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
We describe an observational study of clinical, virologic and drug resistance profiles in HIV-positive antiretroviral adherent subjects with stable low level viremia (LLV) 50 - 1000 copies/mL for more than 12 months. ...We describe an observational study of clinical, virologic and drug resistance profiles in HIV-positive antiretroviral adherent subjects with stable low level viremia (LLV) 50 - 1000 copies/mL for more than 12 months. Subjects were followed from time of first detectable viral load (VL). In total, 102 episodes of LLV were detected among 80 individuals. The median (mean, range) HIV copy number at genotyping was 250 (486, - 3900) copies/mL after 14 (17.9, 0 - 58) months of LLV. Few patients maintained LLV for the entire 9 years period of observation, with half (52%) experiencing viremic progression following a stable period of LLV either spontaneously or after treatment interruption or failed regimen intensification. In the setting of prolonged periods of sustained LLV, mean duration 22 (range 8 - 106) months, drug resistance (DR) was almost universal. Resistance to ≥1 on-treatment drugs was defined in 97% of specimens and DR to all drugs in the treatment regimen in over half of all patients. Evolution of DR mutations during the period of LLV was observed in 20/28 (71%) subjects with specimens available for follow-up testing. This evolution was associated with viremic progression to levels >1000 copies/mL (p = 0.03). Our data suggest that DR present in patients with LLV is likely to impact long term clinical outcomes, highlighting the importance of optimizing techniques to detect the presence of drug resistant HIV in the setting of LLV and the need for larger prospective studies to assess the emergence of DR in the setting of sustained LLV and the impact of this DR on treatment outcomes.展开更多
BACKGROUND Human immunodeficiency virus type 1(HIV-1)infection is characterized by persistent systemic inflammation and immune activation,even in patients receiving effective antiretroviral therapy(ART).Converging dat...BACKGROUND Human immunodeficiency virus type 1(HIV-1)infection is characterized by persistent systemic inflammation and immune activation,even in patients receiving effective antiretroviral therapy(ART).Converging data from many cross-sectional studies suggest that gut microbiota(GM)changes can occur throughout including human immunodeficiency virus(HIV)infection,treated by ART;however,the results are contrasting.For the first time,we compared the fecal microbial composition,serum and fecal microbial metabolites,and serum cytokine profile of treatment-na?ve patients before starting ART and after reaching virological suppression,after 24 wk of ART therapy.In addition,we compared the microbiota composition,microbial metabolites,and cytokine profile of patients with CD4/CD8 ratio<1(immunological non-responders[INRs])and CD4/CD8>1(immunological responders[IRs]),after 24 wk of ART therapy.AIM To compare for the first time the fecal microbial composition,serum and fecal microbial metabolites,and serum cytokine profile of treatment-na?ve patients before starting ART and after reaching virological suppression(HIV RNA<50 copies/m L)after 24 wk of ART.METHODS We enrolled 12 treatment-na?ve HIV-infected patients receiving ART(mainly based on integrase inhibitors).Fecal microbiota composition was assessed through next generation sequencing.In addition,a comprehensive analysis of a blood broad-spectrum cytokine panel was performed through a multiplex approach.At the same time,serum free fatty acid(FFA)and fecal short chain fatty acid levels were obtained through gas chromatography-mass spectrometry.RESULTS We first compared microbiota signatures,FFA levels,and cytokine profile before starting ART and after reaching virological suppression.Modest alterations were observed in microbiota composition,in particular in the viral suppression condition,we detected an increase of Ruminococcus and Succinivibrio and a decrease of Intestinibacter.Moreover,in the same condition,we also observed augmented levels of serum propionic and butyric acids.Contemporarily,a reduction of serum IP-10 and an increase of IL-8 levels were detected in the viral suppression condition.In addition,the same components were compared between IRs and INRs.Concerning the microflora population,we detected a reduction of Faecalibacterium and an increase of Alistipes in INRs.Simultaneously,fecal isobutyric,isovaleric,and 2-methylbutyric acids were also increased in INRs.CONCLUSION Our results provided an additional perspective about the impact of HIV infection,ART,and immune recovery on the"microbiome-immunity axis"at the metabolism level.These factors can act as indicators of the active processes occurring in the gastrointestinal tract.Individuals with HIV-1 infection,before ART and after reaching virological suppression with 24 wk of ART,displayed a microbiota with unchanged overall bacterial diversity;moreover,their systemic inflammatory status seems not to be completely restored.In addition,we confirmed the role of the GM metabolites in immune reconstitution.展开更多
