Low level of hepatitis B viremia is associated with increased risk of hepatocellular carcinoma in compensated cirrhotic patients

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.

New therapeutic options for persistent low-level viremia in patients with chronic hepatitis B virus infection:Increase of entecavir dosage

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.

HIV Drug Resistance Profiles and Clinical Outcomes in Patients with Viremia Maintained at Very Low Levels

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.

Effects of viremia and CD4 recovery on gut“microbiome-immunity”axis in treatment-na?ve HIV-1-infected patients undergoing antiretroviral therapy

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.

Pregnancy and fetal outcomes of chronic hepatitis C mothers with viremia in China

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.

The Prevalence of Human Cytomegalovirus Viremia among HIV-1 Infected Individuals Undergoing Antiretroviral Therapy

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.

Microbial translocation, residual viremia and immune senescence in the pathogenesis of HIV-1 infection

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.

Establishment of Recombinase Polymerase Amplification for Rapid Detection of Spring Viremia of Carp Virus(SVCV)

[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.

免疫磁珠富集水中鲤春病毒血症病毒的初步研究

为建立一种富集水中鲤春病毒血症病毒(SVCV)的技术,本研究利用SVCV多克隆抗体制备免疫磁珠,通过对磁珠耦联抗体量的优化,确定该免疫磁珠有效富集SVCV的最低浓度,建立一种富集SVCV的免疫磁珠分离技术,并联合荧光定量RT-PCR(RT-qPCR)技术对水中SVCV进行检测。结果显示,1 mg磁珠与75μg SVCV多克隆抗体耦联时,耦联的抗体量最大,耦联率为98.48%;耦联后的免疫磁珠对SVCV(200μL,浓度为1.54×10^(6)拷贝/μL)的富集效率最高为91.56%。以该多克隆抗体量制备的免疫磁珠富集10倍倍比稀释的SVCV(3.54×10^(6)拷贝/μL~3.54×10^(3)拷贝/μL),以确定其有效富集SVCV的最低浓度。结果显示,1 mg免疫磁珠能够使200μL病毒液(3.54×10^(3)拷贝/μL)富集率达到61.58%。表明该免疫磁珠能够有效富集SVCV。在免疫磁珠分离技术联合RT-qPCR技术检测水样品中SVCV(浓度约为1.16×10^(4)拷贝/μL)的结果显示,免疫磁珠组富集SVCV核酸量是裸磁珠组富集SVCV核酸量的1.77×10^(3)倍,是未处理组富集SVCV核酸量的1.68×10^(3)倍,免疫磁珠组富集SVCV均极显著高于裸磁珠组和未处理组(P<0.01),裸磁珠组富集的SVCV与未处理组则无显著差异(P>0.05)。本研究首次建立了一种能够有效富集水中SVCV的方法,为SVCV的监测提供了技术手段。

一线核苷(酸)类似物经治的慢性乙型肝炎患者低病毒血症的发生及治疗策略

强效低耐药口服抗病毒治疗可使HBV复制受到强力抑制,但部分患者接受恩替卡韦、替诺福韦酯、丙酚替诺福韦、艾米替诺福韦治疗48周及以上仍存在低病毒血症(LLV)。国内外多项研究结果提示,抗病毒治疗后LLV与慢性乙型肝炎肝纤维化进展、失代偿期肝硬化和肝细胞癌发生风险以及长期生存率降低密切相关。因此,本文聚焦有关一线核苷(酸)类似物治疗后LLV的发生及其危险因素和临床危害以及不同的治疗方案,以期为今后慢性乙型肝炎患者LLV的治疗提供参考。

