Chronic hepatitis B remains the primary cause of liver-related events in China.The World Health Organization set a goal to eliminate viral hepatitis as a public health threat by 2030.However,achieving this goal appear...Chronic hepatitis B remains the primary cause of liver-related events in China.The World Health Organization set a goal to eliminate viral hepatitis as a public health threat by 2030.However,achieving this goal appears challenging due to the current low rates of diagnosis and treatment.The“Treat-all”strategy,which proposes treating all patients with detectable hepatitis B virus(HBV)DNA or even all patients with positive HBsAg,has been suggested to simplify anti-HBV treatment.In 2022,the Chinese Society of Hepatology and the Chinese Society of Infectious Diseases updated the guidelines for the prevention and treatment of chronic hepatitis B in China,expanding antiviral indications and simplifying the treatment algorithm.According to this latest guideline,nearly 95%of patients with detectable HBV DNA are eligible for antiviral treatment.This review aimed to provide a detailed interpretation of the treatment indications outlined in the Chinese Guidelines for the Prevention and Treatment of Chronic Hepatitis B(version 2022)and to identify gaps in achieving the“Treat-all”strategy in China.展开更多
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 fum...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.展开更多
Background and Aims:Tissue inhibitor of metalloproteinase-1(TIMP-1)plays a role in the excessive generation of extracellular matrix in liver fibrosis.This study aimed to explore the pathways through which TIMP-1 contr...Background and Aims:Tissue inhibitor of metalloproteinase-1(TIMP-1)plays a role in the excessive generation of extracellular matrix in liver fibrosis.This study aimed to explore the pathways through which TIMP-1 controls monocyte chemoattractant protein-1(MCP-1)expression and promotes hepatic macrophage recruitment.Methods:Liver fibrosis was triggered through carbon tetrachloride,and an adenoassociated virus containing small interfering RNA targeting TIMP-1(siRNA-TIMP-1)was administered to both rats and mice.We assessed the extent of fibrosis and macrophage recruitment.The molecular mechanisms regulating macrophage recruitment by TIMP-1 were investigated through transwell migration assays,luciferase reporter assays,the use of pharmacological modulators,and an analysis of extracellular vesicles(EVs).Results:siRNA-TIMP-1 alleviated carbon tetrachloride-induced liver fibrosis,reducing macrophage migration and MCP-1 expression.Co-culturing macrophages with hepatic stellate cells(HSCs)post-TIMP-1 downregulation inhibited macrophage migration.In siRNATIMP-1-treated HSCs,microRNA-145(miRNA-145)expression increased,while the expression of Friend leukemia virus integration-1(Fli-1)and MCP-1 was inhibited.Downregulation of Fli-1 led to decreased MCP-1 expression,whereas Fli-1 overexpression increased MCP-1 expression within HSCs.Transfection with miRNA-145 mimics reduced the expression of both Fli-1 and MCP-1,while miRNA-145 inhibitors elevated the expression of both Fli-1 and MCP-1 in HSCs.miRNA-145 bound directly to the 3'-UTR of Fli-1,and mi RNA-145-EN-riched EVs secreted by HSCs after TIMP-1 downregulation influenced macrophage recruitment.Conclusions:TIMP-1 induces Fli-1 expression through miRNA-145,subsequently increasing MCP-1 expression and macrophage recruitment.MiRNA-145-enriched EVs from HSCs can transmit biological information and magnify the function of TIMP-1.展开更多
Background and Aims:Liver iron overload can induce hepatic expression of bone morphogenic protein(BMP)6 and activate the BMP/SMAD pathway.However,serum iron overload can also activate SMAD but does not induce BMP6 exp...Background and Aims:Liver iron overload can induce hepatic expression of bone morphogenic protein(BMP)6 and activate the BMP/SMAD pathway.However,serum iron overload can also activate SMAD but does not induce BMP6 expression.Therefore,the mechanisms through which serum iron overload activates the BMP/SMAD pathway remain unclear.This study aimed to clarify the role of SMURF1 in serum iron overload and the BMP/SMAD pathway.Methods:A cell model of serum iron overload was established by treating hepatocytes with 2 mg/mL of holo-transferrin(Holo-Tf).A serum iron overload mouse model and a liver iron overload mouse model were established by intraperitoneally injecting 10 mg of Holo-Tf into C57BL/6 mice and administering a high-iron diet for 1 week followed by a low-iron diet for 2 days.Western blotting and real-time PCR were performed to evaluate the activation of the BMP/SMAD pathway and the expression of hepcidin.Results:Holo-Tf augmented the sensitivity and responsiveness of hepatocytes to BMP6.The E3 ubiquitin-protein ligase SMURF1 mediated Holo-Tf-induced SMAD1/5 activation and hepcidin expression;specifically,SMURF1 expression dramatically decreased when the serum iron concentration was increased.Additionally,the expression of SMURF1 substrates,which are important molecules involved in the transduction of BMP/SMAD signaling,was significantly upregulated.Furthermore,in vivo analyses confirmed that SMURF1 specifically regulated the BMP/SMAD pathway during serum iron overload.Conclusions:SMURF1 can specifically regulate the BMP/SMAD pathway by augmenting the responsiveness of hepatocytes to BMPs during serum iron overload.展开更多
To facilitate the achieving of the goal of“eliminating viral hepatitis as a major public health threat by 2030”set by the World Health Organization,the Chinese Society of Hepatology together with the Chinese Society...To facilitate the achieving of the goal of“eliminating viral hepatitis as a major public health threat by 2030”set by the World Health Organization,the Chinese Society of Hepatology together with the Chinese Society of Infectious Diseases(both are branches of the Chinese Medical Association)organized a panel of experts and updated the guidelines for prevention and treatment of chronic hepatitis B in China(version 2022).With the support of available evidence,this revision of the guidelines focuses on active prevention,large scale testing,and expansion of therapeutic indication of chronic hepatitis B with the aim of reducing the hepatitis B related disease burden.展开更多
In 2015, the Chinese Society of Hepatology and the Chinese Society of Gastroenterology published a consensus on pri-mary biliary cholangitis (PBC). In the past years, numerous clinical studies have been published in t...In 2015, the Chinese Society of Hepatology and the Chinese Society of Gastroenterology published a consensus on pri-mary biliary cholangitis (PBC). In the past years, numerous clinical studies have been published in the field of PBC. To guide the clinical diagnosis and management of PBC patients, the Chinese Society of Hepatology invited a panel of experts to assess the new clinical evidence and formulate the current guidelines.展开更多
