Response to direct-acting antiviral agents in chronic hepatitis C patients with end-stage renal disease: a clinical experience

SUMMARY OBJECTIVE The recent development of direct-acting antiviral agents (DAAs) has dramatically changed the treatment of chronic hepatitis C, and interferon-based regimes have become a poor treatment choice in clinical practice. Today DAAs offer shorter, well-tolerated, highly effective curative therapies. This study aimed to evaluate the effectiveness and safety of DAAs in patients with end-stage renal disease and HCV genotype 1 infection in real clinical practice. METHODS Thirty-six patients who attended our clinic, were diagnosed with chronic hepatitis C (CHC), undergoing hemodialysis, and fulfilled the criteria of age >18 years, genotype 1 infection, with a detectable HCV RNA level were considered for the study. Patients with GT1a infection received OBV/PTV/r plus DSV plus RBV for 12 weeks; GT1b infected patients received this regimen without RBV for 12 weeks. RESULTS The study was conducted on 33 patients. The mean age was 52.30 ±13.77 years, and 70 % of them were male. By the fourth week of treatment, HCV RNA levels decreased below 15 IU/ml in all patients. Sustained virologic response (SVR) 12 rate was 100%. Nine patients had side effects during treatment. Of the patients with side effects, 89.9% were in group 1a and 11.1% in group 1b. CONCLUSION In this study, treatment with OBV/PTV/r and DSV with or without RBV resulted in high rates of sustained virologic response in HCV GT1-infected patients with end-stage renal disease (ESRD). SVR was achieved in all patients with few side effects.

RESUMO O recente desenvolvimento de agentes antivirais de ação direta (DAAs) mudou drasticamente o tratamento da hepatite C crônica, e os regimes livres de interferon tornaram-se pobres escolhas para tratamento na prática clínica. Hoje os DAAs oferecem terapias curativas mais curtas, bem toleradas e altamente eficazes. O objetivo deste estudo foi avaliar a eficácia e segurança dos DAAs em pacientes com doença renal em estágio terminal e infecção pelo genótipo 1 do HCV na prática clínica real. MÉTODOS Trinta e seis pacientes, que se inscreveram em nossa clínica com diagnóstico de hepatite C crônica (CHC), inclusive no programa de hemodiálise, e preencheram os critérios de idade >18 anos, foram considerados para infecção pelo genótipo 1 com nível detectável de RNA do HCV. Os pacientes com infecção por GT1a receberam OBV/PTV/r mais DSV mais RBV por 12 semanas. Os pacientes infectados com GT1b receberam este regime sem RBV por 12 semanas. RESULTADOS O estudo foi realizado em 33 pacientes. A idade média foi de 52,30±13,77 anos e 70% deles eram do sexo masculino. Na semana 4 do tratamento, os níveis de ARN do VHC diminuíram para menos de 15 UI/ml em todos os pacientes. A taxa de resposta virológica sustentada (RVS) 12 foi de 100%. Nove pacientes apresentaram efeitos colaterais durante o tratamento. Dos pacientes com efeitos colaterais, 89,9% estavam no grupo 1a e 11,1% no grupo 1b. CONCLUSÃO Neste estudo, o tratamento com OBV/PTV/r e DSV com ou sem RBV resultou em altas taxas de resposta virológica sustentada em pacientes infectados pelo VGC GT1 com doença renal em estágio final (ESRD). A RVS foi alcançada em todos os pacientes com poucos efeitos colaterais.

A reduced grade of liver fibros-steatosis after raltegravir, maraviroc and fosamprenavir in an HIV/HCV co-infected patient with chronic hepatitis, cardiomyopathy, intolerance to nelfinavir and a marked increase of serum creatine phosphokinase levels probably related to integrase inhibitor use / Grado reducido de fibroesteatosis tras la administración de raltegravir, maraviroc y fosamprenavir en un paciente co-infectado de VIH/VHC con hepatitis crónica, cardiomiopatía, intolerancia al nelfinavir y un aumento pronunciado de los niveles de creatina fosfoquinasa sérica probablemente debido al uso del inhibidor de la integrasa

The use of new antiretroviral drugs in HIV infection is particularly important in patients with intolerance or resistance to other antiretroviral agents. Raltegravir and maraviroc represent new, important resources in salvage regimens. A reduced grade of liver fibro-steatosis after a combination of raltegravir and maraviroc (second-line) has not been studied and the mechanism by which these new drug classes induced a marked reduction of grade of liver diseases is currently unknown. In the present case report, nested in an ongoing multicentre observational study on the use of new antiretroviral inhibitors in heavy treatment-experienced HIV patients, we evaluated the correlation between a "short therapeutic regimen" raltegravir, maraviroc and fosamprenavir and liver diseases. The aim of this report is to describe the use of a three-drug regimen based on two novel-class antiretroviral agents (raltegravir and maraviroc) plus the protease inhibitor fosamprenavir, in an experienced HIV-infected patient with chronic progressive hepatitis C complicated by liver fibrosis; an overwhelming increased serum creatine kinase level occurred during treatment, and is probably related to integrase inhibitor administration. At present no information is available regarding this correlation.

