometabolic group; and with body weight (β-estimate=14.1, p<0.001), and SGAundernourishment (β-estimate=-171, p=0.007) in the normometabolic group. A transient decrease in most body compartments occurred from T0 to T1, with subsequent catch-up to similar preoperative values. Exceptions were the extracellular water, decreasing from T0 to T2 (mean 18.2 L to 17.8 L, p=0.042), the fat mass (mean 25.1 Kg to 21.7 Kg, p<0.001) and FMI (mean 10.6 Kg.m-2 to 9.3 Kg.m-2, p<0.001), decreasing from T1 to T2. Significant predictors of skeletal muscle and adiposity profiles were found: LMI evolution was associated with handgrip strength (β-estimate=0.06, p<0.001), serum creatinine (β- estimate=2.28, p<0.001) and number of medications (β-estimate=-0.21, p<0.001); BCM evolution was associated with handgrip strength (β-estimate=0.16, p<0.001), serum creatinine (β-estimate=4.17, p<0.001) and number of medications (β-estimate=-0.46, p<0.001); the %FM evolution was associated with handgrip strength (β-estimate=-0.11, p=0.028), history of drug addiction (β-estimate=-5.75, p=0.024), serum creatinine (β-estimate=-5.91, p=0.004) and protein intake (β-estimate=-0.06, p=0.001); and FMI evolution was associated with history of drug addiction (β-estimate=-2.64, p=0.019), serum creatinine (β-estimate=-2.86, p<0.001) and protein intake (β-estimate=-0.02, p<0.001). The %Δ of the aforementioned body compartments from T1 to T2 indicated the influence of immunosuppressive agents on body composition: the cyclosporine-based regimen, compared with tacrolimus-based regimen, was positively associated with %Δ LMI (β-estimate=23.76, p<0.001) and %Δ BCM (β- estimate=26.58, p<0.001), and inversely associated with %Δ FM (β-estimate=-25.64, p<0.001) and %Δ FMI (β-estimate=-25.62, p<0.001). No significant changes in REE or body composition were observed associated with dose or duration of steroid therapy. Conclusions: The SGA-assessed nutritional status improved shortly after LTx, with significant decrease in prevalence undernourished individuals. XXI Preoperative normometabolism was prevalent and was associated with younger age and SGAundernourishment before LTx. Preoperative hypometabolism was associated with history of drug addiction and pre-LTx sarcopenia. Preoperative hypermetabolism was associated with higher LMI and viral etiology of liver disease. A significant normalization of the metabolic status was observed after LTx. The REE profiles were positively predicted by body weight and energy intake in the whole sample, by body weight and percentage of energy intake from lipids in the preoperative hypometabolic patients, and by body weight and SGA–undernourishment in the preoperative normometabolic patients. Different body composition profiles were found after LTx. Skeletal muscle profile was positively associated with handgrip strength and serum creatinine, and inversely with the number of medications. The adiposity profile was inversely associated with history of drug addiction, serum creatinine and protein intake. Additionally, the %FM evolution was inversely associated with handgrip strength. The cyclosporine-based regimen, compared with tacrolimus-based regimen, was independently associated with skeletal muscle increase and adiposity decrease.

Tendències temporals de la mortalitat per càncer de fetge a Catalunya: periode 1983-2002 i projeccions pel 2005

Estudi elaborat a partir d’una estada al Finnish Cancer Registry a Helsinki, Finlandia entre setembre i novembre del 2006. Davant l’increment dels tumors hepàtics en països industrialitzats, s’avaluen les tendències temporals de la malaltia hepàtica a Catalunya durant el període 1983-2002 i s’estima la tendència futura a partir de l’any 2005. L’estudi s’ha basat en dades del Registre de Mortalitat de Catalunya i de l’Institut d’Estadística de Catalunya. La malaltia hepàtica inclou diverses tipologies de tumors hepàtics i la cirrosi hepàtica. Els models edad-període-cohort s’han emprat per estimar els efectes període de mortalitat i cohort de naixement. Els resultats han mostrat que les taxes de mortalitat per cirrosi han disminuït en ambdós sexes, exceptuant els homes d’entre els 35-50 anys, pels quals la mortalitat es mantingué estable. S’han observat increments en la mortalitat per carcinoma hepatocel•lular i en els tumors de vies biliars intrahepàtiques, mentre que les projeccions mostren estabilitat en la tendència d’aquestes malalties durant el període 2005-2009. Les tendències de la mortalitat per malaltia hepàtica constatades poden ser degudes a la implementació de teràpies noves, nous mètodes de diagnòstic, infecció pel virus de l’hepatitis C d’altres factors desconeguts.

Portal vein embolization before right hepatectomy: prospective clinical trial.

OBJECTIVE: To assess the impact of liver hypertrophy of the future liver remnant volume (FLR) induced by preoperative portal vein embolization (PVE) on the immediate postoperative complications after a standardized major liver resection. SUMMARY BACKGROUND DATA: PVE is usually indicated when FLR is estimated to be too small for major liver resection. However, few data exist regarding the exact quantification of sufficient minimal functional hepatic volume required to avoid postoperative complications in both patients with or without chronic liver disease. METHODS: All consecutive patients in whom an elective right hepatectomy was feasible and who fulfilled the inclusion and exclusion criteria between 1998 and 2000 were assigned to have alternatively either immediate surgery or surgery after PVE. Among 55 patients (25 liver metastases, 2 cholangiocarcinoma, and 28 hepatocellular carcinoma), 28 underwent right hepatectomy after PVE and 27 underwent immediate surgery. Twenty-eight patients had chronic liver disease. FLR and estimated rate of functional future liver remnant (%FFLR) volumes were assessed by computed tomography. RESULTS: The mean increase of FLR and %FFLR 4 to 8 weeks after PVE were respectively 44 +/- 19% and 16 +/- 7% for patients with normal liver and 35 +/- 28% and 9 +/- 3% for those with chronic liver disease. All patients with normal liver and 86% with chronic liver disease experienced hypertrophy after PVE. The postoperative course of patients with normal liver who underwent PVE before right hepatectomy was similar to those with immediate surgery. In contrast, PVE in patients with chronic liver disease significantly decreased the incidence of postoperative complications as well as the intensive care unit stay and total hospital stay after right hepatectomy. CONCLUSIONS: Before elective right hepatectomy, the hypertrophy of FLR induced by PVE had no beneficial effect on the postoperative course in patients with normal liver. In contrast, in patients with chronic liver disease, the hypertrophy of the FLR induced by PVE decreased significantly the rate of postoperative complications.

