Background and Aims:Currently,insufficient clinical data are available to address whether low-level viremia(LLV)observed during antiviral treatment will adversely affect the clinical outcome or whether treatment strat...Background and Aims:Currently,insufficient clinical data are available to address whether low-level viremia(LLV)observed during antiviral treatment will adversely affect the clinical outcome or whether treatment strategies should be altered if LLV occurs.This study compared the clinical out-comes of patients with a maintained virological response(MVR)and patients who experienced LLV and their treatment strategies.Methods:A retrospective cohort of 674 patients with chronic hepatitis B virus(HBV)infection who received antiviral treatment for more than 12 months was analyzed for the development of end-stage liver disease and treatment strategies during the follow-up period.End-stage liver disease included decompensated liver cirrhosis and hepatocellular carcinoma(HCC).Results:During a median 42-month follow-up,end-stage liver disease developed more frequently in patients who experienced LLV than in those who experienced MVR(7.73%and 15.85%vs.0.77%and 5.52%at 5 and 10 years,respectively;p=0.000).The trend was consistent after propensity score matching.In the high-risk group of four HCC risk models,LLV patients had a higher risk of HCC development(p<0.05).By Cox proportional hazard model analysis,LLV was an independent risk factor for end-stage liver disease and HCC(hazard ratio[HR]=6.280,confidence interval[CI]=2.081-18.951,p=0.001;HR=5.108,CI=1.392-18.737,respectively;p=0.014).Patients achieved a lower rate of end-stage liver disease by adjusting treatment compared to continuing the original treatment once LLV occurred(p<0.05).Conclusions:LLV is an independent risk factor for end-stage liver disease and HCC,and treatment adjustments can be considered.展开更多
BACKGROUND: There are 8 well-documented genotypes of hepatitis B virus (HBV) at this time point. Genotyping can be accomplished based on a partial sequence of hepatitis B virus (HBV) genome such as the pre-S or S gene...BACKGROUND: There are 8 well-documented genotypes of hepatitis B virus (HBV) at this time point. Genotyping can be accomplished based on a partial sequence of hepatitis B virus (HBV) genome such as the pre-S or S gene. Several methods have been developed and used for HBV genotyping including direct sequencing, restriction fragment length polymorphism, line probe assay and enzyme-linked immunoassay. Recently, a novel, rapid and cost-effective genotyping method based on PCR amplification assay using type-specific primers that can identify all six major genotypes has been developed. This study was undertaken to characterise HBV genotypes and investigate the association between the prevalence of different genotypes and the severity of HBV-induced liver diseases. METHODS: Serum samples from carriers of HBV and patients with HBV-related liver diseases from Zhejiang Province were screened for viral serological markers using commercially available radioimmunoassay (RIA) and enzyme linked immunosorbent assay (ELISA) kits. Serum HBV DNA load was determined by real-time detection PCR. A type-specific primer based the nested-PCR method was employed in the HBV genotyping. The genotype results obtained were confirmed by direct sequencing of nested PCR amplicons of the pre-S region. Ten samples of each genotype (B and C) were sequenced. RESULTS: The survey on a cohort of 125 HBV carriers in and around Hangzhou City, Zhejiang Province showed the existence of HBV genotypes A (0.8%), B (48%), C (40.8%), D (0.8%), mixed B and C (9.6%) and an absence of E and F genotypes. Distribution of HBV genotypes in patients with liver diseases revealed a statistically insignificant higher prevalence of genotype B in mild chronic hepatitis (CH). Among the three genotypes B, C and mixed B/C infections 11 (73.3%), 3 (20%) and 1 (6.7%), (P< 0.05), respectively in subjects with moderate CH, genotype B was significantly predominant. The infection patterns for genotypes B, C and B/C mixed in (i) liver cirrhosis (LC) 4 (23.5%), 10 (58.8%) and3 (17.7%)展开更多
Low-level viremia(LLV)was defined as persistent or intermittent episodes of detectable hepatitis B virus(HBV)DNA(<2000 IU/mL,detection limit of 10 IU/mL)after 48 weeks of antiviral treatment.Effective antiviral the...Low-level viremia(LLV)was defined as persistent or intermittent episodes of detectable hepatitis B virus(HBV)DNA(<2000 IU/mL,detection limit of 10 IU/mL)after 48 weeks of antiviral treatment.Effective antiviral therapies for chronic hepatitis B(CHB)patients,such as entecavir(ETV),tenofovir disoproxil fumarate(TDF),and tenofovir alafenamide(TAF),have been shown to inhibit the replication of HBV DNA and prevent liver-related complications.However,even with long-term antiviral therapy,there are still a number of patients with persistent or intermittent LLV.At present,the research on LLV to address whether adversely affect the clinical outcome is limited,and the follow-up treatment for these patients is open to question.At the same time,the mechanism of LLV is not clear.In this review,we summarize the incidence of LLV,the association between LLV and long-term outcomes,possible mechanisms,and management strategies in these patient populations.展开更多
