Treatment of chronic hepatitis C in patients with chronic kidney disease with Sofosbuvir-basead regimes

ABSTRACT Background: To analyze the effectiveness and the safety of Sofosbuvir-based regimens to treat patients with chronic hepatitis C virus (HCV) infection and chronic kidney disease (CKD). Methods: A retrospective, observational study in patients with chronic HCV infection and CKD treated with Sofosbuvir-based regimens was performed. Liver fibrosis, comorbidities, HCV genotype and sustained virological resposnse (SVR) at 12th week post-treatment were evaluated. Kidney function was accessed by serum creatinine and glomerular filtration rate (GFR). The assumed level of significance was 5 %. Results: Thirty-five patients were treated. The mean age was 52.1 ± 10.9 years, 19 (54.3 %) were women, 32 (91.4 %) were already kidney transplanted and 3 (8.6 %) were on hemodialysis. The SVR by intention to treat was 88.6 %. The mean GFR was 65.8 ± 28.6 and 63.7 ± 28.3 ml/min pre- and post-treatment respectively (p > 0.05). Treatment was interrupted in 1 (2.85 %) patient due to anemia and in 2 (5.7 %) due to loss of kidney function. Conclusion: Sofosbuvir-based regimens are effective to treat HCV in patients with CKD. In patients with mild CKD this type of therapy seems to be safe.

Treatment of chronic hepatitis C in patients with chronic kidney disease with Sofosbuvir-basead regimes.

BACKGROUND: To analyze the effectiveness and the safety of Sofosbuvir-based regimens to treat patients with chronic hepatitis C virus (HCV) infection and chronic kidney disease (CKD). METHODS: A retrospective, observational study in patients with chronic HCV infection and CKD treated with Sofosbuvir-based regimens was performed. Liver fibrosis, comorbidities, HCV genotype and sustained virological resposnse (SVR) at 12th week post-treatment were evaluated. Kidney function was accessed by serum creatinine and glomerular filtration rate (GFR). The assumed level of significance was 5 %. RESULTS: Thirty-five patients were treated. The mean age was 52.1±10.9 years, 19 (54.3 %) were women, 32 (91.4 %) were already kidney transplanted and 3 (8.6 %) were on hemodialysis. The SVR by intention to treat was 88.6 %. The mean GFR was 65.8±28.6 and 63.7±28.3ml/min pre- and post-treatment respectively (p>0.05). Treatment was interrupted in 1 (2.85 %) patient due to anemia and in 2 (5.7 %) due to loss of kidney function. CONCLUSION: Sofosbuvir-based regimens are effective to treat HCV in patients with CKD. In patients with mild CKD this type of therapy seems to be safe.

Perfil dos pacientes com hepatite C crônica em um programa de saúde pública do sul do Brasil / Profile of patients with chronic hepatitis c in a public health program in southern brazil

ABSTRACT BACKGROUND: Chronic hepatitis C (CHC) can progress to cirrhosis and its complications as hepatocellular carcinoma, leading to morbidity and mortality. To know the profile of patients with CHC virus is fundamental to optimize management. OBJECTIVE: To describe the profile of patients with CHC in a public health program in Southern Brazil. METHODS: A retrospective study was carried out in patients with CHC who underwent treatment against hepatitis C virus in a dispensation and pharmaceutical assistance center of the Public Health Department of the State of Rio Grande do Sul, South Brazil. All medical records of patients attended between December/2015 and December/2016 were evaluated. RESULTS: A total of 1,431 records of patients with CHC were evaluated. Males were the most prevalent (802; 56%) patients. The mean age was 58.6±9.9 years, ranging from 18 to 89 years. Genotype 1 was the most frequent (866;60.5%) of the patients. Ninety (6.3%) patients were transplanted from a solid organ, and of these, 73 (5.1%) were transplanted from the liver. The fibrosis evaluation was performed in 1,300 (90.8%) patients. Of these, 566 (39.6%) were evaluated through liver biopsy. Regarding the degree of fibrosis, 779 (54.4%) presented fibrosis grade 4 (cirrhosis). The genotype 3 was the most associated with fibrosis grade 4, and genotype 1 was associated with high viral load. CONCLUSION: The present study made possible the evaluation of the characteristics of patients with CHC in a public health program in South Brazil. There was a predominance of CHC in males, and the mean age was 59 years. They presented a predominance of genotype 1, higher viral load in patients with genotype 1 and greater degree of fibrosis in patients with genotype 3.

RESUMO CONTEXTO: A hepatite crônica C (HCC) pode evoluir para cirrose e suas complicações como carcinoma hepatocelular, acarretando morbimortalidade. Conhecer o perfil dos pacientes portadores do vírus da HCC é fundamental para o melhor manejo do tratamento. OBJETIVO: Descrever o perfil dos pacientes portadores de HCC em um programa de saúde pública do sul do Brasil. MÉTODOS: Foi realizado um estudo retrospectivo onde foram incluídos os pacientes com HCC que realizaram o tratamento contra o vírus C em um polo de dispensação e assistência farmacêutica da Secretaria Estadual da Saúde do Estado do Rio Grande do Sul, Brasil. Foram avaliados todos os prontuários dos pacientes tratados entre dezembro/2015 e dezembro/2016. RESULTADOS: Foram avaliados 1.431 registros de pacientes portadores de HCC. O sexo masculino foi o mais prevalente (802; 56%) pacientes. A idade média dos pacientes foi de 58,6±9,9 anos, com variação de 18 a 89 anos. O genótipo 1 foi o mais frequente, em 866 (60,5%) dos pacientes. Noventa (6,3%) pacientes eram transplantados de órgão sólido, sendo que 73 (5,1%) eram transplantados de fígado. A avaliação de fibrose foi realizada em 1.300 (90,8%) pacientes. Dentre estes, 566 (39,6%) foram avaliados através de biópsia hepática. Em relação ao grau de fibrose, 779 (54,4%) apresentavam fibrose grau 4 (cirrose). Os genótipos foram analisados em relação aos diferentes graus de fibrose, sendo observado que o genótipo 3 está associado com o grau 4 de fibrose. O genótipo 1 está associado com alta carga viral. CONCLUSÃO: O presente estudo possibilitou a avaliação do perfil dos pacientes portadores de HCC em um programa de saúde pública do Brasil. Houve uma predominância de HCC no sexo masculino, e a média de idade foi de 59 anos. Apresentam um predomínio do genótipo 1, maior carga viral nos pacientes portadores do genótipo 1 e maior grau de fibrose nos portadores de genótipo 3.

