First-wave protease inhibitors for hepatitis C genotype 1 treatment: a real-life experience in Brazilian patients

Abstract INTRODUCTION: Licensed for chronic hepatitis C treatment in 2011, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), which have high sustained viral responses (SVR), ushered a new era characterized by the development of direct-action drugs against the hepatitis C virus (HCV). The aim of this study was to analyze the effectiveness and safety of BOC and TVR administered with pegylated interferon and ribavirin and to share the experience of a Brazilian reference center. METHODS: A retrospective descriptive study was conducted in patients with HCV genotype 1 infection who started treatment between July 2013 and December 2015. Data were collected using a computerized system. RESULTS: A total of 115 subjects were included, of which 58 (50.4 %) had liver cirrhosis and 103 (89.6 %) used TVR. The overall SVR rate was 61.7 % (62.1 % for TVR and 58.3 % for BOC). The presence of cirrhosis was associated with a lower SVR rate, whereas patients who relapsed after prior therapy had a greater chance of showing SVR than did non-responders. The incidence of adverse drug reactions (ADRs) was high. Almost all patients (~100 %) presented with hematologic events. Furthermore, treatment had to be discontinued in 15 subjects (13 %) due to severe ADRs. CONCLUSIONS: In conclusion, the SVR rates in our study were lower than those reported in pre-marketing studies but were comparable to real-life data. ADRs, particularly hematological ADRs, were more common compared to those in previous studies and resulted in a high rate of treatment discontinuity.

Basal core promoter and precore mutations among hepatitis B virus circulating in Brazil and its association with severe forms of hepatic diseases

BACKGROUND In Brazil, few studies have investigated the prevalence of infection with the precore (PC) and basal core promoter (BCP) mutants of the hepatitis B virus (HBV). OBJECTIVES This study aimed to analyse the frequency of PC and BCP mutations among patients infected with HBV and to evaluate the association between the variants and advanced hepatic disease. METHODS A total of 161 patients infected with HBV were studied. To identify PC and BCP mutations, a 501-bp fragment of HBV DNA was amplified and sequenced. FINDINGS PC and BCP regions from HBV strains were successfully amplified and sequenced in 129 and 118 cases, respectively. PC and BCP mutations were detected in 61.0% and 80.6% of the cases, respectively. The A1762T/G1764A variant was identified in 36.7% of the patients with grade 1 and 2 liver fibrosis (29/79) and in 81.8% of the patients with grade 3 and 4 liver fibrosis (9/11) (p < 0.01); in 76.9% of the patients with cirrhosis (10/13) and in 38.1% of the patients without cirrhosis (40/105) (p = 0.01); and in 77.8% of the patients with hepatocellular carcinoma (HCC) (7/9) and in 39.4% of the patients without HCC (43/109) (p = 0.03). MAIN CONCLUSIONS A high prevalence of HBV PC and BCP mutants was found. The A1762T/G1764A variant was independently associated with advanced forms of liver fibrosis, hepatic cirrhosis, and HCC.

Distribution of HBV subgenotypes in Ribeirão Preto, Southeastern Brazil: a region with history of intense Italian immigration

Abstract Hepatitis B virus (HBV) is distributed worldwide, with geographical variations regarding prevalence of the different genotypes. The aim of this study was to determine the HBV genotypes and subgenotypes circulating in Southeast Brazil and compare the genetic sequences found with HBV sequences previously described in the world. Sequences from 166 chronic HBV carriers were analyzed using the fragment constituted by 1306 base pairs comprising surface and polymerase regions of the HBV genome. The sequences obtained were submitted to phylogenetic analysis. HBV subgenotypes A1, A2, D1-D4, F2a, and F4 were found. HBV genotype D was the most frequent, found in 99 patients (58.4%). Within this group, subgenotype D3 was the most prevalent, in 73 patients (42.9%). HBV genotype A was identified in 58 (36%) patients, subgenotype A1, in 48 (29.8%) subjects. Genotype F was identified in 9 (5.4%). According to the phylogenetic analysis, the sequences found were grouped with sequences from Europe, Asia and Middle East (subgenotypes D1, D2, D3) and sequences from Latin America and Africa (subgenotype A1). HBV D3 grouped in different clusters inside D3 clade, several of them with sequences isolated in Italy. We also identified eight families whose relatives were infected with the same HBV subgenotype, most with high similarity between sequences. In conclusion, the distribution of the HBV sequences obtained interweaved with sequences from other continents, corresponding to regions from where many immigrants came to this region, in accordance to the hypothesis that the HBV detected over there were brought during the colonization times.

Clinical, demographic and epidemiological characteristics of patients with hepatitis B followed at a university hospital in southeastern Brazil: predominance of HBeAg negative cases / 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 percent of the subjects were males, with a mean age of 38 years-old. The HBeAg-negative serological pattern was verified in 84.4 percent of the patients, among whom the risk of vertical/intrafamily transmission was 43.2 percent (p = 0.02). The consumption of alcohol in amounts exceeding 20g a day was observed in 21.3 percent of the subjects and was more frequent among men (33 percent) (p < 0.001). Among patients with cirrhosis, 54.1 percent were alcohol abusers (p = 0.04), all of them males. The presence of cirrhosis was more frequent in the HBeAg-positive group (24.4 percent) than in the HBeAg-negative group (10.2 percent) (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 por cento eram masculinos, a média de idade foi de 38 anos. O padrão sorológico HBeAg negativo foi encontrado em 84,4 por cento dos pacientes, entre os quais o risco para transmissão vertical/intrafamiliar foi de 43,2 por cento (p = 0,02). Verificou-se uso de álcool em quantidades maiores que 20g ao dia em 21,3 por cento dos indivíduos, sendo mais frequente entre os homens (33 por cento) (p < 0,001). Entre os pacientes com cirrose, 54,1 por cento 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 por cento) que no grupo HBeAg negativo (10,2 por cento) (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.

