Impact of baseline hepatitis B virus viral load on the long-term prognosis of advanced hepatocellular carcinoma treated with immunotherapy

BACKGROUND Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma(HCC),real data on the impact of baseline hepatitis B virus(HBV)-DNA levels on the clinical efficacy of this regimen is still limited.AIM To evaluate the effectiveness of camrelizumab combined with lenvatinib in patients with HCC at varying levels of HBV-DNA.METHODS One hundred and twenty patients with HCC who received camrelizumab and lenvatinib treatment were categorized into two cohorts:HBV-DNA≤2000(n=66)and HBV-DNA>2000(n=54).The main outcomes measured were overall survival(OS)and progression-free survival(PFS),while additional outcomes included the rate of objective response rate(ORR),disease control rate(DCR),and any negative events.Cox proportional hazards regression analysis revealed independent predictors of OS,leading to the creation of a nomogram incorporating these variables.RESULTS The median PFS was 8.32 months for the HBV-DNA≤2000 group,which was similar to the 7.80 months observed for the HBV DNA>2000 group(P=0.88).Likewise,there was no notable variation in the median OS between the two groups,with durations of 13.30 and 14.20 months respectively(P=0.14).The ORR and DCR were compared between the two groups,showing ORR of 19.70%vs 33.33%(P=0.09)and DCR of 72.73%vs 74.07%(P=0.87).The nomogram emphasized the importance of antiviral treatment as the main predictor of patient results,with portal vein tumor thrombus and Barcelona Clinic Liver Cancer staging following closely behind.CONCLUSION The clinical outcomes of patients with HBV-associated HCC treated with camrelizumab in combination with lenvatinib are not significantly affected by HBV viral load.

Virus load and virus shedding of SARS-CoV-2 and their impact onpatient outcomes

BACKGROUND Understanding a virus shedding patterns in body fluids/secretions is importantto determine the samples to be used for diagnosis and to formulate infectioncontrol measures.AIM To investigate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)shedding patterns and its risk factors.METHODS All laboratory-confirmed coronavirus disease 2019 patients with completemedical records admitted to the Shenzhen Third People’s Hospital from January28, 2020 to March 8, 2020 were included. Among 145 patients (54.5% males;median age, 46.1 years), three (2.1%) died. The bronco-alveolar lavage fluid(BALF) had the highest virus load compared with the other samples. The viralload peaked at admission (3.3 × 108 copies) and sharply decreased 10 d afteradmission.RESULTS The viral load was associated with prolonged intensive care unit (ICU) duration.Patients in the ICU had significantly longer shedding time compared to those inthe wards (P < 0.0001). Age > 60 years [hazard ratio (HR) = 0.6;95% confidenceinterval (CI): 0.4-0.9] was an independent risk factor for SARS-CoV-2 shedding,while chloroquine (HR = 22.8;95%CI: 2.3-224.6) was a protective factor.CONCLUSION BALF had the highest SARS-CoV-2 load. Elderly patients had higher virus loads,which was associated with a prolonged ICU stay. Chloroquine was associatedwith shorter shedding duration and increased the chance of viral negativity.

Human bocavirus infection in children hospitalized with lower respiratory tract infections:Does viral load affect disease course?

Objective:To examine the effects of human bocavirus type 1(HBoV1)on the course of lower respiratory tract infections in cases of monoinfection and coinfection,and the effects of HBoV1 viral load on the disease in children under six years old hospitalized with a diagnosis of HBoV1-associated lower respiratory tract infections.Methods:Children under six years of age,who were hospitalized with the diagnosis of lower respiratory tract infection due to HBoV1 between 1 January 2021 and 1 January 2022 were included in the study.Laboratory confirmation of the respiratory pathogens was performed using polymerase chain reaction(PCR).Results:Fifty-four(16.4%)children with HBoV1 among 329 children whose PCR was positive with bacterial/viral agent in nasopharyngeal swab samples were included in the study.There were 28(51.9%)males and 26(48.1%)females with a median age 23.4 months[interquartile range(IQR):13.2,30.0 months](min-max:1 month-68 months).HBoV1 was detected as a monoinfecton in 26(48.1%)children,and as a coinfection with other respiratory agents in 28 children(51.9%).In multiple regression analysis,coinfection(P=0.032)was associated with the length of hospitalization(P<0.001;R^(2)=0.166).There was a negative correlation(r=−0.281,P=0.040)between cough and cycle threshold.Fever was found to be positively correlated with C-reactive protein(r=0.568,P<0.001)and procalcitonin(r=0.472;P=0.001).Conclusions:Although we found a higher HBoV1 viral load in children with more cough symptoms in our study,it had no effect on the severity of the disease,such as length of hospital stay and need for intensive care.Coinfection was found to affect the length of hospitalization.