IMPACT OF MICROBIOLOGICAL CHANGES ON SPONTANEOUS BACTERIAL PERITONITIS IN THREE DIFFERENT PERIODS OVER 17 YEARS.

BACKGROUND: Spontaneous bacterial peritonitis is a serious complication in cirrhotic patients, and changes in the microbiological characteristics reported in the last years are impacting the choice of antibiotic used for treatment. OBJECTIVE: The aim of the present study is to evaluate the changes in the epidemiology and bacterial resistance of the germs causing spontaneous bacterial peritonitis over three different periods over 17 years. METHODS: All cirrhotic patients with spontaneous bacterial peritonitis and positive culture of ascites fluid were retrospectively studied in a reference Hospital in Southern Brazil. Three periods were ramdomly evaluated: 1997-1998, 2002-2003 and 2014-2015. The most frequent infecting organisms and the sensitivity in vitro to antibiotics were registered. RESULTS: In the first period (1997-1998) there were 33 cases, the most common were: E. coli in 13 (36.11%), Staphylococcus coagulase-negative in 6 (16.66%), K. pneumoniae in 5 (13.88%), S. aureus in 4 (11.11%) and S. faecalis in 3 (8.33%). In the second period (2002-2003), there were 43 cases, the most frequent were: Staphylococus coagulase-negative in 16 (35.55%), S. aureus in 8 (17.77%), E. coli in 7 (15.55%) and K. pneumoniae in 3 (6.66%). In the third period (2014-2015) there were 58 cases (seven with two bacteria), the most frequent were: E. coli in 15 (23.1%), S. viridans in 12 (18.5%), K. pneumoniae in 10 (15.4%) and E. faecium 5 (7.7%). No one was using antibiotic prophylaxis. Considering all staphylococci, the prevalence increased to rates of the order of 50% in the second period, with a reduction in the third period evaluated. Likewise, the prevalence of resistant E. coli increased, reaching 14%. CONCLUSION: There was a modification of the bacterial population causing spontaneous bacterial peritonitis, with high frequency of gram-positive organisms, as well as an increase in the resistance to the traditionally recommended antibiotics. This study suggests a probable imminent inclusion of a drug against gram-positive organisms in the empiric treatment of spontaneous bacterial peritonitis.

Impacto das mudanças da microbiologia na peritonite bacteriana espontânea em três diferentes períodos ao longo de 17 anos / Impact of microbiological changes on spontaneous bacterial peritonitis in three different periods over 17 years

ABSTRACT BACKGROUND: Spontaneous bacterial peritonitis is a serious complication in cirrhotic patients, and changes in the microbiological characteristics reported in the last years are impacting the choice of antibiotic used for treatment. OBJECTIVE: The aim of the present study is to evaluate the changes in the epidemiology and bacterial resistance of the germs causing spontaneous bacterial peritonitis over three different periods over 17 years. METHODS: All cirrhotic patients with spontaneous bacterial peritonitis and positive culture of ascites fluid were retrospectively studied in a reference Hospital in Southern Brazil. Three periods were ramdomly evaluated: 1997-1998, 2002-2003 and 2014-2015. The most frequent infecting organisms and the sensitivity in vitro to antibiotics were registered. RESULTS: In the first period (1997-1998) there were 33 cases, the most common were: E. coli in 13 (36.11%), Staphylococcus coagulase-negative in 6 (16.66%), K. pneumoniae in 5 (13.88%), S. aureus in 4 (11.11%) and S. faecalis in 3 (8.33%). In the second period (2002-2003), there were 43 cases, the most frequent were: Staphylococus coagulase-negative in 16 (35.55%), S. aureus in 8 (17.77%), E. coli in 7 (15.55%) and K. pneumoniae in 3 (6.66%). In the third period (2014-2015) there were 58 cases (seven with two bacteria), the most frequent were: E. coli in 15 (23.1%), S. viridans in 12 (18.5%), K. pneumoniae in 10 (15.4%) and E. faecium 5 (7.7%). No one was using antibiotic prophylaxis. Considering all staphylococci, the prevalence increased to rates of the order of 50% in the second period, with a reduction in the third period evaluated. Likewise, the prevalence of resistant E. coli increased, reaching 14%. CONCLUSION: There was a modification of the bacterial population causing spontaneous bacterial peritonitis, with high frequency of gram-positive organisms, as well as an increase in the resistance to the traditionally recommended antibiotics. This study suggests a probable imminent inclusion of a drug against gram-positive organisms in the empiric treatment of spontaneous bacterial peritonitis.

