Treatment of Hepatitis C with Direct-Acting Antivirals does not Induce Significant Arrhythmias

Abstract Background Chronic Hepatitis C (CHC) therapy with direct-acting antivirals (DAAs) has high efficacy and safety, but some cases of bradyarrhythmias have been described. Objective To evaluate heart rhythm disorders during DAA treatments. Methods Forty-eight patients with CHC (mean 61 years of age; 56% males; 73% HCV genotype 1) were evaluated before and during treatment with DAAs, analyzed by a resting 12-lead ECG [PR, QRS, and QT corrected (QTc) intervals measured] and a 24-h-Holter system, to evaluate the heart rate (HR) and the occurrence of arrhythmias. The Student's t-test or the Wilcoxon-Mann-Whitney test for continuous, independent variables were performed with a statistically significant p-value < 0.05. Results The electrocardiographic parameters before and during treatment were: PR interval (147.2 ± 15.6 vs 144.9 ± 15.6 ms; p = 0.21), QTc interval (427 ± 22.3 vs 421.7 ± 25.3 ms; p = 0.24), minimum HR (52.7 ± 8.4 vs 53.2 ± 8.5 bpm; p = 0.49), median HR (74.2 ± 10.4 vs 75.2 ± 9 bpm; p = 0.83), and maximum HR (117.4 ± 16.8 vs 117.9 ± 16.3 bpm; p = 0.25). These parameters proved to be similar among 11 beta-blockers or 22 ribavirin users. During treatment, the 21 cirrhotic patients presented significantly lower median HRs (72.1 ± 9.0 vs 77.9 ± 8.2 bpm; p = 0.02) and maximum HRs (108.9 ± 15.2 vs. 125.1 ± 13.2 bpm, p < 0.0001) through a 24-h-Holter monitoring than the patients without cirrhosis. No clinically relevant arrhythmias were detected. Conclusion DAAs do not significantly influence heart rate or induce significant cardiac arrhythmias in patients with CHC.

Cardiac Disorder in Chronic Hepatitis C

Chronic hepatitis C (CHC) has a high prevalence in the world. In addition to hepatic complications with cirrhosis in about 20% of patients and high risk for hepatocarcinoma, extrahepatic manifestations may also occur. Cardiac involvement in patients with CHC is associated with several factors, such as increased risk for coronary artery disease, primary cardiomyopathies, or hemodynamic and electrophysiological changes observed in liver cirrhosis. Furthermore, antiviral treatment may, in rare cases, causes cardiovascular adverse effects. Cardiac arrhythmias are the main form of clinical presentation, and, often, markers of poor prognosis in individuals with advanced liver disease. Although some mechanisms that justify these changes have already been reported, many questions remain unanswered, especially about the true involvement of the hepatitis C virus in the genesis of primary cardiac abnormalities, and the risk factors for cardiac-related complications of antiviral treatment

Schistosomiasis and hepatopulmonary syndrome: the role of concomitant liver cirrhosis

BACKGROUND Hepatopulmonary syndrome (HPS) is defined as an oxygenation defect induced by intrapulmonary vasodilation in patients with liver disease or portal hypertension. It is investigated in patients with liver cirrhosis and less frequently in those with portal hypertension without liver cirrhosis, as may occur in hepatosplenic schistosomiasis (HSS). OBJECTIVES To investigate the prevalence of HPS in patients with HSS, and to determine whether the occurrence of HPS is influenced by concomitant cirrhosis. METHODS We evaluated patients with HSS with or without concomitant liver cirrhosis. All patients underwent laboratory testing, ultrasound, endoscopy, contrast echocardiography, and arterial blood gas analysis. FINDINGS Of the 121 patients with HSS, 64 were also diagnosed with liver cirrhosis. HPS was diagnosed in 42 patients (35%) and was more frequent among patients with concomitant liver cirrhosis than in those without cirrhosis (42% vs. 26%), but the difference was not significant (p = 0.069). HPS was more common in those with spider naevi, Child-Pugh classes B or C and high model for end stage liver disease (MELD) scores (p < 0.05 each). MAIN CONCLUSIONS The prevalence of HPS was 35% in this study. The occurrence of liver cirrhosis concomitantly with HSS may have influenced the frequency of patients presenting with HPS.

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.