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 percent) with a mean age of 45.6 ± 10 years. Liver cirrhosis was present in 16.1 percent 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 percent) received one treatment course, 29 (16.7 percent) received two courses, and 11 (6.3 percent) received three courses. The distribution of HCV genotypes was: genotype 1 (40.2 percent), genotype 3 (40.8 percent) and genotype 2 (10.3 percent). Genotype was undetermined in 8.7 percent 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.

Hepatitis B among female sex workers in Ribeirão Preto - São Paulo, Brazil

OBJECTIVE: To estimate the prevalence of hepatitis B markers and to study the risk factors for this disease among female sex workers in the city of Ribeirão Preto, Brazil. METHODS: A questionnaire was given to 449 female sex workers in order to obtain information about demographic, socioeconomic and behavioral variables. Blood samples were collected and analyzed by immunoenzymatic techniques for detection of HBsAg, anti-HBs, anti-HBc and anti-HCV markers. RESULTS: The mean age of participants was 23 years, varying from 13 to 64 years. A high spatial mobility was observed, with 47.9 percent of participants residing in places out of the region of Ribeirão Preto or in other Brazilian states. Complete absence of previous vaccine against hepatitis B was referred by 98.2 percent. Overall, the presence of any hepatitis B marker was observed in 106 participants (prevalence of 23.6 percent; 95 percent CI: 19.7 27.5), with 84 positive for anti-HBs (18.7 percent), 100 for anti-HBc (22.3 percent), and only 3 for HBsAg (0.7 percent). The logistic regression analysis showed association between hepatitis B markers and the following co-variables: residence in Ribeirão Preto, age, low socioeconomic level, consumption of crack, intercourse with HIV-infected individuals, history of previous hepatitis, intercourse with a case of hepatitis, and positivity for hepatitis C. CONCLUSIONS: Ribeirão Preto's female sex workers present several risk factors for hepatitis B and almost absence of previous specific vaccination, making it necessary to emphasize this low-cost preventive measure, preferably through the use of a mobile team, taking the vaccine to their places of work.

OBJETIVOS: Estimar a prevalência de marcadores de hepatite B e estudar os fatores de risco para esta doença entre mulheres profissionais do sexo na cidade de Ribeirão Preto, Brasil. MÉTODOS: Foi aplicado um questionário a 449 mulheres profissionais do sexo, com a finalidade de levantar informações demográficas, socioeconômicas e comportamentais. Amostras de sangue das participantes foram analisadas através de técnicas imunoenzimáticas, para detecção dos marcadores HBsAg, anti-HBs e anti-HBc. RESULTADOS: A idade média das participantes foi 23 anos, variando de 13 a 64 anos. Uma elevada mobilidade espacial foi verificada, com 47,9 por cento delas residindo em locais fora da região de Ribeirão Preto ou em outros estados brasileiros. Completa ausência de vacinação prévia contra hepatite B foi referida por 98,2 por cento. No total, observou-se presença de qualquer marcador de hepatite B em 106 participantes (prevalência de 23,6 por cento; IC95 por cento: 19,7 27,5), com 84 positivos para anti-HBs (18,7 por cento), 100 para anti-HBc (22,3 por cento) e apenas 3 para HBsAg (0,7 por cento). A análise por regressão logística evidenciou associação entre marcadores de hepatite B e as seguintes co-variáveis: idade, baixo nível socioeconômico, consumo de crack, relações sexuais com indivíduos infectados pelo HIV, história de hepatite prévia, relações sexuais com pessoas portadoras de hepatite e positividade para hepatite C. CONCLUSÕES: As profissionais do sexo em Ribeirão Preto apresentam diversos fatores de risco para hepatite B e quase total ausência de vacinação prévia específica, tornando necessários esforços concentrados na aplicação dessa medida de baixo custo, preferencialmente através do uso de equipes móveis que levem a vacina até os seus locais de trabalho.

Diagnóstico da compressäo vascular do esôfago por meio da manometria / the manometric diagnosis of esophageal vascular compression

Descrevemos cinco casos de pacientes de sexo feminino com disfagia, nas quais foi possível o diagnóstico pela manometria, de compressäo extrínseca do esôfago de origem vascular. Em três o exame radiológico convencional näo havia revelado a compressäo extrínseca. Destacamos a importância da manometria no esclarecimento da causa da disfagia em pacientes nos quais os outros exames näo säo conclusivos

Esophageal dysfunction in patients with progressive systemic sclerosis and mixed connective tissue diseases

Foi estudada a motilidade esofágica em 37 pacientes com esclerose sistêmica progressiva (ESP), 12 com doença mista do tecido conectivo (DMTC) e 40 controles, utilizando-se o método manométrico com sonda aberta e perfusäo contínua, e o exame radiológico. O exame radiológico foi normal em 17 pacientes com ESP e cinco com DMTC, e anormal em 15 pacientes com ESP e três com DMTC. A anormalidade mais freqüente foi o retarde ao trânsito de contraste. A manometria do corpo do esôfago foi normal em 20 pacientes com ESP e seis com DMTC, e anormal em 17 pacientes com ESP e seis com DMTC. A ausência de contraçöes em segmentos médio e inferior do esôfago foi a anormalidade mais observada. A pressäo do esfíncter inferior do esôfago foi significativamente menor nos pacientes com ESP e DMTC do que nos controles. Disfagia foi referida por dez pacientes com ESP e seis com DMTC. As alteraçöes dos exames radiológico e manométrico na ESP e DMTC foram semelhantes, mas a disfagia foi mais freqüente na DMTC