RESUMO CONTEXTO: A peritonite bacteriana espontânea é uma complicação séria em pacientes cirróticos e as alterações nas características microbiológicas relatadas nos últimos anos podem afetar a escolha do antibiótico utilizado no tratamento. OBJETIVO: Os objetivos do presente estudo são avaliar as mudanças na epidemiologia e perfil de resistência bacteriana dos germes causadores de peritonite bacteriana espontânea em três períodos diferentes ao longo de 17 anos. MÉTODOS: Todos os pacientes cirróticos com peritonite bacteriana espontânea e cultura positiva de fluido ascítico foram estudados retrospectivamente em um hospital de referência no Sul do Brasil. Foram avaliados três diferentes períodos selecionados de forma randômica: 1997-1998, 2002-2003 e 2014-2015. Os organismos infecciosos mais frequentes e a sensibilidade in vitro a antibióticos foram registados. RESULTADOS: No primeiro período (1997-1998) houve 33 casos; os mais comuns foram: E. coli em 13 (36,1%), Staphylococcus coagulase-negativo em 6 (16,7%), K. pneumoniae em 5 (13,9%), S. aureus em 4 (11,1%) e S. faecalis em 3 (8,3%). No segundo período (2002-2003), houve 43 casos, os mais frequentes foram: Staphylococus coagulase-negativo em 16 (35,5%), S. aureus em 8 (17,8%), E. coli em 7 (15,5%) e K. pneumoniae em 3 (6,7%). No terceiro período (2014-2015), houve 58 casos (sete com duas bactérias), os mais frequentes foram: E. coli em 15 (23,1%), S. viridans em 12 (18,5%), K. pneumoniae em 10 (15,4%) e E. faecium 5 (7,7%). Nenhum paciente estava usando profilaxia antibiótica. Quando considerados todos os estafilococos, a prevalência aumentou para taxas da ordem de 50% no segundo período, apresentando redução no terceiro período avaliado. Do mesmo modo, a prevalência de E coli resistente aumentou, chegando a 14%. CONCLUSÃO: Houve modificação da população bacteriana causadora de peritonite bacteriana espontânea, com alta frequência de organismos gram-positivos, bem como aumento da resistência aos antibióticos tradicionalmente recomendados. Este estudo sugere uma provável inclusão iminente de um medicamento contra organismos gram-positivos no tratamento empírico da peritonite bacteriana espontânea.

PROFILE OF PATIENTS WITH CHRONIC HEPATITIS C IN A PUBLIC HEALTH PROGRAM IN SOUTHERN BRAZIL.

BACKGROUND: Chronic hepatitis C (CHC) can progress to cirrhosis and its complications as hepatocellular carcinoma, leading to morbidity and mortality. To know the profile of patients with CHC virus is fundamental to optimize management. OBJECTIVE: To describe the profile of patients with CHC in a public health program in Southern Brazil. METHODS: A retrospective study was carried out in patients with CHC who underwent treatment against hepatitis C virus in a dispensation and pharmaceutical assistance center of the Public Health Department of the State of Rio Grande do Sul, South Brazil. All medical records of patients attended between December/2015 and December/2016 were evaluated. RESULTS: A total of 1,431 records of patients with CHC were evaluated. Males were the most prevalent (802; 56%) patients. The mean age was 58.6±9.9 years, ranging from 18 to 89 years. Genotype 1 was the most frequent (866;60.5%) of the patients. Ninety (6.3%) patients were transplanted from a solid organ, and of these, 73 (5.1%) were transplanted from the liver. The fibrosis evaluation was performed in 1,300 (90.8%) patients. Of these, 566 (39.6%) were evaluated through liver biopsy. Regarding the degree of fibrosis, 779 (54.4%) presented fibrosis grade 4 (cirrhosis). The genotype 3 was the most associated with fibrosis grade 4, and genotype 1 was associated with high viral load. CONCLUSION: The present study made possible the evaluation of the characteristics of patients with CHC in a public health program in South Brazil. There was a predominance of CHC in males, and the mean age was 59 years. They presented a predominance of genotype 1, higher viral load in patients with genotype 1 and greater degree of fibrosis in patients with genotype 3.

IMPACT OF THE PEGYLATED-INTERFERON AND RIBAVIRIN THERAPY ON THE TREATMENT-RELATED MORTALITY OF PATIENTS WITH CIRRHOSIS DUE TO HEPATITIS C VIRUS.

UNLABELLED: Although the protease inhibitors have revolutionized the therapy of chronic hepatitis C (CHC), the concomitant use of pegylated-interferon (PEG-IFN) and ribavirin (RBV) is associated to a high rate of adverse effects. In this study, we evaluated the consequences of PEG-IFN and RBV and their relationship with mortality in patients with cirrhosis. METHODS: Medical records of CHC who underwent treatment with PEG-IFN and RBV in a public hospital in Brazil were evaluated. All the patients with cirrhosis were selected, and their clinical and laboratory characteristics, response to treatment, side effects and mortality were evaluated. RESULTS: From the 1,059 patients with CHC, 257 cirrhotic patients were evaluated. Of these, 45 (17.5%) achieved sustained viral response (SVR). Early discontinuation of therapy occurred in 105 (40.8%) patients, of which 39 (15.2%) were due to serious adverse effects. The mortality rate among the 257 cirrhotic patients was 4.3%, occurring in 06/242 (2.4%) of the Child-A, and in 05/15 (33.3%) of the Child-B patients. In conclusion, the treatment of patients with cirrhosis due to HCV with PEG-IFN and RBV shows a low SVR rate and a high mortality, especially in patients with liver dysfunction.

Percutaneous liver biopsy--2 decades of experience in a public hospital in the South of Brazil.

INTRODUCTION: Liver biopsy is a complementary method for diagnosis, staging and therapeutic guidance in liver diseases, where chronic viral hepatitis are the most acknowledged causes for the indication of histopathological study. The objective is to assess the patients' profile as well as the indication and results of percutaneous liver biopsies in a tertiary hospital. MATERIAL AND METHODS: A descriptive, cross-section study was carried out through the review of medical charts (retrospective cohort) of patients submitted to blind percutaneous liver biopsies (PLB) at a hospital in Porto Alegre, South Brazil, from October 1993 to December 2011. RESULTS: 1,955 PLB were carried out, the mean patients' age was 44.8 years old, and 1,127 (57.65%) were men. Chronic hepatitis C was the main indication (60.5%), followed by HCV-HIV coinfection (12.2%) and chronic hepatitis B (3.5%). Seven cases (0.3%) had complications, without deaths. CONCLUSION: PLB is a safe method and continues to be an important option to assist patients with chronic liver disease.

Progression of liver fibrosis in monoinfected patients by hepatitis C virus and coinfected by HCV and human immunodeficiency virus.