The reduction of serum aminotransferase levels is proportional to the decline of the glomerular filtration rate in patients with chronic kidney disease

OBJECTIVE: This study sought to determine the serum aminotransferase levels of patients with predialysis chronic kidney disease and establish their relationships with serum creatinine levels and glomerular filtration rate. METHODS: Patients with chronic kidney disease were evaluated between September 2011 and May 2012. Aminotransferase and creatinine serum levels were measured using an automated kinetic method, and glomerular filtration rates were estimated using the Cockroft-Gault and Modification of Diet in Renal Disease formulas to classify patients into chronic kidney disease stages. RESULTS: Exactly 142 patients were evaluated (mean age: 64±16 years). The mean creatinine serum level and glomerular filtration rate were 3.3±1.2 mg/dL and 29.1±13 mL/min/1.73 m2, respectively. Patients were distributed according to their chronic kidney disease stages as follows: 3 (2.1%) patients were Stage 2; 54 (38%) were Stage 3; 70 (49.3%) were Stage 4; and 15 (10.5%) were Stage 5. The mean aspartate aminotransferase and alanine aminotransferase serum levels showed a reduction in proportion to the increase in creatinine levels (p=0.001 and p=0.05, respectively) and the decrease in glomerular filtration rate (p=0.007 and p=0.028, respectively). Alanine aminotransferase and aspartate aminotransferase serum levels tended to be higher among patients classified as stage 2 or 3 compared with those classified as stage 4 or 5 (p=0.08 and p=0.06, respectively). CONCLUSIONS: The aspartate aminotransferase and alanine aminotransferase serum levels of patients with predialysis chronic kidney disease decreased in proportion to the progression of the disease; they were negatively correlated with creatinine levels and directly correlated with glomerular filtration rate. .

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 Schistosomiasis mansoni and hepatitis C: systematic review / Associacao entre esquistossomose mansonica e hepatite C: revisao sistematica / Asociacion entre esquistosomiasis mansoni y hepatitis C: revision sistematica

OBJECTIVE: To perform a systematic review of the prevalence of the HCV/ S. mansoni co-infection and associated factors in Schistosoma mansoni -infected populations. METHODS: The bibliographic search was carried out using the Medline, Lilacs, SciELO, Cochrane Library and Ibecs databases. The criteria for the studies' selection and the extraction data were based on systematic review methods. Forty five studies were found, with nine being excluded in a first screening. Thirteen articles were used for data extraction. RESULTS: The HCV infection rates in schistosomiasis populations range from 1% in Ethiopia to 50% in Egypt. Several studies had poorly defined methodologies, even in areas characterized by an association between hepatitis C and schistosomiasis, such as Brazil and Egypt, which meant conclusions were inconsistent. HCV infection rates in schistosomotic populations were heterogeneous and risk factors for acquiring the virus varied widely. CONCLUSIONS: Despite the limitations, this review may help to identify regions with higher rates of hepatitis C and schistosomiasis association. However, more studies are necessary for the development of public health policies on prevention and control of both diseases. .

OBJETIVO: Realizar revisão sistemática sobre a prevalência da confecção do vírus da hepatite C e Schistosoma mansoni e os fatores de risco associados a indivíduos com esquistossomose. MÉTODOS: Revisão realizada nas bases de dados Medline, Lilacs, SciELO, Biblioteca Cochrane e Ibecs. Os critérios de seleção e a obtenção dos dados foram baseados em métodos de revisão sistemática. Foram encontradas 45 referências relevantes, das quais nove foram excluídas na primeira triagem, 14 na leitura dos resumos e nove na leitura completa. Treze artigos foram selecionados para análise. RESULTADOS: A prevalência da associação entre vírus da hepatite C e Schistosoma mansoni variou de 1% na Etiópia a 50% no Egito. Alguns estudos apresentam metodologias pouco definidas, mesmo em áreas caracterizadas pela associação entre vírus da hepatite C e S. mansoni , como Brasil e Egito, o que não permitiu conclusões consistentes. As taxas de infecção pelo VHC em populações esquistossomáticas foram heterogêneas e os fatores de risco para adquirir o vírus foram variáveis. CONCLUSÕES: Apesar das limitações, esta análise pode ajudar a identificar regiões com maiores taxas dessa associação. Outros estudos serão necessários para o desenvolvimento de políticas públicas de prevenção e controle dessas doenças. .

