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 virus genotypes in Southern Brazil

The prevalence of hepatitis C virus (HCV) genotypes in Southern Brazil was studied in the plasma of 100 HCV-RNA-positive patients attended in Porto Alegre, South of Brazil. Reverse transcriptionpolymerase chain reaction (RT-PCR) products from the 5' noncoding region were double digested with Rsal-Haeiii and BstNl-Hinfi and analyzed by restriction fragment length polymorphism (RFLP). Three genotypes (1, 2 and 3) were demonstrable, the most prevalent being HCV type I (55 of 100 patients, 55%), followed by HCV type 3 (37 of 100 patients, 37%) and HCVtype 2 (8 oflOO patients, 8%). There was an unusual high prevalence of genotype 3, in contrast to the majority of published data from the Southeast region

Hepatic steatosis among people living with HIV in Southern Brazil : prevalence and risk factors

Chronic liver disease is an important cause of morbidity and mortality among people living with human immunodefciency virus (HIV) and is frequently related to non-alcoholic fatty liver disease (NAFLD). The objective is to estimate the prevalence and risk factors of hepatic steatosis among consecutive patients with stable HIV infection on antiretroviral therapy (ART). Also, the use of transient elastography (TE) as a mean to identify a subgroup at risk for non-alcoholic steatohepatitis (NASH) and/or liver fbrosis. HIV infected patients were enrolled between August2016 and February2017. Inclusion criteria: ≥18 years with undetectable HIV viral load. Exclusion criteria: pregnancy; alcohol intake ≥20g/day and co-infection B or C viruses. Patients underwent ultrasound (US) to diagnose liver steatosis. Signifcant fbrosis (≥F2) was estimated if at least one of the following were present: APRI>1.0, FIB4>3 and/ or liver stifness ≥7.1kPa. Subjects with TE≥7.1kPa were proposed a liver biopsy and NAFLD Scoring System (NAS)≥3 was considered as diagnosis of NASH. A total of 98 patients were included. Liver steatosis was diagnosed in 31 patients (31.6%) and was independently associated with male gender, BMI, ALT and total bilirubin levels. The prevalence of signifcant fbrosis assessed by TE, APRI and FIB4 was 26.9%, 6.4% and 3.2%, respectively. Seven patients had a TE result ≥7.1kPa. NASH was found in 5 (83.3%). Among HIV infected patients undergoing ART, almost one third have NAFLD. Neither TE, APRI or FIB4 were able to act as surrogates for signifcant liver fbrosis. Nevertheless, TE≥7.1kPa was able to accurately select a subgroup of patients at risk for NASH

Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B

BACKGROUND: Entecavir is a potent and selective antiviral agent that has demonstrated efficacy in phase 2 studies in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. METHODS: In this phase 3, double-blind trial, we randomly assigned 648 patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue to receive 0.5 mg of entecavir or 100 mg of lamivudine once daily for a minimum of 52 weeks. The primary efficacy end point was histologic improvement (a decrease by at least two points in the Knodell necroinflammatory score, without worsening of fibrosis). RESULTS: Histologic improvement after 48 weeks of treatment occurred in 208 of 296 patients in the entecavir group who had adequate baseline liver-biopsy specimens that could be evaluated (70 percent), as compared with 174 of 287 such patients in the lamivudine group (61 percent, P=0.01). More patients in the entecavir group than in the lamivudine group had undetectable serum hepatitis B virus (HBV) DNA levels according to a polymerase-chain- reaction assay (90 percent vs. 72 percent, P<0.001) and normalization of alanine aminotransferase levels (78 percent vs. 71 percent, P = 0.045). The mean reduction in serum HBV DNA levels from baseline to week 48 was greater with entecavir than with lamivudine (5.0 vs. 4.5 log [on a base-10 scale] copies per milliliter, P<0.001). There was no evidence of resistance to entecavir. Safety and adverse-event profiles were similar in the two groups. CONCLUSIONS: Among patients with HBeAg-negative chronic hepatitis B who had not previously been treated with a nucleoside analogue, the rates of histologic improvement, virologic response, and normalization of alanine aminotransferase levels were significantly higher at 48 weeks with entecavir than with lamivudine. The safety profile of the two agents was similar, and there was no evidence of viral resistance to entecavir. Copyright © 2006 Massachusetts Medical Society.published_or_final_versio