CONTEXT: The progression of liver fibrosis in patients coinfected by hepatitis C virus and human immunodeficiency virus (HCV/HIV) has been increasingly studied in the past decade. Studies made before the highly active antiretroviral therapy suggest that HIV can change the natural history of the HCV infection, leading to a faster progression of the liver fibrosis. OBJECTIVE: To evaluate and compare the fibrosis progression in two groups of patients (HCV/HIV coinfected and HCV monoinfected) METHODS: Seventy patients HCV monoinfected and 26 patients HCV/HIV coinfected who had not undertaken HCV treatment and were submitted to serial percutaneous liver biopsies were retrospectively evaluated. There was no difference in the fibrosis progression between the two groups. CONCLUSION: The fibrosis grade evolution was not worse in the coinfected patients. The immunosuppression absence and the shortest time period between the biopsies in the coinfected group are possible explanations.

Progression of iiver fibrosis in monoinfected ptients by hepatitis c virus andd coinfected by hcv and human immunodeficiency virus

Context The progression of liver fibrosis in patients coinfected by hepatitis C virus and human immunodeficiency virus (HCV/HIV) has been increasingly studied in the past decade. Studies made before the highly active antiretroviral therapy suggest that HIV can change the natural history of the HCV infection, leading to a faster progression of the liver fibrosis. Objective To evaluate and compare the fibrosis progression in two groups of patients (HCV/HIV coinfected and HCV monoinfected) Methods Seventy patients HCV monoinfected and 26 patients HCV/HIV coinfected who had not undertaken HCV treatment and were submitted to serial percutaneous liver biopsies were retrospectively evaluated. There was no difference in the fibrosis progression between the two groups. Conclusion The fibrosis grade evolution was not worse in the coinfected patients. The immunosuppression absence and the shortest time period between the biopsies in the coinfected group are possible explanations. .

Contexto A progressão da fibrose hepática em pacientes coinfectados pelos vírus da hepatite C (VHC) e da imunodeficiência humana (VHC/HIV) tem sido mais estudada na última década. Estudos realizados antes da terapia antiretroviral de alta potência (HAART) sugerem que o HIV pode mudar a história natural da infecção pelo VHC, levando a uma progressão mais rápida da fibrose hepática. Objetivo Avaliar e comparar a progressão de fibrose em duas populações de pacientes (coinfectados VHC/HIV e monoinfectados VHC). Métodos Foram avaliados retrospectivamente 70 pacientes monoinfectados VHC e 26 coinfectados VHC/HIV nunca tratados para o VHC e que haviam realizado duas biopsias hepáticas seriadas. Não houve diferença na progressão de fibrose entre os dois grupos. Conclusão A evolução do grau de fibrose não foi pior nos pacientes coinfectados. A ausência de imunodepressão e o menor intervalo de tempo entre as biopsias no grupo de coinfectados são possíveis justificativas. .

Análise dos escores de gravidade como preditores na mortalidade em cirróticos hospitalizados / Evaluation of the prognostic scores to predict mortality in hospitalized cirrhotic patient

Introdução: Diversos índices têm sido propostos na avaliação da gravidade da doença hepática. Objetivo: Analisar os escores de Child-Turcote- Pugh (CTP), APACHE II, MELD e SOFA como índices prognósticos de mortalidade hospitalar em pacientes cirróticos. Metodologia: Foram avaliados prospectivamente todos os cirróticos que se internaram em enfermaria provenientes da emergência de um Hosputal Geral de Porto Alegre, em um período de 6 meses. Os escores CTP, MELD, APACHE II e SOFA foram registrados, bem como o desfecho (alta ou óbito). O nível de significância adotado foi de 5%. Resultados: Foram avaliados 61 cirróticos. Quarenta e três eram homens (70%). A média de idade foi de 54,7±11,7 anos. Álcool e/ou o vírus da hepatite C (HCV) foram responsáveis pela etiologia de 50 (82%) casos. Quanto ao CTP, houve 7 (32%) mortes naqueles CTP A ou B, e 11 (38%) naqueles C (p=0,27). A mediana do escore MELD foi de 15, sendo que houve 3 (11%) mortes naqueles com MELD < 15 e 15 (45%) naqueles com MELD ≥15 (p=0,02). A mediana do escore APACHE II foi de 9, sendo que houve 0 morte naqueles com índice < 9 e 18 (41%) naqueles com índice ≥9 (p<00,1). Em relação ao SOFA, a média foi de 3,6±1,8 naqueles vivos versus 5,6±2,6 naqueles que foram a óbito durante a internação (p=0,005). A mortalidade hospitalar foi de 29% (18 casos). Conclusões: Os escores MELD, APACHE II e SOFA se mostraram bons preditores de mortalidade em cirróticos hospitalizados, mas não a classificação de CTP.

Introduction: A number of indexes have historically been proposed to assess the severity of liver disease. Aim: To evaluate the Child-Turcote-Pugh (CTP), APACHE II, MELD and SOFA scores as prognostic indexes of in-hospital mortality among cirrhotic patients. Methods: This is a prospective analysis of all cirrhotic patients who were admitted to a general hospital of Porto Alegre in a period of 6 months. CTP, MELD, APACHE II and SOFA scores were analyzed, as well as the outcome (discharge or death). The level of significance was 5%. Results: A total of 61 cirrhotic patients were evaluated. Forty-three patients were males (70%) and the mean age was 54.7±11.7 years. Alcohol and/or hepatitis C virus (HCV) were the ethiological agents in 50 (82%) cases. Concerning CTP scores, there were 7 (32%) deaths among CTP A or B and 11 (38%) deaths among CTP C (p=0.27). The median for the MELD scores was 15, and there were 3 (11%) deaths among those with MELD < 15 and 15 (45%) deaths among those with MELD ≥15 (p=0.02). The median for the APACHE II scores was 9, and there were no deaths (0) among patients with indexes ≥9 (p<00.1). Concerning the SOFA, the mean was 3.6±1.8 among living patients versus 5.6±2.6 among those who progressed to death during the hospitalization (p=0.005). The overall in-hospital mortality rate was 29% (18 cases). Conclusions: MELD, APACHE II, and SOFA scores proved to be good predictors of mortality of hospitalized cirrhotic patients, but the CTP did not.

