Genotipagem do vírus da hepatite B de pacientes crônicos com resistência ao tratamento com lamivudina na Cidade de Ribeirão Preto, Estado de São Paulo

INTRODUCTION: Lamivudine is a nucleoside analogue that is used clinically for treating chronic hepatitis B infection. However, the main problem with prolonged use of lamivudine is the development of viral resistance to the treatment. Mutations in the YMDD motif of the hepatitis B virus DNA polymerase gene have been associated with resistance to drug therapy. So far, there have not been many studies in Brazil reporting on genotype-dependent development of resistance to lamivudine. Thus, the aim of the present study was to determine the possible correlation between a certain genotype and increased development of resistance to lamivudine among chronic hepatitis B patients. METHODS: HBV DNA in samples from 50 patients under lamivudine treatment was amplified by means of conventional PCR. Samples were collected at Hospital das Clínicas, FMRP-USP. The products were then sequenced and phylogenetic analysis was performed. RESULTS: Phylogenetic analysis revealed that 29 (58%) patients were infected with genotype D, 20 (40%) with genotype A and one (2%) with genotype F. Mutations in the YMDD motif occurred in 20% of the patients with genotype A and 27.6% of the patients with genotype D. CONCLUSIONS: Despite the small number of samples, our results indicated that mutations in the YMDD motif were 1.38 times more frequent in genotype D than in genotype A.INTRODUÇÃO: Lamivudina é um análogo de nucleosídeo clinicamente utilizado para o tratamento da infecção crônica pela hepatite B. Entretanto, o principal problema do uso prolongado da lamivudina é o desenvolvimento de resistência viral ao tratamento. Mutações no motivo YMDD no gene da DNA polimerase do vírus da hepatite B estão associados com a resistência a terapia medicamentosa. Até o presente momento, não há muitos estudos no Brasil que descrevem o desenvolvimento genótipo-dependente da resistência à lamivudina. Assim, o intuito do trabalho aqui descrito foi determinar a possível correlação entre um determinado genótipo e o desenvolvimento aumentado da resistência à lamivudina em pacientes com hepatite B crônica. MÉTODOS: O HBV DNA foi amplificado por PCR convencional a partir de 50 amostras coletadas de pacientes submetidos ao tratamento com lamivudina no Hospital das Clínicas- FMRP- USP. Posteriormente, os produtos foram seqüenciados e a análise filogenética foi realizada. RESULTADOS: A análise filogenética mostrou que 29 (58%) pacientes foram infectados com o genótipo D, 20 (40%) com o genótipo A e 1 (2%) com o genótipo F. Mutações no motivo YMDD ocorreu em 20% dos pacientes com genótipo A e 27,6% em pacientes do genótipo D. CONCLUSÕES: Apesar do baixo número de amostras, nossos resultados indicaram que mutações no motivo YMDD são 1,38 X mais frequentes no genótipo D em relação ao genótipo A.Universidade de São Paulo USP - FCFR

Efficacy and safety of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir ± Ribavirin for HCV in Brazilian adults with advanced fibrosis

Introduction and aim. Approximately 650,000 people in Brazil have chronic hepatitis C virus (HCV) infection. We evaluated the safety and efficacy of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) plus dasabuvir (DSV) with/without ribavirin (RBV) in an openlabel multicenter phase 3b trial in treatment-naive or interferon (IFN) treatment-experienced Brazilian patients with advanced hepatic fibrosis (METAVIR F3/4) and HCV genotype (GT) 1 infection. Material and methods. All patients received coformulated OBV/ PTV/r daily + DSV twice daily (3-DAA). GT1a-infected patients received 3-DAA plus RBV for 12 weeks, except for prior pegIFN/ RBV nonresponders with cirrhosis who were treated for 24 weeks. GT1b-infected patients received 3-DAA alone (F3) or in combination with RBV (F4) for 12 weeks. The primary endpoint was sustained virologic response (HCV RNA < 15 IU/mL) at post-treatment Week 12 (SVR12). Results. The study enrolled 222 patients, 214 achieved an SVR12 (96.4%; 95% CI, 93.1-98.2%), one GT1a-infected patient experienced virologic breakthrough, six (5 GT1a) relapsed, and one was lost to follow-up. SVR12 was achieved in 111/ 112 (99.1%) GT1b-infected patients, including 42/43 (97.7%) noncirrhotic, and 69/69 (100%) cirrhotic patients; and in 103/110 (93.6%) GT1a-infected patients, including 44/46 (95.7%) noncirrhotic and 59/64 (92.2%) cirrhotic patients. Overall there was a low rate of serious adverse events (n = 6, 2.7%). One patient experienced a treatment-related serious adverse event and one patient discontinued treatment because of an adverse event. Discussion. The results confirm that the 3-DAA regimen with/without RBV is well tolerated and had a favorable safety profile and is efficacious in GT1-infected patients with advanced fibrosis (METAVIR F3/4)