El uso de nuevos medicamentos antiretrovirales para la infección por VIH es particularmente importante en los pacientes con intolerancia o resistencia a otros agentes antiretrovirales. Raltegravir (RTV) y maraviroc (MRV) representan nuevos e importantes recursos en las terapias de salvamento. Un grado reducido de fibroesteatosis hepática después de una combinación de raltegravir y maraviroc (terapia de segunda línea) no ha sido estudiado, y el mecanismo por el cual estas nuevas clases de droga indujeron una marcada reducción de grado de las enfermedades hepáticas se desconoce hasta el momento. Como parte de la realización en curso de un estudio observacional multicentro acerca del uso de nuevos inhibidores antiretrovirales en pacientes de VIH altamente experimentados en el tratamiento, en el presente reporte de caso se evalúa la correlación entre un "régimen terapéutico corto" (raltegravir, maraviroc y fosamprenavir) y las enfermedades del hígado. El objetivo de este reporte es describir el uso de un régimen de tres medicamentos - basado en dos agentes antiretrovirales de nuevo tipo (raltegravir y maraviroc) además del fosamprenavir inhibidor de la proteasa - en un paciente de VIH experimentado. El paciente también sufre de hepatitis C evolutiva, progresiva, crónica, complicada por fibrosis hepática. Durante el tratamiento, se produjo un aumento extraordinario del nivel de creatina quinasa sérica, el cual probablemente esta relacionado con la administración del inhibidor de la integrasa. Actualmente no hay información disponible con respecto a esta correlación.

Comportamento clínico e perfil hematológico de cães intoxicadosexperimentalmente com carbamato (Aldicarb) e submetidosà hemodiálise e hemoperfusão / Clinical evaluation and blood profile of dogs experimentally intoxicated by carbamate (Aldicarb) and submitted to hemodialysis and hemoperfusion

Técnicas dialíticas são estudadas a fim de se verificar suas reais contribuições no tratamento das mais diversas formas deintoxicações. Esta pesquisa foi realizada com o objetivo de avaliar o comportamento clínico e o perfil hematológico de cãesintoxicados com cabamato (Aldicarb) e submetidos a duas diferentes técnicas dialíticas: hemodiálise e hemoperfusão. Quinzecães adultos, sem raça definida foram intoxicados experimentalmente com 4,97mg/kg de peso vivo de Aldicarb, por via oral.Todos os animais, para controle dos efeitos clínicos provocados pela droga, foram medicados 30 minutos e uma hora após aingestão, com sulfato de atropina e benzodiazepínico (Diazepam), ambos na dose de 1mg/kg. Esses cães foram divididos emtrês grupos experimentais, compostos de cinco animais cada, denominados grupos I, II e III. Os animais do grupo II e do grupoIII, três horas após administração do Aldicarb foram submetidos a sessões de duas horas de hemodiálise e de hemoperfusão,respectivamente. Os animais do grupo I serviram de controle, não tendo sido submetidos a nenhum tratamento dialítico. Aintoxicação provocada pelo aldicarb foi capaz de causar alterações clínicas manifestadas por vômito, sialorréia, diarréia,incontinência urinária, fasciculações e alterações no perfil hematológico relacionadas principalmente a hemoconcentração.Houve leucocitose e aumento no número absoluto de neutrófilos em todos os animais 30 minutos após administração docarbamato. Não foram observadas diferenças clínicas entre os animais do grupo controle e os animais tratados por hemodiáliseou hemoperfusão. Após a sessão de hemoperfusão ocorreu discreta redução no número dos leucócitos, com diminuição dosvalores absolutos de eosinófilos, basófilos, monócitos e linfócitos. Nenhuma das técnicas foi efetiva em retirar o Aldicab doorganismo.

The aim of this work was to study the contribution of dialysis techniques, hemodialysis and hemoperfusion, after poisoning byAldicarb (carbamate), an anticholinesterasic compound, in dogs. Fifteen adult mongrel dogs were experimentally intoxicated by4.97mg/kg of Aldicarb orally. All animals, to prevent and treatment of clinical signs received a standard treatment with atropinesulfate (1mg/kg) and benzodiazepine (1mg/kg), administered endovenously 30 minutes and one hour after poisoning. Thedogs were separated in three groups: group I (control), group II (hemodialysis) and group III (hemoperfusion) with five animalsin each. Hemodialysis and hemoperfusion were performed three hours after poisoning, through a double lumen catheterimplanted in the jugular vein. Symptoms like vomiting, diarrhea, urinary incontinence and muscle fasciculation were observedafter poisoning in all groups. It was observed increase of leucocytes and neutrophils, 30 minutes after carbamate administration.Any clinical difference was observed after therapy with hemodialysis and hemoperfusion. After hemoperfusion occurred decreaseof total leukocyte, eosinophil, basophile, monocyte and lymphocyte. None of the techniques were effective to withdraw theAldicarb compound from the organism.

