Inhibitory effects of simeprevir on Staphylococcusepidermidis and itsbiofilm in vitro / 中南大学学报(医学版)

OBJECTIVES@#Staphylococcus epidermidis (S. epidermidis) is a Gram-positive opportunistic pathogen that often causes hospital infections. With the abuse of antibiotics, the resistance of S. epidermidis gradually increases, and drug repurposing has become a research hotspot in the treating of refractory drug-resistant bacterial infections. This study aims to study the antimicrobial and antibiofilm effects of simeprevir, an antiviral hepatitis drug, on S. epidermidis in vitro.@*METHODS@#The micro-dilution assay was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of simeprevir against S. epidermidis. Crystal violet staining assay was used to detect the biofilm inhibitory effect of simeprevir. The antimicrobial activity of simeprevir against S. epidermidis and its biofilm were explored by SYTO9/PI fluorescent staining. The combined effect between simeprevir and gentamycin was assessed by checkerboard assay and was confirmed by time-inhibition assay.@*RESULTS@#Simeprevir showed significant antimicrobial effects against S. epidermidis type strains and clinical isolates with the MIC and MBC at 2-16 μg/mL and 4-32 μg/mL, respectively. The antimicrobial effects of simeprevir were confirmed by SYTO9/PI staining. Simeprevir at MIC could significantly inhibit and break the biofilm on cover slides. Similarly, simeprevir also significantly inhibit the biofilm formation on the surface of urine catheters either in TSB [from (0.700±0.020) to (0.050±0.004)] (t=54.03, P<0.001), or horse serum [from (1.00±0.02) to (0.13±0.01)] (t=82.78, P<0.001). Synergistic antimicrobial effect was found between simeprevir and gentamycin against S. epidermidis with the fractional inhibitory concentration index of 0.5.@*CONCLUSIONS@#Simeprevir shows antimicrobial effect and anti-biofilm activities against S. epidermidis.

Remission of long-term hepatic and renal disease induced by HCV after direct-acting antivirals therapy / Remissão de doença hepática e renal a longo prazo induzida pelo HCV após terapia antiviral de ação direta

Abstract In addition to liver disease, the hepatitis C virus (HCV) has been associated with autoimmune phenomena, such as mixed cryoglobulin and glomerulonephritis (GN). Until recently, both chronic hepatitis and HCV extra-hepatic manifestations were treated with peg-interferon plus ribavirin, however these drugs presented low efficacy and induced severe side effects. Nowadays, the HCV chronic hepatitis has been treated with direct acting antivirals (DAA), but studies on the DAA therapy for HCV-associated glomerulonephritis are scarce. Here, we describe two cases of HCV-associated glomerulonephritis that were treated with DAAs. In these two cases, previously experienced to peg-interferon plus ribavirin, the sofosbuvir plus simeprevir therapy was effective, without significant side effects, and interrupted the evolution of at least 20 years of both hepatic and renal diseases. These cases join the seven previously described cases that were treated with this DAAs association.

Resumo Além da doença hepática, o vírus da hepatite C (HCV) tem sido associado a fenômenos autoimunes, como crioglobulinemia mista (CM) e glomerulonefrite (GN). Até recentemente, a hepatite crônica e as manifestações extra-hepáticas do HCV eram tratadas com peg-interferon com ribavirina; no entanto, essas drogas apresentavam baixa eficácia e induziam efeitos colaterais graves. Atualmente, a hepatite crônica por HCV tem sido tratada com antivirais de ação direta (AAD), mas estudos sobre a terapia com AAD para glomerulonefrite associada ao HCV são escassos. Aqui, descrevemos dois casos de glomerulonefrite associada ao HCV que foram tratados com AAD. Nestes dois casos, previamente tratados com peg-interferon e ribavirina, a terapia com sofosbuvir com simeprevir foi eficaz, sem efeitos colaterais significativos, e interrompeu a evolução de pelo menos 20 anos de doenças hepáticas e renais. Esses casos se juntam aos sete casos descritos anteriormente que foram tratados com essa associação de AAD.

