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.

Remission of long-term hepatic and renal disease induced by HCV after direct-acting antivirals therapy / Remissão de doença hepática e renal a longo prazo induzida pelo HCV após terapia antiviral de ação direta

Abstract In addition to liver disease, the hepatitis C virus (HCV) has been associated with autoimmune phenomena, such as mixed cryoglobulin and glomerulonephritis (GN). Until recently, both chronic hepatitis and HCV extra-hepatic manifestations were treated with peg-interferon plus ribavirin, however these drugs presented low efficacy and induced severe side effects. Nowadays, the HCV chronic hepatitis has been treated with direct acting antivirals (DAA), but studies on the DAA therapy for HCV-associated glomerulonephritis are scarce. Here, we describe two cases of HCV-associated glomerulonephritis that were treated with DAAs. In these two cases, previously experienced to peg-interferon plus ribavirin, the sofosbuvir plus simeprevir therapy was effective, without significant side effects, and interrupted the evolution of at least 20 years of both hepatic and renal diseases. These cases join the seven previously described cases that were treated with this DAAs association.

Resumo Além da doença hepática, o vírus da hepatite C (HCV) tem sido associado a fenômenos autoimunes, como crioglobulinemia mista (CM) e glomerulonefrite (GN). Até recentemente, a hepatite crônica e as manifestações extra-hepáticas do HCV eram tratadas com peg-interferon com ribavirina; no entanto, essas drogas apresentavam baixa eficácia e induziam efeitos colaterais graves. Atualmente, a hepatite crônica por HCV tem sido tratada com antivirais de ação direta (AAD), mas estudos sobre a terapia com AAD para glomerulonefrite associada ao HCV são escassos. Aqui, descrevemos dois casos de glomerulonefrite associada ao HCV que foram tratados com AAD. Nestes dois casos, previamente tratados com peg-interferon e ribavirina, a terapia com sofosbuvir com simeprevir foi eficaz, sem efeitos colaterais significativos, e interrompeu a evolução de pelo menos 20 anos de doenças hepáticas e renais. Esses casos se juntam aos sete casos descritos anteriormente que foram tratados com essa associação de AAD.

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

How are HCV-infected patients being identified in Brazil: a multicenter study

ABSTRACT Background: Hepatitis C is an important health problem. In Brazil, 1-2 million people are infected. Despite this expressive number, and the availability of very successful treatment, many patients remained undiagnosed mainly because of the asymptomatic nature of the infection. Objectives: To describe epidemiological characteristics of HCV-infected patients seen at referral centers in Brazil, the source of referral, and the time spanned to reach a reference center, in order to improve the identification of undiagnosed patients. Methods: Multicenter observational, cross-sectional study carried out in 15 centers of Brazil, between January/2016 and June/2017. Data of patients with a confirmed diagnosis (anti-HCV and HCV-RNA) were collected by interview using standard questionnaires and by review of charts. Results: Two thousand patients were included; 55.1% were male, mean age 58 ± 11 years. Only 14.9% had higher education and 84.2% received up to five monthly minimum Brazilian wages (approximately US$260.00/month). The time between diagnosis and beginning of follow-up was 22.9 months. The most common reasons for testing were check-up (33.2%) and blood donation (19%). General practitioners diagnosed most of the patients (30.1%). Fibrosis stage was mainly evaluated by liver biopsy (61.5%) and 31.3% of the patients were cirrhotic at diagnosis. Conclusions: This multicenter Brazilian study showed that the mean time to reach a referral center for treatment was almost two years. Primary care physicians diagnoses most hepatitis C cases in the country. Population campaigns and medical education should be encouraged to intensify screening of asymptomatic individuals, considering the efficiency of check-ups in identifying new patients.

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. .

Comparison of Doppler Echocardiographic Findings in Patients with Chronic Liver Disease with and without Intrapulmonary Shunt.

