Chronic hepatitis B virus(HBV)infection(CHB)is a public health concern worldwide.Current therapies utilizing nucleos(t)ide analogs(NA)have not resulted in a complete cure for CHB.Furthermore,patients on long-term NA t...Chronic hepatitis B virus(HBV)infection(CHB)is a public health concern worldwide.Current therapies utilizing nucleos(t)ide analogs(NA)have not resulted in a complete cure for CHB.Furthermore,patients on long-term NA treatment often develop low-level viremia(LLV).Persistent LLV,in addition to causing the progression of liver disease or hepatocellular carcinoma,may shed light on the current plight of NA therapy.Here,we review the literature on LLV,NA treatment,and various doses of entecavir to find a strategy for improving the efficacy of this antiviral agent.For LLV patients,three therapeutic options are available,switching to another antiviral monotherapy,interferon-αswitching therapy,and continuing monotherapy.In real-world clinical practice,entecavir overdose has been used in antiviral therapy for CHB patients with NA refractory and persistent LLV,which encouraged us to conduct further in-depth literature survey on dosage and duration related entecavir studies.The studies of pharmacodynamics and pharmacokinetics show that entecavir has the maximal selected index for safety,and has great potential in inhibiting HBV replication,in all of the NAs.In the particular section of the drug approval package published by the United States Food and Drug Administration,entecavir doses 2.5-20 mg/d do not increase adverse events,and entecavir doses higher than 1.0 mg/d might improve the antiviral efficacy.The literature survey led us to two suggestions:(1)Increasing entecavir dose to 1.0 mg/d for the treatment of NA naïve patients with HBV DNA>2×106 IU/mL is feasible and would provide better prognosis;and(2)Further research is needed to assess the long-term toxic effects of higher entecavir doses(2.5 and 5.0 mg/d),which may prove beneficial in treating patients with prior NA treatment,partial virological response,or LLV state.展开更多
AIM： To investigate the genetic characteristics and pathogenicity of hepatitis E virus （HEV） and assess the potential risk factors for sporadic hepatitis E.
AIM To assess the efficacy and safety of in vivo electroporation(EP)-mediated dual-plasmid hepatitis B virus(HBV) DNA vaccine vs placebo for sequential combination therapy with lamivudine(LAM) in patients with chronic...AIM To assess the efficacy and safety of in vivo electroporation(EP)-mediated dual-plasmid hepatitis B virus(HBV) DNA vaccine vs placebo for sequential combination therapy with lamivudine(LAM) in patients with chronic hepatitis B. METHODS Two hundred and twenty-five patients were randomized to receive either LAM + vaccine(vaccine group, n = 109) or LAM + placebo(control group, n = 116). LAM treatment lasted 72 wk. Patients received the DNA vaccine or placebo by intramuscular injection mediated by EP at weeks 12(start of treatment with vaccine or placebo, SOT), 16, 24, and 36(end of treatment with vaccine or placebo, EOT). RESULTS In the modified intent-to-treat population, morepatients had a decrease in HBV DNA > 2 log10 IU/m L in the vaccine group at week 12 after EOT compared with the control group. A trend toward a difference in the number of patients with undetectable HBV DNA at week 28 after EOT was obtained. Adverse events were similar. In the dynamic per-protocol set, which excluded adefovir(ADV) add-on cases at each time point instantly after ADV administration due to LAM antiviral failure, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 and 28 after EOT compared with the control group. More patients with undetectable HBV DNA at week 28 after EOT in the vaccine group were also observed. Among patients with a viral load < 1000 copies/mL at week 12, more patients achieved HBeA g seroconversion in the vaccine group than among controls at week 36 after EOT, as well as less virological breakthrough and YMDD mutations. CONCLUSION The primary endpoint was not achieved using the HBV DNA vaccine. The HBV DNA vaccine could only be beneficial in subjects that have achieved initial virological response under LAM chemotherapy.展开更多
The prevalence of hepatitis C virus(HCV) infection in patients on maintenance hemodialysis(MHD) is relatively higher than those without MHD. Chronic HCV infection detrimentally affects the life quality and expectancy,...The prevalence of hepatitis C virus(HCV) infection in patients on maintenance hemodialysis(MHD) is relatively higher than those without MHD. Chronic HCV infection detrimentally affects the life quality and expectancy, leads to renal transplant rejection, and increases the mortality of MHD patients. With the application of erythropoietin to improve uremic anemia and avoid blood transfusion, the new HCV infections during MHD in recent years are mainly caused by the lack of stringent universal precautions. Strict implementation of universal precautions for HCV transmission has led to markedly decreased HCV infections in many hemodialysis units, but physicians still should be alert for the antiHCV negative HCV infection and occult HCV infection in MHD patients. Standard interferon alpha and pegylated interferon alpha monotherapies at a reduced dose arecurrently the main treatment strategies for MHD patients with active HCV replication, but how to increase the sustained virological response and decrease the side effects is the key problem. IFNα-free treatments with two or three direct-acting antivirals without ribavirin in MHD patients are waiting for future investigations.展开更多