慢乙肝低病毒血症患者继续核苷(酸)类似物治疗的远期临床结局:一项系统评价和Meta分析

背景一线核苷(酸)类似物(nucleos(t)ide analogues,NAs)经治后发生低病毒血症(low-level viremia,LLV)的慢乙肝患者,继续使用NAs治疗的远期临床结局的研究尚缺乏.目的采用系统评价和Meta分析对慢乙肝经一线NAs治疗的LLV患者继续原NAs治疗和更换不同NAs治疗方案远期临床结局情况进行评价.方法经计算机检索PubMed、Embase、Web of Science、Cochrane Library数据库和中国知网(CNKI)、万方数据库,选取符合纳入标准的研究,使用R 4.3.1软件对纳入研究数据进行Meta分析.结果最终纳入11篇文献,涉及3153例慢乙肝LLV患者,其中7篇文献进行HBV DNA阴转率定量Meta分析,结果提示更换NAs方案组继续治疗24 wk[RR=4.23,95%CI(2.47,7.24),P<0.01]和48 wk[RR=2.90,95%CI(1.75,4.81),P<0.01]后HBV DNA阴转率明显高于继续原NAs方案组;纳入6篇文献进行HBeAg阴转率的定量Meta分析,更换NAs治疗方案组24 wk HBeAg阴转率高于继续原方案组[RR=2.31,95%CI(1.28,4.19),P<0.01],但48 wk两组HBeAg阴转率差异无统计学意义[RR=1.50,95%CI(0.88,2.54),P=0.13];纳入3篇文献进行终末期肝病发生率的定性系统评价,结果显示继续NAs治疗的LLV组患者远期终末期肝病发生率均高于维持病毒学应答(maintain virological response,MVR)组,差异均具有统计学意义(P<0.05).结论更换NAs治疗方案可提高慢乙肝LLV患者HBV DNA阴转率和HBeAg阴转率,但继续NAs方案治疗的慢乙肝LLV患者远期终末期肝病发生率较MVR患者高.

中国肾移植受者巨细胞病毒感染临床诊疗指南(2023版)

近几年在实体器官移植(SOT)受者巨细胞病毒(CMV)感染诊疗领域,无论是诊断方法还是新型抗CMV药物都有了一些新的进展,对CMV感染的诊治产生了积极的影响。为了进一步规范中国肾移植术后CMV感染的管理,中华医学会器官移植学分会组织了国内多个学科相关领域专家,参考《中国实体器官移植受者巨细胞病毒感染诊疗指南(2016版)》和国内外已发表的最新文献和指南,制定了《中国肾移植受者巨细胞病毒感染诊疗指南(2023版)》,新版指南更新了CMV流行病学,CMV感染的危险因素和普遍性预防的研究进展,新增CMV感染定义,细化CMV血症和CMV病的诊断标准,并对新型抗CMV药物进行了介绍。

经治慢性乙型肝炎患者低病毒血症发生率和影响因素的Meta分析

目的系统评价慢性乙型肝炎(CHB)患者低病毒血症(LLV)的发生率及其影响因素,为临床有效干预和预防LLV的发生提供循证医学证据。方法本研究根据PRISMA指南完成,PROSPERO注册号:CRD42023455304。计算机检索中国知网、万方数据库、维普、中国生物医学文献服务系统、PubMed、Embase、Web of Science、Cochrane Library中有关CHB患者LLV发生及影响因素的观察性研究,检索时间为建库至2023年7月21日。应用Stata 16.0软件进行Meta分析。结果共纳入文献12篇,总样本量3408例,包括LLV患者1181例。Meta分析结果显示,经治CHB患者LLV发生率为32.8%(95%CI:27.6%~38.3%);HBsAg定量高(OR=2.107,95%CI:1.782~2.491,P<0.001)、HBeAg阳性(OR=3.258,95%CI:2.629~4.038,P<0.001)、高基线HBV DNA水平(OR=1.286,95%CI:1.157~1.430,P<0.001)及有恩替卡韦治疗史(OR=3.089,95%CI:1.880~5.074,P<0.001)是LLV发生的危险因素;抗病毒时间≥3年(OR=0.175,95%CI:0.093~0.331,P<0.001)和高基线ALT水平(OR=0.985,95%CI:0.978~0.992,P<0.001)是LLV的保护因素。敏感性分析显示效应值未发生明显变化,提示Meta分析结果相对稳定。纳入研究漏斗图基本对称,Egger’s检验和Begg’s检验结果提示纳入文献不存在明显发表偏倚。结论临床医生应根据LLV的影响因素,综合临床证据有效指导决策,降低远期临床风险,避免不良结局。