The pathophysiological mechanisms that underlie the progression of human immunodeficiency virus-1(HIV-1) disease to full-blown AIDS are not well understood. Findings suggest that, during HIV-1 infection, plasma lipopo...The pathophysiological mechanisms that underlie the progression of human immunodeficiency virus-1(HIV-1) disease to full-blown AIDS are not well understood. Findings suggest that, during HIV-1 infection, plasma lipopolysaccharide(LPS) levels, which are used as an indicator of microbial translocation(MT), are elevated throughout the acute and chronic phases of HIV-1 disease. The translocation of bacterial products through the damaged gastrointestinal barrier into the systemic circulation has been described as a driver of immune activation. In contrast, comorbidities that are associated with HIV-1 infection have been attributed to chronic inflammation and immune system dysfunction secondary to MT or low-level HIV-1 replication in plasma and cell reservoirs. Moreover, accelerated aging is significantly associated with chronic inflammation, immune activation, and immune senescence. In this review, we aimed to investigate the role of inflammation as a pivotal marker in the pathogenesis of HIV-1 disease. We will discuss the key features of chronic inflammation and immune activation that are observed during the natural course of the disease and those features that are detected in c ART-modified infection. The review will focus on the following aspects of HIV-1 infection:(1) MT;(2) the role of residual viremia; and(3) "immune senescence" or "inflammaging." Many questions remain unanswered about the potential mechanisms that are involved in HIV-1 pathogenesis. Further studies are needed to better investigate the mechanisms that underlie immune activation and their correlation with HIV-1 disease progression.展开更多
BACKGROUND Whether patients with compensated cirrhosis and low-level viremia(LLV)of hepatitis B should receive antiviral therapy(AVT)is still controversial,and published results are inconsistent.AIM To investigate the...BACKGROUND Whether patients with compensated cirrhosis and low-level viremia(LLV)of hepatitis B should receive antiviral therapy(AVT)is still controversial,and published results are inconsistent.AIM To investigate the link between LLV in compensated cirrhosis and prognosis concerning hepatocellular carcinoma(HCC),decompensation,and liver-related events.METHODS The PubMed,EMBASE,and Cochrane Library databases were searched up to March 5,2023.Outcomes of interest were assessed by pooled hazard ratios(HRs).The study was registered with PROSPERO(CRD42023405345).RESULTS Six cohort studies representing 3155 patients were included.Compared with patients with undetectable HBV DNA,patients with LLV was associated with increased risk of HCC(HR:2.06,95%CI:1.36-3.13;Q-statistic-P=0.07,I^(2)=51%)regardless of receiving AVT or not(AVT group:HR:3.14;95%CI:1.73-5.69;Qstatistic-P=0.60,I2=0%;un-AVT group:HR:1.73,95%CI:1.09-2.76;Q-statistic-P=0.11,I2=50%).The pooled results showed no statistical association between LLV and decompensation of cirrhosis(HR:2.06,95%CI:0.89-4.76;Q-statistic-P=0.04,I2=69%),and liver-related events(HR:1.84,95%CI:0.92-3.67;Q-statistic-P=0.03,I2=72%),respectively.Grading of Recommendations Assessment,Development and Evaluation assessment indicated moderate certainty for HCC,very low certainty for decompensation of cirrhosis and liver-related clinical events.CONCLUSION LLV in compensated cirrhotic patients is associated with increased risk of HCC,higher tendency for hepatic decompensation and liver-related events.Closer screening of HCC should be conducted in this population.展开更多
BACKGROUND Data that assess maternal and infant outcomes in hepatitis C virus(HCV)-infected mothers are limited.AIM To investigate the frequency of complications and the associated risk factors.METHODS We performed a ...BACKGROUND Data that assess maternal and infant outcomes in hepatitis C virus(HCV)-infected mothers are limited.AIM To investigate the frequency of complications and the associated risk factors.METHODS We performed a cohort study to compare pregnancy and fetal outcomes of HCVviremic mothers with those of healthy mothers.Risk factors were analyzed with logistic regression.RESULTS Among 112 consecutive HCV antibody-positive mothers screened,we enrolled 79 viremic mothers.We randomly selected 115 healthy mothers from the birth registry as the control.Compared to healthy mothers,HCV mothers had a significantly higher frequency of anemia[2.6%(3/115)vs 19.0%(15/79),P<0.001]during pregnancy,medical conditions that required caesarian section[27.8%(32/115)vs 48.1%(38/79),P=0.004],and nuchal cords[9.6%(11/115)vs 34.2%(27/79),P<0.001].In addition,the mean neonatal weight in the HCV group was significantly lower(3278.3±462.0 vs 3105.1±459.4 gms;P=0.006),and the mean head circumference was smaller(33.3±0.6 vs 33.1±0.7 cm;P=0.03).In a multivariate model,HCV-infected mothers were more likely to suffer anemia[adjusted odds ratio(OR):18.1,95%confidence interval(CI):4.3-76.6],require caesarian sections(adjusted OR:2.6,95%CI:1.4-4.9),and have nuchal cords(adjusted OR:5.6,95%CI:2.4-13.0).Their neonates were also more likely to have smaller head circumferences(adjusted OR:2.1,95%CI:1.1-4.3)and lower birth weights than the average(≤3250 gms)with an adjusted OR of 2.2(95%CI:1.2-4.0).The vertical transmission rate was 1%in HCV-infected mothers.CONCLUSION Maternal HCV infections may associate with pregnancy and obstetric complications.We demonstrated a previously unreported association between maternal HCV viremia and a smaller neonatal head circumference,suggesting fetal growth restriction.展开更多