Broadband terahertz（THz） atmospheric transmission characteristics from 0 to 8 THz are theoretically simulated based on a standard Van Vleck–Weisskopf line shape, considering 1696 water absorption lines and 298 oxyg...Broadband terahertz（THz） atmospheric transmission characteristics from 0 to 8 THz are theoretically simulated based on a standard Van Vleck–Weisskopf line shape, considering 1696 water absorption lines and 298 oxygen absorption lines.The influences of humidity, temperature, and pressure on the THz atmospheric absorption are analyzed and experimentally verified with a Fourier transform infrared spectrometer（FTIR） system, showing good consistency. The investigation and evaluation on high-frequency atmospheric windows are good supplements to existing data in the low-frequency range and lay the foundation for aircraft-based high-altitude applications of THz communication and radar.展开更多
Objective To investigate the association between HBV genotypes and characteristics of rt A181 mutation. Methods Total of 85 chronic hepatitis B(CHB) patients who appeared rt A181 mutation after nucleos(t)ide analogs(N...Objective To investigate the association between HBV genotypes and characteristics of rt A181 mutation. Methods Total of 85 chronic hepatitis B(CHB) patients who appeared rt A181 mutation after nucleos(t)ide analogs(NAs) therapy were enrolled in this study. Levels of serum ALT, AST, HBV DNA and HBs Ag titers were monitored during therapy. HBV reverse transcriptase genes were amplified and sequenced to identify genotypes and resistance mutations. Virions and HBs Ag in Hep G2 cell with rt A181 mutation were also compared between genotypes B and C. Results The majority of sera contained HBV genotypes B(15.7%) and C(84.3%). There were no significant difference of rt A181 mutant patterns between genotypes(P > 0.05). After emergence of rt A181 mutation, serum ALT, AST, HBV DNA levels and HBs Ag titers were decreased than that at baseline(P < 0.05), while these characteristics were not different between genotypes B and C(P > 0.05). In cellular experiment, there were no significant differences between genotypes B and C not only in HBV virions but also in HBs Ag titres(P > 0.05). Conclusions No differences of clinical characteristics and cellular results were found in rt A181 mutation of HBV genotypes B and C.展开更多
文摘Chronic hepatitis B virus(HBV)infection(CHB)is a public health concern worldwide.Current therapies utilizing nucleos(t)ide analogs(NA)have not resulted in a complete cure for CHB.Furthermore,patients on long-term NA treatment often develop low-level viremia(LLV).Persistent LLV,in addition to causing the progression of liver disease or hepatocellular carcinoma,may shed light on the current plight of NA therapy.Here,we review the literature on LLV,NA treatment,and various doses of entecavir to find a strategy for improving the efficacy of this antiviral agent.For LLV patients,three therapeutic options are available,switching to another antiviral monotherapy,interferon-αswitching therapy,and continuing monotherapy.In real-world clinical practice,entecavir overdose has been used in antiviral therapy for CHB patients with NA refractory and persistent LLV,which encouraged us to conduct further in-depth literature survey on dosage and duration related entecavir studies.The studies of pharmacodynamics and pharmacokinetics show that entecavir has the maximal selected index for safety,and has great potential in inhibiting HBV replication,in all of the NAs.In the particular section of the drug approval package published by the United States Food and Drug Administration,entecavir doses 2.5-20 mg/d do not increase adverse events,and entecavir doses higher than 1.0 mg/d might improve the antiviral efficacy.The literature survey led us to two suggestions:(1)Increasing entecavir dose to 1.0 mg/d for the treatment of NA naïve patients with HBV DNA>2×106 IU/mL is feasible and would provide better prognosis;and(2)Further research is needed to assess the long-term toxic effects of higher entecavir doses(2.5 and 5.0 mg/d),which may prove beneficial in treating patients with prior NA treatment,partial virological response,or LLV state.
基金Supported by The 863 National High Technology Research and Development Program of China,No.2006A02Z453the National Natural Science Foundation of China,No.30570063
文摘AIM： To investigate the genetic characteristics and pathogenicity of hepatitis E virus （HEV） and assess the potential risk factors for sporadic hepatitis E.
