Improvement of hepatic fibrosis after tenofovir disoproxil fumarate switching to tenofovir alafenamide for three years

BACKGROUND Both tenofovir alafenamide(TAF)and tenofovir disoproxil fumarate(TDF)are the first-line treatments for chronic hepatitis B(CHB).We have showed switching from TDF to TAF for 96 weeks resulted in further alanine aminotransferase(ALT)improvement,but data remain lacking on the long-term benefits of TDF switching to TAF on hepatic fibrosis.AIM To assess the benefits of TDF switching to TAF for 3 years on ALT,aspartate aminotransferase(AST),and hepatic fibrosis improvement in patients with CHB.METHODS A single center retrospective study on 53 patients with CHB who were initially treated with TDF,then switched to TAF to determine dynamic patterns of ALT,AST,AST to platelet ratio index(APRI),fibrosis-4(FIB-4)scores,and shear wave elastography(SWE)reading improvement at switching week 144,and the associated factors.RESULTS The mean age was 55(28-80);45.3%,males;15.1%,clinical cirrhosis;mean baseline ALT,24.8;AST,25.7 U/L;APRI,0.37;and FIB-4,1.66.After 144 weeks TDF switching to TAF,mean ALT and AST were reduced to 19.7 and 21,respectively.From baseline to switching week 144,the rates of ALT and AST<35(male)/25(female)and<30(male)/19(female)were persistently increased;hepatic fibrosis was also improved by APRI<0.5,from 79.2%to 96.2%;FIB-4<1.45,from 52.8%to 58.5%,respectively;mean APRI was reduced to 0.27;FIB-4,to 1.38;and mean SWE reading,from 7.05 to 6.30 kPa after a mean of 109 weeks switching.The renal function was stable and the frequency of patients with glomerular filtration rate>60 mL/min was increased from 86.5%at baseline to 88.2%at switching week 144.CONCLUSION Our data confirmed that switching from TDF to TAF for 3 years results in not only persistent ALT/AST improvement,but also hepatic fibrosis improvement by APRI,FIB-4 scores,as well as SWE reading,the important clinical benefits of long-term hepatitis B virus antiviral treatment with TAF.

Treatment of Chronic Hepatitis B with Tenofovir Disoproxil Fumarate in Ivory Coast

Little data exist on patients treated with tenofovir in Sub-Saharan Africa. Objective: To describe the clinical and laboratory characteristics of patients with viral hepatitis B treated with tenofovir. Material and methods: A descriptive single-center retrospective study, on chronic viral hepatitis B mono-infected, followed in the hepatogastroenterology department of the University Hospital of Yopougon and treated with tenofovir from February 2012 to February 2015. The studied parameters were demographic, clinical, biochemical, serological, virological, abdominal ultrasound. Liver fibrosis was assessed either by liver biopsy or non-invasive tests. Results: 110 patients were treated with tenofovir disoproxil fumarate with a mean age of 40.4 years and a male predominance. Clinical examination revealed jaundice in 9% of cases, hepatomegaly in 7.3% of cases, splenomegaly in 9.1% of cases and ascites in 15.5% of cases. The AST averaged 77.3 IU/l, the ALT 76.8 IU/l, prothrombin rate at 76.6% , albumin level at 32.3 g/l, total bilirubin at 29.9 g/l, alpha fetoprotein rate at 15.3 ng/ml. HBe antigen was negative in 76.2% of cases. The average rate of DNA at baseline was 7.4 log10 IU/l. 27.5% was cirrhotic. The average time of starting treatment was 23.7 months. Conclusion: TDF is the first-line treatment for chronic hepatitis B in our country, because it is a well-tolerated, potent therapy with a high threshold for resistance development. Our study population had an average age of 40.4 years. Virological profile was dominated by HBe antigen negative patients and high viral load of HVB DNA. One third of patients were at the stage of cirrhosis. This treatment must be delivered free of charge in all the country hospitals, which is going to improve significantly the natural evolution of the disease and to decrease the incidence of the HCC.