Aims: Doppler echocardiography is the gold standard for the diagnosis of intrapulmonary shunt (IPS) and screening for portopulmonary hypertension in chronic liver disease (CLD). Echocardiography has become fundamental to the diagnosis of cirrhotic cardiomyopathy in the last decade. The purpose of this article was to compare echocardiographic changes in patients with CLD, with and without IPS. Methodology: A total of 168 patients with CLD and portal hypertension underwent transthoracic contrast echocardiography and were allocated to two groups: Group 1 – 72 (42.9%) patients with IPS; and Group 2 – 96 (57.1 %) patients without IPS (control group). Echocardiographic variables and the presence/absence of IPS were evaluated in bilateral tests, with the level of statistical significance established at 5% (p < 0.05). Results: A higher prevalence of moderate diastolic dysfunction was found in patients with IPS (24 vs. 16 patients; p = 0.034). Patients with grade II IPS had a greater frequency of moderate diastolic dysfunction than those with grade I (16 vs. 8 patients; p = 0.028). No statistically significant differences between groups were found in left atrial volume (58 vs. 55 ml; p = 0.181) or the occurrence of pulmonary arterial hypertension (25 vs. 33 patients; p = 0.963). Conclusion: In the present study, IPS and grade II IPS were associated with moderate diastolic dysfunction determined by contrast-enhanced transthoracic Doppler echocardiography. Moderate diastolic dysfunction appeared to be a predictive factor for the onset of intrapulmonary shunt.

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.

Correlation beteeen platelet count and both livr fibrosis and spleen diameter in patients with schistosomiasis mansnni / Correlação entre o número de plaquetas e o grau de fibrose hepática e o tamanho do baço em pacientes com Esquistossomose mansoni

Context Studies have described the correlation between platelet count and the stages of fibrosis in chronic viral hepatitis, but few publications have studied this correlation in Schistosomiasis mansoni. Objectives Therefore, this study aimed to correlate platelet count with both the periportal fibrosis pattern and spleen diameter evaluated by ultrasound exam in patients with Schistosomiasis mansoni. Methods Patients with Schistosomiasis mansoni were evaluated by abdominal ultrasound by a single examiner for the determination of periportal fibrosis pattern (Niamey classification) and spleen diameter. Platelet counts were performed in an automated cell counter. Results One hundred eighty-seven patients with Schistosomiasis mansoni (mean age: 50.2 years) were included in the study, 114 of whom (61%) were women. Based on the Niamey classification, the ultrasound analysis revealed that 37, 64, 64 and 22 patients exhibited patterns C, D, E and F, respectively. In these four groups, the mean number of platelets was 264, 196, 127 and 103 x 109/L and mean spleen diameter was 9.2, 11.9, 14.9 and 16.2 centimeters, respectively. A reduction in platelet count was significantly associated with both the progression of the periportal fibrosis and the increase in spleen size. Conclusions Platelet count in patients with Schistosomiasis mansoni was inversely correlated with the severity of periportal fibrosis and spleen diameter. .

Contexto Estudos vem descrevendo correlação entre o número de plaquetas e o grau de fibrose hepática na hepatite viral crônica, mas poucas publicações estudaram esta correlação em pacientes com Esquistossomose mansoni. Objetivos Correlacionar a contagem de plaquetas com o padrão de fibrose periportal e com o diâmetro do baço, avaliados pela ultrassonografia em pacientes com Esquistossomose mansoni. Métodos Os pacientes com Esquistossomose mansoni foram avaliados pela ultrassonografia abdominal, por um único examinador, para determinação do padrão de fibrose periportal (classificação de Niamey) e do diâmetro do baço. A contagem de plaquetas foi realizada em contador automatizado. Resultados Cento e oitenta e sete pacientes com Esquistossomose mansoni com média de idade de 50,2 anos foram incluídos no estudo, 114 (61%) dos quais eram mulheres. De acordo com a classificação de Niamey, a ultrassonografia revelou que 37, 64, 64 e 22 pacientes exibiam padrões C, D, E e F, respectivamente. Nestes quatro grupos, o número médio de plaquetas foi 264, 196, 127 e 103 x 109/L, respectivamente, e o diâmetro médio do baço foi 9,2, 11,9, 14,9 e 16,2 centímetros, respectivamente. Observou-se, portanto, redução significativa na contagem de plaquetas associada à progressão da fibrose periportal e ao aumento do tamanho do baço. Conclusões Neste estudo verificou-se que a contagem de plaquetas foi inversamente correlacionada com o padrão de fibrose periportal, como também com o diâmetro do baço nos pacientes com Esquistossomose mansoni. .

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...

