Hepatitis D virus dual-infection among Chinese hepatitis B patient related to hepatitis B surface antigen,hepatitis B virus DNA and age

The screening practices for hepatitis D virus(HDV)are diverse and nonstandardized worldwide,and the exact prevalence of HDV is uncertain.AIM To estimate HDV prevalence and investigate viral marker quantity trends in patients with hepatitis D.METHODS We collected 5594 serum samples from patients with hepatitis B in Jilin Province,China(3293 males and 2301 females,age range of 2 to 89 years).We then conducted tests for hepatitis B surface antigen(HBsAg),hepatitis B Virus(HBV)DNA,anti-hepatitis D antigen(HDAg),and HDV RNA.RESULTS We found that the prevalence of anti-HDAg and HDV RNA among hepatitis B patient were 3.6%(3.2-4.2%)and 1.2%(0.9-1.5%),respectively,87.69%of hepatitis D patients were 51-70 years old.HDV infection screening positive rate of patients with HBV DNA levels below 2000 IU/mL(2.0%)was higher than those above 2000 IU/mL(0.2%).Among anti-HDAg positive patients,the HDV RNA positive rate was positively correlated with the HBsAg level and anti-HDAg level.There was a weak correlation between HBsAg and anti-HDAg levels among hepatitis D patients.CONCLUSION Our study highlights the importance of considering multiple factors when assessing the severity of HDV infection,comprehensive evaluation of patients’clinical and laboratory parameters is necessary for proper diagnosis and treatment.

Is there a need for universal double reflex testing of HBsAg-positive individuals for hepatitis D infection?

Hepatitis D virus(HDV)can infect HBsAg-positive individuals,causing rapid fibrosis progression,early decompensation,increased hepatocellular carcinoma risk,and higher mortality than hepatitis B virus(HBV)mono-infection.Most countries lack high-quality HDV prevalence data,and the collection techniques employed often bias published data.In recent meta-analyses,HDV prevalence in HBsAg-positive patients reaches 5%-15%and is even significantly higher in endemic areas.Since HBV vaccination programs were implemented,HDV prevalence has decreased among younger populations.However,owing to immigrant influx,it has increased in some Western countries.The current practice of HDV screening in HBsAg-positive individuals is stepwise,based on physician’s discretion,and limited to at-risk populations and may require numerous visits.Double reflex testing,which includes anti-HDV testing in all HBsAg-positive individuals and then HDV RNA testing for anti-HDV-positive ones,is uncommon.Reflex testing can identify more HDV infection cases and link identified patients to further care and follow-up.Moreover,laboratory-based double reflex screening is less biased than physician-led testing.Therefore,health-care providers should learn about reflex testing,and federal and provincial hepatitis control programs should implement laboratory-based double reflex testing to obtain reliable HDV prevalence estimates.The test’s cost-effectiveness depends on the number of HBV-positive patients screened to identify one HDV-positive patient.Such testing may be viable in areas with low HBsAg but high HDV prevalence.However,its economic impact on areas with low HDV prevalence needs further study.

丁型肝炎病毒HDV-IgM筛查状况与感染患者临床特征分析

目的了解乙型肝炎人群丁型肝炎病毒感染筛查情况及感染患者临床特征。方法回顾性分析2014年1月至2023年10月我院乙型肝炎病毒感染(HBsAg阳性)患者丁型肝炎感染筛查(HDV-IgM)结果,分析筛查比例变化及阳性结果临床情况,收集丁型肝炎感染患者(HDV-IgM阳性)的临床资料,与HDV-IgM阴性乙型肝炎患者比较,总结丁型肝炎感染患者的临床特点。结果近10年乙型肝炎感染患者中HDV-IgM的平均筛查比例仅有3.60%(18533/514271),其中2014年的筛查比例最高,为6.67%(3407/51073),2020年的筛查比例最低,为1.84%(855/46413)。2014-2020年筛查比例呈逐年下降的趋势,2021年开始逐渐上升。HDV-IgM筛查阳性共45例,年龄(43.31±13.59)岁(1~80岁),男23例,女22例,其中有1例是乙肝阴性(HBsAg和HBV DNA均阴性)。地区分布是居住在北京的国际友人(主要为蒙古国)27例(60.00%);内蒙古自治区11例(24.44%);北京市4例(8.89%);河北省2例(4.44%);河南省1例(2.22%)。HDV-IgM阳性组与HDV-IgM阴性组比较,年龄、性别、HBV DNA水平差异无统计学意义情况下,HDV-IgM阳性组HBeAg阳性率明显低于HDV-IgM阴性组(P=0.001),且HDV-IgM阳性组ALT、AST和GGT高于HDV-IgM阴性组(P均<0.001)。HDV-IgM阳性组与HDV-IgM阴性组乙肝五项模式分布具有显著性差异(P<0.05)。结论近10年,丁型肝炎的筛查率低,阳性率不高,发病率高的地区应重视HDV的筛查,提高诊断率。HDV感染会加重肝炎病情程度,值得重视。