Pre-Formulation Development of Lamivudine 300 mg and Tenofovir Disoproxil Fumarate (TDF) 300 mg Fixed Dose Combination Tablets

Introduction: In this study, physical and chemical characteristics of Lamivudine, Tenofovir Disoproxil Fumarate (TDF) and potential excipients were systematically followed and documented [1]. Objective: The objective of this scientific work was to carry out pre-formulation studies including compatibility studies on Lamivudine and Tenofovir Disoproxil Fumarate with their potential excipients prior a direct compression process [2]. Methodology: The interaction was studied in three set of environments namely uncontrolled room conditions for Zone VI b (30°C ± 2°C), oven conditions in which the oven was set at 50°C and accelerated climatic conditions in which a climatic chamber was set at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %). Sample preparation was done by mixing the amount of formulation excipients to active substances at a ratio of 1:10, whereas active substance to another active substance at a ratio of 1:1, active substance to coating materials at 1:4, coating materials to the whole set of excipients 1:4. The whole set of samples was geometrically mixed and triturated by mortar and pestle to very fine uniform powder to ensure homogeneity of the mixture. HPLC analytical method was used for simultaneous quantitative determination of lamivudine and tenofovir disoproxil fumarate. Transmittance of the mixture was determined by Near Infra-Red (NIR) technique. Results: The amount of Lamivudine as on day 0 was comparable to day 90 for in all tested conditions (Room, Oven and Climatic Chamber), whereas for Tenofovir Disoproxil Fumarate only the amount of the drug at Room (30°C ± 2°C) was comparable to results on day 90. A significant drop of amount of Tenofovir Disoproxil Fumarate (TDF) exposed to moisture (Climatic chamber at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %)) and temperature of 50°C was observed. Colour change was observed for samples subjected to moisture (Climatic chamber at 40°C ± 2°C/75% ± 5% Relative Humidity (RH %)) and as well picked up in the NIR region 400 to 1500 cm-1 (Finger print region) by a significant shift in Transmittance. Conclusion: It can be concluded that microcrystalline cellulose, cross linked sodium carboxymethyl cellulose, magnesium stearate and sodium carbxymethyl cellulose can be compressed together with Lamivudine and Tenofovir Disoproxil Fumarate (TDF) to produce a pharmaceutically acceptable solid dosage form, tablet. The produced tablets should be packed in moisture and light protective containers as Tenofovir Disoproxil Fumarate (TDF) has diester linkages which can be hydrolysed into the active drug Tenofovir in the presence of moisture.

Differences of Efficacy Between Tenofovir Alafenamide Fumarate and Tenofovir Disoproxil Fumarate in Pregnant Women With Different Hepatitis B Virus DNA Loads

Tenofovir alafenamide fumarate(TAF)has been endorsed by guidelines for blockade ofmother-to-child transmission of hepatitis B virus(HBV),given that its efficacy and safety are comparable to tenofovir disoproxil fumarate(TDF).However,there is a lack of comparative studies regarding the treatment efficacy in patients with diverse viral loads.This study retrospectively analyzed 96 hepatitis B e antigen(HBeAg)–positive pregnant women with HBV DNA levels of≥2×10^(5) IU/mL.Based on viral loads(HBV DNA levels),participants in the TAF and TDF groups were stratified into three subgroups,namely,the High-G(titer≥8 log_(10) IU/mL),Middle-G(7 log_(10) IU/mL≤titer<8 log_(10) IU/mL)and Low-G(titer<7 log_(10) IU/mL)subgroups.The primary endpoint was effectiveness of TAF and TDF in patients with varying viral loads,whereas secondary endpoints were hepatitis B surface antigen(HBsAg)positivity in infants at 7 to 12 months and the safety profile for mothers and children.Compared with baseline levels,median HBV DNA levels in mothers were decreased by 4.51 and 4.09 log_(10) IU/mL in the TAF andTDF groups(P=0.04)predelivery,respectively.In the High-G subgroup,the titers were significantly lower in the TAF group(P=0.045).A higher proportion of patients experienced a virus decline of≥4 log_(10) IU/mL in the TAF group compared with the TDF group,with rates of 78.26% versus 58%(P=0.034),respectively.Moreover,the median serum phosphate levels significantly decreased frombaseline to predelivery in the TDF group(P=0.04).Finally,infants in both cohorts tested negative for HBsAg at 7–12 months after delivery.Overall,our findings indicate that TAF can be considered the preferred option for the treatment of HBeAgpositive pregnant women with HBV DNA levels of≥8 log_(10) IU/mL.

