Alanine Aminotransferase Elevation during Peginterferon Alpha-2a or Alpha-2b plus Ribavirin Treatment

Alanine aminotransferase (ALT) elevation was occassionally observed during the treatment with combination peginterferon alpha plus ribavirin. Two forms of peginterferon are currently available as a standard of care with or without direct-acting antivirals against hepatitis C virus (HCV). Until the appearance of interferon-sparing regimen, peginterferon alpha plus ribavirin will play a central role in the eradication of HCV. In the present study, we compared ALT elevations in response to peginterferon alpha-2a plus ribavirin or peginterferon alpha-2b plus ribavirin in HCV genotype-1-infected patients. There were no significant differences in ALT elevations between treatments with the two peginterferons, but in a comparison of the proportions of patients with transient ALT elevation from baseline between the two groups, transient ALT elevation was observed more in sustained virological response (SVR) patients treated with peginterferon alpha-2a than with peginterferon alpha-2b. However, no patients discontinued treatment due to ALT elevation. Patients with transient ALT elevation from baseline during the treatment had less favorable IL28B rs8099917 genotype in the peginterferon alpha-2b group. Patients achieving SVR tended to have lower ALT levels, although some had persistent ALT elevation during treatment. In conclusion, clinicians should pay attention to possible ALT elevation during the treatment of chronic hepatitis C patients.     

Blood cell, liver function, and response changes by PEG-interferon-α2b plus ribavirin with polaprezinc therapy in patients with chronic hepatitis C

Purpose Zinc has been reported to ameliorate hematologic side effects and improve liver function. In addition to its various effects, zinc supplementation in chronic hepatitis C patients with genotype 1b of high viral load enhanced the response to interferon (IFN) monotherapy. This study was aimed at clarifying whether zinc could improve hematologic side effects, improve liver function, and enhance the response to therapy in patients with chronic hepatitis C treated with pegylated-interferon (PEG-IFN) plus ribavirin (RBV). Methods The 32 patients enrolled in the study were randomly divided into two groups: a PEG-IFN-α2b plus RBV with zinc group (PEG/RBV + zinc, n = 16) and a PEG-IFN-α2b plus RBV group (PEG/RBV, n = 16). HCV-RNA, serum zinc, ALT, white blood cell, red blood cell, platelet, and hemoglobin (Hb) levels were examined. Results Serum zinc levels were significantly higher in the PEG/RBV with zinc group than in the PEG/RBV without zinc group at 4, 8, and 12 weeks. No significant differences were observed in the clearance of HCV-RNA between the two groups. The outcome of the treatment was similar; results of laboratory examinations including ALT before, during, and after therapy revealed no significant differences between the two groups at any point in all items except serum zinc levels. A sustained virological response rate was observed in 50.0% in the PEG/RBV with zinc group and 43.8% in the PEG/RBV without zinc group, with no significant difference between the two groups. Conclusions The study demonstrated no evidence that zinc ameliorates hematologic side effects, improves liver function, and enhances the response to the therapy in chronic hepatitis C receiving PEG-IFN-α2b plus RBV.     

Increased Ribavirin Bioavailability Associated With Telaprevir Use in Hepatitis C Patients Treated With PEGylated -Interferon/Ribavirin/Telaprevir Triple Therapy

Background:

Anemia is more frequent in patients receiving telaprevir with PEGylated interferon/ribavirin (PEG-IFN/RBV) than in those receiving PEG-IFN/RBV alone.

Objectives:

The objective was to measure the impact of telaprevir on RBV bioavailability and to assess the concomitant renal function.

Materials and Methods:

Thirty-seven hepatitis C virus (HCV) patients non-responders to a previous course of PEG-IFN/RBV therapy and re-treated with triple therapy combining PEG-IFN/RBV and telaprevir were analyzed. RBV bioavailability was measured before the triple therapy initiation, during telaprevir treatment at week (W) 4 and W8, and after telaprevir cessation (post W16). The renal function was assessed by estimating the glomerular filtration rate (eGFR).

Results:

At W4, RBV bioavailability, expressed as mg/L/daily dose/kg body weight, was significantly increased (median increase = 0.06 mg/L/dose/kg; P < 0.001). In parallel, the renal function was impaired with a mean eGFR decrease of -6.8 mL/minutes/1.73 m² (P = 0.109). Between W4 and W8, RBV bioavailability continued to increase (P < 0.001) but subsequently decreased slightly after telaprevir discontinuation with a concomitant restoration of the renal function (eGFR increase of 6.34 mL/minutes/1.73 m²).

Conclusions:

Our results indicated a reversible increase in RBV bioavailability after telaprevir exposure, which might be linked to the impairment of the GFR. This also suggests a RBV-telaprevir pharmacological interaction, a possible source of severe anemia observed under triple therapy. These results suggest that RBV pharmacological monitoring may be clinically relevant, especially in the context of first-generation HCV protease inhibitor-based therapy.     

