Daclatasvir Plus Asunaprevir Dual Therapy for Chronic HCV Genotype 1b Infection: Results of Turkish Early Access Program

Abstract: Background. Daclatasvir and asunaprevir dual therapy is approved for the treatment of HCV genotype 1b infection in several countries. Aim. To evaluate the efficacy and safety of daclatasvir and asunaprevir dual therapy in Turkish patients. Material and methods. Sixty-one patients with HCV genotype 1b were enrolled in the Turkish early access program. Most of the patients were in difficult-to-treat category. Patients were visited at each 4 week throughout the follow-up period. Laboratory findings and adverse events were recorded at each visit. Results. Fifty-seven of 61 enrolled patients completed 24 weeks of treatment. Two patients died as a result of underlying diseases at 12-14th weeks of treatment. Two patients stopped the treatment early as a consequence of virological breakthrough, and 2 patients had viral relapse at the post-treatment follow-up. Overall SVR12 rates were 90% (55/61) and 93.2% (55/59) according to intention-to-treat (ITT) and per protocol (PP) analysis respectively. In ITT analysis, SVR12 was achieved by 93% (13/14) in relapsers, 80% (12/15) in interferon-ineligible patients and 91% (20/22) in previous nonresponder patients. SVR12 rates were 86.5% and 91.4% in patients with cirrhosis according to ITT and PP analysis respectively. SVR12 was 95.8% in non-cirrhosis group in both analysis. Patients with previous protease inhibitor experience had an SVR12 of 87.5%. Common adverse events developed in 28.8% of patients. There were no treatment related severe adverse event or grade-4 laboratory abnormality. Conclusions. Daclatasvir and asunaprevir dual therapy is found to be effective and safe in difficult-to-treat Turkish patients with HCV genotype 1b infection.

Efficacy and safety of daclatasvir and asunaprevir for hepatitis C virus genotype 1b infection

BACKGROUND/AIMS: The treatment strategy for hepatitis C virus (HCV) has been changing rapidly since the introduction of direct-acting antivirals such as daclatasvir (DCV) and asunaprevir (ASV). We evaluated the efficacy and safety of DCV and ASV for HCV in real-life practice. METHODS: Patients were treated with 60 mg of DCV once daily plus 200 mg of ASV twice daily for 24 weeks, and followed for 12 weeks. The primary endpoint was a sustained virological response at 12 weeks after treatment (SVR12) and safety. RESULTS: This retrospective study included eight patients with chronic HCV genotype 1b infection. All of the enrolled patients were diagnosed with liver cirrhosis, and their mean age was 65.75 years. One patient was a nonresponder and two patients relapsed with previous pegylated interferon (PegIFN) and ribavirin (RBV) treatment. None of the patient showed NS5A mutation. An SVR12 was achieved in 88% of cases by the DCV and ASV combination therapy. The serum transaminase level and the aspartate-aminotransferase-to-platelet ratio were improved after the treatment. DCV and ASV were well tolerated in most of the patients, with treatment discontinuation due to adverse events (elevated liver enzyme and decompensation) occurring in two patients. CONCLUSIONS: In this study, combination of DCV and ASV treatment achieved a high sustained virological response with few adverse events even in those with cirrhosis, advanced age, and nonresponse/relapse to previous interferon-based therapy. Close monitoring of safety issues may be necessary when treating chronic HCV patients receiving DCV and ASV, especially in older patient and those with cirrhosis.

Tratamiento médico de la enfermedad hidatídica / Medical treatment of the hydatidic disease

Se presenta una puesta al día sobre el tratamiento médico de la enfermedad hidatídica, poniendo especial énfasis en sus indicaciones del pre, postoperatorio y el manejo de la enfermedad hidatídica propiamente tal. Además se analiza el mecanismo de acción, farmacocinética, pautas de administración y efectos adversos tanto de los benzoimidazoles como de las isoquinoleinas, puesto que ambos quimioterápicos son de uso común en esta patología.

The infusion rate of mivacurium or atracurium for cesarean section compared with gynecological procedures

Mivacurium is mainly metabolized by plasma cholinesterase, whereas atracurium is removed by Hofman elimination. The purpose of this study was to compare the infusion rate of atracurium and mivacurium in maintaining surgical relaxation, and to compare their recovery indices between parturients and non-pregnant women. Muscle relaxation was maintained by the continuous infusion of relaxants to retain the first response of train-of-four (TOF) at 5% of control. When mivacurium was used, Bolus-T5 (duration from the end of mivacurium bolus injection to 5% single twitch recovery) was measured. After discontinuing the infusion, the recovery index was measured. The infusion rate of mivacurium, not atracurium, was significantly lower in parturients and Bolus-T5 of parturients was significantly longer than that of non-pregnant women. There was no significant difference in the recovery indices of both relaxants. The authors concluded that the infusion rate of mivacurium in maintaining muscle relaxation in parturients should be reduced compared to the rate in non-pregnant women and measuring Bolus-T5 may be helpful in determining the infusion rate to maintain muscle relaxation.