Life cycle and pathogenesis of hepatitis D virus:A review

Hepatitis D virus(HDV) is a defective RNA virus which requires the help of hepatitis B virus(HBV) virus for its replication and assembly of new virions. HDV genome contains only one actively transcribed open reading frame which encodes for two isoforms of hepatitis delta antigen. Post-translational modifications of small and large delta antigens(S-HDAg and L-HDAg) involving phosphorylation and isoprenylation respectively con- fer these antigens their specific properties. S-HDAg is required for the initiation of the viral genome replica- tion, whereas L-HDAg serves as a principal inhibitor of replication and is essential for the assembly of new virion particles. Immune mediation has usually been implicated in HDV-associated liver damage. The patho- genesis of HDV mainly involves interferon-α signaling inhibition, HDV-specific T-lymphocyte activation and cytokine responses, and tumor necrosis factor-alpha and nuclear factor kappa B signaling. Due to limited protein coding capacity, HDV makes use of host cel- lular proteins to accomplish their life cycle processes, including transcription, replication, post-transcriptional and translational modifications. This intimate host- pathogen interaction significantly alters cell proteome and is associated with an augmented expression of pro-inflammatory, growth and anti-apoptotic factorswhich explains severe necroinflammation and increased cell survival and an early progression to hepatocellular carcinoma in HDV patients. The understanding of the process of viral replication, HBV-HDV interactions, and etio-pathogenesis of the severe course of HDV infection is helpful in identifying the potential therapeutic targets in the virus life cycle for the prophylaxis and treatment of HDV infection and complications.

Vitamin D deficiency and hepatitis viruses-associated liver diseases:a literature review

The secosteroid hormone vitamin D has, in addition to its effects in bone metabolism also functions in the modulation of immune responses against infectious agents and in inhibiting tumorigenesis. Thus, deficiency of vitamin D is associated with several malignancies, but also with a plethora of infectious diseases. Among other communicable diseases, vitamin D deficiency is involved in the pathogenesis of chronic liver diseases caused by hepatitis B and C viruses(HBV, HCV) and high prevalence of vitamin D deficiency with serum levels below 20 mg/mL in patients with HBV and HCV infection are found worldwide. Several studies have assessed the effects of vitamin D supplementation on the sustained virological response(SVR) to interferon(IFN) plus ribavirin(RBV) therapy in HBV and HCV infection. In these studies, inconsistent results were reported. This review addresses general aspects of vitamin D deficiency and, in particular, the significance of vitamin D hypovitaminosis in the outcome of HBVand HCV-related chronic liver diseases. Furthermore,current literature was reviewed in order to understand the effects of vitamin D supplementation in combination with IFN-based therapy on the virological response in HBV and HCV infected patients.

Hepatitis C virus in the new era:Perspectives in epidemiology,prevention,diagnostics and predictors of response to therapy

Despite the great successes achieved in the fields of virology and diagnostics,several difficulties affect improvements in hepatitis C virus(HCV)infection control and eradication in the new era.New HCV infections still occur,especially in some of the poorest regions of the world,where HCV is endemic and long-term sequelae have a growing economic and health burden.An HCV vaccine is still no available,despite years of researches and discoveries about the natural history of infection and host-virus interactions:several HCV vaccine candidates have been developed in the last years,targeting different HCV antigens or using alternative delivery systems,but viral variability and adaption ability constitute major challenges for vaccine development.Many new antiviral drugs for HCV therapy are in preclinical or early clinical development,but different limitations affect treatment validity.Treatment predictors are important tools,as they provide some guidance for the management of therapy in patients with chronic HCV infection:in particular,the role of host genomics in HCV infection outcomes in the new era of direct-acting antivirals may evolve for new therapeutic targets,representing a chance for modulated and personalized treatment management,when also very potent therapies will be available.In the present review we discuss the most recent data about HCV epidemiology,the new perspectives for the prevention of HCV infection and the most recent evidence regarding HCV diagnosis,therapy and predictors of response to it.