[Alpha-interferon versus peg-interferon associated to ribavirin in the treatment of genotype 1 hepatitis C virus and human immunodeficiency virus coinfected patients]. / Interferon convencional versus interferon peguilado associados à ribavirina no tratamento de pacientes coinfectados pelo vírus da hepatite C (genótipo 1) e da imunodeficiência humana.

CONTEXT: It has been suggested that coinfected patients HCV/HIV must be treated with pegylated interferon associated to ribavirin (PEG+RBV), because of better taxes of sustained virological response when compared to those treated with conventional interferon associated to ribavirin (IFN+RBV). There are few studies in the literature comparing these two treatments options in this population. OBJECTIVE: To evaluate the sustained virological response to the treatment with IFN+RBV versus PEG+RBV in coinfected patients HCV/HIV genotype 1, in a public health program. METHODS: It is a cohort study, where the data of the coinfected patients treated with IFN+RBV (before 2002) or PEG+RBV (from 2002) during 48 weeks in the Brazilian Health Ministry program were reviewed. Demographic characteristics were evaluated (age, gender and weight), CD4 cell count and histopathology - inflammatory activity (A) and fibrosis grade, by METAVIR classification. The significance level adopted was 5%. RESULTS: Eighty one patients were evaluated, 22 treated with IFN+RBV and 59 treated with PEG+RBV. Both were similar relating to age, gender, weight, CD4 cell count and fibrosis grade. Those treated with IFN+RBV presented a greater proportion of A2+A3 patients than those treated with PEG+RBV (P<0.01). The sustained virological response was 14% versus 23% in those using IFN+RBV or PEG+RBV respectively (P = 0.54). The Odds Ratio was 1.9 (0.5 to 7.3). CONCLUSION: Coinfected patients HCV/HIV genotype 1 treated with PEG+RBV presented 1.9 more chance to obtain sustained virological response than those treated with IFN+RBV, however without statistical significance.

Interferon convencional versus interferon peguilado associados à ribavirina no tratamento de pacientes coinfectados pelo vírus da hepatite C (genótipo 1) e da imunodeficiência humana / Alpha-interferon versus peg-interferon associated to ribavirin in the treatment of genotype 1 hepatitis C virus and human imunodeficiency virus coinfected patients

CONTEXTO: Tem sido sugerido que os pacientes coinfectados por vírus da hepatite C e da imunodeficiência humana (VHC/HIV) devam ser tratados com interferon peguilado associado à ribavirina (PEG+RBV) porque as taxas de resposta virológica sustentada seriam maiores do que aquelas obtidas com interferon convencional associado à ribavirina (IFN+RBV). No entanto, há escassez de trabalhos na literatura comparando as duas opções de tratamento nesta população de pacientes, em especial fora do cenário de ensaios clínicos. OBJETIVO: Avaliar a resposta virológica sustentada ao tratamento com IFN+RBV versus PEG+RBV em pacientes coinfectados pelo vírus da hepatite C genótipo 1 e vírus da imunodeficiência humana (VHC-1/HIV), no âmbito do programa do Ministério da Saúde. MÉTODOS: Trata-se de estudo de coorte misto, onde foram revisados prontuários de pacientes coinfectados por VHC-1/HIV tratados com IFN+RBV (antes de 2002) ou PEG+RBV (a partir de 2002) pelo período de 48 semanas, no âmbito da Secretaria da Saúde do Estado do Rio Grande do Sul. Foram avaliadas as características demográficas (idade, gênero e peso), contagem de células CD4 e histopatologia - atividade inflamatória (A) e fibrose - segundo classificação METAVIR. O nível de significância adotado na análise estatística foi de 5 por cento. RESULTADOS: Foram avaliados 81 pacientes coinfectados por VHC-1/HIV, 22 que utilizaram IFN+RBV e 59 que utilizaram PEG+RBV por 48 semanas. Os grupos eram semelhantes no que tange à média de idade, gênero, peso, contagem de células CD4 e grau de fibrose. Os pacientes que utilizaram IFN+RBV apresentaram maior atividade histológica com proporção de A2+A3 que superava aqueles que utilizaram PEG+RBV (P<0,01). A resposta virológica sustentada foi 14 por cento no grupo que utilizou IFN+RBV e 23 por cento naqueles que utilizaram PEG+RBV (P = 0,54), com Odds Ratio de 1,9 (0,5 a 7,3). CONCLUSÃO: Os pacientes coinfectados por HCV-1/HIV tratados com PEG+RBV apresentaram...

CONTEXT: It has been suggested that coinfected patients HCV/HIV must be treated with pegylated interferon associated to ribavirin (PEG+RBV), because of better taxes of sustained virological response when compared to those treated with conventional interferon associated to ribavirin (IFN+RBV). There are few studies in the literature comparing these two treatments options in this population. OBJECTIVE: To evaluate the sustained virological response to the treatment with IFN+RBV versus PEG+RBV in coinfected patients HCV/HIV genotype 1, in a public health program. METHODS: It is a cohort study, where the data of the coinfected patients treated with IFN+RBV (before 2002) or PEG+RBV (from 2002) during 48 weeks in the Brazilian Health Ministry program were reviewed. Demographic characteristics were evaluated (age, gender and weight), CD4 cell count and histopathology - inflammatory activity (A) and fibrosis grade, by METAVIR classification. The significance level adopted was 5 percent. RESULTS: Eighty one patients were evaluated, 22 treated with IFN+RBV and 59 treated with PEG+RBV. Both were similar relating to age, gender, weight, CD4 cell count and fibrosis grade. Those treated with IFN+RBV presented a greater proportion of A2+A3 patients than those treated with PEG+RBV (P<0.01). The sustained virological response was 14 percent versus 23 percent in those using IFN+RBV or PEG+RBV respectively (P = 0.54). The Odds Ratio was 1.9 (0.5 to 7.3). CONCLUSION: Coinfected patients HCV/HIV genotype 1 treated with PEG+RBV presented 1.9 more chance to obtain sustained virological response than those treated with IFN+RBV, however without statistical significance.