OBJETIVO: Realizar revisión sistemática sobre la prevalencia de la co-infección del virus de la hepatitis C y Schistosoma mansoni y los factores de riesgo asociados a individuos con esquistosomosis. MÉTODOS: Revisión realizada en las bases de datos MEDLINE, LILACS, SciELO, Biblioteca Cochrane e IBECS. Los criterios de selección y la obtención de los datos fueron basados en métodos de revisión sistemática. RESULTADOS: Fueron encontradas 45 referencias relevantes, de las cuales, nueve fueron excluidas en la primera selección, 14 en la lectura de los resúmenes y nueve en la lectura completa. Trece artículos fueron seleccionados para análisis. La prevalencia de la asociación entre virus de la hepatitis C y Schistosoma mansoni varió de 1% en Etiopia, a 50% en Egipto. Algunos estudios presentan metodologías poco definidas, inclusive en áreas caracterizadas por la asociación entre el virus de la hepatitis C y S. mansoni, como Brasil y Egipto, lo que no permitió conclusiones consistentes. Los cocientes de infección por el VHC en poblaciones esquistosómicas fueron heterogéneos y los factores de riesgo para adquirir el virus fueron variables. CONCLUSIONES: A pesar de las limitaciones, este análisis pudo ayudar a identificar regiones con mayores cocientes de esa asociación. Otros estudios serán necesarios para el desarrollo de políticas públicas de prevención y control de estas enfermedades. .

Relationship between splenomegaly and hematologic findings in patients with hepatosplenic schistosomiasis

BACKGROUND Schistosomiasis is a tropical disease. Patients who develop hepatosplenic schistosomiasis have clinical findings including periportal fibrosis, portal hypertension, cytopenia, splenomegaly and gastrointestinal hemorrhage. OBJECTIVE The aim of this study was to analyze the hemostatic and hematologic findings of patients with schistosomiasis and correlate these to the size of the spleen. METHODS Fifty-five adults with hepatosplenic schistosomiasis and 30 healthy subjects were selected through a history of contact with contaminated water, physical examination and ultrasound characteristics such as periportal fibrosis and splenomegaly in the Gastroenterology Service of the Universidade Federal de Pernambuco. Blood samples were collected to determine liver function, blood counts, prothrombin (international normalized ratio), partial thromboplastin time and fibrinogen and D-Dimer levels using the Pentra 120 hematological analyzer (HORIBA/ABX), Density Plus (test photo-optical Trinity Biotech, Ireland) and COBAS analyzer 6000 (Roche). Furthermore, the longitudinal size of the spleen was measured by ultrasound (Acuson X analyzer 150, Siemens). The Student t-test, the Fisher test and Pearson's correlation were used to analyze the results with statistical significance being set for a p-value < 0.05. RESULTS The mean age was higher for the Study Group than for the Control Group (54 ± 13.9 vs. 38 ± 12.7 years). The average longitudinal diameter of the spleen was 16.9 cm (Range: 12.3-26.3 cm). Anemia is a common finding in patients with schistosomiasis (36.3%). The mean platelet and leukocyte counts of patients were lower than for the Control Group (p-value < 0.001). Moreover, the international normalized ratio (1.42 vs. 1.04), partial thromboplastin time (37.9 vs. 30.5 seconds) and D-Dimer concentration (393 vs. 86.5 ng/mL) were higher for the Study Group compared to the Control Group...

Association between HLA-DRB1* polymorphisms and hepatitis B infection in a brazilian population / Associação entre polimorfismos HLA-DRB1* e infecção por hepatite B em uma população brasileira

OBJECTIVE: The aim of the present study was to determine the genotype association for alleles of class II human leukocyte antigens (HLA) in the DRB1* locus among blood donors at the Fundação Hemope (Brazil) infected by or immunized for the hepatitis B virus (HBV). METHODS: A case-control study was performed, comprising a group of individuals infected by HBV and a control group of immunized individuals at a proportion of 1:4. Blood samples were taken for the HLA typing of the DRB1* locus. Univariate and multivariate analyses were performed for the assessment of associations between the categorical variables using the chi-squared test and Fisher's exact test. RESULTS: A total of 320 blood donors were analyzed (241 males [75%] and 79 females [25%] with a mean age of 39 years). The case group consisted of 64 HBV-infected donors and the control group was composed of 256 HBV-immunized donors. The multivariate analysis stratified by gender revealed that the DRB1*09 allele was associated with infected male donors (p = 0.016) and the DRB1*08 allele was associated with infected donors aged 39 years or younger (p = 0.031). CONCLUSION: The results of the present study reveal that younger blood donors and male blood donors who respectively exhibit the DRB1*08 and DRB1*09 alleles are more susceptible to intensification of HBV infection.

