Insights from respiratory virus co-infections

Respiratory viral co-infections present significant challenges in clinical settings due to their impact on disease severity and patient outcomes.Current diagnostic methods often miss these co-infections,complicating the epidemiology and management of these cases.Research,primarily conducted in vitro and in vivo,suggests that co-infections can lead to more severe illnesses,increased hospitalization rates,and greater healthcare utilization,especially in high-risk groups such as children,the elderly,and immunocompromised individuals.Common coinfection patterns,risk factors,and their impact on disease dynamics highlight the need for advanced diagnostic techniques and tailored therapeutic strategies.Understanding the virological interactions and immune response modulation during co-infections is crucial for developing effective public health interventions and improving patient outcomes.Future research should focus on the molecular mechanisms of co-infection and the development of specific therapies to mitigate the adverse effects of these complex infections.

Outcomes and management of viral hepatitis and human immunodeficiency virus co-infection in liver transplantation

Liver transplantation for human immunodeficiency virus(HIV)positive patients with viral hepatitis co-infection is increasingly offered in many North American and European liver transplant centers.Prior studies have demonstrated acceptable post-transplant outcomes and no increased risk of HIV complications in patients coinfected with hepatitis B virus(HBV).However,liver transplantation in HIV positive patients with hepatitis C virus(HCV)has poorer outcomes overall,requiring careful selection of candidates.This review aims to summarize the published literature on outcomes after transplant in HIV patients with HBV or HCV related end-stage liver disease and recommendations for management.In particular the pre-transplant factors impacting outcomes in HCV/HIV co-infected candidates and importance of multidisciplinary management will be discussed.

Hepatitis B and C virus co-infections in human immunodeficiency virus positive North Indian patients

AIM： To determine the prevalence of hepatitis B and C virus infections in human immunodeficiency virus （HIV） -positive patients at a tertiary care hospital in New Delhi, India. METHODS： Serum samples from 451 HIV positive patients were analyzed for HBsAg and HCV antibodies during three years （Jan 2003-Dec 2005）. The control group comprised of apparently healthy bone-marrow and renal donors. RESULTS： The study population comprised essentially of heterosexually transmitted HIV infection. The prevalence Fate of HBsAg in this population was 5.3% as compared to 1.4% in apparently healthy donors （P 〈 0.001）. Though prevalence of HCV co-infection （2.43%） was lower than HBV in this group of HIV positive patients, the prevalence was significantly higher （P 〈 0.05） than controls （0.7%）. Triple infection of HIV, HBV and HCV was not detected in any patient. CONCLUSION： Our study shows a significantly high prevalence of hepatitis virus infections in HIV infected patients. Hepatitis viruses in HIV may lead to faster progression to liver cirrhosis and a higher risk of antiretroviral therapy induced hepatotoxicity. Therefore, it would be advisable to detect hepatitis virus coinfections in these patients at the earliest.

Hepatitis B and human immunodeficiency virus co-infection

Hepatitis B and human immunodeficiency virus(HBV and HIV)infection share transmission patterns and risk factors,which explains high prevalence of chronic HBV infection in HIV infected patients.The natural course of HBV disease is altered by the HIV infection with less chance to clear acute HBV infection,faster progression to cirrhosis and higher risk of liver-related death in HIVHBV co-infected patients than in HBV mono-infected ones.HIV infected patients with chronic hepatitis B should be counseled for liver damage and surveillance of chronic hepatitis B should be performed to screen early hepatocellular carcinoma.Noninvasive tools are now available to evaluate liver fibrosis.Isolated hepatitis B core antibodies(anti-HBc)are a good predictive marker of occult HBV infection.Still the prevalence and significance of occult HBV infection is controversial,but its screening may be important in the management of antiretroviral therapy.Vaccination against HBV infection is recommended in non-immune HIV patients.The optimal treatment for almost all HIV-HBV co-infectedpatients should contain tenofovir plus lamivudine or emtricitabine and treatment should not be stopped to avoid HBV reactivation.Long term tenofovir therapy may lead to significant decline in hepatitis B surface Antigen.The emergence of resistant HBV strains may compromise the HBV therapy and vaccine therapy.

Study on the blood-borne virus co-infection and T lymphocyte subset among intravenous drug users