HIV infection is an emerging health issue in Libya, particularly among young adults. Human cytomegalovirus (HCMV) is a prevalent infectious agent that presents with subclinical and fatal diseases in immunosuppressed i...HIV infection is an emerging health issue in Libya, particularly among young adults. Human cytomegalovirus (HCMV) is a prevalent infectious agent that presents with subclinical and fatal diseases in immunosuppressed individuals including HIV-infected individuals. Although the impact of HCMV infection in HIV-positive patients is well documented in several regions, epidemiologic estimates concerning HCMV co-infection among HIV-infected individuals remain limited in Libya. Hence, this cross-sectional study was undertaken to derive data regarding the prevalence of active HCMV viremia among HIV-infected individuals undergoing antiretroviral therapy (ART) from Libya. A total of 90 consented HIV-infected subjects followed by the National Center for Disease Control (NCDC) of Benghazi/Libya were recruited in this study and investigated for HCMV-IgG, HCMV-IgM specific antibodies, detection of HCMV lower matrix phosphoprotein (pp65) antigen, and detection of HCMV-DNA using qPCR to assess the prevalence of HCMV viremia. We determined that 77 (85.56%) of subjects were seropositive for HCMV-IgG antibodies, whereas the seropositivity for HCMV-IgM was 3.33% (3/90 subjects). Our results also revealed that 4.44% (4/90) of participants had viral antigenemia based on the laboratory diagnosis of HCMV-pp65. Regarding the PCR, we were able to detect the DNA of HCMV only in 3/90 subjects (3.33%) suggesting an active viremic condition. The detection of HCMV DNA along with the HCMV-pp65 in HIV-positive individuals highlights the necessity of early diagnosis to manage the progression of the disease. Furthermore, we highly recommend the use of anti-HCMV therapy in viremic individuals in combination with ART to reduce the burden of HCMV complications.展开更多
[Objective]The paper was to develop a rapid method for the detection of spring Viremia of carp virus(SVCV).[Method]The specific primers were designed by targeting the G gene of SVCV.The recombinase polymerase amplific...[Objective]The paper was to develop a rapid method for the detection of spring Viremia of carp virus(SVCV).[Method]The specific primers were designed by targeting the G gene of SVCV.The recombinase polymerase amplification(RPA)assay for detecting SVCV was estab-lished by optimizing the reaction conditions.The optimal amplification temperature of RPA assay was 30℃,and the test could be finished within 20 min.[Result]The method was specific with no cross-reaction with other common fish infectious viruses.Sensitivity test showed that the lowest detection limit of the method was 89.2 copies/μL,higher than that of traditional RT-PCR.Moreover,a total of 80 clinical samples were detected by RPA and RT-PCR,respectively.The weak positive samples tested by RT-PCR could be detectable with RPA,indicating that RPA assay could be used in clinical detection.[Conclusion]The method established is rapid,simple,specific and sensitive for testing SVCV,and it will be widely used in grassroots laboratory and on-site inspection.展开更多
Summary What is already known about this topic?Human immunodeficiency virus(HIV)low-level viremia(LLV)during antiretroviral therapy(ART)occurs frequently in Dehong Dai and Jingpo Autonomous Prefecture,Yunnan Province....Summary What is already known about this topic?Human immunodeficiency virus(HIV)low-level viremia(LLV)during antiretroviral therapy(ART)occurs frequently in Dehong Dai and Jingpo Autonomous Prefecture,Yunnan Province.What is added by this report?Among people living with HIV who achieved virological success[viral load(VL)<1,000 copies/mL]after initiating ART in Dehong Prefecture,Southwest China,17.6%experienced first-year LLV of 50–999 copies/mL First-year LLV emerged as an independent risk factor for subsequent viral non-suppression compared with participants maintaining first-year VL<50 copies/mL.展开更多
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
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
Background and aim:Several effective antiviral drugs are now available;however,the risk of liver-related complications is still present.Low-level viremia(LLV),defined as a hepatitis B virus(HBV)deoxy-ribonucleic acid(...Background and aim:Several effective antiviral drugs are now available;however,the risk of liver-related complications is still present.Low-level viremia(LLV),defined as a hepatitis B virus(HBV)deoxy-ribonucleic acid(DNA)load lower than 2000 IU/mL,is one of the major factors responsible for these complications.It has been reported that 22.7e43.1%of patients with HBV experience LLV.Herein,we aimed to explore the risk factors for very LLV(VLLV)during antiviral treatment.Methods:We collected data of patients with chronic hepatitis B(CHB)who received nucleos(t)ide analog treatment from October 2016 to April 2021.VLLV was defined as an HBV DNA load of 9e20 IU/mL.A total of 139 patients with LLV were matched with 139 patients with a sustained virological response at a 1:1 ratio according to age and gender.Results:Seropositivity rates for hepatitis B e antigen(HBeAg)(45.3%vs.17.3%,P<0.001)and hepatitis B surface antigen(HBsAg,3.11±0.68 lg IU/mL vs.2.54±1.04 lg IU/mL,P<0.001)and alanine amino-transferase levels(30.34±15.08 U/L vs.26.15±16.66 U/L,P¼0.040)in the two groups were significantly different.The multivariate analysis showed that both HBeAg seropositivity(adjusted