Sex disparity in viral load, inflammation and liver damage in transgenic mice carrying full hepatitis B virus genome with the W4P mutation in the preS1 region

AIM To study sex disparity in susceptibility to hepatocellular carcinoma(HCC), we created a transgenic mouse model that expressed the full hepatitis B virus(HBV) genome with the W4P mutation.METHODS Transgenic mice were generated by transferring the p HY92-1.1 x-HBV-full genome plasmid(genotype A2) into C57 Bl/6 N mice. We compared serum levels of hepatitis B surface antigen(HBs Ag), interleukin(IL)-6, and the liver enzymes alanine aminotransferase(ALT) and aspartate transaminase(AST), as well as liver histopathological features in male and female transgenic(W4PTG) mice and in nontransgenic littermates of 10 mo of age. RESULTS W4PTG males exhibited more pronounced hepatomegaly, significantly increased granule generation in liver tissue, elevated HBs Ag expression in the liver and serum, and higher serum ALT and IL-6 levels compared to W4PTG females or littermate control groups. CONCLUSION Together, our data indicate that the W4 P mutation in pre S1 may contribute to sex disparity in susceptibility to HCC by causing increased HBV virion replication and enhanced IL-6-mediated inflammation in male individuals. Additionally, our transgenic mouse model that expresses full HBV genome with the W4 P mutation in pre S1 could be effectively used for the studies of the progression of liver diseases, including HCC.

Preparation, characterization and in vivo evaluation of alginate-coated chitosan and trimethylchitosan nanoparticles loaded with PR8 influenza virus for nasal immunization

For efficient mucosal vaccine delivery, nanoparticulate antigens are better taken by microfold cells in the nasal associated lymphoid tissue and also dendritic cells. Nanoparticles based on polymers such as chitosan(CHT) and its water soluble derivative, trimethylchitosan(TMC), could be successfully used as carrier/adjuvant for this purpose. Sodium alginate, a negatively charged biopolymer, could modify the immunostimulatory properties of CHT and TMC NPs and increase their stability. Sodium alginate(ALG)-coated chitosan(CHT)and trimethylchitosan(TMC) nanoparticles(NPs) loaded with inactivated PR8 influenza virus were successfully prepared by direct coating of the virus with CHT or TMC polymers to evaluate their immunoadjuvant potential after nasal immunization. After nasal immunizations in BALB/c mice, PR8-CHT formulation elicited higher IgG2 a and Ig G1 antibody titers compared with PR8-TMC. ALG coating of this formulation(PR8-CHT-ALG) significantly decreased the antibody titers and a less immune response was induced than PR8-TMC-ALG formulation. PR8-TMC-ALG formulation showed significantly higher Ig G2 a/Ig G1 ratio, as criteria for Th1-type immune response, compared with PR8-CHT-ALG and PR8 virus alone. Altogether, the PR8-TMC-ALG formulation could be considered as an efficient intranasal antigen delivery system for nasal vaccines.

