Efficacy and Safety of All-oral,12-week Ravidasvir Plus Ritonavir-boosted Danoprevir and Ribavirin in Treatment-naive Noncirrhotic HCV Genotype 1 Patients:Results from a Phase 2/3 Clinical Trial in China

Background and Aims:Ravidasvir(RDV)is a new generation pangenotypic hepatitis C virus(HCV)NS5A inhibitor,with high barrier to baseline resistance-associated species.This is the first phase 2/3 study conducted in China's Mainland confirming the efficacy and safety of RDV+ritonavir-boosted danoprevir+ribavirin for 12 weeks in treatment-naive noncirrhotic patients with genotype 1 infection in a large population.Methods:In this multicenter,randomized,doubleblinded,placebo-controlled phase 2/3 trial(NCT03362814),we enrolled 424 treatment-nafve,noncirrhotic adult HCV genotype 1 patients.All patients were randomized at 3∶1 ratio to receive a combination of RDV 200mg once daily plus ritonavir-boosted danoprevir 100mg/100mg twice daily and oral ribavirin 1000/1200mg/day(body weight<75/≥75 kg)(n=318)or placebo(n=106)for 12 weeks.The primary end-point was the rate of sustained virologic response 12 weeks after the end of treatment,and the safety was evaluated and compared between treatment and placebo groups.Results:The overall rate of sustained virological response at 12 weeks after treatment is 99%(306/309,95%,CI:97%-100%)under per protocol set analysis.All patients harboring baseline NS5A resistance-associated species in the treatment group(76/76,per protocol set)achieved sustained virological response at 12 weeks after treatment.No treatment-related serious adverse events were reported.Laboratory abnormalities showed mild or moderate severity(grade 1 and grade 2)in liver function tests.Conclusions:In treatment-na(i)ve,noncirrhotic HCV Chinese patients infected with HCV genotype 1,all-oral regimen of RDV+ritonavir-boosted danoprevir+ribavirin for 12 weeks was highly efficacious,safe,and well tolerated.

Prevalence and Severity of HBV-Associated Acute-on-Chronic Liver Failure Due to Irregular Medication of Nucleos(t)ide Analogs

Hepatitis B virus(HBV)represents the commonest etiologic agent of acute-on-chronic liver failure(ACLF)in most Asian countries.Nucleos(t)ide analogs(NAs)are effective in the treatment of chronic HBV infections,but may also exacerbate the disease and stimulate its development into HBV-associated ACLF if not used appropriately.The current study aimed to assess the prevalence and severity of HBV-associated ACLF as a result from irregular medication of NAs(IMNA).A total of 1134 individuals with HBV-associated ACLF in nine hospitals in Heilongjiang Province were enrolled in this study between 2005 and 2015.Among these,777 chronic hepatitis B(CHB)and 357 HBV-associated liver cirrhosis cases were classified based on various predisposing factors,including IMNA,HBV reactivation(HBVR),infections,treatment drugs,alcohol use and others(hepatitis C virus,hepatitis E virus,gastrointestinal bleeding and unknown reasons).The percentage and improvement rate were examined.Among individuals with HBV-associated ACLF and CHB,IMNA was found in 9.01%,HBVR in 46.20%,infections in 9.52%,treatment drugs in 14.67%,alcohol in 11.71%,and others in 24.58%as predisposing factors.Improvement rates in cases with IMNA,HBVR,infections,treatment drugs,alcohol and others were 41.43%,58.50%,58.11%,56.14%,53.85%,and 65.97%,respectively.Multivariable analysis showed that IMNA,others,infections,hepatic encephalopathy and hepatorenal syndrome were associated with prognosis.Only IMNA independently predicted HBV-associated ACLF prognosis.Overall,our study demonstrated that the percentage of IMNAinduced HBV-associated ACLF was 12.61%,and worse disease conditions resulted from IMNA compared with other factors.Thus,the suitability of treatment with NAs should be thoroughly evaluated.

Structure Optimization of a Tesla Turbine Using an Organic Rankine Cycle Technology

The so-called ORC(Organic Rankine Cycle)heat recovery technology has attracted much attention with regard to medium and low temperature waste heat recovery.In the present study,it is applied to a Tesla turbine.At the same time,the effects of the disc speed,diameter and inter-disc gap on the internal flow field and output power of the turbine are also investigated by means of CFD(Computational Fluid Dynamics)numerical simulation,by which the pressure,velocity,and output efficiency of the internal flow field are obtained under different internal and external conditions.The highest efficiency(66.4%)is obtained for a number of nozzles equal to 4,a disk thickness of 1 mm,and a gap of 1 mm between the disks.The results of the study serve as a theoretical basis for the structural design and optimization of Tesla turbines.

HBsAg Loss with Peg-interferon Alfa-2a in Hepatitis B Patients with Partial Response to Nucleos(t)ide Analog:New Switch Study

Background and Aims:Hepatitis B surface antigen(HBsAg)loss is seldom achieved with nucleos(t)ide analog(NA)therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon(Peg-IFN)alfa-2a.We assessed HBsAg loss with 48-and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA.Methods:Hepatitis B e antigen(HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA<200 IU/mL with previous adefovir,lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48(n=153)or 96 weeks(n=150).The primary endpoint of this study was HBsAg loss at end of treatment.The ClinicalTrials.gov identifier is NCT01464281.Results:At the end of 48 and 96 weeks'treatment,14.4%(22/153)and 20.7%(31/150)of patients,respectively,who switched from NA to Peg-IFN alfa-2a cleared HBsAg.Rates were similar irrespective of prior NA or baseline HBeAg seroconversion.Among those who cleared HBsAg by the end of 48 and 96 weeks'treatment,77.8%(14/18)and 71.4%(20/28),respectively,sustained HBsAg loss for a further 48 weeks.Baseline HBsAg<1500 IU/mL and week 24 HBsAg<200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48-and 96-week treatment(51.4%and 58.7%,respectively).Importantly,extending treatment from 48 to 96 weeks enabled 48.3%(14/29)more patients to achieve HBsAg loss.Conclusions:Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a.HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks,although the differences in our study cohort were not statistically significant.Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.