Hepatitis B virus/hepatitis D virus epidemiology: Changes over time and possible future influence of the SARS-CoV-2 pandemic

Hepatitis D virus(HDV)is a defective liver-tropic virus that needs the helper function of hepatitis B virus(HBV)to infect humans and replicate.HDV is transmitted sexually or by a parenteral route,in co-infection with HBV or by super-infection in HBV chronic carriers.HDV infection causes acute hepatitis that may progress to a fulminant form(7%-14%by super-infection and 2%-3%by HBV/HDV co-infection)or to chronic hepatitis(90%by HDV super-infection and 2%-5%by HBV/HDV co-infection),frequently and rapidly progressing to cirrhosis or hepatocellular carcinoma(HCC).Peg-interferon alfa the only recommended therapy,clears HDV in only 10%-20%of cases and,consequently,new treatment strategies are being explored.HDV endemicity progressively decreased over the 50 years from the identification of the virus,due to improved population lifestyles and economic levels,to the use of HBV nuclei(t)side analogues to suppress HBV replication and to the application of universal HBV vaccination programs.Further changes are expected during the severe acute respiratory syndrome coronavirus-2 pandemic,unfortunately towards increased endemicity due to the focus of healthcare towards coronavirus disease 2019 and the consequently lower possibility of screening and access to treatments,lower care for patients with severe liver diseases and a reduced impulse to the HBV vaccination policy.

Hepatitis D virus infection, replication and cross-talk with the hepatitis B virus

Viral hepatitis remains a worldwide public health problem.The hepatitis D virus(HDV)must either coinfect or superinfect with the hepatitis B virus(HBV).HDV contains a small RNA genome(approximately 1.7 kb)with a single open reading frame(ORF)and requires HBV supplying surface antigens(HBsAgs)to assemble a new HDV virion.During HDV replication,two isoforms of a delta antigen,a small delta antigen(SDAg)and a large delta antigen(LDAg),are produced from the same ORF of the HDV genome.The SDAg is required for HDV replication,whereas the interaction of LDAg with HBsAgs is crucial for packaging of HDV RNA.Various clinical outcomes of HBV/HDV dual infection have been reported,but the molecular interaction between HBV and HDV is poorly understood,especially regarding howHBV and HDV compete with HBsAgs for assembling virions.In this paper,we review the role of endoplasmic reticulum stress induced by HBsAgs and the molecular pathway involved in their promotion of LDAg nuclear export.Because the nuclear sublocalization and export of LDAg is regulated by posttranslational modifications(PTMs),including acetylation,phosphorylation,and isoprenylation,we also summarize the relationship among HBsAg-induced endoplasmic reticulum stress signaling,LDAg PTMs,and nuclear export mechanisms in this review.

Molecular interactions between hepatitis B virus and delta virus

As a deficient virus due to the lack of envelope proteins, hepatitis D virus(HDV) causes chronic or fulminant "delta hepatitis" only in people with simultaneous hepatitis B virus(HBV) infection. HBV encodes three types of surface proteins known as small(S), medium(M) and large(L) envelope proteins. All three types of HBV surface antigens(HBs Ags) are present on HDV virions. The envelopment process of HDV occurs through interactions between the HDV ribonucleoprotein(RNP) complex and HBV HBsA gs. While HBsA g is the only protein required by HDV, the exact interaction sites between the S protein and pre-mature HDV are not well defined yet. In fact, these sites are distributed along the S protein with some hot spots for the envelopment process. Moreover, in most clinically studied samples, HDV infection is associated with a dramatically reduced HBV viral load, temporarily or permanently, while HBsA g resources are available for HDV packaging. Thus, beyond interacting with HBV envelope proteins, controlling mechanisms exist by which HDV inhibits HBV-DNA replication while allowing a selective transcription of HBV proteins. Here we discuss the molecular interaction sites between HBs Ag and the HDV-RNP complex and address the proposed indirect mechanisms, which are employed by HBV and HDV to facilitate or inhibit each other's viral replication. Understanding molecular interactions between HBV and HDV may help to design novel therapeutic strategies for delta hepatitis.