odd ratio(aOR),3.63;95% confidence interval(CI):1.98±6.64;P<0.001)and HBsAg levels(aOR,2.21;95% CI:1.53±3.20;P<0.001)are independent risk factors for VLLV.During the multivariate analysis in the subgroup of HBeAg-positive patients,male gender(aOR,3.68;95% CI:1.23±10.76;P=0.017)and high HBsAg(aOR,4.86;95%CI:1.73e13.64;P¼0.003)levels were significantly correlated with VLLV.However,this was not the case in HBeAg-negative patients(P>0.050).HBeAg seropositivity(aOR,5.08;95% CI:2.15±12.02;P<0.001 vs.aOR,2.78;95% CI:1.16±7.00;P=0.022)and HBsAg levels(aOR,2.75;95% CI:1.41e5.37;P=0.003 vs.aOR,2.10;95% CI:1.27±3.46;P=0.004)significantly increased the risk of VLLV,irrespective of the age group.Both HBsAg(area under the receiver operating characteristic curve(AUC),0.681;95% CI:0.623±0.736;P<0.001)and HBeAg(AUC,0.640;95% CI:0.581±0.697;P<0.001)had certain pre-dictive value for VLLV.Conclusion:HBeAg seropositivity and higher HBsAg levels were not only risk factors for VLLV but also predicted its occurrence.When a patient with CHB remains HBeAg seropositive with high HBsAg levels after antiviral treatment for 48 weeks,emphasis should be placed on the potential occurrence of VLLV,warranting the use of highly sensitive HBV DNA detection methods.展开更多
BACKGROUND Sustained viral load(VL)suppression is an important indicator of successful treatment among people living with human immunodeficiency virus(HIV).AIM To assess trends of different VL outcomes before and afte...BACKGROUND Sustained viral load(VL)suppression is an important indicator of successful treatment among people living with human immunodeficiency virus(HIV).AIM To assess trends of different VL outcomes before and after adoption of the Treat All policy among people living with HIV in Rwanda.METHODS Between 2014 and 2017,VL suppression[VL suppression(VLS)<200 copies/mL]was measured among people living with HIV from 28 healthcare facilities in Rwanda.Participant VL was measured at 6 months,18 months,and 30 months.The unit of analysis was visit-pair,with subjects across four visit-pair categories:(1)Sustained VL suppression(VL<200 copies/mL at two consecutive visits);(2)Persistent viremia(VL≥200 copies/mL at two consecutive visits);(3)Viral rebound(VL<200 copies/mL at prior visit only);and(4)Newly suppressed(VL<200 copies/mL at subsequent visit only).Poisson regression models with generalized estimating equations were used to estimate adjusted incidence risk ratio(aIRR)and 95%confidence intervals(CIs)for factors associated with sustained VLS.To handle missing data,multiple imputations was performed.RESULTS A total of 634 participants contributed 973 visit-pairs(295 single pairs and 339 double pairs).The median age was 37 years(interquartile range:32-43 years).The incidence rates of sustained VLS,persistent viremia,viral rebound,and new suppression were 85.2%,4.3%,4.6%,and 5.7%,respectively.Young individuals aged 18-24 years had higher incidence of viral rebound compared to those 25 years or older(14.8%vs 4.3%;P=0.011).Of the visit-pairs that had sustained VLS during the first two visits(49.8%;n=485),56.7%exhibited sustained VLS throughout follow-up.Compared to having no education,having at least primary education was associated with an increased likelihood of sustained VLS(aIRR=1.09;95%CI:1.01-1.17).Those who presented with advanced HIV disease at baseline had a 12%reduced likelihood of sustained VLS(aIRR=0.88;95%CI:0.79-0.99).Achieving sustained VLS did not differ before or after adoption of the Treat All policy.When the analysis was repeated on imputed datasets,similar results were found.CONCLUSION Although most people living with HIV have sustained VLS in Rwanda,individuals without formal education,those presenting with advanced HIV,and younger individuals were lagging on multiple outcomes.Interventions tailored to these individuals would improve treatment outcomes to achieve epidemic control.展开更多
Cytomegalovirus (CMV) retinitis is a significant yet infrequent complication inpediatric hematopoietic stem cell transplant recipients, occurring in approximately4% of cases. Its presentation typically coincides with ...Cytomegalovirus (CMV) retinitis is a significant yet infrequent complication inpediatric hematopoietic stem cell transplant recipients, occurring in approximately4% of cases. Its presentation typically coincides with immune reconstitution,between 6 weeks to 6 months post-transplant, emphasizing the need fortimely detection. Symptoms often develop insidiously, underscoring the role offundus examinations during episodes of CMV viremia. However, the low incidencechallenges the necessity of routine screenings, as they may strain clinicalresources without clear benefits to patient outcomes. Management includes systemicand intravitreal antivirals, such as ganciclovir and foscarnet, and adoptiveT-cell therapy for refractory cases. Tailored follow-up strategies are crucial, withconsiderations for lesion activity and CMV viremia status to determine theduration of therapy. Baseline and post-transplant screenings remain a topic ofdebate, with evolving guidelines needed to balance patient safety and clinicalfeasibility. Future research is needed to address optimal screening intervals andinvestigate the role of pre-existing CMV serostatus in transplant eligibility andoutcomes.展开更多