Effectiveness of chronic hepatitis C treatment with direct-acting antivirals in the Public Health System in Brazil

ABSTRACT Introduction Chronic hepatitis C virus infection is one of the major causes of cirrhosis, hepatocellular carcinoma and liver transplantation. Treatment using direct-acting antivirals has revolutionized the treatment of hepatitis C virus, increasing long-term prognosis after cure. The goal of the present study was to evaluate the effectiveness of direct-acting antivirals in a Public Health System in southern Brazil. Methods A retrospective study evaluated all patients with chronic hepatitis C virus infection who underwent treatment at one center of the Public Health Department of the State of Rio Grande do Sul - Brazil, according to the Brazilian Clinical Protocol and Therapeutic Guidelines. The effectiveness was assessed in terms sustained virological response 12 weeks after the end of treatment. Results A total of 1002 patients who were treated for chronic hepatitis C virus infection were evaluated. The mean age was 58.6 years, 557 patients (55.6%) were male and 550 (54.9%) were cirrhotic. Overall sustained virological response was observed in 936 (93.4%) patients. There was a difference in sustained virological response rate varied according to sex, 91.6% in men and 95.7% in women (p= 0.009), length of treatment in genotype 1, 92.7% with 12 weeks and 99.1 with 24 weeks (p= 0.040), and genotype, 94.7% in genotype 1, 91.7% in genotype 2, and 91.4% in genotype 3 (p= 0.047). Conclusion The treatment of chronic hepatitis C virus infection for genotypes 1, 2 or 3 with the therapeutic regimens established by the Brazilian guidelines showed high rates of SVR, even in cirrhotic patients.

Comparison of simeprevir versus telaprevir plus pegylated interferon alfa and ribavirin in patients with hepatitis C virus genotype 1 infection——a meta-analysis / 中华传染病杂志

Objective To compare the efficacy and safety of simeprevir-based (SMV) or telaprevir-based (TVR) triple therapy [SMV + Pegylated interferon alfa (PegIFNα) and ribavirin (RBV) versus TVR + PegIFNαand RBV] in patients with hepatitis C virus (HCV) genotype 1 infection .Methods A systematic literature searching was conducted in multiple online databases to identify relevant studies .The sustained virologic response rate at 12 (SVR12) and 24 weeks (SVR24) after end of the treatment were used as the efficacy endpoints .The rate of treatment related adverse events (AEs) ,discontinuation due to AEs and overall treatment discontinuation were used as safety endpoints . Patients were divided into multiple subgroups according to the previous treatment history to further compare the efficacy of the two treatment regimen .Statistical analyses were performed using the RevMan 5 .3 software .The Jajad score scale and the Newcastle-Ottawa scale were employed to evaluate the quality of included studies .Results A total of 5 clinical studies including 1666 HCV genotype 1 patients were included in this study .The pooled results showed that SVR12 rates in SMV group and TVR group were 67 .6％ and 68 .3％ , respectively .There was no significant difference in overall SVR12 rate between SMV and TVR groups (OR=0 .95 ,95％ CI:0 .76 -1 .18 , P=0 .65) .There was no significant heterogeneity among studies (P=0 .84 ,I2 = 0％ ) .For SVR24 rate ,the average SVR24 rate in SMV group was 78％ ,which was lower than that in TVR group of 84％ .However ,there was no significant difference in overall SVR24 rate between SMV and TVR groups (OR=0 .71 ,95％ CI:0 .42-1 .20 ,P=0 .20) .Meanwhile ,there was no significant heterogeneity among studies (P= 0 .69 ,I2 = 0％ ) .The subgroup analysis also showed that there was no significant difference in efficacy between SMV and TVR-based triple therapy for treatment-native patients ,prior partial response ,relapse ,and prior null response patients (all P>0 .05) .However , the pooled analysis indicated that both SMV-based and TVR-based triple therapies were most effective for the treatment-naive patients(SMV :85 .7％ ,TVR :85 .6％ ) .For the safety endpoints ,the incidence rate of anemia was significant lower in SMV group compared to TVR group (OR=0 .30 ,P<0 .001) .For the rate of overall treatment discontinuation ,there was no statistically significant difference between SMV and TVR group (OR=0 .48 ,P=0 .12) .Conclusions This meta-analysis suggests that the efficacy of SMV-based triple therapy is non-inferior to TVR-based triple therapy .However ,the SMV-based triple therapy is more tolerable and has a lower incident rate of anemia and discontinuation due to AEs compared to TVR-based triple therapy .