恩替卡韦治疗后慢性乙型肝炎低病毒血症患者序贯联合艾米替诺福韦治疗的效果研究

目的 探讨在恩替卡韦(ETV)治疗后出现低病毒血症(LLV)的慢性乙型肝炎(CHB)患者,采取序贯联合艾米替诺福韦(TMF)治疗的临床效果。方法 选取2021年7月—2023年1月在贵港市人民医院感染科经ETV抗病毒治疗的CHB患者200例。根据治疗期间HBV DNA水平,将患者分为完全病毒学应答组(64例)和LLV组(136例),分析两组临床资料。根据LLV组抗病毒治疗方案,分为3组:续用ETV为对照组(40例)、换用TMF为序贯组(45例)、ETV联合TMF为联合组(51例),持续治疗48周。比较3组治疗48周时HBV DNA转阴率、乙肝表面抗原(HBsAg)、E抗原(HBeAg)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、肌酐(Cr)和肝硬度测定值(LSM)及不良反应发生率。结果 完全病毒学应答组HBeAg阳性率、HBV DNA、PLT、LSM、ALT、AST均低于LLV组(P <0.05)。治疗24周后,完全病毒学应答组Cr、AST、HBeAg阳性率、HBV DNA、PLT均低于LLV组(P <0.05)。治疗48周后,联合组Cr低于对照组和序贯组(P <0.05),HBsAg高于对照组和序贯组(P <0.05);序贯组ALT、AST均低于对照组(P <0.05);序贯组和联合组HBeAg转阴率、HBV DNA转阴率、PLT均高于对照组(P <0.05),LSM低于对照组(P <0.05)。对照组、序贯组、联合组不良反应总发生率比较,差异无统计学意义(P>0.05)。结论 序贯或联合TMF治疗能更有效地提高ETV治疗后LLV患者完全病毒学应答率,并改善患者肝肾功能,减轻肝纤维化程度。

益气逐瘀解毒颗粒联合抗病毒药物治疗低病毒血症的慢性乙型肝炎肝纤维化及肝硬化患者的回顾性疗效观察

目的:评价中药复方益气逐瘀解毒颗粒治疗低病毒血症的慢性乙型肝炎肝纤维化及肝硬化患者(肝郁脾虚型)的临床疗效及联合不同抗病毒药物治疗慢性乙型肝炎肝纤维化的疗效差异。方法:收集2019年1月到2022年12月在成都中医药大学附属医院门诊就诊的165例口服抗病毒药物(ETV或TDF或TAF)和益气逐瘀解毒颗粒治疗低病毒血症的慢性乙型肝炎肝纤维化及肝硬化患者,将其定义为中药联合抗病毒药物治疗组,根据LSM值分为3个程度:轻度纤维化(39例)、显著/进展肝纤维化(54例)及肝硬化(72例),采用自身前后对照的研究方法,回顾性分析中药治疗疗程为3个月的上述患者治疗前后的LSM值、FIB-4、APRI、GPR及S指数,并进行疗效分析。另将165例患者分为中药联合ETV治疗组(94例)和中药联合TDF/TAF治疗组(71例),根据LSM值分为3组:中药联合ETV治疗组(轻度肝纤维化29例、显著/进展肝纤维化27例、肝硬化38例),中药联合TDF/TAF治疗组(轻度肝纤维化10例、显著/进展肝纤维化27例、肝硬化34例),分别组间比较上述指标。结果:中药联合抗病毒药物治疗组的轻度纤维化、显著/进展肝纤维化及肝硬化患者治疗前后LSM值均具有明显差异(P<0.01);中药联合抗病毒药物治疗组仅肝硬化患者治疗前后FIB-4、APRI、GPR、S指数四个指标比较有统计学意义(P<0.01),轻度纤维化及显著/进展肝纤维化患者治疗前后比较四个指标均无统计学意义;中药联合抗病毒药物治疗组的轻度纤维化、显著/进展肝纤维化及肝硬化患者临床有效率分别为46.15%、74.07%、63.89%,合计总有效率为63.03%(n=165)。中药联合ETV治疗组与中药联合TDF/TAF治疗组两组患者基线资料比较无统计学差异(P>0.05),治疗前LSM值、FIB-4、APRI、GPR、S指数无统计学差异(P>0.05),治疗后LSM值、FIB-4、APRI、GPR、S指数无统计学差异(P>0.05)。结论:益气逐瘀解毒颗粒对长期抗病毒治疗(≥5年)的低病毒血症的慢性乙型肝炎肝纤维化及肝硬化患者用药治疗3个月后均有疗效,对显著/进展纤维化患者比轻度纤维化疗效更好;益气逐瘀解毒颗粒联合不同抗病毒药物(ETV或TDF/TAF)治疗肝纤维化及肝硬化患者无明显差异。

