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This study- a secondary analysis of data from a randomized, observer-blinded, non-inferiority study among volunteers between 18–55 y old in Türkiye- evaluated the impact of previous SARS-CoV-2 infection before the first dose of inactive TURKOVAC on post-vaccine local and systemic adverse events (AEs) comparing with CoronaVac. Of 1266 participants analyzed, 27.7% had a previous COVID-19 history. Local and systemic AEs were observed in 37.3% and 39% of the participants. The frequency of AEs was slightly higher in the first 30 minutes and 24 hours among participants with a COVID-19 history; none were severe. 1203 participants had a second dose vaccination, and 27.3% had a history of COVID-19. The frequencies of local and systemic AEs after the second dose were similar between those with and without a COVID-19 history. The TURKOVAC and CoronaVac showed similar frequencies of local and systemic AEs in the first 30 minutes after vaccination.

Objective: The aim of this study is to reveal the relationship between the cytokine plasma levels and symptoms of coronavirus disease-2019 (COVID-19)-positive patients, which is characterized by serious respiratory syndromes. Materials and Methods: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-positive patients were evaluated in four groups. Group 1 patients had no symptoms. Group 2 patients were mildly symptomatic. Group 3 patients had multiple symptoms. Group 4 patients had all symptoms of acute respiratory distress syndrome. Analysis of interleukin (IL)-17A, transforming growth factor-β1 (TGF-β1), and IL-6 concentrations in plasma samples taken from patients were examined by enzyme-linked immunosorbent assay method. Results: IL-17A levels were increased in parallel with the clinical condition in all patients. TGF-β1 was only observed in patients in Groups 3 and 4, and IL-6 was only observed in Group 4 patients. Conclusion: It is known that many cytokines are involved in the development of different viral infections and viral invasion always triggers an inflammatory response. The profile of inflammatory markers may be used to classify COVID-19 patients. In conclusion of this study, it is suggested that the level of cytokines which is changed according to the patient's clinical status should be used to evaluate the response of SARS-CoV-2 treatment. IL-17A, TGF-β1, and IL-6 concentrations in plasma levels could be good prognostic indicators of COVID-19.

We present the interim results of the efficacy, immunogenicity, and safety of the two-dose schedules of TURKOVAC versus CoronaVac. This was a randomized, observer-blinded, non-inferiority trial (NCT04942405). Volunteers were 18–55 years old and randomized at a 1:1 ratio to receive either TURKOVAC or CoronaVac at Day 0 and Day 28, both of which are 3 μg/0.5 mL of inactivated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) adsorbed to aluminum hydroxide. The primary efficacy outcome was the prevention of polymerase chain reaction (PCR)-confirmed symptomatic coronavirus disease 2019 (COVID-19) at least 14 days after the second dose in the modified per-protocol (mPP) group. Safety analyses were performed in the modified intention-to-treat (mITT) group. Between 22 June 2021 and 7 January 2022, 1290 participants were randomized. The mITT group consisted of 915 participants, and the mPP group consisted of 732 participants. During a median follow-up of 90 (IQR 86–90) days, the relative risk reduction with TURKOVAC compared to CoronaVac was 41.03% (95% CI 12.95–60.06) for preventing PCR-confirmed symptomatic COVID-19. The incidences of adverse events (AEs) overall were 58.8% in TURKOVAC and 49.7% in CoronaVac arms (p = 0.006), with no fatalities or grade four AEs. TURKOVAC was non-inferior to CoronaVac in terms of efficacy and demonstrated a good safety and tolerability profile.

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.

Background: Drug resistance development is an expected problem during treatment with protease inhibitors (PIs), this is largely due to the fact that Pls are low-genetic barrier drugs. Resistance-associated variants (RAVs) however may also occur naturally, and prior to treatment with Pls, the clinical impact of this basal resistance remains unknown. In Turkey, there is yet to be an investigation into the hepatitis C (HCV) drug associated resistance to oral antivirals. Materials and methods: 178 antiviral-naïve patients infected with HCV genotype 1 were selected from 27 clinical centers of various geographical regions in Turkey and included in the current study. The basal NS3 Pls resistance mutations of these patients were analyzed. Results: In 33 (18.5%) of the patients included in the study, at least one mutation pattern that can cause drug resistance was identified. The most frequently detected mutation pattern was T54S while R109K was the second most frequently detected. Following a more general examination of the patients studied, telaprevir (TVR) resistance in 27 patients (15.2%), boceprevir (BOC) resistance in 26 (14.6%) patients, simeprevir (SMV) resistance in 11 (6.2%) patients and faldaprevir resistance in 13 (7.3%) patients were detected. Our investigation also revealed that rebound developed in the presence of a Q80K mutation and amongst two V55A mutations following treatment with TVR, while no response to treatment was detected in a patient with a R55K mutation. Conclusion: We are of the opinion that drug resistance analyses can be beneficial and necessary in revealing which variants are responsible for pre-treatment natural resistance and which mutations are responsible for the viral breakthrough that may develop during the treatment.

Objectives: Chronic hepatitis C (CHC) is now a more curable disease with new direct acting antivirals (DAA). Although high sustained virologic response rates, failures still occur in DAA regimens. Our objective in this study was to characterize the real-life presence of clinically relevant resistance – associated substitutions (RASs) in the HCV NS5A gene in CHC patients whose DAA regimen has failed. Methods: The study enrolled 53 CHC patients who experienced failure with DAA regimen as the prospective longitudinal cohort between 2017–2019. Genotypic resistance testing was performed via the viral population sequencing method and The Geno2pheno HCV tool was used for RAS analysis. Results: The most frequent failure category was relapse (88%) followed by non-responder (12%). For a total of 36% of patients, RASs was detected in NS5A, Y93H was the most detected RAS in GT1b infected patients (89%). Conclusions: This study establishes an HCV failure registry for Turkey in which samples were combined with clinical, virologic and molecular data of adult patients whose DAA therapy failed. RASs can occur in CHC patients with DAA treatment failures. Evaluation of RAS after DAA failure is very important before re-treatment is initiated to prevent virologic failure.