HBsAg kinetics after 7 years of therapy with tenofovir disoproxil fumarate in a cohort of naïve patients affected by chronic hepatitis B with different genotypes

Background:The role of different genotypes in nucleos(t)ide analogs(NAs)treatment is still debated.Previous studies conducted on special populations evidenced that the E genotype had the lower virological and serological response.This descriptive study aims to recognize the hepatitis B“s”antigen(HBsAg)decline during tenofovir disoproxil fumarate(TDF)treatment in a cohort of patient affected by chronic hepatitis B(CHB).Methods:We retrospectively included all patients with CHB treated with TDF between April 2007 and March 2012 with a duration of treatment of 7 years.Kinetics of HBsAg was determined as serological response in this cohort.We include 110 subjects;virological response was observed in all subjects with genotypes A,B,and D;in 17 patients with C genotype(94.4%)and 24 with E genotype(96%).HBeAg loss was observed in 2 patients with genotype A(50%),3 with B(100%),0 with C(0%),1 with D(20%),and 1 with E genotype(25%).Results:In multivariate analysis we observed as predictive factors of HBsAg decline the baseline level of HBsAg(OR=1.467;95%CI:1.221–5.113;p=0.017)and viral genotypes(OR=11.218;95%CI:5.441–41.138;p<0.001).Conclusion:This study confirmed higher HBsAg decline after 7 years of treatment in A and B genotypes,and lower in C,E,and D genotypes.However,no evidence is enough to choose a single NAs,but in special populations,as well as in genotype E,the use of TDF should be preferred to entecavir.

Efficacy of tenofovir alafenamide in treatment of hepatitis B virus:A meta-analysis and non-inferiority evaluation

Objective:To evaluate the effect of tenofovir alafenamide versus tenofovir disoproxil fumarate on antiviral efficacy in patients with hepatitis B virus infection.Methods:Randomized controlled trials were searched on CNKI,Wanfang,VIP,China Biomedical Literature Database,PubMed,Cochrane Library,Embase,ClinicalKey,Chinese Clinical Trial Registry and ClinicalTrials.gov from the date of inception to April 2020.The literature was screened according to the inclusion and exclusion criteria,and the efficacy evaluation index of the included RCT was set as the success rate of reaching the endpoint of viral suppression and achieving normalized ALT values at 48 weeks of treatment.Intentionality analysis was adopted and the analysis results were taken as the final conclusion.RevMan 5.3 software was used for this Meta-analysis.Meanwhile,VassarStats was used to evaluate the non-inferiority of TAF and calculate the difference of virus inhibition efficiency rate and 95%confidence interval between experimental group and the control group of each RCT.Results:After the literature search,411 potential articles were found,5 studies were finally included according to the criteria,and 2,120 patients were included.Intentionality analysis showed that TAF regimen and TDF regimen had similar viral suppression success rates(RR=0.97,95%CI:0.94~1.01,P=0.19).The ALT normalization rate in the TAF treatment group was higher than that in the TDF treatment group,and the difference was statistically significant(RR=1.35,95%CI:1.20-1.53,P<0.00001).The non-inferiority margin was set at 10%,and it was found that three RCT studies in the international multi-center all showed that TAF was not inferior to TDF in controlling HBV viral load,while two RCT studies in China's Mainland failed to achieve non-inferiority after calculation.Conclusions:At 48 weeks of treatment,TAF was similar to TDF in controlling HBV viral load.However,the efficacy of TAF in controlling HBV viral load may vary among different populations,which requires further confirmation by more clinical trial evidence.Based on AASLD criteria,the ALT normalization rate of the TAF group was higher than that of the TDF group at 48 weeks of treatment,showing an obvious advantage.