目的探讨核苷(酸)类似物(nucleoside/nucleotide analogues,NAs)治疗后乙型肝炎e抗原(hepatitis B e antigen,HBeAg)阳性慢性乙型肝炎低病毒血症(low-level viremia,LLV)患者的血清乙型肝炎病毒RNA(hepatitis B virus RNA,HBV RNA)水平...目的探讨核苷(酸)类似物(nucleoside/nucleotide analogues,NAs)治疗后乙型肝炎e抗原(hepatitis B e antigen,HBeAg)阳性慢性乙型肝炎低病毒血症(low-level viremia,LLV)患者的血清乙型肝炎病毒RNA(hepatitis B virus RNA,HBV RNA)水平及其在NAs干预后的变化。方法采用巢式病例对照研究,根据LLV病例数1∶1匹配抗病毒治疗后达到维持病毒学应答(maintained virological response,MVR)患者。共纳入62例LLV及62例MVR患者。根据患者治疗意愿将LLV患者分为NAs维持治疗组及更改方案组,收集其临床资料并进行随访。通过实时荧光恒温扩增检测技术(simultaneous amplification and testing,SAT)对血清HBV RNA进行定量检测。结果与MVR组患者相比,LLV组在基线、随访24周及48周时血清HBV RNA水平均较高(P均<0.001)。随访期间LLV患者血清HBV RNA水平较基线有所下降,差异无统计学意义(P均>0.05)。LLV患者在维持治疗组和更改方案组随访至24、48周时血清HBV RNA变化幅度仅在更改方案组的48时有所下降,差异无统计学意义(P均>0.05)。结论与MVR组相比,LLV患者血清HBV RNA水平更高且下降缓慢,调整NAs治疗后HBV RNA水平较维持方案组下降并不明显,提示需要联合其它干预措施以进一步降低HBV转录活性。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We describe an observational study of clinical, virologic and drug resistance profiles in HIV-positive antiretroviral adherent subjects with stable low level viremia (LLV) 50 - 1000 copies/mL for more than 12 months. Subjects were followed from time of first detectable viral load (VL). In total, 102 episodes of LLV were detected among 80 individuals. The median (mean, range) HIV copy number at genotyping was 250 (486, - 3900) copies/mL after 14 (17.9, 0 - 58) months of LLV. Few patients maintained LLV for the entire 9 years period of observation, with half (52%) experiencing viremic progression following a stable period of LLV either spontaneously or after treatment interruption or failed regimen intensification. In the setting of prolonged periods of sustained LLV, mean duration 22 (range 8 - 106) months, drug resistance (DR) was almost universal. Resistance to ≥1 on-treatment drugs was defined in 97% of specimens and DR to all drugs in the treatment regimen in over half of all patients. Evolution of DR mutations during the period of LLV was observed in 20/28 (71%) subjects with specimens available for follow-up testing. This evolution was associated with viremic progression to levels >1000 copies/mL (p = 0.03). Our data suggest that DR present in patients with LLV is likely to impact long term clinical outcomes, highlighting the importance of optimizing techniques to detect the presence of drug resistant HIV in the setting of LLV and the need for larger prospective studies to assess the emergence of DR in the setting of sustained LLV and the impact of this DR on treatment outcomes.
基金Supported by University of Florence,No.XXXV PhD Program。
文摘BACKGROUND Human immunodeficiency virus type 1(HIV-1)infection is characterized by persistent systemic inflammation and immune activation,even in patients receiving effective antiretroviral therapy(ART).Converging data from many cross-sectional studies suggest that gut microbiota(GM)changes can occur throughout including human immunodeficiency virus(HIV)infection,treated by ART;however,the results are contrasting.For the first time,we compared the fecal microbial composition,serum and fecal microbial metabolites,and serum cytokine profile of treatment-na?ve patients before starting ART and after reaching virological suppression,after 24 wk of ART therapy.In addition,we compared the microbiota composition,microbial metabolites,and cytokine profile of patients with CD4/CD8 ratio<1(immunological non-responders[INRs])and CD4/CD8>1(immunological responders[IRs]),after 24 wk of ART therapy.AIM To compare for the first time the fecal microbial composition,serum and fecal microbial metabolites,and serum cytokine profile of treatment-na?ve patients before starting ART and after reaching virological suppression(HIV RNA<50 copies/m L)after 24 wk of ART.METHODS We enrolled 12 treatment-na?ve HIV-infected patients receiving ART(mainly based on integrase inhibitors).Fecal microbiota composition was assessed through next generation sequencing.In addition,a comprehensive analysis of a blood broad-spectrum cytokine panel was performed through a multiplex approach.At the same time,serum free fatty acid(FFA)and fecal short chain fatty acid levels were obtained through gas chromatography-mass spectrometry.RESULTS We first compared microbiota signatures,FFA levels,and cytokine profile before starting ART and after reaching virological suppression.Modest alterations were observed in microbiota composition,in particular in the viral suppression condition,we detected an increase of Ruminococcus and Succinivibrio and a decrease of Intestinibacter.Moreover,in the same condition,we also observed augmented levels of serum propionic and butyric acids.Contemporarily,a reduction of serum IP-10 and an increase of IL-8 levels were detected in the viral suppression condition.In addition,the same components were compared between IRs and INRs.Concerning the microflora population,we detected a reduction of Faecalibacterium and an increase of Alistipes in INRs.Simultaneously,fecal isobutyric,isovaleric,and 2-methylbutyric acids were also increased in INRs.CONCLUSION Our results provided an additional perspective about the impact of HIV infection,ART,and immune recovery on the"microbiome-immunity axis"at the metabolism level.These factors can act as indicators of the active processes occurring in the gastrointestinal tract.Individuals with HIV-1 infection,before ART and after reaching virological suppression with 24 wk of ART,displayed a microbiota with unchanged overall bacterial diversity;moreover,their systemic inflammatory status seems not to be completely restored.In addition,we confirmed the role of the GM metabolites in immune reconstitution.