Relevance of low viral load in haemodialysed patients with chronic hepatitis C virus infection

AIM: To identify predictors of sustained virological response in hemodialysed patients treated by PEGinterferon α for chronic hepatitis C, genotype 1.METHODS: The sustained virological response(SVR) rate, IL28 B genotype, IFNL4 genotype, initial viral load(IVL) and other pretreatment variables in 39 endstage renal disease patients(ESRD) on maintenance haemodialysis(HD) infected with hepatitis C virus(HCV), genotype 1b, were compared with a control group of 109 patients with normal kidney function treated within the same period. All the patients were treatment nave and had well compensated liver disease. The ESRD patients received 135 μg of PEGylated interferon α-2a(Peg IFN-α) weekly and a reduced dose of ribavirin(RBV) was administered to 23/39 patients with an initial haemoglobin level > 10 g/d L. Control group patients were given standard doses of Peg IFN-α and RBV. SVR was assessed as HCV RNA negativity 24 wk post-treatment. A t-test or ANOVA were used for comparisons of the means and a χ2 testcompared the frequencies.Logistic regression was used to determine significant predictors of SVR.Cutoff values for continuous variables were obtained from Receiver Operating Characteristic analysis.RESULTS:The distribution of IL28B rs12979860 CC,CT and TT genotypes in the ESRD group was 28.2%,64.1%and 7.7%,respectively,and 19.3%,62.4%and18.3%in the controls.The IFNL4 genotype was in almost absolute linkage disequlibrium with IL28B.The proportion of patients with a low IVL(<600000 IU/m L)was significantly higher in the ESRD group than in the controls(28/39,71.8%vs 51/109,46.8%,P=0.009),as was the proportion of patients with low IVL in IL28B CC carriers compared with non-CC carriers in the ESRD group(10/11,90.9%vs 18/28,64.3%,P=0.0035).This difference was not found in the controls(7/22,31.8%vs 44/87,50.6%,P=0.9).The overall SVR rate was 64.1%(25/39)in the ESRD group and 50.5%(55/109)in the control group(P=0.19).11/11(100%)and 19/22(86.4%)IL28B CC patients achieved SVR in the ESRD and control groups,respectively.A statistically significant association between SVR and IL28B and IFNL4 variants was found in both groups.The ESRD patients who achieved SVR showed the lowest IVL[median 21000,interquartile range(IQR):6000-23000IU/m L],compared with ESRD individuals without SVR(1680000,IQR:481000-6880000,P=0.001),controls with SVR(387000,IQR:111000-1253000)and controls without SVR(905000,IQR:451000-3020000).In ESRD,an IVL<600000 IU/m L was strongly associated with SVR:24/28(85.7%)patients who achieved SVR had viraemia below this threshold.CONCLUSION:Haemodialysis decreases the viral load,especially in IL28B CC genotype carriers.A low IVL was the strongest predictor of SVR in ESRD patients identified in multivariate analysis.

Hepatitis B virus persistent infection-related single nucleotide polymorphisms in HLA regions are associated with viral load in hepatoma families

BACKGROUND Genome-wide association studies from Asia indicate that HLA-DP and HLA-DQ loci are important in persistent hepatitis B virus(HBV)infections.One of the key elements for HBV-related carcinogenesis is persistent viral replication and inflammation.AIM To examine genetic and nongenetic factors with persistent HBV infection and viral load in families with hepatocellular carcinoma(HCC).METHODS The HCC families included 301 hepatitis B surface antigen(HBsAg)carriers and 424 noncarriers born before the nationwide vaccination program was initiated in 1984.Five HBV-related single nucleotide polymorphisms(SNPs)—rs477515,rs9272105,rs9276370,rs7756516,and rs9277535—were genotyped.Factors associated with persistent HBV infection and viral load were analyzed by a generalized estimating equation.RESULTS In the first-stage persistent HBV study,all SNPs except rs9272105 were associated with persistent infection.A significantly higher area under the reciprocal operating characteristic curve for nongenetic factors vs genetic factors(P<0.001)suggests that the former play a major role in persistent HBV infection.In the second-stage viral load study,we added 8 HBsAg carriers born after 1984.The 309 HBsAg carriers were divided into low(n=162)and high viral load(n=147)groups with an HBV DNA cutoff of 105 cps/mL.Sex,relationship to the index case,rs477515,rs9272105,and rs7756516 were associated with viral load.Based on the receiver operating characteristic curve analysis,genetic and nongenetic factors affected viral load equally in the HCC family cohort(P=0.3117).CONCLUSION In these east Asian adults,the mechanism of persistent HBV infection-related SNPs was a prolonged viral replication phase.