Efficacy and Safety of Simeprevir Plus Ribavirin/Pegylated-Interferon for the Treatment of Hepatitis C Virus Genotype 1: A Meta Analysis / 中国药学杂志

OBJECTIVE: To assess efficacy and safety of simeprevir-based therapy for the treatment of hepatitis C virus genotype 1. METHODS: We searched Pubmed, EMBASE, the Cochrane Library, highwire, CBM, CNKI, Wanfang, VIP Database and literature from some relative paper based magazines also be retrieved. Randomised controlled trials(RCTs)of examining simeprevir plus ribavirin(RBV) and pegylated-interferon(peg-IFN) among adults with chronic HCV infection were included.Select the RCTs according to the inclusion criterion, then appraise them critiically by Cochrane handbook. All outcomes were pooled by the RevMan5.2 software of Cochrane Collaboration. Data were extracted on virological responses including sustained virological response at post-treatment week 12(SVR12), SVR24, serious adverse event(SAE),treat-ment discontinuation due to an adverse event(TDAE). RESULTS: Eight RCTs were finally included involving 2 758 patients who were treated with simeprevir, RBV and peg-IFN. The RESULTS of Meta-analysis showed that SVR12 rates was[OR=3.92,95%CI(2.86,5.39), P<0.000 01], SVR24 rates was[12 week:OR=3.79,95%CI(2.86,5.01), P<0.000 01], [24 week:OR=4.12,95%CI(2.69,6.30), P<0.000 01], SAE rates was[12 week:OR=0.67,95%CI(0.47,0.95),P=0.02], TDAE rates was[12 week:OR=0.85, 95%CI(0.54, 1.33), P=0.48],[24 week:OR=0.82,95%CI(0.42,1.60), P=0.55]. CONCLUSION: Evidence shows that, simeprevir-based treatment(simeprevir plus ribavirin and pegylated-interferon)for treating genotype 1 chronic HCV infection is better than PR treatment in SVR12 rates,SVR24 rates and SAE rates(course of treatment is 12 weeks). However, they are alike in TDAE rates.

Simeprevir-Based Triple Therapy with Reduced Doses of Pegylated Interferon α-2a Plus Ribavirin for Interferon Ineligible Patients with Genotype 1b Hepatitis C Virus

BACKGROUND/AIMS: The present study aimed to evaluate the safety and efficacy of simeprevir-based triple therapy with reduced doses of pegylated interferon (PEG-IFN) and ribavirin for interferon (IFN) ineligible patients, such as elderly and/or cirrhotic patients, and to elucidate the factors contributing to a sustained virologic response (SVR). METHODS: One hundred IFN ineligible patients infected with genotype 1b hepatitis C virus (HCV) were treated. Simeprevir (100 mg) was given orally together with reduced doses of PEG-IFN-α 2a (90 μg), and ribavirin (200 mg less than the recommended dose). RESULTS: The patients’ median age was 70 years, and 70 patients were cirrhotic. Three patients (3%) discontinued treatment due to adverse events. The SVR rate was 64%. Factors that significantly contributed to the SVR included the γ-glutamyl transferase and α-fetoprotein levels, interleukin-28B (IL28B) polymorphism status, and the level and reduction of HCV RNA at weeks 2 and 4. The multivariate analysis showed that the IL28B polymorphism status was the only independent factor that predicted the SVR, with a positive predictive value of 77%. CONCLUSIONS: Simeprevir-based triple therapy with reduced doses of PEG-IFN and ribavirin was safe and effective for IFN ineligible patients infected with genotype 1b HCV. IL28B polymorphism status was a useful predictor of the SVR.