To facilitate the achieving of the goal of“eliminating viral hepatitis as a major public health threat by 2030”set by theWorld Health Organization,the Chinese Society of Hepatology together with the Chinese Society ...To facilitate the achieving of the goal of“eliminating viral hepatitis as a major public health threat by 2030”set by theWorld Health Organization,the Chinese Society of Hepatology together with the Chinese Society of Infectious Diseases(both are branches of the ChineseMedical Association)organized a panel of experts and updated the guidelines for prevention and treatment of chronic hepatitis B in China(version 2022).With the support of available evidence,this revision of the guidelines focuses on active prevention,large-scale testing,and expansion of therapeutic indication of chronic hepatitis B with the aim of reducing the hepatitis B–related disease burden.展开更多
Background and Aims:The clinicopathological features and long-term outcomes of patients with vanishing bile duct syndrome(VBDS)have yet to be elucidated.The study aims to investigate these features and identify factor...Background and Aims:The clinicopathological features and long-term outcomes of patients with vanishing bile duct syndrome(VBDS)have yet to be elucidated.The study aims to investigate these features and identify factors associated with poor prognosis.Methods:This multicenter retrospective study recruited patients with liver biopsy-proven VBDS who were followed up at five hospitals in northern China from January 2003 to April 2022.Clinical and pathological data at time of biopsy were reviewed.Clinical outcomes including cirrhosis,decompensation events,liver transplantation(LT),and liver-related death were recorded.Cox regression analysis was used to identify the risk factors associated with poor outcomes.Results:A total of 183 patients were included.The median age was 47 years,with 77.6%being women.During a median follow-up of 4.8 years,88 patients developed compensated or decompensated cirrhosis,27 died,and 15 received LT.Multivariate Cox regression analysis showed that hepatocellular cholestasis(HR 2.953,95%CI:1.437–6.069),foam cells(HR 2.349,95%CI:1.092–5.053),and advanced fibrosis(HR 2.524,95%CI:1.313–4.851)were independent predictors of LT or liver-related deaths.A nomogram formulated with the above factors showed good consistency with a concordance index of 0.746(95%CI:0.706–0.785).Conclusions:Nearly half of VBDS patients studied progressed to end-stage liver disease and 23%of them had LT or liver-related death within two years of diagnosis.Hepatocellular cholestasis,foam cells and advanced fibrosis rather than the degree of bile duct loss or underlying etiologies were independently associated with poor prognosis in VBDS patients.展开更多
This guideline is established to standardize the prevention,diagnosis and antiviral therapy of chronic hepatitis B(CHB).For other treatment regimens and methods involving CHB,please refer to relevant guidelines and co...This guideline is established to standardize the prevention,diagnosis and antiviral therapy of chronic hepatitis B(CHB).For other treatment regimens and methods involving CHB,please refer to relevant guidelines and consensuses.The Chinese Society of Hepatology,Chinese Medical Association(CMA)and the Society of Infectious Diseases,CMA organized relevant native experts to establish this Guideline of Prevention and Treatment for Chronic Hepatitis B(1st version)in 2005,and made the first revision in 2010.In the past 5 years,great progress has been made in the native and foreign fundamental and clinical research with respect to CHB,necessitating additional revision of this guideline.展开更多
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...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.展开更多
Background and Aims:Genotype(GT)1 remains the predominant hepatitis c virus(HCV)GT in Chinese patients.Over 80%of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860,which is favorable ...Background and Aims:Genotype(GT)1 remains the predominant hepatitis c virus(HCV)GT in Chinese patients.Over 80%of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860,which is favorable for interferon-based treatment regimens.This phaseⅢclinical trial aimed to evaluate the efficacy and safety of the ritonavirboosted danoprevir plus pegylated-interferonα-2a and ribavirin regimen for 12 weeks in treatment-na(i)ve mainland Chinese patients infected with HCV GT1 without cirrhosis.Methods:One hundred and forty-one treatment-na(i)ve,non-cirrhotic HCV GT1 Chinese patients(age≥18 years)were enrolled for this single-arm,multicenter,phaseⅢMANASA study(NCT03020082).Patients received a combination of ritonavir-boosted danoprevir(100 mg/100 mg)twice a day plus subcutaneous injection of weekly pegylated-interferonα-2a(180μg)and oral ribavirin(1000/1200 mg/day body weight<75/≥75 kg)for 12 weeks.The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment.The secondary end-points were safety outcomes,tolerability,virologic response over time and relapse rate.Results:All enrolled patients were HCV GT1-infected,and most among them(97.9%,123/141)had the HCV GT1b subtype.Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype(87.2%,123/141).Overall,140 patients completed the 12-week treatment,and 97.1%(136/140)patients achieved sustained virologic response at 12 weeks(per protocol population group,95%confidence interval:92.9-99.2%).Only drug-related serious adverse event occurred.Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction.One patient discontinued treatment because of severe head injury in a car accident.Conclusions:The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferonα-2a and ribavirin produced a sustained virologic response rate of 97.1%after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients,and was safe and well tolerated.展开更多