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:Cytokine release by macrophages critically determines the type of immune response to an antigen.Therefore,we studied hepatitis C virus(HCV)-specific induction of interleukins-1β,-10,-12(IL-1β,IL-10,IL-12),and tu...AIM:Cytokine release by macrophages critically determines the type of immune response to an antigen.Therefore,we studied hepatitis C virus(HCV)-specific induction of interleukins-1β,-10,-12(IL-1β,IL-10,IL-12),and tumor necrosis factor-α(TNF-α)in monocytes. METHODS:Intracallular cytokine expression was studied by flow cytometry in 23 patients with chronic hepatitis C,14 anti-HCV seropositives without viremia and 11 controls after stimulation of peripheral blood mononuclear calls with recombinant core,NS3,NS4,NSSa and NSSb proteins. RESULTS:Patients with HCV viremia revealed greater spontaneous expression of IL-1β,TNF-α,and IL-10. Furthermore,greater than twofold higher IL-10 expression was induced by the HCV antigens in chronic hepatitis C than in the other two groups(P<0.05).In contrast,neither IL- 12 nor TNF-α was induced preferentially. CONCLUSION:In chronic hepatitis C antigen-specific cytokine induction in monocytes is apparently shifted towards predominant IL-10 induction-not counterbalanced by antiviral type 1 cytokines.This may contribute to persistent viral replication.展开更多
Objective： To review the recent literatures related to the factors associated with the size of the HIV reservoir and their clinical significance. Data Sources： Literatures related to the size of HIV DNA was collecte...Objective： To review the recent literatures related to the factors associated with the size of the HIV reservoir and their clinical significance. Data Sources： Literatures related to the size of HIV DNA was collected from PubMed published from 1999 to June 2016. Study Selection： All relevant articles on the HIV DNA and reservoir were collected and reviewed, with no limitation of study design. Results： The composition and development of the HIV- 1 DNA reservoir in either treated or untreated patients is determined by integrated mechanism comprising viral characteristics, immune system, and treatment strategies. The HIV DNA reservoir is a combination of latency and activity. The residual viremia from the stochastic activation of the reservoir acts as the fuse, continuing to stimulate the immune system to maintain the activated microenvironment for the rebound of competent virus once treatment with antiretroviral therapy is discontinued. Conclusion： The size of the HIV-1 DNA pool and its composition has great significance in clinical treatment and disease progression.展开更多
基金the National Science and Technology Major Project of China(2017ZX10202203-007,2017ZX10202203-008 and 2018ZX10302-206-003)the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University N/A and Guizhou Science and Technology Project QiankeheJC(2016)1086.
文摘Background and Aims:Currently,insufficient clinical data are available to address whether low-level viremia(LLV)observed during antiviral treatment will adversely affect the clinical outcome or whether treatment strategies should be altered if LLV occurs.This study compared the clinical out-comes of patients with a maintained virological response(MVR)and patients who experienced LLV and their treatment strategies.Methods:A retrospective cohort of 674 patients with chronic hepatitis B virus(HBV)infection who received antiviral treatment for more than 12 months was analyzed for the development of end-stage liver disease and treatment strategies during the follow-up period.End-stage liver disease included decompensated liver cirrhosis and hepatocellular carcinoma(HCC).Results:During a median 42-month follow-up,end-stage liver disease developed more frequently in patients who experienced LLV than in those who experienced MVR(7.73%and 15.85%vs.0.77%and 5.52%at 5 and 10 years,respectively;p=0.000).The trend was consistent after propensity score matching.In the high-risk group of four HCC risk models,LLV patients had a higher risk of HCC development(p<0.05).By Cox proportional hazard model analysis,LLV was an independent risk factor for end-stage liver disease and HCC(hazard ratio[HR]=6.280,confidence interval[CI]=2.081-18.951,p=0.001;HR=5.108,CI=1.392-18.737,respectively;p=0.014).Patients achieved a lower rate of end-stage liver disease by adjusting treatment compared to continuing the original treatment once LLV occurred(p<0.05).Conclusions:LLV is an independent risk factor for end-stage liver disease and HCC,and treatment adjustments can be considered.