The Monitoring Interest of BK Virus Load in Renal Allograft Tunisian Recipients: Prospective Study

BK virus (BKV) may cause nephropathy in renal transplant recipients receiving immunosuppressive therapy, resulting in renal dysfunction and, possibly graft loss. However, the positive and negative predictive values of BK viral load are still controversial. In this prospective, single-center study, BKV DNA was measured 1, 3 and 6 months after transplantation. The viral load in urine and plasma was quantified with the real-time Q-PCR (Argen kit) in 73 renal allograft recipients Three of them showed acute rejection. To determine the cutoff value of viral load, 60 sera samples of healthy blood donors, matched for age and sex, were tested. The mean plasmatic viral load one month post-transplantation was statistically higher in renal transplant recipients (17.23 copies/ml) compared to that in controls (2 copies/ml) (p: 0.06). This difference of the distribution of viremia values is more evident in the third and sixth month (p: 0.002 and 0.010 respectively). Furthermore, analysis of the kinetic of viral load revealed an average rise of viremia at 3 months (1589.14 copies/ml) followed by its decrease at 6 months (249.75 copies/ml). However, the difference was not statistically significant. The same is true for the distribution of values of viruria and in all cases the average viral load was statistically higher in urine than in plasma. In addition, this study did not shown significant relationsheep between viremia/viruria and the occurrence of acute rejection, the renal function deterioration, the source of allograft or immunosuppressive therapy protocol. If the results of this study demonstrate the importance of the replication of BKV in renal transplant patients from the first month compared to that in immunocompetent subjects, the screening of the DNA of this virus does not appear to have a prognostic value in the occurrence of acute rejection. However, the plasma and urine monitoring of BKV load beyond 6 months , not appear to exclude the relationsheep between these two biomarkers and the occurrence of chronic graft dysfunction.

Emerging role of liquid biopsy in rat sarcoma virus mutated metastatic colorectal cancer:A case report

BACKGROUND In patients with metastatic colorectal cancer(mCRC),the treatment options are limited and have been proved to be affected by rat sarcoma virus(RAS)mutational status.In RAS wild-type(wt)patients,the combination of antiepidermal growth factor receptor(EGFR)monoclonal antibodies with chemotherapy(CT)is more effective than CT alone.On the other hand,RAS-mutated patients are not eligible for treatment with anti-EGFR antibodies.CASE SUMMARY Eleven patients with initially RAS-mutated mCRC were followed from diagnosis to May 2022.At the time of cell-free DNA determination,five patients had undergone one CT line,five patients had undergone two CT lines,and one patient had undergone three CT lines(all in combination with bevacizumab).At the second and third treatment lines[second line(2L),third line(3L)],patients with neo-RAS wt received a combination of CT and cetuximab.In neo-RAS wt patients treated with anti-EGFR,our findings indicated an increase in progression-free survival for both 2L and 3L(14.5 mo,P=0.119 and 3.9 mo,P=0.882,respectively).Regarding 2L overall survival,we registered a slight increase in neo-RAS wt patients treated with anti-EGFR(33.6 mo vs 32.4 mo,P=0.385).At data cut-off,two patients were still alive:A RAS-mutated patient undergoing 3L treatment and a neo-RAS wt patient who received 2L treatment with anti-EGFR(ongoing).CONCLUSION Our case series demonstrated that monitoring RAS mutations in mCRC by liquid biopsy may provide an additional treatment line for neo-RAS wt patients.