HBsAg stimulates NKG2D receptor expression on natural killer cellsand inhibits hepatitis C virus replication

Background： Higher hepatitis B surface antigen （HBsAg） facilitates hepatitis C virus （HCV） clearance inpatients with hepatitis B virus （HBV）/HCV co-infection. We investigated the effect of exogenous HBsAgon the inhibition of HCV replication mediated by natural killer （NK） cells.

Innate immune recognition and modulation in hepatitis D virus infection

Hepatitis D virus(HDV)is a global health threat with more than 15 million humans affected.Current treatment options are largely unsatisfactory leaving chronically infected humans at high risk to develop liver cirrhosis and hepatocellular carcinoma.HDV is the only human satellite virus known.It encodes only two proteins,and requires Hepatitis B virus(HBV)envelope protein expression for productive virion release and spread of the infection.How HDV could evolve and why HBV was selected as a helper virus remains unknown.Since the discovery of Na+-taurocholate co-transporting polypeptide as the essential uptake receptor for HBV and HDV,we are beginning to understand the interactions of HDV and the immune system.While HBV is mostly regarded a stealth virus,that escapes innate immune recognition,HBV-HDV coinfection is characterized by a strong innate immune response.Cytoplasmic RNA sensor melanoma differentiation antigen 5 has been reported to recognize HDV RNA replication and activate innate immunity.Innate immunity,however,seems not to impair HDV replication while it inhibits HBV.In this review,we describe what is known up-to-date about the interplay between HBV as a helper and HDV’s immune evasion strategy and identify where additional research is required.

Searching for nuclear export elements in hepatitis D virus RNA

AIM: To search for the presence of cis elements in hepatitis D virus(HDV) genomic and antigenomic RNA capable of promoting nuclear export. METHODS: We made use of a well characterized chloramphenicol acetyl-transferase reporter system based on plasmid p DM138. Twenty c DNA fragments corresponding to different HDV genomic and antigenomic RNA sequences were inserted in plasmid pD M138, and used in transfection experiments in Huh7 cells. The relative amounts of HDV RNA in nuclear and cytoplasmic fractions were then determined by realtime polymerase chain reaction and Northern blotting. The secondary structure of the RNA sequences that displayed nuclear export ability was further predicted using a web interface. Finally, the sensitivity to leptomycin B was assessed in order to investigate possible cellular pathways involved in HDV RNA nuclear export.RESULTS: Analysis of genomic RNA sequences did not allow identifying an unequivocal nuclear export element. However, two regions were found to promote the export of reporter m RNAs with efficiency higher than the negative controls albeit lower than the positive control. These regions correspond to nucleotides 266-489 and 584-920, respectively. In addition, when analyzing antigenomic RNA sequences a nuclear export element was found in positions 214-417. Export mediated by the nuclear export element of HDV antigenomic RNA is sensitive to leptomycin B suggesting a possible role of CRM1 in this transport pathway. CONCLUSION: A cis-acting nuclear export element is present in nucleotides 214-417 of HDV antigenomic RNA.

Inhibition of Hepatitis B Virus Replication and Expression in Vitro and in Vivo by the Hammerhead Ribozymes Targeted Different Sites