Background: Diffusion-weighted imaging (DWI) has become an established diagnostic modality for the evaluation of liver parenchymal changes in diseases such as diffuse liver fibrosis. Aims: To evaluate the parenchymal apparent diffusion coefficient value (ADC) changes using diffusion-weighted imaging (DWI) during telaprevir-based triple therapy. Study Design: Diagnostic accuracy study. Methods: Seventeen patients with chronic hepatitis C virus (HCV) virus and twenty-five normal volunteers were included. All of the patients took 12-weeks of telaprevir-based triple therapy followed by 12-weeks of PEGylated interferon and ribavirin therapy. They were examined before treatment (BT), as well as 12-weeks (W12) and 24-weeks (W24) after treatment by 3 Tesla magnetic resonance imaging (MRI). DWI was obtained using a breath-hold single-shot echo-planar spin echo sequence. Histopathologically, liver fibrosis was classified in accordance with the modified Knodell score described by Ishak. Quantitatively, liver ADCs were compared between patients and normal volunteers to detect the contribution of DWI in the detection of fibrosis. In addition, liver ADCs were compared during the therapy to analyze the effect of antiviral medication on liver parenchyma. Results: The liver ADC values of fibrotic liver parenchyma were significantly lower than those of the healthy liver parenchyma (p

Background: Before the introduction of direct-acting antivirals in the treatment of chronic hepatitis C patients, the combination of peginterferon alpha and ribavirin was the standard therapy. Observational studies that investigated sustained virological response (SVR) rates by these drugs yielded different outcomes. Aims: The goal of the study was to demonstrate real life data concerning SVR rate achieved by peginterferon alpha plus ribavirin in patients who were treatment-naïve. Study Design: A multicenter, retrospective observational study. Methods: The study was conducted retrospectively on 1214 treatment naïve-patients, being treated with peginterferon alpha-2a or 2b plus ribavirin in respect of the current guidelines between 2005 and 2013. The patients’ data were collected from 22 centers via a standard form, which has been prepared for this study. The data included demographic and clinical characteristics (gender, age, body weight, initial Hepatitis C virus RNA (HCV RNA) level, disease staging) as well as course of treatment (duration of treatment, outcomes, discontinuations and adverse events). Renal insufficiency, decompensated liver disease, history of transplantation, immunosuppressive therapy or autoimmune liver disease were exclusion criteria for the study. Treatment efficacy was assessed according to the patient’s demographic characteristics, baseline viral load, genotype, and fibrosis scores. Results: The mean age of the patients was 50.74 (±0.64) years. Most of them were infected with genotype 1 (91.8%). SVR was achieved in 761 (62.7%) patients. SVR rate was 59.1% in genotype 1, 89.4% in genotype 2, 93.8% in genotype 3, and 33.3% in genotype 4 patients. Patients with lower viral load yielded higher SVR (65.8% vs. 58.4%, p=0.09). SVR rates according to histologic severity were found to be 69.3%, 66.3%, 59.9%, 47.3%, and 45.5% in patients with fibrosis stage 0, 1, 2, 3 and 4, respectively. The predictors of SVR were male gender, genotype 2/3, age less than 45 years, low fibrosis stage, low baseline viral load and presence of early virological response. SVR rates to each peginterferon were found to be similar in genotype 1/4 although SVR rates were found to be higher for peginterferon alpha-2b in patients with genotype 2/3. The number of patients who failed to complete treatment due to adverse effects was 33 (2.7%). The number of patients failed to complete treatment due to adverse effects was 33 (2.7%). Conclusion: Our findings showed that the rate of SVR to dual therapy was higher in treatment-naïve Turkish patients than that reported in randomized controlled trials. Also peginterferon alpha-2a and alpha-2b were found to be similar in terms of SVR in genotype 1 patients.

Background: The use of pegylated interferon alpha and ribavirin (PegIFN/RBV) for the retreatment of chronic hepatitis C virus (HCV) infection without a sustained virological response (SVR) prior to PegIFN/RBV treatment has resulted in low success rates. Aims: To investigate the efficacy and safety of telaprevir (TVR) in combination with PegIFN/RBV in patients infected with HCV genotypes 1 and 4 who were previously treated with PegIFN/RBV and failed to achieve SVR. Study Design: Multi-center, retrospective, cross-sectional study. Methods: The study included 111 patients: 80 prior relapsers, 25 prior null responders, and six prior partial responders to PegIFN/RBV treatment. The patients were given TVR/PegIFN/RBV for 12 weeks, followed by a 12-week PegIFN/RBV treatment; virological response results were assessed at weeks 4, 12, and 24. Treatment was discontinued in patients with HCV RNA >1000 IU/mL at week 4 or with negative RNA results at week 4 but >1000 IU/mL at week 12. Rapid virological response (RVR), early virological response (EVR), extended rapid virological response (eRVR), and virological response at 24th week of treatment were evaluated. The side effects of combination therapy and the rates of treatment discontinuation were investigated. Results: The mean age of the patients was 56.02±9.96 years and 45.9% were male. Ninety-one percent of the patients were infected with viral genotype 1, 69.6% with the interleukin (IL) 28B genotype CT and 20.2% were cirrhotic. The RVR rate was 86.3% in prior relapsers, 56% in prior null responders, and 50% in prior partial responders (p=0.002). EVR rates in those groups were 91.3%, 56%, and 83.3%, respectively (p