Epstein-Barr virus DNA loads in the peripheral blood cells predict the survival of locoregionally-advanced nasopharyngeal carcinoma patients

Objective:Circulating cell-free Epstein-Barr virus(EBV)DNA has been shown to be a valuable biomarker for population screening and prognostic surveillance for nasopharyngeal carcinoma(NPC).Despite important insights into the biology of persistence,few studies have addressed the clinical significance of cell-based EBV-DNA loads in peripheral blood cells(PBCs).Methods:A prospective observational cohort study was conducted involving 1,063 newly diagnosed,locoregionally-advanced NPC patients at Sun Yat-sen University Cancer Center from 2005 to 2007.Cox regression analysis was conducted to identify the association of PBC EBV DNA loads to overall survival(OS)and other prognostic outcomes.Prognostic nomograms were developed based on PBC EBV DNA loads to predict survival outcomes for NPC patients.Results:After a median follow-up of 108 months,patients with higher PBC EBV-DNA loads had significantly worse OS[hazard ratio(HR)of medium,medium-high,and high vs.low were 1.50,1.52,and 1.85 respectively;Ptrend<0.001].Similar results were found for progression-free survival and distant metastasis-free survival.The concordance index of the prognostic nomogram for predicting OS in the training set and validation set were 0.70 and 0.66,respectively.Our data showed that the PBC EBV DNA load was an independent and robust survival biomarker,which remained significant even after adjusting for plasma EBV DNA loads in a subset of 205 patients of the cohort(HR:1.88;P=0.025).Importantly,a combination of PBC EBV DNA load and plasma EBV DNA load improved the predicted OS.Conclusions:The EBV-DNA load in PBCs may be an independent prognosis marker for NPC patients.

The Viral Load of Epstein-Barr Virus in Blood of Children after Hematopoietic Stem Cell Transplantation

Objective To detect the Epstein-Barr virus(EBV)viral load of children after hematopoietic stem cell transplantation(HSCT)using chip digital PCR(cdPCR).Methods The sensitivity of cdPCR was determined using EBV plasmids and the EBV B95-8 strain.The specificity of EBV cdPCR was evaluated using the EBV B95-8 strain and other herpesviruses(herpes simplex virus 1,herpes simplex virus 2,varicella zoster virus,human cytomegalovirus,human herpesvirus 6,and human herpesvirus 7).From May 2019 to September 2020,64 serum samples of children following HSCT were collected.EBV infection and the viral load of serum samples were detected by cdPCR.The epidemiological characteristics of EBV infections were analyzed in HSCT patients.Results The limit of detection of EBV cdPCR was 110 copies/mL,and the limit of detection of EBV quantitative PCR was 327 copies/mL for the pUC57-BALF5 plasmid.The result of EBV cdPCR was up to 121 copies/mL in the EBV B95-8 strain,and both were more sensitive than that of quantitative PCR.Using cdPCR,the incidence of EBV infection was 18.75%in 64 children after HSCT.The minimum EBV viral load was 140 copies/mL,and the maximum viral load was 3,209 copies/mL using cdPCR.The average hospital stay of children with EBV infection(184±91 days)was longer than that of children without EBV infection(125±79 days),P=0.026.Conclusion EBV cdPCR had good sensitivity and specificity.The incidence of EBV infection was 18.75%in 64 children after HSCT from May 2019 to September 2020.EBV cdPCR could therefore be a novel method to detect EBV viral load in children after HSCT.

Mechanical responses of anchoring structure under triaxial cyclic loading

Dynamic load on anchoring structures(AS)within deep roadways can result in cumulative damage and failure.This study develops an experimental device designed to test AS under triaxial loads.The device enables the investigation of the mechanical response,failure mode,instability assessment criteria,and anchorage effect of AS subjected to combined cyclic dynamic-static triaxial stress paths.The results show that the peak bearing strength is positively correlated with the anchoring matrix strength,anchorage length,and edgewise compressive strength.The bearing capacity decreases significantly when the anchorage direction is severely inclined.The free face failure modes are typically transverse cracking,concave fracturing,V-shaped slipping and detachment,and spallation detachment.Besides,when the anchoring matrix strength and the anchorage length decrease while the edgewise compressive strength,loading rate,and anchorage inclination angle increase,the failure intensity rises.Instability is determined by a negative tangent modulus of the displacement-strength curve or the continued deformation increase against the general downward trend.Under cyclic loads,the driving force that breaks the rock mass along the normal vector and the rigidity of the AS are the two factors that determine roadway stability.Finally,a control measure for surrounding rock stability is proposed to reduce the internal driving force via a pressure relief method and improve the rigidity of the AS by full-length anchorage and grouting modification.