文摘The pathophysiological mechanisms that underlie the progression of human immunodeficiency virus-1(HIV-1) disease to full-blown AIDS are not well understood. Findings suggest that, during HIV-1 infection, plasma lipopolysaccharide(LPS) levels, which are used as an indicator of microbial translocation(MT), are elevated throughout the acute and chronic phases of HIV-1 disease. The translocation of bacterial products through the damaged gastrointestinal barrier into the systemic circulation has been described as a driver of immune activation. In contrast, comorbidities that are associated with HIV-1 infection have been attributed to chronic inflammation and immune system dysfunction secondary to MT or low-level HIV-1 replication in plasma and cell reservoirs. Moreover, accelerated aging is significantly associated with chronic inflammation, immune activation, and immune senescence. In this review, we aimed to investigate the role of inflammation as a pivotal marker in the pathogenesis of HIV-1 disease. We will discuss the key features of chronic inflammation and immune activation that are observed during the natural course of the disease and those features that are detected in c ART-modified infection. The review will focus on the following aspects of HIV-1 infection:(1) MT;(2) the role of residual viremia; and(3) "immune senescence" or "inflammaging." Many questions remain unanswered about the potential mechanisms that are involved in HIV-1 pathogenesis. Further studies are needed to better investigate the mechanisms that underlie immune activation and their correlation with HIV-1 disease progression.
基金Supported by the National Natural Science Foundation of China,No.82070574。
文摘BACKGROUND Whether patients with compensated cirrhosis and low-level viremia(LLV)of hepatitis B should receive antiviral therapy(AVT)is still controversial,and published results are inconsistent.AIM To investigate the link between LLV in compensated cirrhosis and prognosis concerning hepatocellular carcinoma(HCC),decompensation,and liver-related events.METHODS The PubMed,EMBASE,and Cochrane Library databases were searched up to March 5,2023.Outcomes of interest were assessed by pooled hazard ratios(HRs).The study was registered with PROSPERO(CRD42023405345).RESULTS Six cohort studies representing 3155 patients were included.Compared with patients with undetectable HBV DNA,patients with LLV was associated with increased risk of HCC(HR:2.06,95%CI:1.36-3.13;Q-statistic-P=0.07,I^(2)=51%)regardless of receiving AVT or not(AVT group:HR:3.14;95%CI:1.73-5.69;Qstatistic-P=0.60,I2=0%;un-AVT group:HR:1.73,95%CI:1.09-2.76;Q-statistic-P=0.11,I2=50%).The pooled results showed no statistical association between LLV and decompensation of cirrhosis(HR:2.06,95%CI:0.89-4.76;Q-statistic-P=0.04,I2=69%),and liver-related events(HR:1.84,95%CI:0.92-3.67;Q-statistic-P=0.03,I2=72%),respectively.Grading of Recommendations Assessment,Development and Evaluation assessment indicated moderate certainty for HCC,very low certainty for decompensation of cirrhosis and liver-related clinical events.CONCLUSION LLV in compensated cirrhotic patients is associated with increased risk of HCC,higher tendency for hepatic decompensation and liver-related events.Closer screening of HCC should be conducted in this population.
基金Supported by The Ministry of Science and Technology of China for the National Five-Year Key Projects in Infectious Diseases,No. 2015ZX10004801
文摘BACKGROUND Data that assess maternal and infant outcomes in hepatitis C virus(HCV)-infected mothers are limited.AIM To investigate the frequency of complications and the associated risk factors.METHODS We performed a cohort study to compare pregnancy and fetal outcomes of HCVviremic mothers with those of healthy mothers.Risk factors were analyzed with logistic regression.RESULTS Among 112 consecutive HCV antibody-positive mothers screened,we enrolled 79 viremic mothers.We randomly selected 115 healthy mothers from the birth registry as the control.Compared to healthy mothers,HCV mothers had a significantly higher frequency of anemia[2.6%(3/115)vs 19.0%(15/79),P<0.001]during pregnancy,medical conditions that required caesarian section[27.8%(32/115)vs 48.1%(38/79),P=0.004],and nuchal cords[9.6%(11/115)vs 34.2%(27/79),P<0.001].In addition,the mean neonatal weight in the HCV group was significantly lower(3278.3±462.0 vs 3105.1±459.4 gms;P=0.006),and the mean head circumference was smaller(33.3±0.6 vs 33.1±0.7 cm;P=0.03).In a multivariate model,HCV-infected mothers were more likely to suffer anemia[adjusted odds ratio(OR):18.1,95%confidence interval(CI):4.3-76.6],require caesarian sections(adjusted OR:2.6,95%CI:1.4-4.9),and have nuchal cords(adjusted OR:5.6,95%CI:2.4-13.0).Their neonates were also more likely to have smaller head circumferences(adjusted OR:2.1,95%CI:1.1-4.3)and lower birth weights than the average(≤3250 gms)with an adjusted OR of 2.2(95%CI:1.2-4.0).The vertical transmission rate was 1%in HCV-infected mothers.CONCLUSION Maternal HCV infections may associate with pregnancy and obstetric complications.We demonstrated a previously unreported association between maternal HCV viremia and a smaller neonatal head circumference,suggesting fetal growth restriction.