OBJETIVO: O objetivo do presente estudo foi determinar a associação genotípica dos alelos de classe II dos antígenos leucocitários humanos (HLA) presentes no locus DRB1* entre doadores de sangue da Fundação Hemope (Brasil), infectados pelo ou imunizados contra o vírus da hepatite B (HBV). MÉTODOS: Estudo caso-controle foi realizado com um grupo de indivíduos infectados pelo HBV e um grupo controle composto de indivíduos imunizados na proporção de 1:4. Amostras de sangue foram coletadas para a tipagem HLA do locus DRB1*. Análises univariada e multivariada foram realizadas para a avaliação de associações entre as variáveis categóricas pelo teste do qui-quadrado e teste exato de Fisher. RESULTADOS: Um total de 320 doadores de sangue foram analisados (241 homens [75%] e 79 do sexo feminino [25%], com idade média de 39 anos). O grupo de casos consistiu de 64 doadores infectados pelo HBV e o grupo controle foi composto de 256 doadores imunes ao HBV. A análise multivariada estratificada por sexo revelou que o alelo DRB1*09 foi associado com os doadores infectados do sexo masculino (p = 0,016) e do alelo DRB1*08 foi associado com os doadores infectados com idade entre 39 anos ou mais jovens (p = 0,031). CONCLUSÃO: Os resultados do presente estudo revelam que doadores de sangue mais jovens e doadores de sangue do sexo masculino que exibem, respectivamente, os alelos DRB1*08 e DRB1*09, são mais suscetíveis à cronificação da infecção pelo HBV.

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.

Ultrasound versus biological markers in the evaluation of periportal fibrosis in human Schistosoma mansoni

In this paper, the authors review the literature and share their experience of the principal biological markers of fibrosis for the evaluation of periportal fibrosis (PPF) caused by mansoni schistosomiasis. These biological markers are compared to diagnostic ultrasound (US) scans as means of grading PPF. We also review procollagen type I and III, collagen type IV, laminin, hyaluronic acid (HA), immunoglobulin G, platelets, aspartate aminotransferase to platelet ratio index (APRI) and gamma-glutamyl transpeptidase as markers of the disease. Although there are several good markers for evaluating PPF and portal hypertension, such as HA, platelets or APRI, none can yet replace US. These markers may, however, be used to identify patients at greater risk of developing advanced disease in endemic areas and determine who will need further care and US studies.

Ocorrência de síndrome hepatopulmonar em pacientes cirróticos candidatos a transplante de fígado / Occurrence of hepatopulmonary syndrome in patients with cirrhosis who are candidates for liver transplantation

OBJETIVO: Verificar a ocorrência da síndrome hepatopulmonar (SHP) em pacientes cirróticos candidatos a transplante de fígado; comparar as características demográficas, clínicas, laboratoriais e espirométricas, resultados de ecocardiografia, análise de gases arteriais e da gravidade da doença hepática nos pacientes com e sem SHP; e descrever a ocorrência de SHP no subgrupo de pacientes com cirrose associada à esquistossomose mansônica (doença hepática mista). MÉTODOS: Entre janeiro e novembro de 2007, foram avaliados 44 pacientes inscritos no Ambulatório de Transplante Hepático do Hospital das Clínicas da Universidade Federal de Pernambuco, em Recife (PE). Os critérios diagnósticos para SHP foram a presença de dilatações vasculares intrapulmonares, identificadas por ecocardiografia transtorácica, assim como diferença alveoloarterial de oxigênio > 15 mmHg ou PaO2 < 80 mmHg. RESULTADOS: A idade média foi 52 anos, e 31 pacientes (70 por cento) eram do sexo masculino. A causa mais frequente de cirrose foi uso de etanol. A esquistossomose esteve presente em 28 pacientes (64 por cento). Dos 44 pacientes, 20 (45,5 por cento) foram diagnosticados com SHP. Não foram observadas diferenças significativas em relação às características estudadas. No subgrupo de pacientes com cirrose associada à esquistossomose, 10/28 (35,7 por cento) receberam o diagnóstico de SHP. CONCLUSÕES: A SHP apresentou elevada prevalência nesta população estudada, não sendo observadas associações entre a sua ocorrência e as variáveis analisadas.