Background and Aims:Tenofovir alafenamide(TAF)has similar efficacy to tenofovir disoproxil fumarate(TDF)but with improved renal and bone safety in chronic hepatitis B patients studied outside of China.We report 3-year...Background and Aims:Tenofovir alafenamide(TAF)has similar efficacy to tenofovir disoproxil fumarate(TDF)but with improved renal and bone safety in chronic hepatitis B patients studied outside of China.We report 3-year results from two phase 3 studies with TAF in China(Clinicaltrials.gov:NCT02836249 and NCT02836236).Methods:Chinese hepatitis B e antigen(HBeAg)-positive and-negative chronic hepatitis B patients with viremia and elevated alanine aminotransferase were randomized 2:1 to TAF or TDF treatment groups and treated in a double-blind fashion for 144 weeks(3 years).Efficacy responses were assessed by individual study while safety was assessed by a pooled analysis.Results:Of the 334 patients(180 HBeAg-positive and 154 HBeAg-negative)randomized and treated,baseline characteristics were similar between groups.The overall mean age was 38 years and 73%were male.The mean HBV DNA was 6.4 log10 IU/mL.The median alanine aminotransferase was 88 U/L,and 37%had a history of antiviral use.At week 144,the proportion with HBV DNA<29 IU/mL was similar among the two groups,with TAF at 83%vs.TDF at 79%,and TAF at 93%vs.TDF at 92%for the HBeAg-positive and-negative patients,respectively.In each study,higher proportions of TAF than TDF patients showed normalized alanine aminotransferase(via the American Association for the Study of Liver Diseases and the China criteria)and showed loss of HBsAg;meanwhile,the HBeAg seroconversion rates were similar.Treatment was well-tolerated among the TAF patients,who showed a smaller median decline in creatinine clearance(−0.4 vs.−3.2 mL/min;p=0.014)and less percentage change in bone mineral density vs.TDF at hip(−0.95%vs.−1.93%)and spine(+0.35%vs.−1.40%).Conclusions:In chronic hepatitis B patients from China,TAF treatment provided efficacy similar to TDF but with better renal and bone safety at 3 years.展开更多
Background and Aims: Chronic hepatitis B virus(HBV)in-fection remains a major public health problem globally.Here,we describe the baseline characteristics and treatment pro-files of HBV-infected patients recruited to ...Background and Aims: Chronic hepatitis B virus(HBV)in-fection remains a major public health problem globally.Here,we describe the baseline characteristics and treatment pro-files of HBV-infected patients recruited to the China Registry of Hepatitis B.Methods: Inclusion criteria were patients with different stages of chronic HBV infection and complete key data.Exclusion criteria were patients with hepatocellular car-cinoma.The baseline clinical,laboratory and treatment pro-files were analyzed.Results: Finally,40,431 patients were included.The median age was 43 years,with 65.2%being men and 51.3%being positive for hepatitis B e antigen(HBeAg).The most common initial diagnosis was chronic hep-atitis B(81.0%),followed by cirrhosis(9.3%),inactive carrier of hepatitis B surface antigen(HBsAg)(6.7%),and immune tolerant phase of hepatitis B infection(3.0%).Among the 21,228 patients who were on treatment,88.0%,10.0%and 2.0%received nucleos(t)ide analogues(NAs),interferon or combination of NAs and interferon,respectively.The propor-tion of patients who received preferred NAs(entecavir or te-nofovir disoproxil fumarate)had increased from 13.5%in 2003 to 79.7%in 2016.Conclusions: We concluded that middle-aged men accounted for most of the patients with chronic hepatitis B in this cross-sectional study.About half of the patients were HBeAg-positive.NAs were the most com-monly used therapy,and use of the preferred NAs had steadily increased in the past decade.展开更多
Exosomes are small extracellular vesicles that contain a potpourri of nucleic acids,including microRNAs(miRNAs).Importantly,exosomes and these miRNAs are actively secreted from multiple cell populations and play a cri...Exosomes are small extracellular vesicles that contain a potpourri of nucleic acids,including microRNAs(miRNAs).Importantly,exosomes and these miRNAs are actively secreted from multiple cell populations and play a critical role in intercellular communication.The exosomal miRNA profile reflects the cellular pathophysiological status and modulates multiple biological processes.Accumulating evidence indicates that exosomes and miRNAs are biomarkers for disease diagnosis and may have therapeutic targets.Research studies on exosomal miRNAs have brought new insights into understanding autoimmune diseases.This article summarizes the detection methodologies and updates the potential applications of exosomal miRNAs in autoimmune diseases.展开更多
Background and Aims:The National Centralized Drug Procurement(NCDP)policy was launched in China's Mainland in April 2019,with entecavir(ETV)and tenofovir disoproxil fumarate(TDF)being included in the procurement l...Background and Aims:The National Centralized Drug Procurement(NCDP)policy was launched in China's Mainland in April 2019,with entecavir(ETV)and tenofovir disoproxil fumarate(TDF)being included in the procurement list.We conducted the current study to investigate the impact of the NCDP policy on the utilization and expenditures of antiviral therapy for chronic hepatitis B(CHB)in China.Methods:Procurement records,including monthly purchase volume,expenditure,and price of nucleos(t)ide analogs(NAs),were derived from the National Healthcare Security Administration from April 2018 to March 2021.The changes in volumes and expenditures of the first-line NAs and bid-winning products were calculated.The effects of price,volume,and structure related to drug expenditure were calculated by the Addis and Magrini(AM)Index System Analysis.Results:The purchase volume of NAs significantly increased from 134.3 to 318.3 million DDDs,whereas the expenditure sharply decreased from 1,623.41 to 490.43 million renminbi(RMB)or 241.94 to 73.09 million US dollars(USD).The proportions of firstline NAs rose from 72.51%(ETV:69.00%,TDF:3.51%)to 94.97%(ETV:77.42%,TDF:17.55%).AM analysis showed that the NCDP policy decreased the expenditure of all NAs(S=0.91)but increased that of the first-line NAs in the bidwinning list(S=1.13).Assuming the population size of CHB patients remains stable and a compliance rate of≥75%,the proportion of CHB patients receiving first-line antiviral therapy would increase from 6.36–8.48%to 11.56–15.41%.Conclusions:The implementation of the NCDP policy significantly increased the utilization of first-line NAs for CHB patients at a lower expenditure.The findings provided evidence for optimizing antiviral therapy strategy and allocating medical resources in China.展开更多