The efficacy of repaglinide monotherapy and in combination with metformin in Indonesian type 2 diabetes mellitus patients.

AIM: To investigate the efficacy and safety of repaglinide alone and in combination with metformin therapy. METHODS: Seventy-two type 2 diabetes patients who were oral anti-diabetic drugs (OAD)-naive or currently on OAD for </=36 months with HbA1c </=9% and fasting plasma glucose (FPG) pound 13 mmol/L were recruited. Patients were titrated for 6 weeks to a dose level which maintained fasting blood glucose at 4.4-7.0 mmol/L and continued treatment for 8 weeks. Dose regimen started with 0.5 mg repaglinide each main meal, progressing to 1.0 mg repaglinide, 1.0 mg repaglinide + metformin 500 mg b.i.d. and 1.0 mg repaglinide + metformin 500 mg t.i.d., depending on patients' glycaemic status. Patients' glycaemic control (HbA(1c) and FPG), body weight and other safety parameters were evaluated. RESULTS: Thirty-seven patients completed the trial. Patients were overweight (mean BMI 25.5 +/- 4.1 kg/m(2)) with mean age 52.5 +/- 8.8 years and mean diabetes duration of 2.4 +/- 3.8 years. Mean HbA1c (2.26 +/- 0.22%, [p <0.05]) and FPG (3.31 +/- 0.47 mmol/L, [p <0.05]) decreased significantly from baseline. Body weight did not change significantly (0.85 +/-0.45 kg, p=0.068). Of the 33 patients who had baseline FPG >7.0 mmol/L, it appeared that repaglinide alone at doses 0.5 or 1.0 mg achieved FBG <7.0 mmol/L in 67% of patients. The majority of the treatment emergent adverse events were mild and unlikely related to trial product. Episodes of symptomatic hypoglycaemia were low (9.3%) in frequency. The changes in haematology, clinical biochemistry and urinalysis were mostly minor or remained unchanged. Vital signs and the results of physical examination also remained unchanged. Three of the four withdrawals were due to adverse events but were unlikely related to trial product. CONCLUSION: treatment with repaglinide alone and in combination with metformin was efficacious in glycaemic control in OAD-naive or previous users. Most of the patients appeared to achieve good control with repaglinide alone. The treatment regimens were safe (317 words).

Nightmares without atonia as an early symptom of diffuse Lewy bodies disease

A male 70 years old patient with diffuse or ''pure'' Lewy body disease is described. The diagnosis was made based on clinical features of nightmares with no atonia, attention deficits with fluctuation in cognitive function, incapacity to find his way around the neighbourhood and other formerly familiar environments and mild neuropsychiatric symptoms. Neuropsychological assessment showed memory deficits, visuospatial and visuo-constructive disturbances. He had neither parkinsonism nor recurrent visual hallucinations typically well formed and detailled. Neuroimaging (computed tomography and magnetic resonance spectroscopy) showed mild diffuse cortical atrophy, mostly on the left temporal lobe and a decrease of N-acetil-aspartate levels. A cholinesterase inhibitor was prescribed to this patient during 6 months with clinically relevant behavioral effect. Diagnosis confirmation was made by post-mortem neuropathological findings. Macroscopical features were mild atrophy on the frontal, parietal and temporal lobes, notedly on the frontal lobes. Microscopically, there was neuronal loss and diffuse classic Lewy bodies. Brainstem (substantia nigra, raphe nucleus, locus coeruleus, pedunculopontine nucleus), limbic cortex, and neocortex (frontal, parietal and temporal) were the areas of predilection for Lewy bodies. Hematoxylin-eosin and Bielschowsky staining did not show neuronal swelling (balooned cell), argyrophilic inclusion (Pick's bodies), neurofibrillary tangles nor senile plaques. Immunohistochemical staining for anti-tau, anti-beta-amyloid, and anti-prion protein were negative. Antiubiquitine reaction was positive for Lewy body in the cerebral cortex and brainstem

Rivastigmine in the treatment of alcohol-induced persisting dementia

A case of Alcohol-Induced Persisting Dementia (AIPD) in a 62-year-old man is presented. His progress on treatment with the acetylcholinesterase inhibitor, rivastigmine, is followed. The significant improvement observed suggests that AIPD may be a new indication for this class of drug