OBJECTIVE: To determine the occurrence of hepatopulmonary syndrome (HPS) in patients with cirrhosis who are candidates for liver transplantation; to compare demographic, clinical, laboratory, and spirometric characteristics, as well as echocardiography results, arterial blood gas analysis, and severity of liver disease between the groups of patients with and without HPS; and to describe the occurrence of HPS in the subgroup of patients with cirrhosis and schistosomiasis mansoni (mixed liver disease). METHODS: Between January and November of 2007, we evaluated 44 patients under treatment at the Liver Transplant Outpatient Clinic of the Federal University of Pernambuco Hospital das Clínicas, in the city of Recife, Brazil. The diagnostic criteria for HPS were intrapulmonary vascular dilatation, identified by transthoracic echocardiography, and an alveolar-arterial oxygen tension difference > 15 mmHg or a PaO2 < 80 mmHg. RESULTS: The mean age of the patients was 52 years, and 31 patients (70 percent) were male. The most common cause of cirrhosis was alcohol use. Schistosomiasis was present in 28 patients (64 percent). Of the 44 patients, 20 (45.5 percent) were diagnosed with HPS. No significant differences were found between those patients and the patients without HPS in terms of any of the characteristics studied. Of the 28 patients with cirrhosis and schistosomiasis, 10 (35.7 percent) were diagnosed with HPS. CONCLUSIONS: In the population studied, HPS was highly prevalent and did not correlate with any of the variables analyzed.

Correlation of biological serum markers with the degree of hepatic fibrosis and necroinflammatory activity in hepatitis C and schistosomiasis patients

Liver biopsy is the gold-standard method to stage fibrosis; however, it is an invasive procedure and is potentially dangerous. The main objective of this study was to evaluate biological markers, such as cytokines IL-13, IFN-ã, TNF-á and TGF-â, platelets, bilirubins (Bil), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total proteins, ã-glutamil transferase (ã-GT) and alkaline phosphatase (AP), that could be used to predict the severity of hepatic fibrosis in schistosomiasis and hepatitis C (HC) as isolated diseases or co-infections. The following patient groups were selected: HC (n = 39), HC/hepatosplenic schistosomiasis (HSS) (n = 19), HSS (n = 22) and a control group (n = 13). ANOVA and ROC curves were used for statistical analysis. P < 0.05 was considered significant. With HC patients we showed that TNF-á (p = 0.020) and AP (p = 0.005) could differentiate mild and severe fibrosis. With regard to necroinflammatory activity, AST (p = 0.002), ã-GT (p = 0.034) and AP (p = 0.001) were the best markers to differentiate mild and severe activity. In HC + HSS patients, total Bil (p = 0.008) was capable of differentiating between mild and severe fibrosis. In conclusion, our study was able to suggest biological markers that are non-invasive candidates to evaluate fibrosis and necroinflammatory activity in HC and HC + HSS.

Hepatopulmonary syndrome: an update / Síndrome hepatopulmonar: atualização

Hepatopulmonary syndrome (HPS) is a clinical threesome composed of liver disease, intrapulmonary vascular dilatation (IPVD) and arterial gas abnormalities. Its occurrence has been described in up to 32 percent of cirrhotic candidates for liver transplantation. It also affects non-cirrhotic patients with portal hypertension. Its pathogenesis is not well defined, but an association of factors such as imbalance in the endothelin receptor response, pulmonary microvascular remodeling and genetic predisposition is thought to lead to IPVD. Diagnosis is based on imaging methods that identify these dilatations, such as contrast echocardiography or perfusion scintigraphy with 99mTc, as well as analysis of arterial gases to identify elevated alveolar-arterial differences in O2 or hypoxemia. There is no effective pharmacological treatment and complete resolution only occurs through liver transplantation. The importance of diagnosing HPS lies in prioritizing transplant candidates, since presence of HPS is associated with worse prognosis. The aim of this paper was to review the pathogenetic theories and current diagnostic criteria regarding HPS, and to critically analyze the prioritization of patients with HPS on the liver transplant waiting list. Searches were carried out in the Medline (Medical Literature Analysis and Retrieval System Online) via PubMed, Cochrane Library and Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) databases for articles published between January 2002 and December 2007 involving adults and written either in English or in Portuguese, using the term hepatopulmonary syndrome. The studies of greatest relevance were included in the review, along with text books and articles cited in references that were obtained through the review.