Five-year Treatment with Tenofovir Alafenamide Achieves High Rates of Viral Suppression,Alanine Aminotransferase Normalization,and Favorable Bone and Renal Safety in Chinese Chronic Hepatitis B Patients

Background and Aims:After 3-years(144 week)of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies,tenofovir alafenamide(TAF)showed similar efficacy to tenofovir disoproxil fumarate(TDF),with improved renal and bone safety.In this study,we aimed to report the 5-year results from 2 years into the open-label TAF treatment phase.Methods:All participants completing the 144-week double-blind treatment were eligible to receive open-label TAF 25 mg once daily up to week 384.Serial analysis of viral suppression(hepatitis B virus DNA<29 IU/mL),alanine aminotransferase normalization,serological responses,and safety outcomes at year 5(week 240)was performed.Results:The openlabel phase included 93%(311/334)of the enrolled participants,which included 212 who switched from double-blind TAF to open-label TAF(TAF-TAF)and 99 who switched from double-blind TDF to open-label TAF(TDF-TAF).Baseline characteristics were comparable.Week 240 viral suppression rates were similar between groups[93.4%vs.93.9%;difference:-1.5%,(95%CI:-6.4 to-3.5),p=0.857].Alanine aminotransferase normalization and serological response rates were higher in the TAF-TAF group than in the TDF-TAF group.The frequencies of adverse events and laboratory abnormalities were low and similar between groups.Both groups had similar small numerical declines from baseline in estimated glomerular filtration rate at year 5(week 240,-2.85 mL/min vs.-3.29 mL/min,p=0.910).The greater declines in renal and bone parameters in the TDF-TAF group through week 144 improved after switching to TAF.Conclusions:The 5-year TAF treatment efficacy was high and similar to that of 3-year TDF followed by 2-year TAF in Chinese chronic hepatitis B patients.Favorable effects on bone and renal parameters were sustained with TAF treatment alone and were observed following the switch from TDF to TAF.

Prevention of vertical transmission of hepatitis B virus infection

Hepatitis B virus(HBV)is the leading cause of chronic viral hepatitis.Annually,almost two million children younger than 5 years acquire the infection,mostly through vertical or horizontal transmission in early life.Vertical transmission of HBV is a high efficacy phenomenon ranging,in the absence of any preventive interventions,from 70%to 90%for hepatitis e antigen positive mothers and from 10%to 40%for hepatitis e antigen-negative mothers.Maternal viraemia is a preeminent risk factor for vertical transmission of HBV.Maternal screening is the first step to prevent vertical transmission of HBV.Hepatitis B passive and active immunoprophylaxis at birth together with antiviral treatment of highly viraemic mothers are the key strategies for global elimination of HBV infection.Strategies are needed to promote implementation of birth-dose vaccination and hepatitis B immunoglobulins in low-and middle-income countries where the prevalence of the infection is at the highest.