SARS-CoV-2 Disinfection of Air and Surface Contamination by TiO2 Photocatalyst-Mediated Damage to Viral Morphology,RNA, and Protein

SARS-CoV-2 is the causative agent of COVID-19, which is a global pandemic. SARS-CoV-2 is transmitted rapidly via contaminated surfaces and aerosols, emphasizing the importance of environmental disinfection to block the spread of virus. Ultraviolet C radiation and chemical compounds are effective for SARS-CoV-2 disinfection, but can only be applied in the absence of humans due to their toxicities. Therefore, development of disinfectants that can be applied in working spaces without evacuating people is needed. Here we showed that TiO₂-mediated photocatalytic reaction inactivates SARS-CoV-2 in a time-dependent manner and decreases its infectivity by 99.9% after 20 min and 120 min of treatment in aerosol and liquid, respectively. The mechanistic effects of TiO₂ photocatalyst on SARS-CoV-2 virion included decreased total observed virion count, increased virion size, and reduced particle surface spike structure, as determined by transmission electron microscopy. Damage to viral proteins and genome was further confirmed by western blotting and RT-qPCR, respectively. The multi-antiviral effects of TiO₂-mediated photocatalytic reaction implies universal disinfection potential for different infectious agents. Notably, TiO₂ has no adverse effects on human health, and therefore, TiO₂-induced photocatalytic reaction is suitable for disinfection of SARS-CoV-2 and other emerging infectious disease-causing agents in human habitation.     

Investigation of the Powder Aerosol Deposition Method Using Shadowgraph Imaging

The powder aerosol deposition method (PAD) is a vacuum-based spray coating technology. It allows for production of highly dense coatings at room temperature, especially of brittle-breaking materials. This yields new options for coating substrate materials that even melt at low temperatures. The film formation mechanism is called room temperature impact consolidation (RTIC). The occurrence of this mechanism is strongly linked to the gas jet used in the process. The velocity and direction of the particles in the gas jet forming between the nozzle orifice and the substrate are the main factors influencing the quality of the coating. This dependency aimed to be elaborated with a measurement setup and coating experiments and is shown in this work. We investigated the gas jet formation using a shadow optical imaging system. Regions of different gas density are visualized by this technique. Several parameter sets, in particular gas flow rates and chamber pressures, were investigated. In addition, coatings were produced on glass substrates with the same parameters. As a coating material, the superconducting ceramic-like magnesium diboride (MgB₂) was chosen. A correlation between shadow images and thickness profiles of the coatings shows how the gas jet formation affects the uniformity of thickness. Shadow optical images provide valuable information on the flight direction of the particles and allow validation of simulation results.     

基因1b型丙型肝炎病毒NS5A区变异及其与聚乙二醇干扰素α-2a联合利巴韦林治疗应答的相关性

目的探讨基因1b型慢性丙型肝炎患者NS5A区基因变异与聚乙二醇干扰素α-2a（PEG—IFNα-2a）联合利巴韦林（RBV）抗病毒治疗疗效的关系。方法回顾性选择15例应用PEG—IFNα-2a／RBV抗病毒治疗的基因1b型慢性丙型肝炎患者,其中7例为快速应答（RVR）,8例为无应答（NR）,应用RT—PCR法扩增NS5A全长片段,用克隆测序方法进行核苷酸和氨基酸序列测定。结果没有发现与治疗应答相关的单个氨基酸或基序变异,RVR组和NR组在NS5A、ISDR、PKRBD和IRRDR区的氨基酸突变数目差别均无统计学意义,RVR组在V3区（aa2356～2379）的氨基酸突变数目高于NR组（分别为5．3±0.5和3．4±0．6,P=0．03）。结论V3区的氨基酸突变数目与PEG—IFNα-2a联合RBV抗病毒疗效可能相关。     

Immunogenicity of recombinant hepatitis B vaccine in treatment-naive and treatment-experienced chronic hepatitis C patients： The effect of pegylated interferon plus ribavirin treatment

