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

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

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

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

‘Real-life’ experience with direct-acting antiviral agents for HCV after kidney transplant

Introductions and Objectives: The introduction of direct-acting antiviral (DAA) agents promises to change dramatically the management of hepatitis C in kidney transplant recipients, a patient group where the treatment of hepatitis C is historically challenging. The purpose of the current study was to assess (in a ‘real-life’ setting) the safety and efficacy of all-oral, interferon-free, direct-acting antiviral agents in kidney transplant recipients with HCV. Material and Methods: We performed a single-arm, multi-center study in a cohort (n = 95) of kidney transplant recipients who underwent antiviral therapy with DAAs. The primary end-point was sustained virologic response (SVR) (serum HCV RNA < 15 IU/mL, 12 weeks after treatment ended; SVR12). We recorded data on on-treatment adverse events (AEs), serious AEs, and laboratory abnormalities. Results: Various regimens were adopted at the discretion of the treating physician: elbasvir/grazoprevir (n = 11), paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) regimens ± ribavirin (n = 23), and sofosbuvirbased regimens ± ribavirin (n = 61). The SVR12 rate was 93.7% (89/95) (95% CI, 88%; 98%), according to intention-to-treat analysis; three patients without viral response (n = 3) were found. Ribavirin was administered in 8 (8.4%) allograft recipients. The frequency of drop-outs was 4.2% (4/95) (95% CI, 0.2%; 8.2%); these were related to arthralgia/myalgia (n = 2), fatigue (n = 1), and lowered estimated glomerular filtration rate (eGFR) (n = 1). There were no differences with regard to serum creatinine and eGFR before and after antiviral therapy and during follow-up in the whole cohort. The patient who interrupted antiviral treatment due to raised serum creatinine was on sofosbuvir/daclatasvir regimen; one of the four dropouts obtained SVR. Conclusions: All-oral, interferon-free therapy with DAAs for chronic HCV after kidney transplantation was effective and well-tolerated in a ‘real–life’ clinical setting. Identical results have been observed in patients with intact kidneys or advanced chronic kidney disease. Careful evaluation of kidney function over follow-up in kidney transplant recipients who received DAAs regimens is recommended. Clinical trials aimed to assess whether sustained viral response translates into improved patient/graft survival are under way

52-week efficacy and safety of telbivudine with conditional tenofovir intensification at week 24 in HBeAg-positive chronic Hepatitis B

Background and Aims: The Roadmap concept is a therapeutic framework in chronic hepatitis B for the intensification of nucleoside analogue monotherapy based on early virologic response. The efficacy and safety of this approach applied to telbivudine treatment has not been investigated. Methods: A multinational, phase IV, single-arm open-label study (ClinicalTrials.gov ID NCT00651209) was undertaken in HBeAg-positive, nucleoside-naive adult patients with chronic hepatitis B. Patients received telbivudine (600 mg once-daily) for 24 weeks, after which those with undetectable serum HBV DNA (<300 copies/mL) continued to receive telbivudine alone while those with detectable DNA received telbivudine plus tenofovir (300 mg once-daily). Outcomes were assessed at Week 52. Results: 105 patients commenced telbivudine monotherapy, of whom 100 were included in the efficacy analysis. Fifty-five (55%) had undetectable HBV DNA at Week 24 and continued telbivudine monotherapy; 45 (45%) received tenofovir intensification. At Week 52, the overall proportion of undetectable HBV DNA was 93% (93/100) by last-observation-carried-forward analysis (100% monotherapy group, 84% intensification group) and no virologic breakthroughs had occurred. ALT normalization occurred in 77% (87% monotherapy, 64% intensification), HBeAg clearance in 43% (65% monotherapy, 16% intensification), and HBeAg seroconversion in 39% (62% monotherapy, 11% intensification). Six patients had HBsAg clearance. Myalgia was more common in the monotherapy group (19% versus 7%). No decrease in the mean glomerular filtration rate occurred in either treatment group at Week 52. Conclusions: Telbivudine therapy with tenofovir intensification at Week 24, where indicated by the Roadmap strategy, appears effective and well tolerated for the treatment of chronic hepatitis B. Trial Registration: ClinicalTrials.gov NCT0065120