A síndrome hepatopulmonar (SHP) é considerada uma tríade clínica composta de doença hepática, dilatações vasculares intrapulmonares (IPVD) e alterações de gases arteriais. Há descrição de sua ocorrência em até 32 por cento dos cirróticos candidatos ao transplante de fígado, acometendo também não cirróticos com hipertensão portal. Sua etiopatogenia não está bem definida, mas se especula que a associação de fatores como o desequilíbrio na resposta dos receptores vasculares de endotelina, o remodelamento microvascular pulmonar e a predisposição genética propiciem as IPVD. O diagnóstico baseia-se em métodos de imagem que identifiquem essas dilatações, como a ecocardiografia com contraste ou a cintilografia de perfusão com 99mTc, além da análise de gases arteriais, para identificar elevação da diferença alvéolo-arterial de O2 ou hipoxemia. Não existe tratamento medicamentoso eficaz e sua resolução completa ocorre apenas com o transplante de fígado. A importância do diagnóstico da SHP está em priorizar os candidatos ao transplante, uma vez que sua presença está associada ao pior prognóstico. O objetivo deste artigo é fazer revisão das teorias de etiopatogenia da SHP, dos seus critérios diagnósticos atuais, além de realizar análise crítica sobre a prioridade dos pacientes com a síndrome na lista de espera pelo transplante de fígado. Buscaram-se na base de dados Medline (Medical Literature Analysis and Retrieval System Online) via PubMed, Cochrane Library e Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde), os artigos publicados no período de janeiro de 2002 a dezembro de 2007, envolvendo adultos, escritos nos idiomas inglês ou português, que apresentassem o termo síndrome hepatopulmonar. Os estudos de maior relevância foram incluídos, além de livros-texto e artigos citados nas referências obtidas na revisão.

Serum alanine aminotransferase levels, hematocrit rate and body weight correlations before and after hemodialysis session

PURPOSE: To evaluate alanine aminotransferase levels before and after a hemodialysis session and to correlate these values with the hematocrit rate and weight loss during hemodialysis. PATIENTS AND METHODS: The serum alanine aminotransferase levels, hematocrit rate and body weight were measured and correlated before and after a single hemodialysis session for 146 patients with chronic renal failure. An receiver operating characteristic (ROC) curve for the serum alanine aminotransferase levels collected before and after hemodialysis was plotted to identify hepatitis C virus-infected patients. RESULTS: The mean weight loss of the 146 patients during hemodialysis was 5.3 percent (p < 0.001). The mean alanine aminotransferase levels before and after hemodialysis were 18.8 and 23.9 IU/, respectively, denoting a significant 28.1 percent increase. An equally significant increase of 16.4 percent in the hematocrit rate also occurred after hemodialysis. The weight loss was inversely correlated with the rise in both the alanine aminotransferase level (r = 0.3; p < 0.001) and hematocrit rate (r = 0.5; p < 0.001). A direct correlation was found between the rise in alanine aminotransferase levels and the hematocrit during the hemodialysis session (r = 0.4; p < 0.001). Based on the ROC curve, the upper limit of the normal alanine aminotransferase level should be reduced by 40 percent relative to the upper limit of normal if the blood samples are collected before the hemodialysis session or by 60 percent if blood samples are collected after the session. CONCLUSION: In the present study, significant elevations in the serum alanine aminotransferase levels and hematocrit rates occurred in parallel to a reduction in body weight after the hemodialysis session. These findings suggest that one of the factors for low alanine aminotransferase levels prior to hemodialysis could be hemodilution in patients with chronic renal failure.

Divertículo esofágico de tração de localização incomum secundário a processo cicatricial de tuberculose pulmonar: relato de caso / Traction esophageal diverticulum of uncommon location, secondary to scarring process of pulmonary tuberculosis: a case report

Os divertículos esofágicos de tração ocorrem como consequência de forças de adesão externa ao órgão provocado por processos inflamatórios adjacentes. Geralmente localizados em região mediotorácica, são considerados como sequelas de acometimento dos linfonodos mediastinais principalmente por tuberculose e histoplasmose. Relata-se o caso de um paciente do sexo masculino com 61 anos que desenvolveu um divertículo de tração localizado no esôfago superior mediante adesão do órgão ao processo cicatricial fibrótico em ápice de pulmão direito por tuberculose pulmonar. Através da endoscopia digestiva alta e da imagem radiológica do esofagograma foi possível evidenciar o divertículo ocupando partes da região cervical e torácica alta do órgão.