AIM: To retrospectively evaluate the vaccination-induced anti-HBs seroconversion rates in treatment-naive and treatment-experienced chronic hepatitis C (CHC) patients. Also to prospectively evaluate the seroconversion rates in CHC patients during pegylated interferon (PEG) plus ribavirin (RIB) treatment. METHODS: Seventy treatment-naive CHC patients (group A), 22 sustained virological responders-SVR following interferon (IFN) plus RIB treatment CHC patients (group B) and 121 healthy subjects (group C) had been participated in the same HBV vaccination schedule (20 microg, 0-1-6 mo). Seroconversion was considered if anti-HBs levels were above 10 mIU/mL within 3 mo following the third dose of the vaccine. Moreover, we prospectively selected 30 non-cirrhotic CHC patients and evaluated them for the efficacy of the same vaccine schedule randomizing them in two groups: Group-1, 15 CHC patients received the first dose of the vaccine in parallel with the initiation of PEG plus RIB treatment and Group-2, 15 patients received the same vaccination schedule without concomitant treatment. Determination of anti-HBs was performed at mo 1, 2, and 7. Statistical analysis of data was based on ANOVA student's t-test and chi-square analysis (P < 0.05). RESULTS: Fifty-eight of 70 group A patients (82.85%), 20/22 group B (90.9%) and 112/121 healthy subjects (92.56%) had been seroconverted. The seroconversion rates were significantly higher in the control group than in treatment-naive CHC patients (P = 0.04). The corresponding rates were comparable between group A and group B CHC patients (P = 0.38). The vast majority of non-responders (10/14, 71.43%) had been infected by genotype-1 of HCV. The seroconversion rates were comparable between group 1 and 2 CHC patients at mo 1 (20% versus 26.7%, P = 0.67), mo 2 (46.7% vs 60%, P = 0.46) and mo 7 (86.7% versus 93.3%, P = 0.54) of follow-up. CONCLUSION: The immunogenicity of HBV vaccine seems to be lower in CHC patients compared to healthy subjects. SVR following IFN plus RIB treatment does not affect the antibody response to HBV vaccine. Infection by genotype-1 seems to negatively influence the seroconversion rates. Vaccination against HBV during PEG plus RIB combination treatment is not beneficial in terms of anti-HBs seroconversion rates.     

利巴韦林对肠道病毒体外抑制作用的研究

目的研究抗病毒药物利巴韦林体外抗肠道病毒（EV）的效果。方法采用细胞病变效应（CPE）法和MTT分析法,观察利巴韦林对肠道病毒（EV71、CAV16、CBV3、ECH011、EV84）的抑制作用。结果利巴韦林对Vero细胞的半数毒性浓度（TC50）为2．09mg／mL,0．2mg／mL浓度的利巴韦林对5种肠道病毒均有抑制作用,对CAV16、EV71、ECHO11、EV84、CBV3的抑制率分别为13％、27％、36％、23％、58％。对EV84、EV71病毒,利巴韦林浓度为0．1mg／mL时其抑制率为16．5％、29．5％;对CBV3病毒,利巴韦林抗病毒作用与其剂量呈正相关,半数有效浓度（IC50）为0．125mg／mL,治疗指数（TI）为16．72。结论利巴韦林在体外对肠道病毒具有抑制作用,对不同的肠道病毒其抑制效率不同,对CVB3的抑制率较高。     

利巴韦林注射液在细胞水平上抑制EV71病毒复制的初步研究

目的 通过体外实验,观察利巴韦林注射液对肠道病毒71型(EV71)病毒在横纹肌肉瘤传代细胞(RD-A细胞)复制的抑制作用和体外灭活作用.方法 使用在2008年4月安徽阜阳疫情中分离到的EV71病毒,通过三种体外细胞实验:药物在细胞中抑制EV71病毒复制的药效测定实验;药物对细胞的保护作用实验;药物体外对EV71病毒的灭活作用的药效测定实验.观察利巴韦林注射液对EV71病毒感染横纹肌肉瘤传代细胞(RD-A细胞)中所起的作用.结果 在利巴韦林注射液在细胞中抑制EV71病毒复制的药效测定实验中,1:640利巴韦林注射液稀释度组较病毒对照组延迟病变出现2 d,细胞生长未受到影响.在药物对细胞的保护作用实验中,1:8利巴韦林稀释度组较病毒对照组延迟病变出现4 d.在利巴韦林注射液药物体外对EV71病毒的灭活作用的药效测定研究中,1:40稀释度组较病毒对照组延迟病变出现2 d,而细胞生长未受到影响.结论 利巴韦林注射液在体外有抑制EV71病毒复制和部分灭活病毒的作用;并有一定的保护细胞抑制EV71病毒感染的作用.本研究对于临床上EV71感染的早期预防和治疗具有一定的指导意义.     

吡硫翁锌气雾剂联合复方氨肽素片治疗头皮银屑病疗效观察

目的观察吡硫翁锌气雾剂联合复方氨肽素片治疗头皮银屑病的疗效。方法将70例银屑病患者随机分为两组：治疗组35例患者口服复方氨肽素片,外用吡硫翁锌气雾剂;对照组35例患者口服复方氨肽素片,外用2％酮康唑洗剂外洗头皮。观察并评价两组患者治疗后第4周的临床疗效。结果治疗组痊愈21例,显效11例,总有效率为91．42％;对照组痊愈13例,显效12例,总有效率为71．42％,两组总有效率比较差异有统计学意义（P〈0．05）。结论口服复方氨肽素片联合外用吡硫翁锌气雾剂治疗寻常型银屑病,疗效好,不良反应小。