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
Hepatitis B virus(HBV)infection is a global public health issue.Interferon-α(IFN-α)treatment has been used to treat hepatitis B for over 20 years,but fewer than 5%of Asians receiving IFN-αtreatment achieve function...Hepatitis B virus(HBV)infection is a global public health issue.Interferon-α(IFN-α)treatment has been used to treat hepatitis B for over 20 years,but fewer than 5%of Asians receiving IFN-αtreatment achieve functional cure.Thus,IFN-αretreatment has been introduced to enhance antiviral function.In recent years,immune-related studies have found that the complex interactions between immune cells and cytokines could modulate immune response networks,including both innate and adaptive immunity,triggering immune responses that control HBV replication.However,heterogeneity of the immune system to control HBV infection,particularly HBV-specific CD8^(+)T cell heterogeneity,has consequential effects on T cell-based immunotherapy for treating HBV infection.Altogether,the host’s genetic variants,negative-feedback regulators and HBV components affecting the immune system's ability to control HBV.In this study,we reviewed the literature on potential immune mechanisms affecting the immune control of HBV and the clinical effects of IFN-αtreatment and retreatment.展开更多
Gastric cancer(GC)is the fourth leading cause of cancer-related death.The occurrence and development of GC is a complex process involving multiple biological mechanisms.Although traditional regulation modulates molecu...Gastric cancer(GC)is the fourth leading cause of cancer-related death.The occurrence and development of GC is a complex process involving multiple biological mechanisms.Although traditional regulation modulates molecular functions related to the occurrence and development of GC,the comprehensive mechanisms remain unclear.Ultraconserved region(UCR)refers to a genome sequence that is completely conserved in the homologous regions of the human,rat and mouse genomes,with 100%identity,without any insertions or deletions,and often located in fragile sites and tumour-related genes.The transcribed UCR(T-UCR)is transcribed from the UCR and is a new type of long noncoding RNA.Recent studies have found that the expression level of T-UCRs changes during the occurrence and development of GC,revealing a new mechanism underlying GC.Therefore,this article aims to review the relevant research on T-UCRs in GC,as well as the function of T-UCRs and their regulatory role in the occurrence and development of GC,to provide new strategies for GC diagnosis and treatment.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.
文摘Hepatitis B virus(HBV)infection is a global public health issue.Interferon-α(IFN-α)treatment has been used to treat hepatitis B for over 20 years,but fewer than 5%of Asians receiving IFN-αtreatment achieve functional cure.Thus,IFN-αretreatment has been introduced to enhance antiviral function.In recent years,immune-related studies have found that the complex interactions between immune cells and cytokines could modulate immune response networks,including both innate and adaptive immunity,triggering immune responses that control HBV replication.However,heterogeneity of the immune system to control HBV infection,particularly HBV-specific CD8^(+)T cell heterogeneity,has consequential effects on T cell-based immunotherapy for treating HBV infection.Altogether,the host’s genetic variants,negative-feedback regulators and HBV components affecting the immune system's ability to control HBV.In this study,we reviewed the literature on potential immune mechanisms affecting the immune control of HBV and the clinical effects of IFN-αtreatment and retreatment.
基金Supported by National Natural Science Foundation of China,No.81672379 and No.81101858Natural Science Foundation of Shandong Province,China,No.ZR2016HM16.
文摘Gastric cancer(GC)is the fourth leading cause of cancer-related death.The occurrence and development of GC is a complex process involving multiple biological mechanisms.Although traditional regulation modulates molecular functions related to the occurrence and development of GC,the comprehensive mechanisms remain unclear.Ultraconserved region(UCR)refers to a genome sequence that is completely conserved in the homologous regions of the human,rat and mouse genomes,with 100%identity,without any insertions or deletions,and often located in fragile sites and tumour-related genes.The transcribed UCR(T-UCR)is transcribed from the UCR and is a new type of long noncoding RNA.Recent studies have found that the expression level of T-UCRs changes during the occurrence and development of GC,revealing a new mechanism underlying GC.Therefore,this article aims to review the relevant research on T-UCRs in GC,as well as the function of T-UCRs and their regulatory role in the occurrence and development of GC,to provide new strategies for GC diagnosis and treatment.