文摘HIV infection is an emerging health issue in Libya, particularly among young adults. Human cytomegalovirus (HCMV) is a prevalent infectious agent that presents with subclinical and fatal diseases in immunosuppressed individuals including HIV-infected individuals. Although the impact of HCMV infection in HIV-positive patients is well documented in several regions, epidemiologic estimates concerning HCMV co-infection among HIV-infected individuals remain limited in Libya. Hence, this cross-sectional study was undertaken to derive data regarding the prevalence of active HCMV viremia among HIV-infected individuals undergoing antiretroviral therapy (ART) from Libya. A total of 90 consented HIV-infected subjects followed by the National Center for Disease Control (NCDC) of Benghazi/Libya were recruited in this study and investigated for HCMV-IgG, HCMV-IgM specific antibodies, detection of HCMV lower matrix phosphoprotein (pp65) antigen, and detection of HCMV-DNA using qPCR to assess the prevalence of HCMV viremia. We determined that 77 (85.56%) of subjects were seropositive for HCMV-IgG antibodies, whereas the seropositivity for HCMV-IgM was 3.33% (3/90 subjects). Our results also revealed that 4.44% (4/90) of participants had viral antigenemia based on the laboratory diagnosis of HCMV-pp65. Regarding the PCR, we were able to detect the DNA of HCMV only in 3/90 subjects (3.33%) suggesting an active viremic condition. The detection of HCMV DNA along with the HCMV-pp65 in HIV-positive individuals highlights the necessity of early diagnosis to manage the progression of the disease. Furthermore, we highly recommend the use of anti-HCMV therapy in viremic individuals in combination with ART to reduce the burden of HCMV complications.
基金Supported by National Key Research and Development Program (2017YFF0211103)Scientific Research Project of General Administration of Quality Supervision,Inspection and Quarantine (2017IK232)
文摘[Objective]The paper was to develop a rapid method for the detection of spring Viremia of carp virus(SVCV).[Method]The specific primers were designed by targeting the G gene of SVCV.The recombinase polymerase amplification(RPA)assay for detecting SVCV was estab-lished by optimizing the reaction conditions.The optimal amplification temperature of RPA assay was 30℃,and the test could be finished within 20 min.[Result]The method was specific with no cross-reaction with other common fish infectious viruses.Sensitivity test showed that the lowest detection limit of the method was 89.2 copies/μL,higher than that of traditional RT-PCR.Moreover,a total of 80 clinical samples were detected by RPA and RT-PCR,respectively.The weak positive samples tested by RT-PCR could be detectable with RPA,indicating that RPA assay could be used in clinical detection.[Conclusion]The method established is rapid,simple,specific and sensitive for testing SVCV,and it will be widely used in grassroots laboratory and on-site inspection.
文摘Summary What is already known about this topic?Human immunodeficiency virus(HIV)low-level viremia(LLV)during antiretroviral therapy(ART)occurs frequently in Dehong Dai and Jingpo Autonomous Prefecture,Yunnan Province.What is added by this report?Among people living with HIV who achieved virological success[viral load(VL)<1,000 copies/mL]after initiating ART in Dehong Prefecture,Southwest China,17.6%experienced first-year LLV of 50–999 copies/mL First-year LLV emerged as an independent risk factor for subsequent viral non-suppression compared with participants maintaining first-year VL<50 copies/mL.
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.
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.
基金This work was supported by the grant from Zhuhai Medical and Health Technology Project(20181117E030074)the Department of Science and Technology of Guangdong Province of China(2021A1515010458).