Publications>Journals>Journal of Clinical and Translational Hepatology>Article Full Text ORIGINAL ARTICLE OPEN ACCESS Efficacy and Safety of All-oral Emitasvir and Sofosbuvir in Patients with Genotype 1b HCV ...Publications>Journals>Journal of Clinical and Translational Hepatology>Article Full Text ORIGINAL ARTICLE OPEN ACCESS Efficacy and Safety of All-oral Emitasvir and Sofosbuvir in Patients with Genotype 1b HCV Infections without Cirrhosis Huiying Rao1,Xingxiang Yang2,Youwen Tan3,Qin Ning4,Daokun Yang5,Jiefei Wang6,Yongfeng Yang7,Sujun Zheng8,Dongliang Yang9,Jinlin Hou10,Qing Xie11,Caiyan Zhao12,Lunli Zhang13,Xiaorong Mao14,Tong Sun15,Lang Bai16,Fuchun Zhang17,Jinglan Jin18,Yingren Zhao19,Maorong Wang20,Wen Xie21,Yingjie Ma22,Jun Quan23,Xuebing Yan24,Ping An25,Feng Lin26,Jidong Jia27,Xiaoxuan Hu28,Zuojiong Gong29,Jie Wu30,Yongping Chen31,Zhansheng Jia32,Minghua Lin33,Guiqiang Wang34,Yueyong Zhu35,Yingjun Zhang*,36,Hongming Xie36,Lin Luo36,Qingyun Ren36,Rui Huang1 and Lai Wei*,37 Author information Journal of Clinical and Translational Hepatology 2020;8(3):255-261DOI:10.14218/JCTH.2020.00031 Abstract Background and Aims:Emitasvir is a new type of hepatitis C virus(HCV)nonstructural protein 5A(NS5A)inhibitor,and the data of phase 2 trial has shown emitasvir-sofosbuvir to have good safety and tolerance.We conducted this phase 3 trial to further verify the efficacy and safety.Methods:We evaluated the antiviral activity and safety of a 12-week regimen of emitasvir phosphate(100 mg)combined with sofosbuvir(400 mg)once daily in non-cirrhotic patients with genotype 1 HCV infection.The primary endpoint was a sustained virological response at 12 weeks(SVR12)after the end of treatment.Results:Of the 362 patients enrolled in the trial,39.8%were male,99.2%had HCV genotype 1b,0.8%had genotype 1a and 79.8%were treatment-naïve.The average age was 47.2 years.All patients completed the treatment and follow-up.All 3 patients with genotype 1a achieved SVR.Two genotype 1b treatment-naïve patients experienced virologic relapse.The rate of SVR12 was 99.7%(358/359),and SVR24 was 99.4%(357/359)in genotype 1b.Overall,36.2%had resistance-associated substitutions(RASs)in NS5A and 98.3%had RASs in NS5B at baseline.The RASs at baseline had no effect on the rates of response.Serious adverse events were reported in 16 patients and were not related to emitasvir-sofosbuvir.Most adverse events did not require therapy.Conclusions:The 12 weeks of treatment with emitasvir-sofosbuvir was a highly efficient and safe treatment for a wide range of patients with HCV genotype 1b infection without cirrhosis,who had not been treated or who had been treated with interferon-based regimen previously.展开更多
Background and Aims:Data are limited on the use of pegylated-interferon alpha-2a(peg-IFNα)in Chinese patients with chronic hepatitis B virus(HBV)infection(CHB).We evaluated the effectiveness and safety of peg-IFNαin...Background and Aims:Data are limited on the use of pegylated-interferon alpha-2a(peg-IFNα)in Chinese patients with chronic hepatitis B virus(HBV)infection(CHB).We evaluated the effectiveness and safety of peg-IFNαin Chinese patients with hepatitis B envelope antigen-negative CHB in routine clinical practice.Methods:In this prospective,multicenter,observational,non-interventional cohort study,patients were assessed for up to 1 year after peg-IFNαtreatment cessation.Treating physicians established the dosing and treatment duration according to Chinese clinical practice.Effectiveness of peg-IFNαtreatment was measured by the percentage of:patients with HBV DNA<2000 IU/mL and loss of hepatitis B surface antigen(commonly known as HBsAg);HBV DNA level at end of treatment(EOT),and 6 months and 1 year posttreatment;and time course change in quantitative HBV DNA and HBsAg.Results:At EOT,6 months posttreatment,and 1 year posttreatment,the percentage of patients with HBV DNA<2000 IU/mL was 90.0%,81.8%,and 82.2%,and that of patients with HBsAg loss was 6.5%,9.4%,and 9.5%,respectively.The HBV DNA level decreased from 5.61 log IU/mL at baseline to 2.48 log IU/mL at EOT and 2.67 log IU/mL at 1 year posttreatment.The HBsAg level decreased from 3.08 log IU/mL at baseline to 2.24 log IU/mL at EOT and 2.10 log IU/mL at 1 year posttreatment.The incidence of adverse events was 52.0%.Conclusions:Peg-IFNαhas the potential to provide functional cure(HBsAg loss)for CHB and is well tolerated in hepatitis B envelope antigen-negative CHB patients in routine clinical practice in China.展开更多
The World Health Organization(WHO)has set the goal of eliminating hepatitis as a threat to public health by 2030.Blocking mother-to-child transmission(MTCT)of hepatitis B virus(HBV)is not only the key to eliminating v...The World Health Organization(WHO)has set the goal of eliminating hepatitis as a threat to public health by 2030.Blocking mother-to-child transmission(MTCT)of hepatitis B virus(HBV)is not only the key to eliminating viral hepatitis,but also a hot issue in the field of hepatitis B prevention and treatment.To standardize the clinical management of preventing MTCT of HBV and achieve zero HBV infection among infants,the Chinese Foundation for Hepatitis Prevention and Control organized experts to compile a management algorithm for prevention of MTCT of HBV based on the latest research progress and guidelines,including 10 steps of pregnancy management and postpartum follow-up,among which screening,antiviral treatment,and infant immunization are its core components.展开更多
Senescence-related decline in liver function is a common complication in the elderly that can lead to impaired health in older individuals.Dietary nitrate supplements have physiological and therapeutic effects on orga...Senescence-related decline in liver function is a common complication in the elderly that can lead to impaired health in older individuals.Dietary nitrate supplements have physiological and therapeutic effects on organ function by nitrate(NO_3^-)-nitrite(NO_2^-)-nitric oxide(NO)pathway.However,the role of dietary nitrate on the senescence-related decline in liver function is unclear.The findings of the present study showed that nitrate levels in the serum and liver decreased,whereas the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum increased in ageing mice.Consistently,cell senescence,decreased glycogen levels and increased lipid deposition were found in the liver of aged mice,both glucokinase(GCK)and phosphoenolpyruvate carboxykinase(PCK)were down-regulated(n=10).Daily nitrate intake(0.5 mmol L^(-1))restored nitrate levels,decreased ALT and AST levels,and prevented cell senescence and structural and glucose and lipid metabolism degeneration in liver tissue both in D-galactose(D-gal)-induced ageing mice(n=10)and in natural aged mice(n=10).In conclusion,the present study demonstrated that the reduction of nitrate levels was correlated with liver degeneration in ageing individuals and that dietary supplement of nitrate could restore the nitrate levels in serum and the liver and prevent ageing-related liver degeneration.展开更多
In the last three decades,China has made extraordinary effort and achieved great progress in the control of hepatitis B.Thanks to the adoption of universal administering of HBV vaccinations for newborns since 1992,the...In the last three decades,China has made extraordinary effort and achieved great progress in the control of hepatitis B.Thanks to the adoption of universal administering of HBV vaccinations for newborns since 1992,the prevalence of hepatitis B surface antigen(HBsAg)in the population born after 1992 decreased significantly resulting in a decline in the general population from 9.75%to about 6%(1).展开更多
基金supported by the National Key Research and Development Program(2023YFC2306900)the Beijing Municipal Science&Technology Commission(Z221100007422115).