Blocking VLDL secretion causes hepatic steatosis but does not affect peripheral lipid stores or insulin sensitivity in mice

The liver secretes triglyceride-rich VLDLs, and the triglycerides in these particles are taken up by peripheral tissues, mainly heart, skeletal muscle, and adipose tissue. Blocking hepatic VLDL secretion interferes with the delivery of liver-derived triglycerides to peripheral tissues and results in an accumulation of triglycerides in the liver. However, it is unclear how interfering with hepatic triglyceride secretion affects adiposity, muscle triglyceride stores, and insulin sensitivity. To explore these issues, we examined mice that cannot secrete VLDL [due to the absence of microsomal triglyceride transfer protein (Mttp) in the liver]. These mice exhibit markedly reduced levels of apolipoprotein B-100 in the plasma, along with reduced levels of triglycerides in the plasma. Despite the low plasma triglyceride levels, triglyceride levels in skeletal muscle were unaffected. Adiposity and adipose tissue triglyceride synthesis rates were also normal, and body weight curves were unaffected. Even though the blockade of VLDL secretion caused hepatic steatosis accompanied by increased ceramides and diacylglycerols in the liver, the mice exhibited normal glucose tolerance and were sensitive to insulin at the whole-body level, as judged by hyperinsulinemic euglycemic clamp studies. Normal hepatic glucose production and insulin signaling were also maintained in the fatty liver induced by Mttp deletion. Thus, blocking VLDL secretion causes hepatic steatosis without insulin resistance, and there is little effect on muscle triglyceride stores or adiposity

Connective tissue growth factor, steatosis and fibrosis in patients with chronic hepatitis C.

BACKGROUND/AIM: Both steatosis and insulin resistance have been linked to accelerated fibrosis in chronic hepatitis C. Connective tissue growth factor (CTGF) plays a major role in extracellular matrix production in fibrotic disorders including cirrhosis, and its expression is stimulated in vitro by insulin and glucose. We hypothesized that CTGF may link steatosis, insulin resistance and fibrosis. METHODS: We included 153 chronic hepatitis C patients enrolled in the Swiss Hepatitis C Cohort Study and for whom a liver biopsy and plasma samples were available. CTGF expression was assessed quantitatively by immunohistochemistry. In 94 patients (57 with genotypes non-3), plasma levels of glucose, insulin and leptin were also measured. CTGF synthesis was investigated by immunoblotting on LX-2 stellate cells. RESULTS: Connective tissue growth factor expression was higher in patients with steatosis (P=0.039) and in patients with fibrosis (P=0.008) than those without these features. CTGF levels were neither associated with insulinaemia or with glycaemia, nor with inflammation. By multiple regression analysis, CTGF levels were independently associated with steatosis, a past history of alcohol abuse, plasma leptin and HCV RNA levels; when only patients with genotypes non-3 were considered, CTGF levels were independently associated with a past history of alcohol abuse, plasma leptin levels and steatosis. Leptin stimulated CTGF synthesis in LX-2 cells. CONCLUSIONS: In patients with chronic hepatitis C and steatosis, CTGF may promote fibrosis independently of inflammation. CTGF may link steatosis and fibrosis via increased leptin levels.

Prevalence and determinants of QT interval prolongation in medical inpatients.

BACKGROUND: QT interval prolongation carries an increased risk of torsade de pointes and death. AIM: We sought to determine the prevalence of QT prolongation in medical inpatients and to identify determinants of this condition. METHODS: We enrolled consecutive patients who were admitted to the internal medicine ward and who had an electrocardiogram performed within 24 h of admission. We collected information on baseline patient characteristics and the use of QT-prolonging drugs. Two blinded readers manually measured the QT intervals. QT intervals were corrected for heart rate using the traditional Bazett formula and the linear regression-based Framingham formula. We used logistic regression to identify patient characteristics and drugs that were independently associated with QTc prolongation. RESULTS: Of 537 inpatients, 22.3% had a prolonged QTc based on the Bazett formula. The adjusted odds for QTc prolongation based on the Bazett correction were significantly higher in patients who had liver disease (OR 2.9, 95% CI: 1.5-5.6), hypokalaemia (OR 3.3, 95% CI: 1.9-5.6) and who were taking ≥1 QT-prolonging drug at admission (OR 1.7, 95% CI: 1.1-2.6). Overall, 50.8% of patients with QTc prolongation received additional QT-prolonging drugs during hospitalisation. CONCLUSIONS: The prevalence of QTc prolongation was high among medical inpatients but depended on the method used to correct for heart rate. The use of QT-prolonging drugs, hypokalaemia and liver disease increased the risk of QTc prolongation. Many patients with QTc prolongation received additional QT-prolonging drugs during hospitalisation, further increasing the risk of torsade de pointes and death.