Association of core promoter mutations of hepatitis B virus and viral load is different in HBeAg(+) and HBeAg(-) patients

AIM:To identify the prevalence of hepatitis B e antigen (HBeAg) and to assess the association of hepatitis B virus (HBV) core promoter mutations and viral load in Indonesian patients.METHODS:Sixty-four patients with chronic hepatitis,65 with liver cirrhosis and 50 with hepatocellular carcinoma were included in this study.HBeAg and hepatitis B e antibody (HBeAb) tests were performed using enzyme-linked immunosorbent assay and the mutations were analyzed by sequencing.Viral load was measured by real-time polymerase chain reaction.RESULTS:Of 179 patients,108 (60.3%) were HBeAg(-) and 86 (79.6%) of these HBeAg(-) patients had been seroconverted.The A1896 mutation was not found in HBeAg(+) patients,however,this mutation was detected in 70.7% of HBeAg(-) patients.This mutation was frequently found when HBeAg was not expressed (87.7%),compared to that found in HBeAg seroconverted patients (65.1%).The A1899 mutation was also more prevalent in HBeAg(-) than in HBeAg(+) patients (P=0.004).The T1762/A1764 mutation was frequently found in both HBeAg(+) and HBeAg(-) patients,however,the prevalence of this mutation did not significantly differ among the two groups (P=0.054).In HBeAg(+) patients,the T1762/A1764 mutation was correlated with lower HBV DNA (P < 0.001).The A1899 mutation did not correlate with HBV DNA (P=0.609).In HBeAg(-) patients,the T1762/A1764 mutation alone was not correlated with HBV DNA (P=0.095),however,the presence of either the T1762/A1764 or A1896 mutations was associated with increased HBV DNA (P < 0.001).CONCLUSION:The percentage of HBeAg(-) patients is high in Indonesia,and most of the HBeAg(-) patients had been seroconverted.The A1896 mutation was most likely the major cause of HBeAg loss.The T1762/A1764 mutation alone was associated with lower viral loads in HBeAg(+) patients,but not in HBeAg(-) patients.

A novel approach to the dynamic response analysis of Euler-Bernoulli beams resting on a Winkler soil model and subjected to impact loads

This work presents a novel approach to the dynamic response analysis of a Euler-Bernoulli beam resting on a Winkler soil model and subjected to an impact loading.The approach considers that damping has much less importance in controlling the maximum response to impulsive loadings because the maximum response is reached in a very short time,before the damping forces can dissipate a significant portion of the energy input into the system.The development of two sine series solutions,relating to different types of impulsive loadings,one involving a single concentrated force and the other a distributed line load,are presented.This study revealed that when a simply supported Euler-Bernoulli beam,resting on a Winkler soil model,is subject to an impact load,the resulting vertical displacements,bending moments and shear forces produced along the span of the beam are considerably affected.In particular,the quantification of this effect is best observed,relative to the corresponding static solution,via an amplification factor.The computed impact amplification factors,for the sub-grade moduli used in this study,were in magnitude greater than 2,thus confirming the multiple-degree-of-freedom nature of the problem.

Current status of liver transplantation for human immunodeficiency virus-infected patients in China's Mainland

According to the report from the Chinese Center for Disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase of about 80000 cases.The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%,almost twice the rate of the general population in China.In addition to the well-documented susceptibility to opportunistic infections and new malignancies,HIV infected patients frequently experience liver-related organ damage,with the liver and kidneys being the most commonly affected.This often leads to the development of end-stage liver and kidney diseases.Therefore,organ transplantation has emerged as an important part of active treatment for HIV infected patients.However,the curative effect is not satisfactory.HIV infection has been considered a contraindication for organ transplantation.Until the emergence of highly active anti-retroviral therapy in 1996,the once intractable replication of retrovirus was effectively inhibited.With prolonged survival,the failure of important organs has become the main cause of death among HIV patients.Therefore,transplant centers worldwide have resu-med exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion.This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation(LT)in main-land China.To date,our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV,and all but one,who died two months postoperatively due to sepsis and progressive multi-organ failure,have survived.Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions,cytomegalovirus infection,bacteremia,pulmonary infections,acute kidney injury,new-onset cancers,or vascular and biliary complications.