文摘Chronic hepatitis B remains the primary cause of liver-related events in China.The World Health Organization set a goal to eliminate viral hepatitis as a public health threat by 2030.However,achieving this goal appears challenging due to the current low rates of diagnosis and treatment.The“Treat-all”strategy,which proposes treating all patients with detectable hepatitis B virus(HBV)DNA or even all patients with positive HBsAg,has been suggested to simplify anti-HBV treatment.In 2022,the Chinese Society of Hepatology and the Chinese Society of Infectious Diseases updated the guidelines for the prevention and treatment of chronic hepatitis B in China,expanding antiviral indications and simplifying the treatment algorithm.According to this latest guideline,nearly 95%of patients with detectable HBV DNA are eligible for antiviral treatment.This review aimed to provide a detailed interpretation of the treatment indications outlined in the Chinese Guidelines for the Prevention and Treatment of Chronic Hepatitis B(version 2022)and to identify gaps in achieving the“Treat-all”strategy in China.
文摘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.
基金supported by a grant from the National Natural Science Foundation of China(grant numbers 81570542 and 82170614)the WBE Liver Fibrosis Foundation(grant number CFHPC2021042).
文摘Background and Aims:Tissue inhibitor of metalloproteinase-1(TIMP-1)plays a role in the excessive generation of extracellular matrix in liver fibrosis.This study aimed to explore the pathways through which TIMP-1 controls monocyte chemoattractant protein-1(MCP-1)expression and promotes hepatic macrophage recruitment.Methods:Liver fibrosis was triggered through carbon tetrachloride,and an adenoassociated virus containing small interfering RNA targeting TIMP-1(siRNA-TIMP-1)was administered to both rats and mice.We assessed the extent of fibrosis and macrophage recruitment.The molecular mechanisms regulating macrophage recruitment by TIMP-1 were investigated through transwell migration assays,luciferase reporter assays,the use of pharmacological modulators,and an analysis of extracellular vesicles(EVs).Results:siRNA-TIMP-1 alleviated carbon tetrachloride-induced liver fibrosis,reducing macrophage migration and MCP-1 expression.Co-culturing macrophages with hepatic stellate cells(HSCs)post-TIMP-1 downregulation inhibited macrophage migration.In siRNATIMP-1-treated HSCs,microRNA-145(miRNA-145)expression increased,while the expression of Friend leukemia virus integration-1(Fli-1)and MCP-1 was inhibited.Downregulation of Fli-1 led to decreased MCP-1 expression,whereas Fli-1 overexpression increased MCP-1 expression within HSCs.Transfection with miRNA-145 mimics reduced the expression of both Fli-1 and MCP-1,while miRNA-145 inhibitors elevated the expression of both Fli-1 and MCP-1 in HSCs.miRNA-145 bound directly to the 3'-UTR of Fli-1,and mi RNA-145-EN-riched EVs secreted by HSCs after TIMP-1 downregulation influenced macrophage recruitment.Conclusions:TIMP-1 induces Fli-1 expression through miRNA-145,subsequently increasing MCP-1 expression and macrophage recruitment.MiRNA-145-enriched EVs from HSCs can transmit biological information and magnify the function of TIMP-1.
基金supported by the National Natural Science Foundation of China(No.82370898)Beijing Natural Science Foundation(No.7202034).
文摘Background and Aims:Liver iron overload can induce hepatic expression of bone morphogenic protein(BMP)6 and activate the BMP/SMAD pathway.However,serum iron overload can also activate SMAD but does not induce BMP6 expression.Therefore,the mechanisms through which serum iron overload activates the BMP/SMAD pathway remain unclear.This study aimed to clarify the role of SMURF1 in serum iron overload and the BMP/SMAD pathway.Methods:A cell model of serum iron overload was established by treating hepatocytes with 2 mg/mL of holo-transferrin(Holo-Tf).A serum iron overload mouse model and a liver iron overload mouse model were established by intraperitoneally injecting 10 mg of Holo-Tf into C57BL/6 mice and administering a high-iron diet for 1 week followed by a low-iron diet for 2 days.Western blotting and real-time PCR were performed to evaluate the activation of the BMP/SMAD pathway and the expression of hepcidin.Results:Holo-Tf augmented the sensitivity and responsiveness of hepatocytes to BMP6.The E3 ubiquitin-protein ligase SMURF1 mediated Holo-Tf-induced SMAD1/5 activation and hepcidin expression;specifically,SMURF1 expression dramatically decreased when the serum iron concentration was increased.Additionally,the expression of SMURF1 substrates,which are important molecules involved in the transduction of BMP/SMAD signaling,was significantly upregulated.Furthermore,in vivo analyses confirmed that SMURF1 specifically regulated the BMP/SMAD pathway during serum iron overload.Conclusions:SMURF1 can specifically regulate the BMP/SMAD pathway by augmenting the responsiveness of hepatocytes to BMPs during serum iron overload.
文摘To facilitate the achieving of the goal of“eliminating viral hepatitis as a major public health threat by 2030”set by the World Health Organization,the Chinese Society of Hepatology together with the Chinese Society of Infectious Diseases(both are branches of the Chinese Medical Association)organized a panel of experts and updated the guidelines for prevention and treatment of chronic hepatitis B in China(version 2022).With the support of available evidence,this revision of the guidelines focuses on active prevention,large scale testing,and expansion of therapeutic indication of chronic hepatitis B with the aim of reducing the hepatitis B related disease burden.
文摘In 2015, the Chinese Society of Hepatology and the Chinese Society of Gastroenterology published a consensus on pri-mary biliary cholangitis (PBC). In the past years, numerous clinical studies have been published in the field of PBC. To guide the clinical diagnosis and management of PBC patients, the Chinese Society of Hepatology invited a panel of experts to assess the new clinical evidence and formulate the current guidelines.