Treatment of hepatitis B virus infection in children and adolescents

Hepatitis B virus(HBV)infection is one of the main causes of morbidity and mortality worldwide.Most children acquire the infection perinatally or during early childhood and develop a chronic hepatitis characterized by a high viral replication and a low-inflammation phase of infection,with normal or only slightly raised aminotransferases.Although a conservative approach in children is usually recommended,different therapies exist and different therapeutic approaches are possible.The main goals of antiviral treatment for children with chronic HBV infection are to suppress viral replication and to warn the disease progression to cirrhosis and hepatocellular carcinoma,although these complications are rare in children.Both United States Food and Drug Administration(USFDA)and European Medicines Agency(EMA)have approved interferon alfa-2b for children aged 1 year and older,pegylated interferon alfa-2a and lamivudine for children aged 3 years and older,entecavir for use in children aged 2 years and older,and adefovir for use in those 12 years of age and older.Tenofovir disoproxil fumarate is approved by EMA for children aged 2 years and older and by USFDA for treatment in children aged 12 years and older.Finally,EMA has approved the use of tenofovir alafenamide for treatment of children aged 12 years and older or for children weighing more than 35 kg independent of age.This narrative review will provide the framework for summarizing indications to antiviral therapy in the management of chronic HBV infection in children and adolescents.

Rapid Recovery in COVID-19 Patients with Chronic Hepatitis B Virus Infection Treated with Tenofovir Disoproxil Fumarate

The coronavirus disease 2019(COVID-19)pandemic continues worldwide.We report here two cases of chronic hepatitis B patients with acute respiratory syndrome coronavirus 2 infection treated with tenofovir disoproxil fumarate who demonstrated a favorable outcome.This report adds some evidence that concurrent HBV infection may not worsen COVID-19 infection and tenofovir disoproxil fumarate treatment may have partial positive effect on COVID-19 rapid recovery.

Dynamic changes of estimated glomerular filtration rate are conversely related to triglyceride in non-overweight patients

BACKGROUND Correlation between Triglyceride(TG)and estimated glomerular filtration rate(eGFR)remains largely unknown in overweight and non-overweight patients.AIM To investigated the dynamic changes of eGFR and lipid profiles during 3-year tenofovir disoproxil fumarate(TDF)treatment in patients with chronic hepatitis B(CHB)and overweight.METHODS A total of 202 CHB patients who received TDF treatment at the Third People's Hospital of Changzhou(Changzhou,China)and Nanjing Drum Tower Hospital(Nanjing,China)between January 2016 and May 2018 were retrospectively enrolled.According to the body mass index(BMI)at the initiation of TDF treatment,CHB patients were divided into overweight(BMI≥25 kg/m^(2))and nonoverweight(BMI<25 kg/m^(2))groups.Logistic regression was applied for the analysis of risk factors for eGFR<90 mL/(min·1.73 m^(2)).RESULTS There is no significant difference in hepatitis B virus DNA(HBV DNA)negativity and hepatitis Be antigen(HBeAg)loss between patients with overweight and nonoverweight(both P>0.05).More patients in non-overweight group achieved alanine aminotransferase normalization compared with those in overweight group(χ^(2)=11.036,P<0.01).In non-overweight patients,the eGFR significantly declined in the 1^(st) year(P<0.01),then remained at a relatively lower level.TG significantly declined in the 2^(nd) year(P=0.02)and increased in the 3^(rd) year.Moreover,TG was negatively correlated with GFR at the four-time points(P=0.002,0.030,0.007,0.008,respectively).In overweight patients,eGFR and TG remained relatively stable during the 3-year treatment,and eGFR showed no significant relationship with TG.Moreover,multivariate analysis showed that age[P<0.01,95%CI(0.97-1.005)]and baseline eGFR[P<0.01,95%CI(5.056-33.668)]were independent risk factors for eGFR<90 mL/(min·1.73 m^(2))at the 3^(rd) year.CONCLUSION Dynamic changes in renal function were conversely related to TG during TDF treatment in patients with CHB and normal BMI,but not with overweight.