Preditores laboratoriais de atividade inflamatória e de fibrose hepática em pacientes com infecção pelo vírus da hepatite C / Laboratorial tests predictive of inflamatory activity and liver fibrosis in patients with hepatitis C virus infection

Objetivos: Avaliar a relação entre parâmetros laboratoriais e o grau de fibrose e atividade inflamatória na biópsia hepática. Metodologia: Estudo transversal de análise de dados laboratoriais e histopatológicos obtidos de forma consecutiva em 210 pacientes com infecção por VHC que foram submetidos à biópsia hepática às cegas. Foram avaliados alanina e aspartato-aminotransferase (ALT e AST), plaquetas, albumina, tempo de protrombina (TP) e o índice APRI (AST/plaquetas). O exame histopatológico foi classificado segundo o escore METAVIR. Para análise estatística, foi adotado um nível de significância de 5%. Resultados: A população foi constituída por 109 (51,9%) homens e 101 mulheres. A média de idade foi de 48,47 ± 1,31 anos. Quanto ao TP, albumina e AST isoladamente, não houve correlação com atividade ou fibrose. Houve correlação negativa entre plaquetas e o grau de fibrose. Utilizando os dados combinados através de índices APRI e ALT/plaquetas, as correlações são mais consistentes e significativas. Ambos os índices apresentaram boa correlação com o grau de fibrose. Conclusões: Dentre os parâmetros bioquímicos avaliados no presente estudo, o índice APRI e a relação ALT/plaquetas apresentaram melhor correlação com o grau de fibrose. Entretanto, não houve marcador que mostrasse uma relação sensibilidade/especificidade adequada para não justificar a realização de biópsia hepática (AU)

Objective: To correlate biochemical parameters with liver biopsy findings regarding fibrosis grade and inflammatory activity. Methods: A cross sectional study was designed to access the association of liver tests and histopathological data of 210 patients with hepatitis C virus. Platelets count, alanine and aspartate-aminotransferases (ALT and AST), albumin, the protrombin time (PT) and the APRI score (AST/platelets) were correlated with histopathological findings classified by METAVIR score. A significance level of 5% was used to test the association between variables. Results: There were 109 (51.9%) men and 101 women. The mean age was 48.47 +/- 1.31 years. PT, albumin and AST showed no correlation with inflammatory activity or fibrosis grade. There was a negative correlation between platelets and the fibrosis grade. This correlation was consistent with APRI score and ALT/platelets index. Both scores presented a good correlation with the fibrosis grade. Conclusions: APRI and ALT/platelets score presented significant correlation with the fibrosis grade. However, none of those tests showed sensitivity and specificity enough to replace liver biopsy (AU)

[Spontaneous bacterial peritonitis: impact of microbiological changes]. / Peritonite bacteriana espontânea: impacto das mudanças da microbiologia.

BACKGROUND: Spontaneous bacterial peritonitis is a serious complication in cirrhotic patients, and the changes in the microbiological characteristics reported in the last years are impacting the choice of antibiotic used in the treatment. AIM: To evaluate the change in the epidemiology and antibiotic resistance of the bacteria causing spontaneous bacterial peritonitis in a 7 years period. METHODS: All the cases of cirrhotic patients with spontaneous bacterial peritonitis with positive cultural examination were retrospectively studied. Two periods were evaluated: 1997-1998 and 2002-2003. The most frequent infecting organisms and the sensitivity in vitro to antibiotics were registered. RESULTS: In the first period (1997-1998) there were 33 cases, 3 (9%) with polymicrobial infection. The most common were: E.coli in 13 (36,11%), Staphylococcus coagulase-negative in 6 (16,66%), K. pneumoniae in 5 (13,88%), S. aureus in 4 (11,11%) and S. faecalis in 3 (8,33%). In 2003-2004, there were 43 cases, 2 (5%) with polymicrobial infection. The most frequent were: Staphylococus coagulase-negative in 16 (35,55%), S. aureus in 8 (17,77%), E. coli in 7 (15,55%) and K. pneumoniae in 3 (6,66%). No one was using antibiotic prophilaxys. The prevalence of S. aureus methicillin-resitant to quinolone and trimethoprim-sulfamethoxazole changed from 25% to 50%, and vancomicin was the only one with absolute activity during all the period. In the same way, the prevalence of E. coli resistant to third generation cephalosporin and to quinolone changed from 0% to 16%. CONCLUSION: There was a modification of the bacterial population causing spontaneous bacterial peritonitis, with high frequency of gram-positive organisms, as well as an increase in the resistance to the traditionally recommended antibiotics. This study suggests a probable imminent inclusion of a drug against gram-positive organisms in the empiric treatment of spontaneous bacterial peritonitis.

Peritonite bacteriana espontânea: impacto das mudanças da microbiologia / Spontaneous bacterial peritonitis: impact of microbiological changes

RACIONAL: A peritonite bacteriana espontânea é uma complicação grave nos pacientes cirróticos com ascite, sendo as alterações das características microbiológicas relatadas nos últimos anos de impacto na escolha do tratamento antibiótico. OBJETIVO: Avaliar as mudanças na epidemiologia e na resistência antibiótica de bactérias causadoras de peritonite bacteriana espontânea em um período de 7 anos. MÉTODOS: Foram avaliados retrospectivamente todos os casos de pacientes cirróticos com peritonite bacteriana espontânea cuja cultura do líquido de ascite foi positiva, sendo estudados dois períodos: 1997-1998 e 2002-2003. Foram verificados os microorganismos mais freqüentes e a sensibilidade in vitro aos antibióticos. RESULTADOS: No primeiro período (1997-1998) houve 33 casos, sendo 3 (9 por cento) com infecção polimicrobiana. As bactérias mais freqüentes foram: E. coli em 13 (36,11 por cento), estafilococos coagulase-negativos em 6 (16,66 por cento), K. pneumoniae em 5 (13,88 por cento), S. aureus em 4 (11,11 por cento) e S. faecalis em 3 (8,33 por cento). Em 2002-2003, houve 43 casos, sendo 2 (5 por cento) com infecção polimicrobiana. As bactérias mais freqüentes foram: estafilococos coagulase-negativos em 16 (35,55 por cento) S. aureus em 8 (17,77 por cento), E. coli em 7 (15,55 por cento) e K. pneumoniae em 3 (6,66 por cento). Nenhum paciente realizava profilaxia para peritonite bacteriana espontânea. A prevalência de S. aureus meticilino-resistentes aumentou, no decorrer desse período, de 25 por cento para 75 por cento, tendo a resistência desse patógeno às quinolonas e a sulfametoxazol-trimetoprim evoluído de 25 por cento para 50 por cento; somente a vancomicina demonstrou atividade absoluta no decorrer do referido período. Da mesma forma, a prevalência de E. coli resistente às cefalosporinas de terceira geração e às quinolonas aumentou de 0 por cento para 16 por cento. CONCLUSÃO: Houve modificação da população bacteriana causadora de peritonite...

