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.

Daclatasvir plus asunaprevir dual therapy for chronic HCV genotype 1b infection: results of Turkish early access program.

 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.

Thyroid hormone levels predict mortality in intensive care patients with cirrhosis.

INTRODUCTION: Mortality rates of intensive care patients are quite high. The aim of this study was to determine the availability of thyroid function tests and predictive scoring systems on the outcome of cirrhotic patients admitted to the intensive care unit. METHODS: A total of 106 patients were included in the final analysis, of which 32 were men (30.2%) and 74 were women (69.8%). Predictors of mortality that were investigated include acute physiology and chronic health evaluation (APACHE II), model for end-stage liver disease (MELD), Child-Turcotte-Pugh (CTP) and sequential organ failure assessment (SOFA) scores and thyroid function tests including free triiodo-L-thryronin (fT3), free tetraiodothyronine/thyroxine (fT4) and thyroid-stimulating hormone/thyrotropin (TSH) levels. RESULTS: High APACHE II, MELD, CTP and SOFA score and suppression of fT3 were all found to be associated with higher mortality in our intensive care patients who have cirrhosis (P < 0.001). Suppression of fT3 was also found to be reciprocally correlated with high APACHE II, MELD, CTP and SOFA scores (P < 0.001). fT4 had also reciprocal correlation with APACHE II, MELD, CTP and mortality. There is no correlation between TSH levels and predictive scores or mortality. CONCLUSIONS: Calculation of APACHE II, MELD, CTP and SOFA scores and measurement of fT3 and fT4 levels may all be useful as predictors of mortality in intensive care patients who have cirrhosis.

Assessment of adenosine deaminase levels in rheumatoid arthritis patients receiving anti-TNF-alpha therapy.

Anti-TNF-alpha agents are increasingly used in rheumatoid arthritis (RA) treatment and that is known to increase the risk of tuberculosis (TB) reactivation. Adenosine deaminase (ADA) levels are shown to increase to high levels in TB patients. Our aim is to investigate the serum ADA levels in RA patients being treated with anti-TNF-alpha and to compare the results with the patients on DMARD therapy. The study groups comprised of 56 RA patients (45 female, mean age 49) who were treated either with two or three DMARDs, 32 RA patients with anti-TNF-alpha treatment (26 female, mean age 46) and 20 healthy controls (10 female, mean age 48). All patients fulfilled the 1987 ACR criteria for RA. DAS28 score was calculated for all subjects. When compared to healthy controls, ADA levels were measured statistically higher both in patient groups (P = 0.046, 0.002). ADA levels in anti-TNF-alpha group were similar to conventional therapy (11.3 +/- 2.7, 10.9 +/- 4.01; P = 0.76). PPD was positive in 17 RA patients in the anti-TNF-alpha treatment group (%53). The ADA levels were found to be similar in the anti-TNF-alpha group when compared according to the PPD positivity (positive, 12.4 +/- 3.7; negative, 10.5 +/- 2.1; P = 0.02). No correlation was found between the ADA levels and age, disease duration, ESR, CRP, DAS 28 and HAQ score. In this study, we observed that RA patients at remission taking DMARD or anti-TNF-alpha therapy have similar levels of serum ADA. Although serum ADA levels during TB infection increase much higher, in our study, ADA levels of all RA patients were lower than 15 IU/L. Elevated ADA levels may be a clue for diagnosis of TB in patients who were on anti-TNF-alpha therapy.