Doença de Ménétrier

The article discusses the case of a 32-year old, black woman, with a 10-year historyof chronic anemia and a cerebral abscess in 1996. She came to the EmergencyRoom at Hospital de Clínicas de Porto Alegre with a 15-day history of progressivedyspnea and pleural chest pain. She had signs of respiratory distress, diminishedvesicular breath sounds at both lung bases, and peripheral edema. Abdominalultrasonographic examination showed hepatomegaly and thickened gastric walls.Esophagogastroduodenoscopy showed an infiltrating lesion in the gastric fundus andbody, and a polypoid lesion in the gastric fundus. Endosonography showed an increasein gastric mucosal and submucosal thickness. On the 6th day after admission, thepatient had an episode of pulmonary thromboembolism. She was submitted toexploratory laparotomy. Abdominal lymph biopsy and liver biopsy were performed. Thepatient had an episode of venous thrombosis in the right superior limb. Subsequently,she presented anasarca and poor general state. On the 60th day, she presented dyspnea, and died as a result of cardiorespiratory arrest.&nbsp;O artigo discute o caso de uma paciente de 32 anos, negra, com história de anemiacrônica há 10 anos e abscesso cerebral em 1996, que procurou a emergência doHospital de Clínicas de Porto Alegre devido à piora de dispnéia e dor torácicaventilatório-dependente, com 15 dias de evolução. Apresentava sinais de dificuldaderespiratória, murmúrio vesicular diminuído em bases pulmonares e edema demembros inferiores. Ecografia de abdômen evidenciou aumento das dimensões dofígado e espessamento de paredes gástricas. Endoscopia digestiva alta mostroulesão infiltrativa em corpo e fundo gástrico e lesão polipóide no fundo. Naecoendoscopia, estômago apresentava espessamento da mucosa e submucosa.No sexto dia de internação, apresentou episódio de tromboembolismo pulmonar. Foisubmetida à laparotomia exploradora, onde foram feitas biópsias hepática e delinfonodos abdominais. Apresentou quadro de trombose venosa em membro superiordireito. Evoluiu com anasarca e piora clínica progressiva. No 60odia de internação, apresentou dispnéia e evoluiu para parada cardiorrespiratória e óbito

Resposta sustentada após 1 ano de interferon isolado ou associado a ribavirina em pacientes com cirrose pelo vírus C

OBJECTIVE: The objective of this study was to assess the rate of end of treatmentcomplete response and sustained response in positive HCV cirrhotic patients thatwere either treated with interferon only, or with interferon in combination with ribavirin.PATIENTS AND METHODS: A total of 33 ambulatory HCV-positive cirrhotic patients,without any other identifiable etiology of liver disease and classified as Child-Pugh Awere divided in a non-randomized manner into the following groups: Group 1 (n=13),treated with subcutaneous doses of interferon (3 UM), three times per week, for 12months; Group 2 (n=20), treated with the same interferon schedule as describedabove, though associated with oral ribavirin (1000 mg/day) twice a day for 12 months.Among the 33 patients, 24 (73%) were male, and the age of all patients ranged from35 to 72 years (mean of 50.7 + 9 years).RESULTS: The rate of end of treatment complete response and of sustained responsefor Group 1 was 1/13 (8%) and 0/13 (0%) respectively, versus 11/20 (55%) and 7/20(35%) for Group 2 (P&lt;0.005). The groups did not differ significantly with respect toage, sex, serum, serum ferritin, gamaglutamyl-transpeptidase, estimated diseaseduration, degree of necro-inflammatory activity, and HCV genotype. Upon comparingpatients that did not present a sustained response (n=26) with patients that didpresent a sustained response (n=7), we observed that the only predictor of sustainedresponse with statistical significance was the type of treatment employed (P&lt;0.002).CONCLUSIONS: Ambulatory patients with compensated cirrhosis caused by theHCV, when submitted to the interferon and ribavirin treatment for 1 year, presenteda statistically significant higher rate of sustained response than patients submittedto the interferon only treatment for the same period of time. There was no statisticallysignificant difference between the groups in terms of frequency of side-effects.OBJETIVO: Este trabalho teve por objetivo avaliar a taxa de resposta completa aofinal do tratamento e de resposta sustentada em pacientes com cirrose pelo vírusda hepatite C tratados com interferon isolado ou combinado com ribavirina.PACIENTES E MÉTODOS: Um total de 33 pacientes cirróticos ambulatoriais, VHCpositivos, sem outras causas identificáveis de doença hepática, compensados eclassificados como Child-Pugh A, foram divididos em dois grupos, de forma nãorandomizada: Grupo 1 (n=13), tratado com interferon 3 MU, subcutâneo, três vezespor semana, por 12 meses; Grupo 2 (n=20), tratado com interferon na mesmaposologia anterior, associado a ribavirina, 1000 mg/dia, via oral, em duas tomadas,diariamente, por 12 meses.RESULTADOS: Dos 33 pacientes, 24 (73%) eram homens e a idade variou entre35 e 72 anos (média de 50,7 ± 9 anos). A taxa de resposta completa ao final dotratamento e de resposta sustentada foi, respectivamente, de 1/13 (8%) e 0/13(0%) no Grupo 1 versus 11/20 (55%) e 7/20 (35%) no Grupo 2 (P&lt;0,005). Ambos osgrupos eram semelhantes quanto a idade, sexo, ferritina sérica, gamaglutamiltranspeptidase, tempo estimado de doença, grau de atividade necro-inflamatória egenótipo do VHC. Comparando-se os pacientes não-respondedores (n=26) comaqueles que obtiveram resposta sustentada (n=7), observou-se que o único fatorpreditivo de resposta estatisticamente significativo foi o tipo de tratamento utilizado(P&lt;0,002).CONCLUSÕES: Pacientes ambulatoriais com cirrose compensada causada peloVHC apresentam taxa de resposta sustentada significativamente superior quandotratados com 1 ano de interferon combinado com ribavirina, em comparação cominterferon isolado pelo mesmo período. Não houve diferença estatística na freqüênciade efeitos adversos entre os grupos