疫情常态化防控期间不规律随访对肾移植术后BK病毒再激活时的病毒载量及受者预后影响

目的探讨在新型冠状病毒肺炎疫情常态化防控期间不规律随访对肾移植受者术后BK病毒(BKV)再激活情况及预后的影响。方法回顾性分析363例肾移植受者的临床资料,按随访时间分为疫情前随访组与疫情期间随访组,随访期限为1年。比较疫情前随访组和疫情期间随访组的随访时间间隔,分析两组BKV感染情况,分析BKV感染进程与移植肾功能的相关性。结果疫情前随访共计1790例次,疫情期间随访共计2680例次。与疫情期间随访组比较,疫情前随访组术后3个月内、3~6个月、7~12个月的随访时间间隔较短,差异均有统计学意义(均为P<0.05)。在肾移植术后1年内,疫情前随访组35例(32%)检出BKV尿症、3例(3%)检出BKV血症、1例(1%)检出BKV相关肾病(BKVAN),疫情期间随访组53例(25%)检出BKV尿症、3例(1%)检出BKV血症、1例(1%)检出BKVAN,差异均无统计学意义(均为P>0.05)。疫情前随访组术后首次检出BKV尿症时间长于疫情期间随访组,首次再激活尿BKV载量小于疫情期间随访组,差异均有统计学意义(均为P<0.05)。首次再激活尿BKV载量与尿BKV载量峰值,BKV再激活后第1、3个月血清肌酐与基线血清肌酐差值呈正相关(均为P<0.05)。结论肾移植术后不规律随访可导致BKV再激活时间提前、首次尿BKV载量检出值更高,以及延迟诊断和干预,并造成不良预后。亟待建立远程随访体系以满足发生公共卫生事件时肾移植受者的随访需求。

中华鲟IFNe2的抗病毒天然免疫作用

为探究中华鲟干扰素e2(AsIFNe2)的免疫调控作用,本实验通过原核表达获得了重组中华鲟干扰素e2蛋白(rAsIFNe2),并分析其对抗病毒相关基因的影响及其抗病毒活性。实时荧光定量PCR(RT-qPCR)结果显示,rAsIFNe2能显著激活中华鲟鳍细胞中干扰素刺激基因(IFN-stimulated genes,ISGs)的表达,如Mx、PKR、Viperin和ADAR4。此外,rAsIFNe2还能通过激活IRFs和IFNes基因的表达,从而帮助宿主细胞迅速建立抗病毒状态。在鲤春病毒血症病毒(SVCV)感染鲤上皮细胞(EPC)模型中,rAsIFNe2能够诱导EPC细胞中Mx、PKR和Viperin的表达,并降低EPC细胞中SVCV病毒G、N和P基因的表达,减少病变效应的产生。研究表明,AsIFNe2在宿主抗病毒天然免疫反应中发挥作用。本研究为深入了解中华鲟的干扰素免疫系统以及治疗病毒性疾病提供理论依据。

基于高敏检测的乙肝肝硬化低病毒血症患者的预后分析

目的 探讨经核苷类药物治疗的乙肝肝硬化低病毒血症患者的临床特点及预后。方法 收集2020年至2022年就诊于太原市第三人民医院的经核苷类药物治疗乙型肝炎肝硬化患者,通过乙肝病毒高敏检测分为未测到靶标组、低于检测下限组、低病毒血症组,平均随访48周,观察患者临床特点、肝硬化相关并发症、肝细胞癌(HCC)发生率,评估其预后及影响因素。结果 251例经核苷类药物治疗乙肝肝硬化患者中低病毒血症组(HBV DNA 10~2 000 U/ml)25例,低于检测下限组(HBV DNA<10 U/ml)107例,未测到靶标组(HBV DNA未检测到)119例,3组间丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、白蛋白(ALB)、总胆红素(TBIL)、凝血酶原活动度(PTA)%差异有统计学意义。3组患者既往核苷类药物治疗史及干扰素治疗史具有统计学意义,多数患者接受1~2种核苷类药物抗病毒治疗,且过半患者可达到HBV DNA检测不到的效果。随访期间3组患者均发现新增肝硬化相关并发症,38例(15.1%)发生HCC,其中7例死亡。结论 HBV DNA控制越好,肝损伤越轻,肝脏合成功能越好。接受抗病毒治疗核苷类药物(NAs)或干扰素(IFN)能显著降低乙肝病毒DNA。乙型肝炎肝硬化患者不论抗病毒治疗完全应答与否,均应定期检查,及早发现肝硬化相关并发症、原发性肝癌并予积极治疗,降低相关死亡率。