Changes in blood lipid levels and influencing factors among treatment-naïve adult male HlV/AlDS patients following BlC/FTC/TAF vs.3TC+EFV+TDF

Background:Antiretroviral therapy(ART)was often associated with dyslipidemia among human immunodeficiency virus(HIV)/acquired immunodeficiency syndrome(AIDS)patients.This study aimed to assess treatment-naïve adult male patients with HIV/AIDS who initiated ART with either co-formulated bictegravir,emtricitabine,and tenofovir alafenamide(BIC/FTC/TAF)or lamivudine,efavirenz,and tenofovir disoproxil fumarate(3TC+EFV+TDF),monitoring at weeks 4,12,24,and 48.Methods:A case-control retrospective study was conducted.The newly diagnosed HIV-infected individuals attending the sexual transmission disease(STD)/AIDS clinic of Beijing Youan Hospital,Capital Medical University,from January to December 2021.The patients were divided into BIC/FTC/TAF group or 3TC+EFV+TDF group.High-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),triglyceride(TG),and total cholesterol(TC)at different time points over 48 weeks between two groups were compared.A multivariate Cox regression model was used to identify relevant influencing factors for the population at high risk of increased LDL-C.Results:A total of 870 participants,with 510 in BIC/FTC/TAF group and 360 in 3TC+EFV+TDF group.There were no statistically significant differences in median age,baseline CD4/CD8 ratio,median body mass index(BMI)between the two groups.In both two groups,levels of TG,TC,and LDL-C were higher at 4 weeks,12 weeks,and 24 weeks of treatment(all P<0.05),and there were no statistically significant differences at 48 weeks compared to those at baseline(all P>0.05).In addition,the differences in average changes of the level of TG,TC,HDL-C,and LDL-C from weeks 4,12,24,and 48 to baseline between two groups were not statistically significant(all P>0.05).Multivariate Cox proportional risk model analysis showed that initiating ART with HIV RNA≥10^(5)copies/mL(compared with<10^(5)copies/mL)was associated with an increased risk of elevated LDL-C(hazard ratio=1.26,95%confidence interval:1.07-1.48,P=0.005).Conclusions:Transient elevations in blood lipid levels(TC,TG,HDL-C,and LDL-C)were observed in treatment-naïve adult male HIV/AIDS patients with BIC/FTC/TAF at 4 weeks,12 weeks,and 24 weeks of treatment.However,these levels did not differ significantly from baseline after 48 weeks of treatment,regardless of whether patients were in the BIC/FTC/TAF or 3TC+EFV+TDF group.

Efficacy and Safety of Tenofovir and Lamivudine in Combination with Efavirenz in Patients Co-infected with Human Immunodeficiency Virus and Hepatitis B Virus in China

Background： The prevalence of hepatitis B virus （HBV） infection is high among individuals infected with human immunodeficiency virus （HIV） in China.Both HIV and HBV can be treated with tenofovir disoproxil fumarate （TDF） and lamivudine （3TC）, so we evaluated the safety and efficacy of combination antiretroviral therapy （ART） that included TDF, 3TC, and efavirenz （EFV） among ART-naive individuals who were co-infected with HIV and HBV.Methods： One hundred HIV/HBV co-infected ARV-naive individuals were started on the regimen ofTDF, 3TC, and EFV, and the levels of plasma HBV DNA, HIV RNA, and biochemical evaluation related to the function of liver and kidney were analyzed.Results： Concerning efficacy, this study found that by week 48, the vast majority co-infected participants receiving this ART regimen had undetectable HBV DNA levels （71%） and/or HIV RNA levels （90%）.Concerning safety, this study found that the median estimated glomerular filtration rate of participants decreased from baseline （109 ml＆#183;min-1＆#183; 1.73 m-2） to week 12 （104 ml＆#183;min-1＆#183; 1.73 m-2） but was almost back to baseline at week 48 （1 1 1 ml＆#183;min-1＆#183; 1.73 m-2）.Conclusion： This combination ART regimen is safe and effective for patients with HIV/HBV co-infection.Trial Registration： ClinicalTrials.gov, NCT01751555;https：//clinicaltrials.gov/ct2/show/NCT01751555.