Objective To develop an effective and specific medicine targeting hepatitis B virus(HBV) pregenome. Based on the identified accessible target sites for hammerhead ribozyme in our previous researches, a recombinant hepatitis delta virus(HDV) ribozyme was chosen and used to demonstrate the effective cleavage in vitro and in vivo. Methods Three hammerhead ribozymes for potential target sites(S, X and C genes) and co-expression plasmid(pTr-dB, pTdδ-dB, pTrX-dB and pTrC-dB) as well as four HDV-ribozyme chimera constructs with HBV(pTdXX, pTdXC, pTdSX and pTdSC) were severally chosen to validate the inhibition of the replication and expression of HBV. The co-expression plasmids(pTdδ and pTr-Db) in physiological saline were hydrodynamically injected to mice by tail vein. Results Compared with the group injected with pTr-dB in Huh-7 cell, hepatitis B surface antigen(HBsAg) was reduced by 31% in the group injected with pTdδ-dB, by 54%, 26%, 72% and 97% in the group injected with recombinant-ribozymes pTdSX, pTdSC, pTdXC and pTdXX, respectively. The inhibiting effects of endogenous ribozymes RzX and RzC on the HBsAg expression were 66% and 57%, respectively. Compared with the positive control, the amount of HBsAg was decreased in mice injected with pTdXX through tail vein by 88% and 96% on the second day and the third day, respectively. HBsAg was undetectable on the 6th day and could not primitively be detected on the 9th day in the sera from all mice. HBV DNA was not detected in the sera of BALB/c mice injected with pTdXX-dB, pTrX-dB or replicating-defective plasmid pHBV, while HBV DNA replication in control group could be detected on the 6th day. While HBcAg could not be detected in liver tissues of mice injected with plasmid pTdXX-dB on the 3rd day. Conclusions Encoding regions of HBV S, C and X gene were the effective cleavage sites for hammerhead ribozyme in vitro and in vivo, which provides basis for further construction of therapeutic recombinant HDV and the development of targeting antiviral gene therapy.

Hepatitis B and D viruses replication interference: Influence of hepatitis B genotype

AIM: To study the hepatitis B virus(HBV) and hepatitis D virus(HDV) replication interferences in patients with chronic hepatitis delta infected with different HBV genotypes.METHODS: We conducted a transversal study including 68 chronic hepatitis delta(CHD)(37 HIVpositive) patients and a control group of 49 chronic hepatitis B(CHB)(22 HIV-positive) patients. In addition, a dynamic follow-up was performed in 16 CHD patients. In all the samples, the surface antigen of hepatitis B(HBs Ag) serum titers were analyzed with the Monolisa HBs Ag Ultra system(Bio-Rad), using as quantification standard a serial dilution curve of an international HBs Ag standard. Serum HBV-DNA titers were analyzed using the Roche Cobas Taq Man(Roche, Barcelona, Spain), and the serum HDV-RNA using an in-house real-time q RT-PCR method, with Taq Man probes. HBV genotype was determined with the line immunoassay Li PA HBV genotyping system(Innogenetics, Ghent, Belgium). In those patients negative for Li PA assay, a nested PCR method of complete HBs Ag coding region, followed by sequence analysis was applied.RESULTS: No differences in the HBV-DNA levels were found in CHB patients infected with different HBV genotypes. However, in CHD patients the HBV-DNA levels were lower in those infected with HBV-A than in those with HBV-D, both in HIV negative [median(IQR): 1.25(1.00-1.35) vs 2.95(2.07-3.93) log10(copies/m L), P = 0.013] and HIV positive patients [2.63(1.24-2.69) vs 7.25(4.61-7.55) log10(copies/m L), P < 0.001]. This was confirmed in the dynamic study of the HBV/HDV patients. These differences induce an under-estimation of HBV-A incidence in patients with CHD analyzed with Li PA assay. Finally, the HBs Ag titers reflected no significant differences in CHD patients infected with HBV-A or D.CONCLUSION: Viral replication interference between HBV and HDV is HBV-genotype dependent, and more evident in patients infected with HBV-genotype A, than with HBV-D or E.

Vitamin D in addition to peg-interferon-alpha/ribavirin in chronic hepatitis C virus infection: ANRS-HC25-VITAVIC study

AIM: To investigate if correction of hypovitaminosis D before initiation of Peg-interferon-alpha/ribavirin(Peg IFN/RBV) therapy could improve the efficacy of Peg IFN/RBV in previously null-responder patients with chronic genotype 1 or 4 hepatitis C virus(HCV) infection.METHODS:Genotype 1 or 4 HCV-infected patients with null response to previous Peg IFN/RBV treatment and with hypovitaminosis D(<30 ng/m L)prospectively received cholecalciferol 100000 IU per week for 4 wk[from week-4(W-4)to W0],followed by 100000 IUper month in combination with Peg IFN/RBV for 12 mo(from W0 to W48).The primary outcome was the rate of early virological response defined by an HCV RNA<12 IU/m L after 12 wk Peg IFN/RBV treatment.RESULTS:A total of 32 patients were included,19(59%)and 13(41%)patients were HCV genotype1 and 4,respectively.The median baseline vitamin D level was 15 ng/m L(range:7-28).In modified intention-to-treat analysis,29 patients who received at least one dose of Peg IFN/RBV were included in the analysis.All patients except one normalized their vitamin D serum levels.The rate of early virologic response was 0/29(0%).The rate of HCV RNA<12IU/m L after 24 wk of Peg IFN/RBV was 1/27(4%).The safety profile was favorable.CONCLUSION:Addition of vitamin D to Peg IFN/RBV does not improve the rate of early virologic response in previously null-responders with chronic genotype 1or 4 HCV infection.