Hepatitis C among former athletes: association with the use of injectable stimulants in the past

This study was performed with the purpose of testing the hypothesis that the high prevalence of hepatitis C among former athletes is associated with their past use of injectable stimulants. The study involved the participation of 208 former professional and amateur soccer and basketball players from the region of Ribeirão Preto, Brazil, who answered a questionnaire regarding their exposure to risk factors, including the use of injectable stimulants in the time they were engaged in sporting activities. ELISA tests were used to detect infection by the hepatitis C virus, and confirmed with PCR and genotyping for the positive cases. It was observed that the former use of injectable stimulants was a practice disseminated among the participants (24.5%), reaching 50.8% in the professionals. The overall prevalence for hepatitis C was 7.2%, with values of 11% among professionals and 5.5% among amateurs. In both categories, the presence of infection was markedly higher among those who admitted past use of injectable stimulants when compared to those who denied such practice (36% and 0.8% among amateurs; 21.9% and 0% among professionals, respectively). Multivariate analysis showed that the use of those substances was the only variable associated with the risk of hepatitis C. This confirms previous observations, performed with reduced sample sizes and without comparison groups, which indicated that the use of injectable vitamins was a risk factor of hepatitis C among former athletes.CNPqUSP - FAEP

Addition of n-butyl cyanoacrylate to classic transarterial chemoembolization may improve the radiological response in patients with hepatocellular carcinoma

OBJECTIVE: Transarterial chemoembolization is the treatment of choice for intermediate-stage hepatocellular carcinoma. However, there are no clear data supporting transarterial chemoembolization vs . transarterial embolization or regarding the best chemotherapeutic agent, which may suggest a preponderant role of ischemia over chemotherapeutic action. This study sought to evaluate the radiological response and outcome of transarterial chemoembolization modified by n-butyl cyanoacrylate addition compared to conventional transarterial chemoembolization in hepatocellular carcinoma patients. MATERIALS AND METHODS: A retrospective review identified forty-seven patients who underwent modified chemoembolization and thirty-three who underwent conventional chemoembolization between June 2006 and December 2011. The radiological response was reassessed using the modified Response Evaluation Criteria in Solid Tumors. The sustained complete response, time to progression and overall survival rates were also analyzed. RESULTS: Complete response rates were significantly higher in patients who had undergone modified chemoembolization compared to those who had undergone conventional treatment (61.7% and 24.3%, respectively;

Long-term follow-up of patients with chronic hepatitis C with sustained virologic response to interferon

BACKGROUND AND AIM: The durability of the sustained virologic response (SVR) in patients with chronic hepatitis C after treatment and the ideal follow-up time for these patients remains undefined. The objective of the study was to evaluate the durability of the virologic response in patients with chronic hepatitis C followed up for at least 12 months after SVR at HCFMRP-USP. METHODS: The study was conducted on 174 patients with chronic hepatitis C treated with different antiviral regimens who had achieved SVR. Qualitative serum HCV-RNA was determined by the commercial kit (COBAS AMPLICOR HCV, v2.0). RESULTS: There was predominance of male (73%) with a mean age of 45.6 ± 10 years. Liver cirrhosis was present in 16.1% of the study subjects. Mean follow-up time after SVR was 47 months (12-156 months). Twenty-two patients received monotherapy with interferon; 94 received interferon plus ribavirin, and 58 received pegylated interferon plus ribavirin. A total of 134 patients (77.0%) received one treatment course, 29 (16.7%) received two courses, and 11 (6.3%) received three courses. The distribution of HCV genotypes was: genotype 1 (40.2%), genotype 3 (40.8%) and genotype 2 (10.3%). Genotype was undetermined in 8.7% of cases. None of the 174 patients had recurrence of HCV infection. Two cirrhotic patients developed hepatocellular carcinoma (HCC) during follow-up. CONCLUSIONS: Among patients with SVR there was no recurrence of HCV infection or evidence of liver disease progression in any patient followed up for a mean of 47 months after SVR, except for patients with advanced hepatic disease before treatment, who may develop HCC despite SVR. Therefore, one can assume that SVR is associated with long term good prognosis.(FAEPA) Fundação de Apoio ao Ensino Pesquisa e Assistênci

A Day-4 Lille Model Predicts Response to Corticosteroids and Mortality in Severe Alcoholic Hepatitis