56 Years of the Marburg Virus—A Review of Therapeutics

Background: The Marburg virus (MARV) is the causative agent of Marburg virus disease (MVD). This filovirus first appeared in 1967 and has since caused several outbreaks with case fatality rates between 23% and 90%. The earliest cases of MVD are thought to be caused by exposure to an infected animal, either a reservoir host (some bat species, e.g., Rousettus aegyptiacus) or a spill-over host, such as non-human primates. The virus is spread between people by direct contact with blood or other bodily fluids (including saliva, sweat, faeces, urine, tears, and breast milk) from infected individuals. Despite the high fatality rate, the Marburg virus has no vaccine or drug treatment. Recent outbreaks of the virus in 2023 in Tanzania and Equatorial Guinea have reignited the need to develop effective therapeutics, especially in the wake of the COVID-19 pandemic. Purpose: This review seeks to highlight the drug discovery efforts aimed at developing vaccines or possible treatments as potential therapeutics. Several existing antiviral agents are being probed, and vaccines are in pre-clinical and clinical stages. Natural products are also an important source of possible drugs or lead compounds and when coupled with computational techniques, these strategies offer possible therapeutics for the Marburg virus, especially in Africa, which has a high disease burden. Methods: Using the search engines Google Scholar and PubMed;keywords e.g. Marburg virus, Marburg treatments, Marburg virus drug discovery were utilized. Several results were yielded, and articles published in recent years were accepted into the final list.Results and Conclusion: This study shows there is a growing interest in therapeutics for the Marburg virus, especially with the recent outbreaks and pandemic preparedness. Initiatives that to support vaccine development and access like the MARVAC consort time are critical to fighting this public health threat.

Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection:How to achieve a better outcome

BACKGROUND Although the benefits of antiviral therapy for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)have been proven,researchers have not con-firmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time(at least 24 wk)and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC.AIM To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC.METHODS A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi’an Jiaotong University from January 2016 to June 2019 was conducted.Considering the history of antiviral therapy,patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups.RESULTS Kaplan–Meier analysis revealed significant differences in overall survival(P<0.0001)and disease-free survival(P=0.035)between the two groups.Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival(hazard ratio=0.27;95%confidence interval:0.08-0.88;P=0.030).CONCLUSION In patients with HBV-related HCC,it is ideal to receive preoperative long-term antiviral therapy,which helps patients tolerate more extensive hepatectomy;however,remedial antiviral therapy,which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL,can also result in improved outcomes.

Cytomegalovirus infection in non-immunocompromised critically ill patients:A management perspective

Critically ill patients are a vulnerable group at high risk of developing secondary infections.High disease severity,prolonged intensive care unit(ICU)stay,sepsis,and multiple drugs with immunosuppressive activity make these patients prone to immuneparesis and increase the risk of various opportunistic infections,including cytomegalovirus(CMV).CMV seroconversion has been reported in up to 33%of ICU patients,but its impact on patient outcomes remains a matter of debate.Even though there are guidelines regarding the management of CMV infection in immunosuppressive patients with human immunodeficiency virus/acquired immuno deficiency syndrome,the need for treatment and therapeutic approaches in immunocompetent critically ill patients is still ambiguous.Even the diagnosis of CMV infection may be challenging in such patients due to non-specific symptoms and multiorgan involvement.Hence,a better understanding of the symptomatology,diagnostics,and treatment options may aid intensive care physicians in ensuring accurate diagnoses and instituting therapeutic interventions.