Incidence and factors associated with hepatitis B surface antigen seroclearance in patients co-infected with HBV/HIV during antiretroviral therapy in Guangdong,China

Background:Hepatitis B surface antigen(HBsAg)clearance is vital for a functional cure of hepatitis B virus(HBV)infection.However,the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus(HIV)remain largely unknown in Guangdong,China.Methods:Between 2009 and 2019,patients co-infected with HBV/HIV undergoing antiretroviral therapy(ART)in Guangzhou Eighth People’s Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31,2020.The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses.Results:A total of 1550 HBV/HIV co-infected patients were included in the study,with the median age of 42 years and 86.0%(1333/1550)males.Further,98.3%(1524/1550)received ART containing tenofovir disoproxil fumarate(TDF)plus lamivudine(3TC).HBV DNA was examined in 1283 cases at the last follow-up.Over the median 4.7 years of follow-up,8.1%(126/1550)patients achieved HBsAg seroclearance,among whom 50.8%(64/126)obtained hepatitis B surface antibody,28.1%(137/488)acquired hepatitis B e antigen seroconversion,and 95.9%(1231/1283)undetectable HBV DNA.Compared with patients who maintained HBsAg positive,cases achieving HBsAg seroclearance showed no differences in age,gender,CD4+T cell count,alanine aminotransferase(ALT)level,or fibrosis status;however,they presented lower HBV DNA levels,lower HBsAg levels,and higher rates of HBV genotype B at the baseline.Multivariate analysis showed that baseline HBsAg<1500 cutoff index(COI)(adjusted hazard ratio[aHR],2.74,95%confidence interval[95%CI]:1.48-5.09),ALT elevation>2×upper limit of normal during the first six months after receiving ART(aHR,2.96,95%CI:1.53-5.77),and HBV genotype B(aHR,3.73,95%CI:1.46-9.59)were independent predictors for HBsAg seroclearance(all P<0.01).Conclusions:Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients.Lower baseline HBsAg levels,HBV genotype B,and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.

Immunomodulatory and Antiviral Therapy Improved Functional Cure Rate in CHB Patients with High HBsAg Level Experienced NA

Background and Aims:A functional cure,or hepatitis B virus(HBV)surface antigen(HBsAg)loss,is difficult to achieve in patients with hepatitis B virus e antigen(HBeAg)-positive chronic hepatitis B.The HBV vaccine and granulocyte-macrophage colony-stimulating factor(GM-CSF)have been reported to help reduce HBsAg levels and promote HBsAg loss.In this prospective randomized trial,we evaluated HBsAg loss in patients receiving pegylated interferon α2b(PEGIFN-α2b)and tenofovir disoproxil fumarate(TDF),with and without GM-CSF and HBV vaccination.Methods:A total of 287 patients with HBeAg positive chronic hepati-tis B and seroconversion after nucleot(s)ide analog treat-ment were assigned randomly to three treatment groups for 48 weeks,TDF alone(control),PEGIFN-α2b+TDF,and PEGIFN-α2b+TDF+GM-CSF+HBV vaccine.The prima-ry endpoints were the proportions of patients with HBsAg loss and seroconversion at 48 and 72 weeks.Resu/ts:The cumulative HBsAg loss rates in the control,PEGIFN-α2b+TDF,and PEGIFN-α2b+TDF+GM-CSF+HBV vaccine groups at week 48 were 0.0%,28.3%,and 41.1%,respec-tively.The cumulative HBsAg seroconversion rates in these groups at week 48 were 0.0%,21.7%,and 33.9%,respec-tively.Multivariate regression analysis showed that GM-CSF use plus HBV vaccination was significantly associated with HBsAg loss(p=0.017)and seroconversion(p=0.030).Con-clusions:In patients with HBeAg-positive chronic hepatitis B and seroconversion after nucleot(s)ide analog treatment,immunomodulatory/antiviral treatment regimens effective-ly improved HBsAg loss,and the regimen including GM-CSF and HBV vaccination was most effective.

An Odyssey in antiviral drug development—50 years at the Rega Institute:1964–2014

I.How it started I entered the Rega Institute for Medical Research in August 1964,as a medical student,to start working under the guidance of Prof.Piet De Somer,then professor of microbiology at the Leuven School of Medicine.When I graduated