Linfomas em pacientes com a forma hepatoesplênica da esquistossomose mansônica / Lymphoma in patients harboring hepatosplenic mansonic schistosomiasis

RACIONAL: Cada vez mais se estabelece a correlação entre agentes infecciosos e doenças linfoproliferativas, sobretudo vírus e bactérias, através da ativação de linfócitos. OBJETIVO: Descrever 6 novos casos, de uma série de 254 pacientes (2,36 por cento) com esquistossomose mansônica na forma hepatoesplênica. CASUÍSTICA E MÉTODOS: São descritos 6 pacientes, dentre os 254 portadores de esquistossomose mansônica na forma hepatoesplênica, acompanhados nos últimos 13 anos no Serviço de Cirurgia Geral do Hospital das Clínicas da Universidade Federal de Pernambuco, Recife, PE. RESULTADOS: Todos os seis casos ocorreram em mulheres. Os exames histopatológicos evidenciaram dois casos de linfomas de zona marginal esplênica, um de linfoma de grandes células com imunoblastos, um de linfoma difuso de grandes células, um de linfoma maligno de grandes células não clivadas, e um outro caso de doença de Hodgkin. Metade das seis pacientes evoluiu para o óbito entre 4 a 15 meses após o diagnóstico. As outras três persistem em acompanhamento no Serviço de Oncologia da mesma instituição. CONCLUSÃO: A incidência de linfoma nos 254 pacientes acompanhados foi de 2,36 por cento. Pretende-se chamar a atenção para a ocorrência de linfomas nos baços de pacientes com esquistossomose mansônica, na forma hepatoesplênica.

BACKGROUND: Correlation between infectious agents and linfoproliferative diseases are more stablished, over all virus and bacteria, through the activation of linfocytes. AIM: To describe six new cases, of a series of 254 patients (2,36 percent) with mansonic schistosomiasis, in the hepatosplenic form. METHODS: Six patients will be described, amongst the 254 carriers of mansonic schistosomiasis, in the hepatosplenic form, followed in the last 13 years. RESULTS: All the six cases had occurred in women. The histopathologic examinations had evidenced two cases of marginal splenic zone lymphomas, one of great cells with immunoblasts lymphomas, one diffuse lymphomas, a great cells malignant lymphomas, a great not clivads cells, and another case of Hodgkin. Half of the six evolved for the death 4-15 months after the diagnosis. The others three persist in accompaniment in the Oncology Division of the Clinics Hospital. CONCLUSION: The incidence of lymphomas in the 254 mansonic schistosomiasis patients followed in our clinic was of 2,36 percent. At last, this article intends to call the attention, for the occurrence of lymphomas, in the spleen of patients with mansonic schistosomiasis, in the hepatosplenic form.

The influence of periportal (pipestem) fibrosis on long term results of surgical treatment for schistosomotic portal hypertension

AIM: To evaluate the degree of influence that periportal fibrosis has on clinical development and the long term results of surgical treatment on patients with hepatic-splenic schistosomiasis with previous gastrointestinal hemorrhages. METHODS: During the period of 1992-1998, 111 patients underwent surgical treatment for the treatment of hepatic-splenic schistosomiasis with previous gastrointestinal hemorrhages. The degree of fibrosis was classified as: degree I - the portal spaces show a rich increase of young connective cells, a slight collagen production and a varying presence of inflammatory infiltrate. The periportal blade unchangeable (29/111); degree II - there is an expansion of the connective tissue with the emission of radial collagen septa, producing a star shaped aspect (38/111); degree III - the connective septa form bridges with other portal spaces or with the vein, with evident angiomatoid neo-formation (44/111). CONCLUSION: The patients with periportal fibrosis degree I present recurrent hemorrhages statistically less than patients with periportal fibrosis degrees II and III, and that the intensity of the periportal fibrosis is not the only pathophysiological factor of the esophageal varices, gastric varices, prevalence of post-operative portal vein thrombosis and hematological and biochemical alterations of the patients with pure mansoni schistosomiasis.

Varizes de fundo gástrico na hipertensão portal esquistossomótica: resultados cirúrgicos / Gastric fundus varices in schistossomotic portal hypertension: surgical results