BACKGROUND: Spontaneous bacterial peritonitis is a serious complication in cirrhotic patients, and the changes in the microbiological characteristics reported in the last years are impacting the choice of antibiotic used in the treatment. AIM: To evaluate the change in the epidemiology and antibiotic resistance of the bacteria causing spontaneous bacterial peritonitis in a 7 years period. METHODS: All the cases of cirrhotic patients with spontaneous bacterial peritonitis with positive cultural examination were retrospectively studied. Two periods were evaluated: 1997-1998 and 2002-2003. The most frequent infecting organisms and the sensitivity in vitro to antibiotics were registered. RESULTS: In the first period (1997-1998) there were 33 cases, 3 (9 percent) with polymicrobial infection. The most common were: E.coli in 13 (36,11 percent), Staphylococcus coagulase-negative in 6 (16,66 percent), K. pneumoniae in 5 (13,88 percent), S. aureus in 4 (11,11 percent) and S. faecalis in 3 (8,33 percent). In 2003-2004, there were 43 cases, 2 (5 percent) with polymicrobial infection. The most frequent were: Staphylococus coagulase-negative in 16 (35,55 percent), S. aureus in 8 (17,77 percent), E. coli in 7 (15,55 percent) and K. pneumoniae in 3 (6,66 percent). No one was using antibiotic prophilaxys. The prevalence of S. aureus methicillin-resitant to quinolone and trimethoprim-sulfamethoxazole changed from 25 percent to 50 percent, and vancomicin was the only one with absolute activity during all the period. In the same way, the prevalence of E. coli resistant to third generation cephalosporin and to quinolone changed from 0 percent to 16 percent. CONCLUSION: There was a modification of the bacterial population causing spontaneous bacterial peritonitis, with high frequency of gram-positive organisms, as well as an increase in the resistance to the traditionally recommended antibiotics. This study suggests a probable imminent inclusion of a drug...

Prevalência ambulatorial em um hospital geral de marcadores para hepatites B e C em pacientes com infecção pelo vírus da imunodeficiência humana / Ambulatorial prevalence of hepatitis B and C markers in patients with human immunodeficiency virus infection in a general hospital

RACIONAL: Os vírus das hepatites B (VHB) e C (VHC) e da imunodeficiência humana (HIV) utilizam a mesma rota de transmissão, sendo a prevalência de VHB e VHC em pacientes infectados pelo HIV maior do que aquela encontrada na população em geral. OBJETIVO: Determinar a prevalência de marcadores para hepatites B e C em uma população de pacientes com HIV, bem como os fatores de risco envolvidos. PACIENTES E MÉTODOS: Dentre os 5 870 prontuários de pacientes com HIV em acompanhamento no Serviço de Infectologia do Hospital Nossa Senhora da Conceição, Porto Alegre, RS, foram aleatoriamente selecionados 587 prontuários. Destes, foram considerados para análise retrospectiva aqueles em que havia sido pesquisado algum marcador para hepatites B (HBsAg, anti-HBc ou anti-HBs) ou C (anti-VHC), perfazendo o total de 343 pacientes. RESULTADOS: O HBsAg foi positivo em 14 de 306 (4,6 por cento) pacientes, anticorpo anti-HBs, em 40 de 154 (26,0 por cento) pacientes, e anti-HBc em 79 de 205 (38,5 por cento) pacientes. Dentre aqueles que realizaram anti-VHC, 126 de 330 (38,2 por cento) tinham-no positivo. Co-infecção por vírus B e C foi observada em 7 dentre os 296 pacientes que realizaram tanto o HBsAg, quanto o anti-VHC (2,4 por cento). Dentre aqueles HBsAg positivos, a principal categoria de exposição foi o relacionamento homossexual masculino (50,0 por cento). Dentre aqueles anti-VHC positivos, a principal categoria de exposição foi o uso de drogas ilícitas injetáveis (75,3 por cento). Naqueles monoinfectados com HIV (185 pacientes), o fator de risco mais prevalente foi relacionamento heterossexual promíscuo ou com cônjuge infectado por HIV em 83 pacientes (44,9 por cento). CONCLUSÃO: Em nosso meio, as co-infecções VHB-HIV e VHC-HIV são freqüentes, sendo observado maior impacto na associação do VHC com o HIV.

BACKGROUND: Hepatitis B and C viruses and human immunodeficiency virus share the same route of transmission, and the prevalence of HBV and HCV infection in patients infected with HIV is greater than it is in the general population. AIM: To determine the prevalence of hepatitis B and C markers in a population of patients with HIV as well as the risk factors involved. PATIENTS AND METHODS: From 5,870 registration forms of patients with HIV of an Infectology Unit, 587 were randomly selected. From these, the 343 which had investigated the presence of any hepatitis B (HBsAg, anti-HBc or anti-HBs) or C (anti-HCV) marker were retrospectively analyzed. RESULTS: HBsAg was positive in 14/306 (4.6 percent), anti-HBs was positive in 40/154(26.0 percent), and anti-HBc in 79/205 (38.5 percent). The anti-HCV test was reactive in 126/330 (38.2 percent). HBV and HCV co-infection was observed in 7 of the 296 patients who had both HBsAg and anti-HCV tests (2.4 percent). For those who were HBsAg positive, the main exposure factor was homosexual intercourse (50.0 percent). For those who were anti-HCV reactive, the main risk factor was intravenous drug use (75.3 percent). In the HIV mono-infected (185 patients), the most prevalent exposure risk factor was promiscuous heterosexual practices or sexual intercourse with a spouse infected with HIV (83 patients - 44.9 percent). CONCLUSION: In our environment HBV-HIV and HCV-HIV co-infections are frequent, a greater relevance being observed in the association between HCV and HIV.