Enhancement of CTLs induced by DCs loaded with ubiquitinated hepatitis B virus core antigen

AIM:To investigate whether hepatitis B virus (HBV) could induce a hepatitis B virus core antigen (HBcAg)specific cytotoxic T lymphocyte (CTL) response in vitro by dendritic cells (DCs) transduced with lentiviral vector-encoding ubiquitinated hepatitis B virus core antigen (LV-Ub-HBcAg).METHODS:Recombinant LV-Ub-HBcAg were transfected into highly susceptible 293 T cells to obtain high virus titres.Bone marrow-derived DCs isolated from BALB/c mice were cultured with recombinant granulocyte-macrophage colony-stimulating factor and recombinant interleukin (IL)-4.LV-Ub-HBcAg,lentiviral vector-encoding hepatitis B virus core antigen (LV-HBcAg),lentiviral vector (LV) or lipopolysaccharide were added to induce DC maturation,and the DC phenotypes were analyzed by flow cytometry.The level of IL-12 in the supernatant was detected by enzyme-linked immunosorbent assay (ELISA).T lymphocytes were proliferated using Cell Counting Kit-8.DCs were cultured and induced to mature using different LVs,and co-cultured with allogeneic T cells to detect the secretion levels of IL-2,IL-4,IL-10 and interferon-γ in the supernatants of T cells by ELISA.Intracellular cytokines of proliferative T cells were analyzed by flow cytometry,and specific CTL activity was measured by a lactate dehydrogenase release assay.RESULTS:LV-Ub-HBcAg-induced DCs secreted more IL-12 and upregulated the expression of CD80,CD86 and major histocompatibility class Ⅱ.DCs sensitised by different LVs effectively promoted cytokine secretion;the levels of IL-2 and interferon-γ induced by LV-UbHBcAg were higher than those induced by LV-HBcAg.Compared with LV-HBcAg-transduced DCs,LV-UbHBcAg-transduced DCs more efficiently stimulated the proliferation of T lymphocytes and generated HBcAgspecific cytotoxic T lymphocytes.CONCLUSION:LV-Ub-HBcAg effectively induced DC maturation.The mature DCs efficiently induced T cell polarisation to Th1 and generated HBcAg-specific CTLs.

New combination test for hepatitis C virus genotype and viral load determination using Amplicor GT HCV MONITOR test v2.0

AIM: To develop a new sensitive and inexpensive hepatitis C virus (HCV) combination test (HCV Guideline test) that enables the determination of HCV genotypes 1, 2 and 3,and simultaneous determination of HCV viral load using commercial Amplicor GT HCV MONITOR test v2.0 (microwell version).METHODS: The HCV Guideline test used the PCR product generated in commercial Amplicor GT HCV Monitor test v2.0 for viral load measurement using microwell plate version of Amplicor HCV Monitor and also captured on separate plates containing capture probes and competitive oligonucleotide probes specific for HCV genotypes 1, 2 and 3, The HCV genotype was subsequently determined using the biotin-labeled PCR product and five biotin-labeled HCV-specific probes.RESULTS: The sensitivity of the HCV Guideline test was 0.5 KIU/mL. Specificity of the HCV Guideline test was confirmed by direct sequencing of HCV core region and molecular evolutionary analyses based on a panel of 31 samples. The comparison of the HCV Guideline test and an in-house HCV core genotyping assay using 252 samples from chronic hepatitis C patients indicated concordant results for 97.2% of samples (59.5% genotype 1, 33.7% genotype 2, 6.0% genotype 3, and 0.8% mixed genotypes).Similarly, the HCV Guideline test showed concordance with a serological test, and the serological test failed to assign any serotype in 12.7% of the samples, indicating a better sensitivity of the HCV Guideline test.CONCLUSION: Clinically, both viral load and genotypes (1, 2 and 3) have been found to be major predictors of antiviral therapy outcome regarding chronic hepatitis C based on guidelines and they are, in normal circumstances,performed as separate stand-alone assays. The HCV Guideline test is a useful method for screening large cohorts in a routine clinical setting for determining the treatment regimen and for predicting the outcome of antiviral therapy of chronic hepatitis C.