OBJECTIVES: Prednisolone therapy increases the risk of infections in patients with severe alcoholic hepatitis (SAH). We evaluated whether the use of the Lille Model at day 4 (LM4) is useful to predict response to prednisolone compared with the classic day 7 (LM7) in order to limit a futile exposure to corticosteroids. METHODS: We performed a retrospective analysis of a large multinational cohort of patients with SAH with Maddrey's discriminant function (DF) ≥32. Response to corticosteroids was assessed with LM4 and LM7, according to the validated cutoff value (CUV>0.45). Receiver operating characteristics (ROC) curves were constructed to determine the optimal CUV for LM4 and to compare accuracy between LM4, LM7, MELD (Model for End-Stage Liver Disease), and ABIC (age, bilirubin, international normalized ratio, and creatinine). Logistic regression models were constructed to predict 28- and 90-day mortality. Cox regression analysis was performed to assess long-term survival. RESULTS: A total of 163 (62.7%) out of 260 patients received corticosteroids. The median DF for the patients treated with corticosteroids was 64.1 (47.9-81.3). Overall 90-day mortality was 35.9%. The median LM4 and LM7 for the patients who received treatment was 0.39 (0.19-0.83) and 0.36 (0.13-0.77). LM4 was a strong independent predictor of 28-day mortality (OR 25.4, (95% confidence interval (CI) 5.1-126.8), P0.45, 28- and 90-day survival was significantly higher for responders (90% and 76%) than non-responders (66% and 40%), P<0.001. Importantly, the area under the ROC curve for predicting mortality for LM4 was similar than the classic LM7 (0.77 vs. 0.75, respectively: P=0.558). CONCLUSIONS: LM4 is as accurate as LM7 in predicting response to corticosteroids, as well as 28- and 90-day mortality. Assessing the efficacy of prednisolone at an earlier time point can avoid a more prolonged futile use of this therapy

Características clínicas, demográficas e epidemiológicas dos pacientes com hepatite B em seguimento em hospital universitário no sudeste do Brasil: predominância de casos HBeAg negativos

INTRODUCTION: Hepatitis B is common in Brazil, although there are regional differences regarding the degree of endemicity, the most frequent forms of transmission and the presence of different evolutive stages of chronic disease. The present study aimed to determine the clinical, demographic and epidemiological characteristics of patients chronically infected with hepatitis B virus (HBV) residing in the Ribeirão Preto region, southeastern Brazil. METHODS: A total of 529 medical records of individuals with HBV monoinfection were reviewed. RESULTS: More than 60% of the subjects were males, with a mean age of 38 years-old. The HBeAg-negative serological pattern was verified in 84.4% of the patients, among whom the risk of vertical/intrafamily transmission was 43.2% (p = 0.02). The consumption of alcohol in amounts exceeding 20g a day was observed in 21.3% of the subjects and was more frequent among men (33%) (p < 0.001). Among patients with cirrhosis, 54.1% were alcohol abusers (p = 0.04), all of them males. The presence of cirrhosis was more frequent in the HBeAg-positive group (24.4%) than in the HBeAg-negative group (10.2%) (p < 0.001). CONCLUSIONS: High proportions of HBV-infected subjects with an HBeAg-negative pattern were observed, with a higher risk of vertical/intrafamily transmission. Alcohol abuse was associated with male subjects and with cirrhosis of the liver in this group. A tendency toward an increase in the number of HBeAg-negative cases was observed over time.INTRODUÇÃO: No Brasil, a hepatite B é comum. No entanto, há diferenças regionais no que diz respeito ao grau de endemicidade, as formas de transmissão mais encontradas e a presença dos diferentes estágios evolutivos da doença crônica. O objetivo deste trabalho foi o de conhecer características clínicas, demográficas e epidemiológicas de pacientes cronicamente infectados pelo vírus da hepatite B (HBV), residentes na região de Ribeirão Preto, no sudeste do Brasil. MÉTODOS: Foi realizada a análise retrospectiva de 529 prontuários de indivíduos com monoinfecção pelo HBV. RESULTADOS: Mais de 60% eram masculinos, a média de idade foi de 38 anos. O padrão sorológico HBeAg negativo foi encontrado em 84,4% dos pacientes, entre os quais o risco para transmissão vertical/intrafamiliar foi de 43,2% (p = 0,02). Verificou-se uso de álcool em quantidades maiores que 20g ao dia em 21,3% dos indivíduos, sendo mais frequente entre os homens (33%) (p < 0,001). Entre os pacientes com cirrose, 54,1% faziam uso abusivo de bebidas alcoólicas (p = 0,04), sendo todos estes do gênero masculino. A presença de cirrose foi maior no grupo HBeAg positivo (24,4%) que no grupo HBeAg negativo (10,2%) (p < 0,001). CONCLUSÕES: Observaram-se elevadas proporções de indivíduos com infecção pelo HBV com padrão sorológico HBeAg negativo, entre os quais houve maior risco para a transmissão vertical/intrafamiliar. O uso abusivo de álcool esteve associado a indivíduos do sexo masculino e, neste grupo, à cirrose hepática. Observou-se tendência ao aumento no número de casos HBeAg negativo ao longo do tempo.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Peginterferon still has a place in the treatment of hepatitis C caused by genotype 3 virus