Studies on paragonimiasis: treatment with mebendazole, emetine with mebendazole and praziquantel.

One hundred cases of paragonimiasis from Saraburi province, Thailand were studied with respect to epidemiology, clinical manifestations, radiography and treatment. Highly endemic areas were Cha-om and Sum-pugpaew villages in Kang-koy district. The ratio of male to female was 48:52. Uncooked crabs and shrimps are the second intermediate hosts of Paragonimus. Hemoptysis and chronic cough were the main symptoms; with crepitations and rhonchi in both lungs. There was no specific changes in chest X-rays of the lungs, except in cases of hemoptysis where changes in pulmonary vessels were observed. Tomograms of the lungs provided 100% accuracy and confirmation of diagnosis of pulmonary paragonimiasis. Praziquantel 25 my/kg body weight three times a day for 2 days gave a cure rate of 90%, mebendazole plus emetine hydrochloride gave a cure rate of 70% and mebendazole alone was not effective.

Subcutaneous and cerebral cysticercosis treated with praziquantel.

Subcutaneous and cerebral cysticercosis, the latter visualized in computer tomography, occurred in a 38 year-old Filipina who had multiple asymptomatic subcutaneous nodules and headache. Treatment with praziquantel was given at 35 mg/day for 10 days, dexamethasone and carbamazepine were also given to reduce side effects. Three months after praziquantel therapy most of the subcutaneous nodules, the headache and the intracranial lesion disappeared and at 9 months 23 of the original 26 subcutaneous nodules had disappeared. Computer tomography is a valuable adjunct to the diagnosis and follow up of cerebral cysticercosis and praziquantel was found to be very effective in the treatment of the parasitoses.

Increased efficacy of liposomes-encapsulated praziquantel in treatment of opisthorchiasis in hamsters.

An increased efficacy of liposomes-encapsulated praziquantel was observed in the treatment of hamster opisthorchiasis. A single intracardial dose of 1.5 mg/kg of encapsulated praziquantel is as effective as an intracardial dose of 30 mg/kg or an oral dose of 100 mg/kg of free praziquantel. The suppressing activity of both free and liposomes-encapsulated praziquantel significantly decrease as the infection times increase from 1 to 5 weeks, suggesting that the young liver flukes are more susceptible to praziquantel than the adult flukes.

Clinical and laboratory evaluation of praziquantel in opisthorchiasis.

A total of 122 patients were treated with a single dose of praziquantel 40 mg per kilogramme body weight, with 96 patients completing the follow up period of 60 days. The parasitological cure rate was 95.8% by single faecal examination. These patients had mild clinical manifestations. The hematological, biochemical and the liver function tests were within the normal limits. High eosinophilia was observed in 84.5% but there were no significant difference after eradication of the flukes. No significant changes were observed in the laboratory investigation at day 60 post treatment.

Field trial on the treatment of fasciolopsiasis with praziquantel.

Eight-five of 816 (10.7%) students attending a primary school in Central Thailand were examined and found infected with Fasciolopsis buski. All of students ate fresh water lily stems and most ate other fresh water plants including caltrop, water cress and morning glory. The 85 students were given praziquantel in randomized single doses of 15, 25 or 40 mg/kg body weight. Side effects were mild and transient and consisted of headache, dizziness, nausea, sleepiness, abdominal discomfort, anorexia, diarrhea, epigastric pain, vomiting and lassitude. Those receiving the highest dosages had more side effects than students in the other 2 groups. Large blisters were observed on the tegument of F. buski passed in feces and this was believed to be caused by the drug. The authors recommend a single dose of praziquantel in a dosage of 15 mg/kg of body weight for the treatment of parasitosis.

Mass treatment of opisthorchiasis in Northeast Thailand.

In an attempt to control opisthorchiasis, a single dose of 40 mg/kg of Praziquantel was given to 666 people in the three villages of Nam Pong Water Resource Development Project, Khon Kaen, Northeast Thailand. The results showed a cure rate after 1 month was 95.9%. The side effect was minimized by alternation of the time of treatment from after breakfast to after dinner. The use of Praziquantel for the mass treatment in control of opisthorchiasis is possible. However, to achieve the objective of control programme other measures such as environmental sanitation improvement, health education and change in eating habits must be integrated into the programme.