"Defective" mutations of hepatitis D viruses in chronic hepatitis D patients

AIM: To verify whether 'defective' mutations existed in hepatitis D virus (HDV).METHODS: Hepatitis delta antigen (HDAg)-codingsequences were amplified using Pfu DNA polymerases with proof-reading activities from sera of five patients with chronic hepatitis D. Multiple colonies were sequenced for each patient. Pfu analyzed a total of 270 HDV clones.Three representative defective HDV clones were constructed in expression plasmids and transfected into a human hepatoma cell line. Cellular proteins were extracted and analyzed by Western blot.RESULTS: Four of five cases (80%) showed defective HDV genomes in their sera. The percentage of defective genomes was 3.7% (10/270). The majority (90%) of the defective mutations were insertions or deletions that resulted in frameshift and abnormal stop translation of the HDAg. The predicted mutated HDAg ranged from 45amino acids to ＞214 amino acids in length. Various domains of HDAg associated with viral replication or packaging were affected in different HDV isolates. Western blot analysis showed defected HDAg in predicted positions.CONCLUSION: 'Defective' viruses do exist in chronic HDV infected patients, but represented as minor strains. The clinical significance of the 'defected' HDV needs further study to evaluate.

Molecular and clinical aspects of hepatitis D virus infections

Hepatitis D virus(HDV) is a defective virus with circular, single-stranded genomic RNA which needs hepatitis B virus(HBV) as a helper virus for virion assembly and infectivity. HDV virions are composed of a circular shape HDV RNA and two types of viral proteins, small and large HDAgs, surrounded by HBV surface antigen(HBs Ag). The RNA polymerase Ⅱ from infected hepatocytes is responsible for synthesizing RNAs with positive and negative polarities for HDV, as the virus does not code any enzyme to replicate its genome. HDV occurs as co-infection or super-infection in up to 5% of HBs Ag carriers. A recent multi-center study highlighted that pegylated interferon α-2a(PEG-IFN) is currently the only treatment option for delta hepatitis. Nucleotide/nucleoside analogues, which are effective against HBV, have no relevant effects on HDV. However, additional clinical trials combining PEG-IFN and tenofovir are currently ongoing. The molecular interactions between HDV and HBV are incompletely understood. Despite fluctuating patterns of HBV viral load in the presence of HDV in patients, several observations indicate that HDV has suppressive effects on HBV replication, and even in triple infections with HDV, HBV and HCV, replication of both concomitant viruses can be reduced. Additional molecular virology studies are warranted to clarify how HDV interacts with the helper virus and which key cellular pathways are used by both viruses. Further clinical trials are underway to optimize treatment strategies for delta hepatitis.

Association of vitamin D and polymorphisms of its receptor with antiviral therapy in pregnant women with hepatitis B