Esteato-hepatite não-alcoólica em pré-operatório de bypass gástrico: ausência de correlação com grau de obesidade / Nonalcoholic steatohepatitis on preoperative period of gastric bypass: lack of correlation with degree of obesity

RACIONAL: Alterações metabólicas têm elevada correlação com formas graves da doença hepática gordurosa não-alcoólica. Todavia, ainda não há método não-invasivo que promova sua adequada estratificação sendo que a biópsia permanece como meio diagnóstico ideal. OBJETIVO: Avaliar a prevalência dessa doença em obesos no pré-operatório de bypass gástrico em Y-de-Roux e correlacionar fatores metabólicos com a histopatologia hepática. MÉTODOS: Do total de 47 pacientes, foram incluídos 35 em pré-operatório e excluídos 12 devido à doenças hepáticas e ingestão alcoólica >80 g/semana. Foi realizada avaliação clínico-laboratorial antes da operação e biópsia hepática transoperatória. A intensidade da esteatohepatite foi classificada nos graus: I (leve a moderada), II (difusa e inflamatória), III (fibrose periportal) e IV (cirrose). Foram comparadas as seguintes variáveis: tempo de obesidade, índice de massa corpórea, relação cintura-quadril, diabete melito tipo 2, hipertensão arterial e dislipidemia. RESULTADOS: Trinta e cinco pacientes (68,6% mulheres, média de idade de 37 anos) foram avaliados. O índice de massa corpórea médio pré-operatório foi de 53,04 kg/m2. Esteatohepatite não-alcoólica foi encontrada em 31 pacientes (88,6%), sendo grau I 32,2% (n=10), grau II 45,2% (n=14), e grau III 25,6% (n=7). A relação cintura-quadril mostrou associação com esteatose hepática; hipertrigliceridemia foi o marcador que melhor se correlacionou com maior grau; não houve correlação entre aminotransferase e a intensidade da doença; houve correlação da intensidade com fatores relacionados à resistência insulínica. CONCLUSÃO: Esteatohepatite não-alcoólica tem elevada prevalência em obesos graves, porém não foi observada correlação positiva entre aminotransferases e o grau de obesidade com histopatologia hepática. Hipertrigliceridemia e relação cintura-quadril correlacionaram-se positivamente com a intensidade de doença.

BACKGROUND: Metabolic disorders have high correlation with severe forms of nonalcoholic fatty liver disease. However, there is no non-invasive method that promotes its proper stratification and biopsy remains the ideal diagnostic tool. AIM: To evaluate the prevalence of this disease in obese in preoperative period of Roux-en-Y gastric bypass and metabolic factors correlated with liver histopathology. METHODS: From a total of 47 patients, 35 were enrolled in the inclusion criteria and 12 excluded due to liver disease and alcohol intake >80 g/week. Were performed clinical and laboratory evaluation before the surgery and intraoperative liver biopsy . The intensity was ranked in grade of steatohepatitis: I (mild to moderate) and II (diffuse inflammation), III ( periportal fibrosis) and IV (cirrhosis). Were compared the following variables: duration of obesity, body mass index, waist-hip ratio, type 2 diabetes mellitus, hypertension and dyslipidemia. RESULTS: Thirty -five patients (68.6 % women , mean age 37 years) were evaluated. The mean body mass index preoperatively was 53.04 kg/m². Nonalcoholic steatohepatitis was found in 31 patients (88.6 %) and 32.2% were in grade I (n=10), grade II 45.2% (n=14), and 25.6% grade III (n=7). The waist-hip ratio was associated with hepatic steatosis; hypertriglyceridemia was the marker that had best correlation with higher grade; there was no correlation between aminotransferase and intensity of the disease; there was correlation of intensity with factors related to insulin resistance. CONCLUSION: Nonalcoholic steatohepatitis is highly prevalent in morbidly obese patients, but there was no positive correlation between aminotransferases and degree of obesity and liver histopathology. Hypertriglyceridemia and waist-hip ratio were positively correlated with the intensity of disease.

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.

Frequency and risk factors associated with non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus / Frequência e fatores de risco associados à doença hepática gordurosa não alcoólica em pacientes com diabetes melito tipo 2

OBJECTIVE: To evaluate the frequency of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (DM2) and to describe its risk factors. SUBJECTS AND METHODS: Blood samples of 78 patients were collected for assessment of glycemic and lipid profile, liver enzymes, TNF-α and HOMA-IR. The diagnosis of NAFLD was established by ultrasound. RESULTS: NAFLD was observed in 42 percent of patients who had greater BMI (p < 0.001), and frequency of hypertension (p < 0.001). Metabolic syndrome was more frequent in those with NAFLD (p = 0.019). The levels of aspartate, alanine aminotransferase, γ-glutamyl transpeptidase, uric acid, TNF-α, insulin and HOMA-IR were significantly higher in patients with NAFLD than those without NAFLD. CONCLUSION: Almost half of patients with DM2 were found to have NAFLD, and they have more elevated BMI, as well as higher levels of aminotransferases, γ-GT, uric acid, TNF-α, insulin and HOMA-IR than subjects without NAFLD.