文摘Background and aim:Several effective antiviral drugs are now available;however,the risk of liver-related complications is still present.Low-level viremia(LLV),defined as a hepatitis B virus(HBV)deoxy-ribonucleic acid(DNA)load lower than 2000 IU/mL,is one of the major factors responsible for these complications.It has been reported that 22.7e43.1%of patients with HBV experience LLV.Herein,we aimed to explore the risk factors for very LLV(VLLV)during antiviral treatment.Methods:We collected data of patients with chronic hepatitis B(CHB)who received nucleos(t)ide analog treatment from October 2016 to April 2021.VLLV was defined as an HBV DNA load of 9e20 IU/mL.A total of 139 patients with LLV were matched with 139 patients with a sustained virological response at a 1:1 ratio according to age and gender.Results:Seropositivity rates for hepatitis B e antigen(HBeAg)(45.3%vs.17.3%,P<0.001)and hepatitis B surface antigen(HBsAg,3.11±0.68 lg IU/mL vs.2.54±1.04 lg IU/mL,P<0.001)and alanine amino-transferase levels(30.34±15.08 U/L vs.26.15±16.66 U/L,P¼0.040)in the two groups were significantly different.The multivariate analysis showed that both HBeAg seropositivity(adjusted odd ratio(aOR),3.63;95% confidence interval(CI):1.98±6.64;P<0.001)and HBsAg levels(aOR,2.21;95% CI:1.53±3.20;P<0.001)are independent risk factors for VLLV.During the multivariate analysis in the subgroup of HBeAg-positive patients,male gender(aOR,3.68;95% CI:1.23±10.76;P=0.017)and high HBsAg(aOR,4.86;95%CI:1.73e13.64;P¼0.003)levels were significantly correlated with VLLV.However,this was not the case in HBeAg-negative patients(P>0.050).HBeAg seropositivity(aOR,5.08;95% CI:2.15±12.02;P<0.001 vs.aOR,2.78;95% CI:1.16±7.00;P=0.022)and HBsAg levels(aOR,2.75;95% CI:1.41e5.37;P=0.003 vs.aOR,2.10;95% CI:1.27±3.46;P=0.004)significantly increased the risk of VLLV,irrespective of the age group.Both HBsAg(area under the receiver operating characteristic curve(AUC),0.681;95% CI:0.623±0.736;P<0.001)and HBeAg(AUC,0.640;95% CI:0.581±0.697;P<0.001)had certain pre-dictive value for VLLV.Conclusion:HBeAg seropositivity and higher HBsAg levels were not only risk factors for VLLV but also predicted its occurrence.When a patient with CHB remains HBeAg seropositive with high HBsAg levels after antiviral treatment for 48 weeks,emphasis should be placed on the potential occurrence of VLLV,warranting the use of highly sensitive HBV DNA detection methods.
文摘BACKGROUND Sustained viral load(VL)suppression is an important indicator of successful treatment among people living with human immunodeficiency virus(HIV).AIM To assess trends of different VL outcomes before and after adoption of the Treat All policy among people living with HIV in Rwanda.METHODS Between 2014 and 2017,VL suppression[VL suppression(VLS)<200 copies/mL]was measured among people living with HIV from 28 healthcare facilities in Rwanda.Participant VL was measured at 6 months,18 months,and 30 months.The unit of analysis was visit-pair,with subjects across four visit-pair categories:(1)Sustained VL suppression(VL<200 copies/mL at two consecutive visits);(2)Persistent viremia(VL≥200 copies/mL at two consecutive visits);(3)Viral rebound(VL<200 copies/mL at prior visit only);and(4)Newly suppressed(VL<200 copies/mL at subsequent visit only).Poisson regression models with generalized estimating equations were used to estimate adjusted incidence risk ratio(aIRR)and 95%confidence intervals(CIs)for factors associated with sustained VLS.To handle missing data,multiple imputations was performed.RESULTS A total of 634 participants contributed 973 visit-pairs(295 single pairs and 339 double pairs).The median age was 37 years(interquartile range:32-43 years).The incidence rates of sustained VLS,persistent viremia,viral rebound,and new suppression were 85.2%,4.3%,4.6%,and 5.7%,respectively.Young individuals aged 18-24 years had higher incidence of viral rebound compared to those 25 years or older(14.8%vs 4.3%;P=0.011).Of the visit-pairs that had sustained VLS during the first two visits(49.8%;n=485),56.7%exhibited sustained VLS throughout follow-up.Compared to having no education,having at least primary education was associated with an increased likelihood of sustained VLS(aIRR=1.09;95%CI:1.01-1.17).Those who presented with advanced HIV disease at baseline had a 12%reduced likelihood of sustained VLS(aIRR=0.88;95%CI:0.79-0.99).Achieving sustained VLS did not differ before or after adoption of the Treat All policy.When the analysis was repeated on imputed datasets,similar results were found.CONCLUSION Although most people living with HIV have sustained VLS in Rwanda,individuals without formal education,those presenting with advanced HIV,and younger individuals were lagging on multiple outcomes.Interventions tailored to these individuals would improve treatment outcomes to achieve epidemic control.
文摘Cytomegalovirus (CMV) retinitis is a significant yet infrequent complication inpediatric hematopoietic stem cell transplant recipients, occurring in approximately4% of cases. Its presentation typically coincides with immune reconstitution,between 6 weeks to 6 months post-transplant, emphasizing the need fortimely detection. Symptoms often develop insidiously, underscoring the role offundus examinations during episodes of CMV viremia. However, the low incidencechallenges the necessity of routine screenings, as they may strain clinicalresources without clear benefits to patient outcomes. Management includes systemicand intravitreal antivirals, such as ganciclovir and foscarnet, and adoptiveT-cell therapy for refractory cases. Tailored follow-up strategies are crucial, withconsiderations for lesion activity and CMV viremia status to determine theduration of therapy. Baseline and post-transplant screenings remain a topic ofdebate, with evolving guidelines needed to balance patient safety and clinicalfeasibility. Future research is needed to address optimal screening intervals andinvestigate the role of pre-existing CMV serostatus in transplant eligibility andoutcomes.