Tratamento de pacientes com infecção crônica pelo genótipo 1 do vírus da hepatite C com interferon peguilado e ribavirina: a experiência da Secretaria da Saúde do Rio Grande do Sul / Treatment of patients with chronic hepatitis C virus genotype 1 infection with pegylated interferon and ribavirin: the experience of the Rio Grande do Sul health department

A infecção pelo virus da hepatite C (HCV) é atualmente considerada como um problema de saúde pública. Este estudo visa avaliar a resposta sustentada ao tratamento de pacientes com hepatite crônica pelo genótipo 1 do HCV no âmbito de um programa desenvolvido na Secretaria Estadual da Saúde do Rio Grande do Sul. É um estudo de coorte misto, onde foram revisados os processos/prontuários administrativos de tratamento de pacientes com hepatite crônica C através da administração de interferon peguilado associado à ribavirina. O esquema de tratamento disponibilizado é o que segue: interferon peguilado alfa-2a 180 mcg ou interferon peguilado alfa-2b na dose 1,5 mcg/kg administrados via subcutânea uma vez por semana, mais ribavirina 1000 mg/dia para pacientes com menos de 75 kg ou 1250 mg/dia para pacientes com 75 kg ou mais, por um período de 48 semanas. Não havendo a Resposta Virológica Precoce (RVP) o tratamento era interrompido. O nível de significância adotado, na análise estatística, foi de cx = 0,05. Os resultados observados são os que seguem: a coorte constituiu-se de 323 indivíduos. Cento e oitenta (55,7%) eram do gênero masculino. A média foi 51,1+- 10,1 anos. O IMC foi de 26,8+- 4,4Kg/m2. A carga viral pré- tratamento mediana foi de 645.000 Ul/ml, observando-se que 57% da população estudada apresentava alta carga viral. Houve elevado percentual - 73,9% - de pacientes com fibrose avançada (F3 e F4). Em 33 (10,2%) pacientes o tratamento foi suspenso devido à ocorrência de eventos adversos....(AU)

Tratamento de pacientes com infecção crônica pelo genótipo 1 do vírus da hepatite C com interferon peguilado e ribavirina: a experiência da Secretaria da Saúde do Rio Grande do Sul / Treatment of patients with chronic hepatitis C virus genotype 1 infection with pegylated interferon and ribavirin: the experience of the Rio Grande do Sul Health Department

A infecção pelo virus da hepatite C (HCV) é atualmente considerada como um problema de saúde pública. Este estudo visa avaliar a resposta sustentada ao tratamento de pacientes com hepatite crônica pelo genótipo 1 do HCV no âmbito de um programa desenvolvido na Secretaria Estadual da Saúde do Rio Grande do Sul. É um estudo de coorte misto, onde foram revisados os processos/prontuários administrativos de tratamento de pacientes com hepatite crônica C através da administração de interferon peguilado associado à ribavirina. O esquema de tratamento disponibilizado é o que segue: interferon peguilado alfa-2a 180 mcg ou interferon peguilado alfa-2b na dose 1,5 mcg/kg administrados via subcutânea uma vez por semana, mais ribavirina 1000 mg/dia para pacientes com menos de 75 kg ou 1250 mg/dia para pacientes com 75 kg ou mais, por um período de 48 semanas. Não havendo a Resposta Virológica Precoce (RVP) o tratamento era interrompido. O nível de significância adotado, na análise estatística, foi de cx = 0,05. Os resultados observados são os que seguem: a coorte constituiu-se de 323 indivíduos. Cento e oitenta (55,7%) eram do gênero masculino. A média foi 51,1+- 10,1 anos. O IMC foi de 26,8+- 4,4Kg/m2. A carga viral pré- tratamento mediana foi de 645.000 Ul/ml, observando-se que 57% da população estudada apresentava alta carga viral. Houve elevado percentual - 73,9% - de pacientes com fibrose avançada (F3 e F4). Em 33 (10,2%) pacientes o tratamento foi suspenso devido à ocorrência de eventos adversos....(AU)

Sarcoidose induzida por tratamento com interferon peguilado para hepatite C crônica: relato de caso / Sarcoidosis induced by a pegylated interferon treatment for chronic C hepatitis: a case report

O interferon (IFN), utilizado no tratamento da hepatite C crônica, produz vários efeitos adversos, dentre os quais a indução e/ ou agravamento de sarcoidose - doença multissistêmica, de etiologia desconhecida e patogênese supostamente relacionada à liberaçãp de mediadores inflamatórios. Relata-se o caso de paciente feminina, 44 anos, portadora de hepatite C crônica , genótipo 1, que fez uso de interferon peguilado (Peg-IFN) e ribavirina. A partir do quinto mês de tratamento, apresentou dispnéia progressiva, emagrecimento e sudorese noturna. Ao exame físico, observava-se lesão papular eritematosa em joelho direito. Tomografia de tórax evidenciou importante infiltrado intersticial em vidro fosco em metades superiores dos campos pulmonares, com presença de micronódulos pulmonares e pleurais, espessamento pleural, dilatação brônquica difusa e adenomegalias mediastinais. A biópsia pulmonar apresentou granulomas confluentes, sem necrose com fibrose circunjacente em parênquima pulmonar periférico, sugestiva de sarcoidose, à semelhança do encontrado na biópsia de pele. Conclusão: Apesar de ter sido relatado em poucos casos na literatura, a sarcoidose deve ser lembrada em casos de terapia antiviral com IFN ou Peg-INF, quando ocorrerem manifestações pulmonares e adenopatias