OBJETIVO: Avaliar a frequência de doença hepática gordurosa não alcoólica (DHGNA) em pacientes com diabetes mellitus tipo 2 (DM2) e descrever seus fatores de risco. SUJEITOS E MÉTODOS: Amostras de sangue foram coletadas de 78 pacientes para avaliação dos perfis glicídico e lipídico, enzimas hepáticas, TNF-α e HOMA-IR. O diagnóstico de DHGNA foi estabelecido por ultrassonografia. RESULTADOS: NAFLD foi observada em 42 por cento dos pacientes que apresentaram maior IMC (p < 0,001). Hipertensão arterial sistêmica (p < 0,001) e síndrome metabólica foram mais frequentes naqueles com DHGNA (p = 0,019). Os níveis de aspartato aminotransferase, alanina aminotransferase, γ-glutamil transpeptidase, ácido úrico, TNF-α, insulina e HOMA-IR foram significativamente maiores nos pacientes com do que naqueles sem DHGNA. CONCLUSÃO: Quase metade dos pacientes com DM2 apresentaram DHGNA, os quais tiveram IMC mais elevado, bem como maiores níveis de aminotransferases, γ-GT, ácido úrico, TNF-α, insulina e HOMA-IR do que os indivíduos sem DHGNA.

Níveis séricos de globulinas e a intensidade da fibrose hepática em pacientes com esquistossomose mansônica / Serum globulin levels and intensity of hepatic fibrosis in patients with mansonic schistosomiasis

CONTEXTO: Tem sido descrita correlação entre os níveis séricos de globulinas e o grau de fibrose hepática nas hepatites crônicas, mas não se encontram relatos na esquistossomose mansônica. OBJETIVO: Avaliar os níveis séricos de globulinas e de IgG, e a intensidade da fibrose periportal mensurada pela ultrassonografia em pacientes com esquistossomose mansônica. MÉTODOS: Entre novembro de 2006 e fevereiro de 2007, foram estudados 41 pacientes que preencheram ficha clínica e realizaram dosagens de IgG por imunoturbidimetria e de globulinas indiretamente pelo método do biureto. A ultrassonografia foi realizada por um único pesquisador, seguindo os protocolos do Cairo e de Niamey. RESULTADOS: A média de idade foi 41 anos, sendo 25 pacientes (61 por cento) do sexo feminino. Dez dos 41 pacientes (24 por cento) apresentaram elevação dos níveis séricos de globulinas e 21 (51 por cento) dos de IgG. Conforme a classificação do Cairo, 21 pacientes apresentaram grau I de fibrose, 18 grau II e 2 grau III, e pela classificação de Niamey 8 apresentavam padrão C, 20 D e 13 E. Aqueles com graus II ou III de fibrose tiveram maiores níveis de IgG do que os de grau I (P = 0,047), assim como aqueles que apresentaram padrões D e E em relação ao C (P = 0,011). Não houve associação entre os níveis de globulinas e o grau ou padrão de fibrose. CONCLUSÃO: Em pacientes com esquistossomose mansônica, observou-se elevação dos níveis séricos de IgG de acordo com a progressão do grau e do padrão de fibrose periportal, mas o mesmo não se observou com os níveis de globulinas.

BACKGROUND: A correlation between the levels of serum globulins and the hepatic fibrosis degree in chronic hepatitis was described, but reports in schistosomiasis mansoni have not been found. OBJECTIVE: To evaluate the serum globulins and IgG levels, and periportal fibrosis intensity measured by ultrasound in patients with schistosomiasis mansoni. METHODS: Between November, 2006 and February 2007, 41 patients which were eligible, filled them a questionnaire and had their levels of serum IgG measured by immunoturbidimetry and globulins indirectly measured by the Biuret method. The ultrasound was carried out by a single researcher, according to the Cairo and Niamey protocols. RESULTS: The average age was 41 years old and 25 female patients (61 percent). Ten patients (24 percent) from 41 showed serum globulins levels raised and 21 (51 percent) presented elevated IgG levels. According to the Cairo classification, 21 patients showed grade I of fibrosis, 18 grade II and 2 grade III; and by the Niamey classification 8 showed standard C, 20 D, and 13 E. Those with grade II or III of fibrosis had higher IgG levels than the ones with grade I (P = 0,047), as well as those who showed standards D and E as compared to C (P = 0,011). There was no association between the globulins levels and the intensity of fibrosis. CONCLUSION: In patients with schistosomiasis mansoni, an increase of the IgG serum levels was observed according to the progression from periportal fibrosis intensity, but the same was not founded with globulins levels.