文摘To facilitate the achieving of the goal of“eliminating viral hepatitis as a major public health threat by 2030”set by theWorld Health Organization,the Chinese Society of Hepatology together with the Chinese Society of Infectious Diseases(both are branches of the ChineseMedical Association)organized a panel of experts and updated the guidelines for prevention and treatment of chronic hepatitis B in China(version 2022).With the support of available evidence,this revision of the guidelines focuses on active prevention,large-scale testing,and expansion of therapeutic indication of chronic hepatitis B with the aim of reducing the hepatitis B–related disease burden.
基金supported by National Natural Science Foundation of China(No.82100633 to LTT).
文摘Background and Aims:The clinicopathological features and long-term outcomes of patients with vanishing bile duct syndrome(VBDS)have yet to be elucidated.The study aims to investigate these features and identify factors associated with poor prognosis.Methods:This multicenter retrospective study recruited patients with liver biopsy-proven VBDS who were followed up at five hospitals in northern China from January 2003 to April 2022.Clinical and pathological data at time of biopsy were reviewed.Clinical outcomes including cirrhosis,decompensation events,liver transplantation(LT),and liver-related death were recorded.Cox regression analysis was used to identify the risk factors associated with poor outcomes.Results:A total of 183 patients were included.The median age was 47 years,with 77.6%being women.During a median follow-up of 4.8 years,88 patients developed compensated or decompensated cirrhosis,27 died,and 15 received LT.Multivariate Cox regression analysis showed that hepatocellular cholestasis(HR 2.953,95%CI:1.437–6.069),foam cells(HR 2.349,95%CI:1.092–5.053),and advanced fibrosis(HR 2.524,95%CI:1.313–4.851)were independent predictors of LT or liver-related deaths.A nomogram formulated with the above factors showed good consistency with a concordance index of 0.746(95%CI:0.706–0.785).Conclusions:Nearly half of VBDS patients studied progressed to end-stage liver disease and 23%of them had LT or liver-related death within two years of diagnosis.Hepatocellular cholestasis,foam cells and advanced fibrosis rather than the degree of bile duct loss or underlying etiologies were independently associated with poor prognosis in VBDS patients.
文摘This guideline is established to standardize the prevention,diagnosis and antiviral therapy of chronic hepatitis B(CHB).For other treatment regimens and methods involving CHB,please refer to relevant guidelines and consensuses.The Chinese Society of Hepatology,Chinese Medical Association(CMA)and the Society of Infectious Diseases,CMA organized relevant native experts to establish this Guideline of Prevention and Treatment for Chronic Hepatitis B(1st version)in 2005,and made the first revision in 2010.In the past 5 years,great progress has been made in the native and foreign fundamental and clinical research with respect to CHB,necessitating additional revision of this guideline.
基金Ascletis BioScience Co.,Ltd.provided financial support for this study
文摘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.
基金Ascletis Pharmaceuticals Co.,Ltd.provided financial support for this study(MANASA)
文摘Background and Aims:Genotype(GT)1 remains the predominant hepatitis c virus(HCV)GT in Chinese patients.Over 80%of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860,which is favorable for interferon-based treatment regimens.This phaseⅢclinical trial aimed to evaluate the efficacy and safety of the ritonavirboosted danoprevir plus pegylated-interferonα-2a and ribavirin regimen for 12 weeks in treatment-na(i)ve mainland Chinese patients infected with HCV GT1 without cirrhosis.Methods:One hundred and forty-one treatment-na(i)ve,non-cirrhotic HCV GT1 Chinese patients(age≥18 years)were enrolled for this single-arm,multicenter,phaseⅢMANASA study(NCT03020082).Patients received a combination of ritonavir-boosted danoprevir(100 mg/100 mg)twice a day plus subcutaneous injection of weekly pegylated-interferonα-2a(180μg)and oral ribavirin(1000/1200 mg/day body weight<75/≥75 kg)for 12 weeks.The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment.The secondary end-points were safety outcomes,tolerability,virologic response over time and relapse rate.Results:All enrolled patients were HCV GT1-infected,and most among them(97.9%,123/141)had the HCV GT1b subtype.Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype(87.2%,123/141).Overall,140 patients completed the 12-week treatment,and 97.1%(136/140)patients achieved sustained virologic response at 12 weeks(per protocol population group,95%confidence interval:92.9-99.2%).Only drug-related serious adverse event occurred.Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction.One patient discontinued treatment because of severe head injury in a car accident.Conclusions:The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferonα-2a and ribavirin produced a sustained virologic response rate of 97.1%after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients,and was safe and well tolerated.
基金This study was sponsored by Gilead Sciences,Inc.
文摘Background and Aims:Tenofovir alafenamide(TAF)has similar efficacy to tenofovir disoproxil fumarate(TDF)but with improved renal and bone safety in chronic hepatitis B patients studied outside of China.We report 3-year results from two phase 3 studies with TAF in China(Clinicaltrials.gov:NCT02836249 and NCT02836236).Methods:Chinese hepatitis B e antigen(HBeAg)-positive and-negative chronic hepatitis B patients with viremia and elevated alanine aminotransferase were randomized 2:1 to TAF or TDF treatment groups and treated in a double-blind fashion for 144 weeks(3 years).Efficacy responses were assessed by individual study while safety was assessed by a pooled analysis.Results:Of the 334 patients(180 HBeAg-positive and 154 HBeAg-negative)randomized and treated,baseline characteristics were similar between groups.The overall mean age was 38 years and 73%were male.The mean HBV DNA was 6.4 log10 IU/mL.The median alanine aminotransferase was 88 U/L,and 37%had a history of antiviral use.At week 144,the proportion with HBV DNA<29 IU/mL was similar among the two groups,with TAF at 83%vs.TDF at 79%,and TAF at 93%vs.TDF at 92%for the HBeAg-positive and-negative patients,respectively.In each study,higher proportions of TAF than TDF patients showed normalized alanine aminotransferase(via the American Association for the Study of Liver Diseases and the China criteria)and showed loss of HBsAg;meanwhile,the HBeAg seroconversion rates were similar.Treatment was well-tolerated among the TAF patients,who showed a smaller median decline in creatinine clearance(−0.4 vs.−3.2 mL/min;p=0.014)and less percentage change in bone mineral density vs.TDF at hip(−0.95%vs.−1.93%)and spine(+0.35%vs.−1.40%).Conclusions:In chronic hepatitis B patients from China,TAF treatment provided efficacy similar to TDF but with better renal and bone safety at 3 years.