BACKGROUND The interruption of mother-to-child transmission(MTCT)is considered important to decrease the individual and population morbidity of hepatitis B virus(HBV)infection as well as the global burden of hepatitis B.Serum vitamin D(VD)is associated with hepatitis B.AIM To assess whether baseline VD levels and single nucleotide polymorphisms of the VD receptor gene(VDR SNPs)are associated with the efficacy of tenofovir disoproxil fumarate(TDF)in the prevention of MTCT in pregnant women with high HBV viral loads.METHODS Thirty-eight pregnant women who were at high risk for MTCT of HBV(those with an HBV DNA level≥2×10^(5)IU/mL during 12-24 wk of gestation)receiving antiviral therapy of TDF between June 1,2019 and June 30,2021 in Mianyang were included in this retrospective study.The women received 300 mg TDF once daily from gestational weeks 24-28 until 3 mo after delivery.To further characterize the clinical relevance of maternal serum HBV DNA levels,we stratified patients according to HBV DNA level as follows:Those with levels<2×10_(5)(full responder group)vs those levels≥2×10^(5)IU/mL(partial responder group)at delivery.Serum levels of 25-hydroxyvitamin D[25(OH)D],liver function markers,virological parameters,VDR SNPs and other clinical parameters were collected to analyze their association with the efficacy of TDF.The Mann-Whitney U test or t test was used to analyze the serum levels of 25(OH)D in different groups.Multiple linear regressions were utilized to analyze the determinants of the maternal HBV DNA level at delivery.Univariate and multivariate logistic regression analyses were employed to explore the association of targeted antiviral effects with various characteristics at baseline and delivery.RESULTS A total of 38 pregnant women in Mianyang City at high risk for MTCT of HBV were enrolled in the study.The MTCT rate was 0%.No mother achieved hepatitis B e antigen or hepatitis B surface antigen(HBsAg)clearance at delivery.Twenty-three(60.5%)participants were full responders,and 15(39.5%)participants were partial responders according to antiviral efficacy.The present study showed that a high percentage(76.3%)of pregnant women with high HBV viral loads had deficient(<20 ng/mL)or insufficient(≥20 but<31 ng/mL)VD levels.Serum 25(OH)D levels in partial responders appeared to be significantly lower than those in full responders both at baseline(25.44±9.42 vs 17.66±5.34 ng/mL,P=0.006)and delivery(26.76±8.59 vs 21.24±6.88 ng/mL,P=0.044).Serum 25(OH)D levels were negatively correlated with maternal HBV DNA levels[log(10)IU/mL]at delivery after TDF therapy(r=-0.345,P=0.034).In a multiple linear regression analysis,maternal HBV DNA levels were associated with baseline maternal serum 25(OH)D levels(P<0.0001,β=-0.446),BMI(P=0.03,β=-0.245),baseline maternal log10 HBsAg levels(P=0.05,β=0.285)and cholesterol levels at delivery(P=0.015,β=0.341).Multivariate logistic regression analysis showed that baseline serum 25(OH)D levels(OR=1.23,95%CI:1.04-1.44),maternal VDR Cdx2 TT(OR=0.09,95%CI:0.01-0.88)and cholesterol levels at delivery(OR=0.39,95%CI:0.17-0.87)were associated with targeted antiviral effects(maternal HBV DNA levels<2×10^(5) at delivery).CONCLUSION Maternal VD levels and VDR SNPs may be associated with the efficacy of antiviral therapy in pregnant women with high HBV viral loads.Future studies to evaluate the therapeutic value of VD and its analogs in reducing the MTCT of HBV may be justified.

我国部分地区慢性HBV感染者HDV感染情况调查

目的了解目前我国部分地区慢性HBV感染者丁型肝炎病毒(HDV)感染流行情况。方法2021年3月—2022年6月从全国10个省市自治区收集3131例慢性HBV感染者血清,用抗-HDV IgG酶联免疫试剂检测全部血清标本。对抗-HDV IgG阳性标本用巢式逆转录聚合酶链式反应(nRT-PCR)法检测HDV RNA。对HDV RNA阳性标本的nRT-PCR扩增产物测序后进行序列分析,确定HDV基因型。分析抗-HDV IgG阳性患者的临床特征。计量资料两组间比较采用Mann-Whitney U秩和检验。计数资料两组间比较采用χ^(2)检验或Fisher精确检验。结果3131例慢性HBV感染者的抗-HDV IgG阳性率为0.70%(22/3131),内蒙古自治区、新疆维吾尔自治区、北京市和湖南省慢性HBV感染者的抗-HDV IgG阳性率分别为1.81%(16/886)、0.88%(2/226)、0.28%(2/708)和1.00%(2/200),其中内蒙古自治区慢性HBV感染者抗-HDV IgG阳性率显著高于北京市(P=0.004),其余地区间比较差异均无统计学意义(P值均>0.05)。对内蒙古自治区慢性HBV感染者临床特征分析发现,抗-HDV IgG阳性组蒙古族患者(P=0.001)、ALT异常患者(P=0.007)和抗病毒治疗患者(P=0.029)的比例显著高于抗-HDV IgG阴性组,而中位HBV DNA水平明显较低(P=0.030)。共检出19例HDV RNA阳性标本,均为HDV基因1型。结论我国不同地区HDV流行率差异较大,内蒙古自治区慢性HBV感染者中HDV流行率较高。我国北方部分省市的HDV流行基因型主要为1型。