基金Supported by Yigan Biological Products Co.,Ltd.of Guangzhou Pharmaceutical Holdings Ltd.(GPC,Guangzhou,China)Guangdong Provincial Sci.&Tech.Project,No.2012A080204009+2 种基金Guangdong Provincial Natural Science Fund,No.2014A030313 770Guangdong Provincial Public Benefit Foundation,No.2015A010107011National Key Program for Management of AIDS and Viral Hepatitis during the China "11~(th) 5-Year Plan" Period,No.2008ZX10002-003
文摘AIM To assess the efficacy and safety of in vivo electroporation(EP)-mediated dual-plasmid hepatitis B virus(HBV) DNA vaccine vs placebo for sequential combination therapy with lamivudine(LAM) in patients with chronic hepatitis B. METHODS Two hundred and twenty-five patients were randomized to receive either LAM + vaccine(vaccine group, n = 109) or LAM + placebo(control group, n = 116). LAM treatment lasted 72 wk. Patients received the DNA vaccine or placebo by intramuscular injection mediated by EP at weeks 12(start of treatment with vaccine or placebo, SOT), 16, 24, and 36(end of treatment with vaccine or placebo, EOT). RESULTS In the modified intent-to-treat population, morepatients had a decrease in HBV DNA > 2 log10 IU/m L in the vaccine group at week 12 after EOT compared with the control group. A trend toward a difference in the number of patients with undetectable HBV DNA at week 28 after EOT was obtained. Adverse events were similar. In the dynamic per-protocol set, which excluded adefovir(ADV) add-on cases at each time point instantly after ADV administration due to LAM antiviral failure, more patients had a decrease in HBV DNA > 2 log10 IU/mL in the vaccine group at week 12 and 28 after EOT compared with the control group. More patients with undetectable HBV DNA at week 28 after EOT in the vaccine group were also observed. Among patients with a viral load < 1000 copies/mL at week 12, more patients achieved HBeA g seroconversion in the vaccine group than among controls at week 36 after EOT, as well as less virological breakthrough and YMDD mutations. CONCLUSION The primary endpoint was not achieved using the HBV DNA vaccine. The HBV DNA vaccine could only be beneficial in subjects that have achieved initial virological response under LAM chemotherapy.
文摘The prevalence of hepatitis C virus(HCV) infection in patients on maintenance hemodialysis(MHD) is relatively higher than those without MHD. Chronic HCV infection detrimentally affects the life quality and expectancy, leads to renal transplant rejection, and increases the mortality of MHD patients. With the application of erythropoietin to improve uremic anemia and avoid blood transfusion, the new HCV infections during MHD in recent years are mainly caused by the lack of stringent universal precautions. Strict implementation of universal precautions for HCV transmission has led to markedly decreased HCV infections in many hemodialysis units, but physicians still should be alert for the antiHCV negative HCV infection and occult HCV infection in MHD patients. Standard interferon alpha and pegylated interferon alpha monotherapies at a reduced dose arecurrently the main treatment strategies for MHD patients with active HCV replication, but how to increase the sustained virological response and decrease the side effects is the key problem. IFNα-free treatments with two or three direct-acting antivirals without ribavirin in MHD patients are waiting for future investigations.
基金supported by the National Basic Research Program of China(Grant Nos.2014CB339802 and 2015CB755403)the National Natural Science Foundation of China(Grant Nos.61675146,61275102,and 61271066)the Science and Technology Support Program of Tianjin,China(Grant No.14ZCZDGX00030)
文摘Broadband terahertz（THz） atmospheric transmission characteristics from 0 to 8 THz are theoretically simulated based on a standard Van Vleck–Weisskopf line shape, considering 1696 water absorption lines and 298 oxygen absorption lines.The influences of humidity, temperature, and pressure on the THz atmospheric absorption are analyzed and experimentally verified with a Fourier transform infrared spectrometer（FTIR） system, showing good consistency. The investigation and evaluation on high-frequency atmospheric windows are good supplements to existing data in the low-frequency range and lay the foundation for aircraft-based high-altitude applications of THz communication and radar.
文摘Objective To investigate the association between HBV genotypes and characteristics of rt A181 mutation. Methods Total of 85 chronic hepatitis B(CHB) patients who appeared rt A181 mutation after nucleos(t)ide analogs(NAs) therapy were enrolled in this study. Levels of serum ALT, AST, HBV DNA and HBs Ag titers were monitored during therapy. HBV reverse transcriptase genes were amplified and sequenced to identify genotypes and resistance mutations. Virions and HBs Ag in Hep G2 cell with rt A181 mutation were also compared between genotypes B and C. Results The majority of sera contained HBV genotypes B(15.7%) and C(84.3%). There were no significant difference of rt A181 mutant patterns between genotypes(P > 0.05). After emergence of rt A181 mutation, serum ALT, AST, HBV DNA levels and HBs Ag titers were decreased than that at baseline(P < 0.05), while these characteristics were not different between genotypes B and C(P > 0.05). In cellular experiment, there were no significant differences between genotypes B and C not only in HBV virions but also in HBs Ag titres(P > 0.05). Conclusions No differences of clinical characteristics and cellular results were found in rt A181 mutation of HBV genotypes B and C.