Despite recent advances in therapy for chronic hepatitis C (CHC), the disease caused by genotype 3 virus (GEN3) is still considered a treatment challenge in certain patient subgroups. The aim of this retrospective study was to evaluate the effectiveness and safety of the peginterferon (Peg-IFN) and ribavirin (RBV) combination treatment for GEN3/CHC patients, and to evaluate sustained virological response (SVR) indicators and early treatment interruption due to serious adverse events (SAE). This was a retrospective observational study of GEN3/CHC patients, co-infected or not by HIV and treated with Peg-IFN/RBV in nine Brazilian healthcare centers. The study sample included 184 GEN3/CHC patients; 70 (38%) were co-infected with HIV. The overall SVR rate was 57.1% (95% CI 50-64). Among co-infected and mono-infected patients, the SVR rate was 51.4% (36/70) and 60.5% (69/114), respectively (p=0.241). Thirty-four (18.5%) patients experienced SAE and interrupted treatment. SVR was negatively associated with the use of Peg-IFN alpha 2b (PR 0.75; 95% CI 0.58-0.99; p=0.045) and to early treatment interruption due to SAE (PR 0.36; 95% CI 0.20-0.68; p=0.001). Early treatment interruption due to SAE was associated with age (PR 1.06; 95% CI 1.02-1.10;

Peginterferon still has a place in the treatment of hepatitis C caused by genotype 3 virus

Despite recent advances in therapy for chronic hepatitis C (CHC), the disease caused by genotype 3 virus (GEN3) is still considered a treatment challenge in certain patient subgroups. The aim of this retrospective study was to evaluate the effectiveness and safety of the peginterferon (Peg-IFN) and ribavirin (RBV) combination treatment for GEN3/CHC patients, and to evaluate sustained virological response (SVR) indicators and early treatment interruption due to serious adverse events (SAE). This was a retrospective observational study of GEN3/CHC patients, co-infected or not by HIV and treated with Peg-IFN/RBV in nine Brazilian healthcare centers. The study sample included 184 GEN3/CHC patients70 (38%) were co-infected with HIV. The overall SVR rate was 57.1% (95% CI 50-64). Among co-infected and mono-infected patients, the SVR rate was 51.4% (36/70) and 60.5% (69/114), respectively (p=0.241). Thirty-four (18.5%) patients experienced SAE and interrupted treatment. SVR was negatively associated with the use of Peg-IFN alpha 2b (PR 0.7595% CI 0.58-0.99p=0.045) and to early treatment interruption due to SAE (PR 0.3695% CI 0.20-0.68p=0.001). Early treatment interruption due to SAE was associated with age (PR 1.0695% CI 1.02-1.10p<0.001) and occurrence of liver cirrhosis (PR 2.0695% CI 1.11-3.83p=0.022). In conclusion, Peg-IFN/RBV might represent an adequate treatment option, mainly in young patients without advanced liver disease or when the use of direct-action drugs is limited to specific patient groups.Univ Sul Santa Catarina, Fac Med, Dept Ciencias Biol & Saude & Ciencias Sociais Apl, Disciplina Doencas Infecciosas, Av Pedra Branca 25, BR-88137270 Palhoca, SC, BrazilUniv Fed Sao Paulo, Disciplina Infectol, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med, Div Gastroenterol & Hepatol, Sao Paulo, SP, BrazilUniv Fed Estado Rio de Janeiro, Dept Clin Med, Disciplina Gastroenterol, Rio De Janeiro, RJ, BrazilUniv Fed Espirito Santo, Serv Infectol, Vitoria, ES, SpainUniv Sao Paulo, Fac Med Ribeirao Preto, Div Gastroenterol, Ribeirao Preto, SP, BrazilInst Infectol Emilio Ribas, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med, Dept Doencas Infecciosas & Parasitarias, Sao Paulo, SP, BrazilSecretaria Estadual Saude, Unidade Mista Saude, Unimista 508 509, Brasilia, DF, BrazilUniv Sao Paulo, Inst Med Trop Sao Paulo, Lab Virol, LIM 52, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Disciplina Infectol, Sao Paulo, SP, BrazilWeb of Scienc