文摘BACKGROUND: There are 8 well-documented genotypes of hepatitis B virus (HBV) at this time point. Genotyping can be accomplished based on a partial sequence of hepatitis B virus (HBV) genome such as the pre-S or S gene. Several methods have been developed and used for HBV genotyping including direct sequencing, restriction fragment length polymorphism, line probe assay and enzyme-linked immunoassay. Recently, a novel, rapid and cost-effective genotyping method based on PCR amplification assay using type-specific primers that can identify all six major genotypes has been developed. This study was undertaken to characterise HBV genotypes and investigate the association between the prevalence of different genotypes and the severity of HBV-induced liver diseases. METHODS: Serum samples from carriers of HBV and patients with HBV-related liver diseases from Zhejiang Province were screened for viral serological markers using commercially available radioimmunoassay (RIA) and enzyme linked immunosorbent assay (ELISA) kits. Serum HBV DNA load was determined by real-time detection PCR. A type-specific primer based the nested-PCR method was employed in the HBV genotyping. The genotype results obtained were confirmed by direct sequencing of nested PCR amplicons of the pre-S region. Ten samples of each genotype (B and C) were sequenced. RESULTS: The survey on a cohort of 125 HBV carriers in and around Hangzhou City, Zhejiang Province showed the existence of HBV genotypes A (0.8%), B (48%), C (40.8%), D (0.8%), mixed B and C (9.6%) and an absence of E and F genotypes. Distribution of HBV genotypes in patients with liver diseases revealed a statistically insignificant higher prevalence of genotype B in mild chronic hepatitis (CH). Among the three genotypes B, C and mixed B/C infections 11 (73.3%), 3 (20%) and 1 (6.7%), (P< 0.05), respectively in subjects with moderate CH, genotype B was significantly predominant. The infection patterns for genotypes B, C and B/C mixed in (i) liver cirrhosis (LC) 4 (23.5%), 10 (58.8%) and3 (17.7%)
基金the National Science and Technology Major Project of China(Nos 2017ZX10202203-007,2017ZX10202203-008,and 2018ZX10302-206-003).
文摘Low-level viremia(LLV)was defined as persistent or intermittent episodes of detectable hepatitis B virus(HBV)DNA(<2000 IU/mL,detection limit of 10 IU/mL)after 48 weeks of antiviral treatment.Effective antiviral therapies for chronic hepatitis B(CHB)patients,such as entecavir(ETV),tenofovir disoproxil fumarate(TDF),and tenofovir alafenamide(TAF),have been shown to inhibit the replication of HBV DNA and prevent liver-related complications.However,even with long-term antiviral therapy,there are still a number of patients with persistent or intermittent LLV.At present,the research on LLV to address whether adversely affect the clinical outcome is limited,and the follow-up treatment for these patients is open to question.At the same time,the mechanism of LLV is not clear.In this review,we summarize the incidence of LLV,the association between LLV and long-term outcomes,possible mechanisms,and management strategies in these patient populations.
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a generous grant of the Joachim Kuhlinann AIDS-Stiftung
文摘AIM:Cytokine release by macrophages critically determines the type of immune response to an antigen.Therefore,we studied hepatitis C virus(HCV)-specific induction of interleukins-1β,-10,-12(IL-1β,IL-10,IL-12),and tumor necrosis factor-α(TNF-α)in monocytes. METHODS:Intracallular cytokine expression was studied by flow cytometry in 23 patients with chronic hepatitis C,14 anti-HCV seropositives without viremia and 11 controls after stimulation of peripheral blood mononuclear calls with recombinant core,NS3,NS4,NSSa and NSSb proteins. RESULTS:Patients with HCV viremia revealed greater spontaneous expression of IL-1β,TNF-α,and IL-10. Furthermore,greater than twofold higher IL-10 expression was induced by the HCV antigens in chronic hepatitis C than in the other two groups(P<0.05).In contrast,neither IL- 12 nor TNF-α was induced preferentially. CONCLUSION:In chronic hepatitis C antigen-specific cytokine induction in monocytes is apparently shifted towards predominant IL-10 induction-not counterbalanced by antiviral type 1 cytokines.This may contribute to persistent viral replication.
文摘Objective： To review the recent literatures related to the factors associated with the size of the HIV reservoir and their clinical significance. Data Sources： Literatures related to the size of HIV DNA was collected from PubMed published from 1999 to June 2016. Study Selection： All relevant articles on the HIV DNA and reservoir were collected and reviewed, with no limitation of study design. Results： The composition and development of the HIV- 1 DNA reservoir in either treated or untreated patients is determined by integrated mechanism comprising viral characteristics, immune system, and treatment strategies. The HIV DNA reservoir is a combination of latency and activity. The residual viremia from the stochastic activation of the reservoir acts as the fuse, continuing to stimulate the immune system to maintain the activated microenvironment for the rebound of competent virus once treatment with antiretroviral therapy is discontinued. Conclusion： The size of the HIV-1 DNA pool and its composition has great significance in clinical treatment and disease progression.