文摘Background and Aims: Chronic hepatitis B virus(HBV)in-fection remains a major public health problem globally.Here,we describe the baseline characteristics and treatment pro-files of HBV-infected patients recruited to the China Registry of Hepatitis B.Methods: Inclusion criteria were patients with different stages of chronic HBV infection and complete key data.Exclusion criteria were patients with hepatocellular car-cinoma.The baseline clinical,laboratory and treatment pro-files were analyzed.Results: Finally,40,431 patients were included.The median age was 43 years,with 65.2%being men and 51.3%being positive for hepatitis B e antigen(HBeAg).The most common initial diagnosis was chronic hep-atitis B(81.0%),followed by cirrhosis(9.3%),inactive carrier of hepatitis B surface antigen(HBsAg)(6.7%),and immune tolerant phase of hepatitis B infection(3.0%).Among the 21,228 patients who were on treatment,88.0%,10.0%and 2.0%received nucleos(t)ide analogues(NAs),interferon or combination of NAs and interferon,respectively.The propor-tion of patients who received preferred NAs(entecavir or te-nofovir disoproxil fumarate)had increased from 13.5%in 2003 to 79.7%in 2016.Conclusions: We concluded that middle-aged men accounted for most of the patients with chronic hepatitis B in this cross-sectional study.About half of the patients were HBeAg-positive.NAs were the most com-monly used therapy,and use of the preferred NAs had steadily increased in the past decade.
文摘Exosomes are small extracellular vesicles that contain a potpourri of nucleic acids,including microRNAs(miRNAs).Importantly,exosomes and these miRNAs are actively secreted from multiple cell populations and play a critical role in intercellular communication.The exosomal miRNA profile reflects the cellular pathophysiological status and modulates multiple biological processes.Accumulating evidence indicates that exosomes and miRNAs are biomarkers for disease diagnosis and may have therapeutic targets.Research studies on exosomal miRNAs have brought new insights into understanding autoimmune diseases.This article summarizes the detection methodologies and updates the potential applications of exosomal miRNAs in autoimmune diseases.
基金This work was supported by the National Healthcare Security Administration,The Key Technical and Executive Measures to Improve Early Phase Clinical Trials on Innovative Drugs for Liver Diseases(No.Z191100007619037)High-level Public Health Technical Talents of the Beijing Municipal Health Commission(XUEKEGUGAN-010-018).
文摘Background and Aims:The National Centralized Drug Procurement(NCDP)policy was launched in China's Mainland in April 2019,with entecavir(ETV)and tenofovir disoproxil fumarate(TDF)being included in the procurement list.We conducted the current study to investigate the impact of the NCDP policy on the utilization and expenditures of antiviral therapy for chronic hepatitis B(CHB)in China.Methods:Procurement records,including monthly purchase volume,expenditure,and price of nucleos(t)ide analogs(NAs),were derived from the National Healthcare Security Administration from April 2018 to March 2021.The changes in volumes and expenditures of the first-line NAs and bid-winning products were calculated.The effects of price,volume,and structure related to drug expenditure were calculated by the Addis and Magrini(AM)Index System Analysis.Results:The purchase volume of NAs significantly increased from 134.3 to 318.3 million DDDs,whereas the expenditure sharply decreased from 1,623.41 to 490.43 million renminbi(RMB)or 241.94 to 73.09 million US dollars(USD).The proportions of firstline NAs rose from 72.51%(ETV:69.00%,TDF:3.51%)to 94.97%(ETV:77.42%,TDF:17.55%).AM analysis showed that the NCDP policy decreased the expenditure of all NAs(S=0.91)but increased that of the first-line NAs in the bidwinning list(S=1.13).Assuming the population size of CHB patients remains stable and a compliance rate of≥75%,the proportion of CHB patients receiving first-line antiviral therapy would increase from 6.36–8.48%to 11.56–15.41%.Conclusions:The implementation of the NCDP policy significantly increased the utilization of first-line NAs for CHB patients at a lower expenditure.The findings provided evidence for optimizing antiviral therapy strategy and allocating medical resources in China.
基金supported by the National Major Scientific and Technological Special Project for“Significant New Drugs Development”during the Thirteenth Five-Year Plan Period of China(Nos.2017ZX09201006004 and 2017ZX09201006009)the Chinese National Research Grant of the Thirteenth Five-Year Plan for the Key Projects in Infectious Diseases(No.2017ZX10202202)+1 种基金the Key Research and Development Program of Guangdong(No.2019B02021002)funded by Sunshine Lake Pharma Co.,Ltd.(ClinicalTrials.gov number,NCT 03487107).
文摘Publications>Journals>Journal of Clinical and Translational Hepatology>Article Full Text ORIGINAL ARTICLE OPEN ACCESS Efficacy and Safety of All-oral Emitasvir and Sofosbuvir in Patients with Genotype 1b HCV Infections without Cirrhosis Huiying Rao1,Xingxiang Yang2,Youwen Tan3,Qin Ning4,Daokun Yang5,Jiefei Wang6,Yongfeng Yang7,Sujun Zheng8,Dongliang Yang9,Jinlin Hou10,Qing Xie11,Caiyan Zhao12,Lunli Zhang13,Xiaorong Mao14,Tong Sun15,Lang Bai16,Fuchun Zhang17,Jinglan Jin18,Yingren Zhao19,Maorong Wang20,Wen Xie21,Yingjie Ma22,Jun Quan23,Xuebing Yan24,Ping An25,Feng Lin26,Jidong Jia27,Xiaoxuan Hu28,Zuojiong Gong29,Jie Wu30,Yongping Chen31,Zhansheng Jia32,Minghua Lin33,Guiqiang Wang34,Yueyong Zhu35,Yingjun Zhang*,36,Hongming Xie36,Lin Luo36,Qingyun Ren36,Rui Huang1 and Lai Wei*,37 Author information Journal of Clinical and Translational Hepatology 2020;8(3):255-261DOI:10.14218/JCTH.2020.00031 Abstract Background and Aims:Emitasvir is a new type of hepatitis C virus(HCV)nonstructural protein 5A(NS5A)inhibitor,and the data of phase 2 trial has shown emitasvir-sofosbuvir to have good safety and tolerance.We conducted this phase 3 trial to further verify the efficacy and safety.Methods:We evaluated the antiviral activity and safety of a 12-week regimen of emitasvir phosphate(100 mg)combined with sofosbuvir(400 mg)once daily in non-cirrhotic patients with genotype 1 HCV infection.The primary endpoint was a sustained virological response at 12 weeks(SVR12)after the end of treatment.Results:Of the 362 patients enrolled in the trial,39.8%were male,99.2%had HCV genotype 1b,0.8%had genotype 1a and 79.8%were treatment-naïve.The average age was 47.2 years.All patients completed the treatment and follow-up.All 3 patients with genotype 1a achieved SVR.Two genotype 1b treatment-naïve patients experienced virologic relapse.The rate of SVR12 was 99.7%(358/359),and SVR24 was 99.4%(357/359)in genotype 1b.Overall,36.2%had resistance-associated substitutions(RASs)in NS5A and 98.3%had RASs in NS5B at baseline.The RASs at baseline had no effect on the rates of response.Serious adverse events were reported in 16 patients and were not related to emitasvir-sofosbuvir.Most adverse events did not require therapy.Conclusions:The 12 weeks of treatment with emitasvir-sofosbuvir was a highly efficient and safe treatment for a wide range of patients with HCV genotype 1b infection without cirrhosis,who had not been treated or who had been treated with interferon-based regimen previously.