恩替卡韦经治乙肝肝硬化患者低病毒血症对肝癌发病的影响

目的探讨恩替卡韦经治乙肝肝硬化患者低病毒血症对肝癌发病的影响。方法选择2017年1-12月收治的乙肝肝硬化患者140例,均应用恩替卡韦治疗>1年,对患者进行为期5年的随访。根据患者乙肝病毒(hepatitis B virus,HBV)DNA检测情况,将其分为低病毒血症(low-level viremia,LLV)组68例与持续病毒学应答(maintained virological response,MVR)组72例,观察导致LLV的影响因素,对两组5年内肝癌发病与病死情况进行分析。结果LLV组与MVR组年龄、治疗前基线乙肝病毒e抗原(hepatitis B e antigen,HBeAg)(阳性)、HBV DNA水平以及乙肝表面抗原(hepatitis B s antigen,HBsAg)滴度差异均有统计学意义(P<0.05),性别、身体质量指数(body mass index,BMI)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)及丙氨酸氨基转移酶(alanine aminotransferase,ALT)差异均无统计学意义(P>0.05);采用二元logistic回归模型进行分析,结果显示治疗前基线HBeAg(阳性)、HBV DNA水平以及HBsAg滴度为导致LLV的影响因素(P<0.05);经过对患者的5年随访,结果显示LLV组肝癌发生率为23.5%,MVR组肝癌发生率为9.7%,LLV组肝癌发生率明显高于MVR组(P<0.05);LLV组肝癌患者病死率为43.8%,MVR组肝癌患者病死率为42.8%,两组病死率差异无统计学意义(P>0.05)。结论LLV导致肝癌风险增加,临床应重视恩替卡韦经治肝硬化患者,采用有效治疗方案,使LLV转变为持续病毒学应答,减少肝癌的发生风险。

鲤Rhbdd3重组乳酸菌微生物制剂的开发及效果评价

鱼类Rhbdd3(Rhomboid domain-containing protein 3)蛋白具有抗水生病毒感染功能,然而生产实践中缺乏其大量制备及应用方案。为研制鲤Rhbdd3蛋白重组微生物制剂,利用乳酸菌NICE表达系统,构建了Rhbdd3蛋白重组表达质粒pNZ8148-rhbdd3,并转化获得了重组乳酸乳球菌pNZ8148-rhbdd3 NZ9000。利用乳酸链球菌素nisin进行Rhbdd3蛋白的诱导表达,并通过SDS-PAGE和Western blotting进行验证。进一步,将重组乳酸乳球菌进行饲料拌喂并开展鲤春病毒血症病毒(SVCV)人工感染实验,检测鱼体免疫因子表达水平及攻毒后鱼体组织病毒载量。结果显示:经nisin诱导后,pNZ8148-rhbdd3 NZ9000能够表达约为39 kDa的特异性蛋白,与Rhbdd3蛋白大小一致。重组乳酸乳球菌的最佳nisin诱导浓度为100 ng/mL,最佳诱导时间为5 h。重组乳酸乳球菌饲喂后14 d,与对照组相比,实验组鲤鱼组织中免疫相关基因IFN1、IRF7、Viperin、Mx1和ISG15的表达水平均显著上调。此外,SVCV攻毒后,重组乳酸乳球菌饲喂组鱼体组织中病毒滴度较对照组显著降低,表明其可以抑制病毒的增殖。研究结果为Rhbdd3蛋白的大量制备和应用提供了一种可行方案,并为鱼类病毒性疾病的防控提供了一种有效措施。