Tratamiento de la neurocisticercosis con praziquantel en Colombia / Treatment of neurocysticercosis with praziquantel in Colombia

Se estudiaron y trataron con praziquantel 39 casos de neurocisticercosis, de los cuales 3 tenian cisticercos subcutaneos. El diagnostico se hizo con tecnicas especializadas que incluyen la escanografia (TC) y la prueba de hemaglutinacion (HG). Se describen 4 sindromes principales: epilepsia (E) en 17 casos, hipertension intracraneana (HIC) en 8 casos, combinacion de los 2 sindromes en 8 y cefalea en 3 casos; en 2 casos se presentaron epilepsia, cefalea y vertigo. Se operaron 16 casos y en 11 se extirpo un cisticerco; en 4 se hicieron derivaciones para la hidrocefalia y en 1 la cirugia tuvo como objeto una calcificacion que no se encontro. Solamente se trataron 22 pacientes con prazinquantel. De 36 que tuvieron control posterior se observo la siguiente evolucion: en 8 con HIC, 7 curados (87%) y 1 mejorado; en 16 con epilepsia, 11 asintomaticos (69%), 4 mejorados y 1 sin cambios; en 8 con HIC y E, 5 asintomaticos (62.5%), 2 muertes y 1 mejorado; en 2 con cefalea, uno asintomatico y otro mejorado; en 2 con epilepsia, cefalea y vertigo, no hubo modificaciones en su cuadro clinico. La escanografia mostro mas de una fase de involucion del cisticerco en 17 casos. En 15 casos en que hay control de TC despues del tratamiento de las fases I-II-III, desaparecieron las imagenes en 9 (60%); en 4 (27%), basicamente permanecieron sin modificaciones; ..

Tratamiento con praziquantel en 6 casos de cisticercosis subcutanea y en un caso ocular / Treatment with prazinquantel in 6 cases of subcutaneous cysticercosis and an ocular case

Se presenta el resultado del tratamiento con praziquantel en 6 casos de cisticerosis subcutanea, 3 de los cuales tenian al mismo tiempo cisticerosis cerebral. En los pacientes sin compromiso del sistema nervioso central que presentaban unicamente de 1 a 3 quistes la dosis fue 30-45 mg/kg/dia asociados con prednisona en 2 de ellos; la curacion se obtuvo al cabo de 2 meses.Los casos con compromiso del cerebro presentaban de 4 a 11 quistes en la piel, uno de ellos recibio 30 mg/kg/dia por 6 dias en 2 veces con intervalo de 1 mes y los otros 50 mg/kg/dia por 10 dias consecutivos, asociados con prednisona. El paciente con 11 quistes curo completamente, 7 quistes desaparecieron en 15 dias y los 4 restantes en 4 meses. El paciente con 4 quistes aun presentaba uno al cabo de 10 meses, mientras que el paciente con 5 quistes curo de ellos en un mes y presento un quiste de nuevo a los 3 meses; a los 6 meses de control aun persistian 4 quistes antiguos y el nuevo. Un caso cisticerco unico en el humor vitreo no curo y al extraer quirurgicamente el quiste a los 7 meses del tratamiento, el parasito mostro caracteristicas de haber estado vivo

Field trial of praziquantel in human opisthorchiasis in Thailand.

Praziquantel is an excellent drug for treatment against Opisthorchis viverrini infection. Sixty cases of Opisthorchis viverrini infection were treated with Praziquantel, 3 x 25 mg/kg body weight for one day, except one case that was retreated with the same regimen at one month after the first treatment, and the cure rate was 100.0% at one year after the treatment. The side effects of the drug were headache, lassitude, sleepiness, and diarrhoea, but most of these were only in mild degree. Other laboratory findings showed no abnormal changes.

Studies on the chemotherapy of human opisthorchiasis in Thailand: I. Clinical trial of praziquantel.

Praziquantel (Embay 8440) was found to be effective in eliminating egg of Opishtorchis viverrini. from the stools of 49 patients. Two regimens were used: Group I patients received 25 mg/kg body weight three times daily after meals for two consecutive days: and Group II patients received 25 mg/kg body weight three times daily after meals for one day. In both groups eggs were not detected in the faeces by day 60 and up to 4-8 months post treatment. Mild transient side effects were present in approximately 80% of patients of Group I, with milder side effects reported in Group II. Severe diarrhoea was present on day 0 in one patient from each group. Side reactions included headache, dizziness, myalgia and lassitude, however, no laboratory evidence of toxicity was detected.