基金The authors wish to thank all of the investigators and participating study sites,which are listed in Supplemental Table 1,as well as all the patients who participated in this studyThe authors also wish to thank Michelle Belanger,MD,of Edanz Medical Writing for providing medical writing assistance,which was funded by Shanghai Roche Pharmaceuticals Ltd.The study was funded by Shanghai Roche Pharmaceuticals Ltd
文摘Background and Aims:Data are limited on the use of pegylated-interferon alpha-2a(peg-IFNα)in Chinese patients with chronic hepatitis B virus(HBV)infection(CHB).We evaluated the effectiveness and safety of peg-IFNαin Chinese patients with hepatitis B envelope antigen-negative CHB in routine clinical practice.Methods:In this prospective,multicenter,observational,non-interventional cohort study,patients were assessed for up to 1 year after peg-IFNαtreatment cessation.Treating physicians established the dosing and treatment duration according to Chinese clinical practice.Effectiveness of peg-IFNαtreatment was measured by the percentage of:patients with HBV DNA<2000 IU/mL and loss of hepatitis B surface antigen(commonly known as HBsAg);HBV DNA level at end of treatment(EOT),and 6 months and 1 year posttreatment;and time course change in quantitative HBV DNA and HBsAg.Results:At EOT,6 months posttreatment,and 1 year posttreatment,the percentage of patients with HBV DNA<2000 IU/mL was 90.0%,81.8%,and 82.2%,and that of patients with HBsAg loss was 6.5%,9.4%,and 9.5%,respectively.The HBV DNA level decreased from 5.61 log IU/mL at baseline to 2.48 log IU/mL at EOT and 2.67 log IU/mL at 1 year posttreatment.The HBsAg level decreased from 3.08 log IU/mL at baseline to 2.24 log IU/mL at EOT and 2.10 log IU/mL at 1 year posttreatment.The incidence of adverse events was 52.0%.Conclusions:Peg-IFNαhas the potential to provide functional cure(HBsAg loss)for CHB and is well tolerated in hepatitis B envelope antigen-negative CHB patients in routine clinical practice in China.
基金Supported by the National Natural Science Foundation of China(Grant No.81673243)Sanming Project of Medi-cine in Shenzhen(SZSM201911001).
文摘The World Health Organization(WHO)has set the goal of eliminating hepatitis as a threat to public health by 2030.Blocking mother-to-child transmission(MTCT)of hepatitis B virus(HBV)is not only the key to eliminating viral hepatitis,but also a hot issue in the field of hepatitis B prevention and treatment.To standardize the clinical management of preventing MTCT of HBV and achieve zero HBV infection among infants,the Chinese Foundation for Hepatitis Prevention and Control organized experts to compile a management algorithm for prevention of MTCT of HBV based on the latest research progress and guidelines,including 10 steps of pregnancy management and postpartum follow-up,among which screening,antiviral treatment,and infant immunization are its core components.
基金supported by the National Natural Science Foundation of China (91649124)Beijing Municipality Government grants (Beijing Scholar Program- PXM2016_014226_000034, PXM2016_014226_000006, PXM2015_014226_000116, PXM2015_ 014226_000055, PXM2015_014226_000052, PXM2014_014226_000048, PXM2014_014226_000013, PXM2014_014226_000053, Z121100005212004, PXM2013_014226_000055, PXM2013_014226_000021, PXM 2013_014226_07_000080, TJSHG201310025005)
文摘Senescence-related decline in liver function is a common complication in the elderly that can lead to impaired health in older individuals.Dietary nitrate supplements have physiological and therapeutic effects on organ function by nitrate(NO_3^-)-nitrite(NO_2^-)-nitric oxide(NO)pathway.However,the role of dietary nitrate on the senescence-related decline in liver function is unclear.The findings of the present study showed that nitrate levels in the serum and liver decreased,whereas the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum increased in ageing mice.Consistently,cell senescence,decreased glycogen levels and increased lipid deposition were found in the liver of aged mice,both glucokinase(GCK)and phosphoenolpyruvate carboxykinase(PCK)were down-regulated(n=10).Daily nitrate intake(0.5 mmol L^(-1))restored nitrate levels,decreased ALT and AST levels,and prevented cell senescence and structural and glucose and lipid metabolism degeneration in liver tissue both in D-galactose(D-gal)-induced ageing mice(n=10)and in natural aged mice(n=10).In conclusion,the present study demonstrated that the reduction of nitrate levels was correlated with liver degeneration in ageing individuals and that dietary supplement of nitrate could restore the nitrate levels in serum and the liver and prevent ageing-related liver degeneration.
文摘In the last three decades,China has made extraordinary effort and achieved great progress in the control of hepatitis B.Thanks to the adoption of universal administering of HBV vaccinations for newborns since 1992,the prevalence of hepatitis B surface antigen(HBsAg)in the population born after 1992 decreased significantly resulting in a decline in the general population from 9.75%to about 6%(1).