OBJETIVO: Apresentar dados epidemiológicos de pacientes esquistossomóticos na forma hepatoesplênica com varizes do fundo gástrico, assim como avaliar os resultados de uma estratégia cirúrgica no manuseio destas varizes. MÉTODO: No período de janeiro de 1992 à julho de 2001 foram acompanhados no Serviço de Cirurgia Geral do Hospital das Clínicas da Universidade Federal de Pernambuco 125 pacientes submetidos à esplenectomia com ligadura da veia gástrica esquerda (LVGE), desvascularização da grande curvatura do estômago e esclerose endoscópica pós-operatória, para o tratamento da hipertensão portal esquistossomótica com antecedentes de hemorragia digestiva. Quando da presença de varizes de fundo gástrico (44/125) foi associado ao procedimento cirúrgico, a abertura do estômago e sutura das varizes. RESULTADOS: Varizes de fundo gástrico foram identificadas em 35,2 por cento (44/125) dos pacientes com esquistossomose hepatoesplênica e antecedentes de hemorragia digestiva alta. Durante o seguimento de 26 meses o procedimento cirúrgico erradicou 76,5 por cento das varizes de fundo gástrico. A incidência de trombose da veia porta no período pós-operatório foi maior no grupo de pacientes sem varizes de fundo gástrico (16,3 por cento) quando comparado com os pacientes portadores de varizes de fundo gástrico (8,8 por cento), sem que, no entanto, esta diferença tivesse respaldo estatístico (p = 0,62). Não se identificou correlação entre a presença de varizes do fundo gástrico e o grau de fibrose periportal e o peso do baço. Na análise bioquímica e hematológica, no período pré-operatório dos grupos estudados, o número de leucócitos foi estatisticamente menor no grupo de pacientes que apresentavam varizes de fundo gástrico. CONCLUSÃO: A esplenectomia associada a desvascularização da grande curvatura do estômago, ligadura da veia gástrica esquerda, gastrotomia e sutura da varizes de fundo gástrico, erradicou 76,5 por cento das varizes de fundo gástrico...

BACKGROUND: The aim of this study is to present epidemiological data and evaluate a surgical approach in the treatment of gastric fundus varices in patients with hepatosplenic shistosomiasis. METHODS: During the period of January 1992 and July 2001, 125 patients underwent splenectomy, ligation of the left gastric vein (LLGV), devascularization of the great stomach curvature and post-operative endoscopic sclerotherapy for the treatment of hepatic-splenic schistosomiasis with previous gastrointestinal haemorrhages. In the patients who presented gastric varices in the pre-operative endoscopy (44/125), a gastrotomy and an obliterating running suture were also performed intraoperatively. RESULTS: Gastric fundus varices were observed in 35,2 percent of all patients with hepatic-splenic schistosomiasis with previous gastrointestinal haemorrhages (44/125). The surgical treatment proposed eradicated 76,5 percent of the gastric fundus varices in a mean follow-up period of 26 months. Portal vein thrombosis was higher in the group of patients without fundus grastric varices (16,3 percent) when compared with fundus gastric varices patients (8,8 percent). This difference was not statistically significant (p=0,62). There was no correlation between the presence of fundus gastric varices and the degree of periportal fibrosis or the weight of the spleen. Despite a statistically lower number of white blood cells in the gastric fundus varices, no other differences were identified in the preoperative haematological and biochemical data. CONCLUSIONS: The authors concluded that patients underwent splenectomy, ligation of the left gastric vein, devascularisation of the great stomach curvature, post-operative endoscopic sclerotherapy, gastrotomy and an obliterating running suture of the fundus gastric varices, eradicated 76,5 percent of the fundus gastric varices, in a follow-up of 26 months.

Custo do transplante hepático no Hospital das Clínicas da Universidade Federal de Pernambuco / Liver transplantation cost analysis at the Hospital das Clínicas da Universidade Federal de Pernambuco

Objetivos: estipular o custo do procedimento cirúrgico do transplante de fígado realizado no Hospital das Clínicas da Universidade Federal de Pernambuco (HC/UFPE). Métodos: foram analisados os primeiros quatro transplantes de fígado realizados no HC/UFPE. Os pacientes foram classificados conforme o índice de gravidade da United Network for Organ sharing em classe um - dois pacientes: classe dois - um paciente; classe quatro - um paciente. Os custos foram determinados da seguinte maneira: diárias, taxas de sala e aparelhagem - estimativa realizada pelo setor de faturamento do HC/UFPE em julho de 2001; taxa de oxigênio, materiais descartáveis, medicamentos; exames e hemoterapia. Não foram levantados os custos da retirada do fígado, assim como não foram considerados os custos de equipe médica, de enfermagem, técnicos e paramédicos envolvidos no procedimento. Resultados: o item de materiais descartáveis foi o que mais onerou o transplante, correspondendo a cerca de 48,5 por cento do custo total, seguido pelas diárias e medicamentos com 17,9 por cento e 16,1 por cento respectivamente. Conclusões: concluiu-se que o custo médio do procedimento cirúrgico do transplante hepático no HC/UFPE foi no período de 1998 a 2001 de R$22.184,40 (US$8.873,76; U$1,00 = R$2,50).