AIM： To investigate the features of various blood- borne virus infections and co-infection in intravenous drug users （IDUs）, and to examine the correlation of T lymphocyte subsets with virus co-infection. METHODS： Four hundred and six IDUs without any clinical manifestation of hepatitis and 102 healthy persons were enrolled in this study. HBV-DNA and HCV-RNA were detected by fluorescence quantitative PCR. HBsAg, HBeAg, anti-HBc, anti-HCV, HDV-Ag, anti-HGV, anti-HIV, and HCMV-IgM were assayed by enzyme-linked immunosorbent assay （ELISA） and immunochromatographic tests. The levels of Th1 and Th2 cytokines were measured by ELISA and radioactive immune assay （RIA）. The T lymphocyte subpopulation was detected by using fluorescence immunoassay. The similar indices taken from the healthy persons served as controls. RESULTS： The viral infection rate among IDUs was 36.45% for HBV, 69.7% for HCV, 47.3% for HIV, 2.22% for HDV, 1.97% for HGV, and 3.45% for HCMV. The co- infection rate of blood-borne virus was detected in 255 of 406 （62.81%） IDUs. More than 80% （161/192） of subjects infected with HIV were co-infected with the other viruses, such as HBV, HCV. In contrast, among the controls, the infection rate was 17.65% for HBV and 0% for the other viruses. Our investigation showed that there was a profound decrease in the proportion of CD4/CD8 and the percentage of CD3 and CD4, but not in the percentage of CD8. The levels of PHA-induced cytokines （IFN-γ and IL-4） and serum IL-2 were obviously decreased in IDUs. On the other hand, the level of serum IL-4 was increased. The level of IFN-γ and the percentage of CD4 were continuously decreased when the IDUs were infected with HIV or HIV co-infection. IDUs with HIV and HBV co-infection was 15.1% （29/192）. Of those 29 IDU with HIV and HBV co-infection, 51.72% （15/29） and 37.93% （11/29） were HBV-DNA-positive and HBeAg-positive, respectively. But, among IDUs without HIV infection, only 1.68% （2/119） of cases were HBV- DNA-positive.CONCLUSION： HCV, HBV and HIV infections are common in this population of IDU, leading to a high incidence of impaired Thl cytokine levels and CD4 lymphocyte. IDUs with HIV and HBV/HCV co-infection have lower expression of Th1 cytokine with enhancement of the Th2 response. HIV may be causing HBV replication by decreasing Thl function.

Insights into human immunodeficiency virus-hepatitis B virus co-infection in India

Shared routes of transmission lead to frequent human immunodeficiency virus(HIV)-hepatitis B virus(HBV) coinfection in a host which results in about 10% of HIV positive individuals to have chronic hepatitis B infection worldwide. In post-antiretroviral therapy era, liverdiseases have emerged as the leading cause of morbidity and mortality in HIV-infected individuals and HBV coinfection have become the major health issue among this population particularly from the regions with endemic HBV infection. In setting of HIV-HBV co-infection, HIV significantly impacts the natural history of HBV infection, its disease profile and the treatment outcome in negative manner. Moreover, the epidemiological pattern of HBV infection and the diversity in HBV genome(genotypic and phenotypic) are also varied in HIV co-infected subjects as compared to HBV mono-infected individuals. Several reports on the abovementioned issues are available from developed parts of the world as well as from sub-Saharan African countries. In contrast, most of these research areas remained unexplored in India despite having considerable burden of HIV and HBV infections. This review discusses present knowledge from the studies on HIV-HBV co-infection in India and relevant reports from different parts of the world. Issues needed for the future research relevant to HIV-HBV co-infection in India are also highlighted here, including a call for further investigations on this field of study.

Occult hepatitis B virus co-infection in human immunodeficiency virus-positive patients: A review of prevalence, diagnosis and clinical significance

The prevalence of human immunodeficiency virus(HIV) and hepatitis B virus(HBV) co-infection is high as they share similar mechanisms of transmission. The development and widespread use of highly sensitive tests for HBV diagnosis has demonstrated that a significant proportion of apparently healthy individuals with evidence of exposure to HBV continue to carry fully functional HBV DNA in their hepatocytes, a situation that predisposes them to the development of progressive liver disease and hepatocellular carcinoma. The presence of co-infections frequently influences the natural evolution of each of the participating infections present by either facilitating their virulence or competing for resources. Furthermore, the drugs used to treat these infections may also contribute to changes in the natural course of these infections, making the analysis of the impact of co-infection more difficult. The majority of studies has examined the impact of HIV on overt chronic hepatitis B, finding that co-infection carries an increased risk of progressive liver disease and the development of hepatocellular carcinoma. Although the effect of HIV on the natural history of occult hepatitis B infection(OBI) has not been fully assessed, all available data suggest a persisting risk of repeated flares of hepatitis and progressive liver disease. We describe studies regarding the diagnosis, prevalence and clinical significance of OBI in HIVpositive patients in this short review. Discrepancies in worldwide prevalence show the urgent need for the standardization of diagnostic criteria, as established by the Taormina statements. Ideally, standardized protocols for testing should be employed to enable the comparison of data from different groups. Additional studies are needed to define the differences in risk for OBI without HIV and in HIV-HBV co-infected patients with or without overt disease.

Chronic hepatitis B-associated liver disease in the context of human immunodeficiency virus co-infection and underlying metabolic syndrome

Globally,a shift in the epidemiology of chronic liver disease has been observed.This has been mainly driven by a marked decline in the prevalence of chronic hepatitis B virus infection(CHB),with the greatest burden restricted to the Western Pacific and sub-Saharan African regions.Amidst this is a growing burden of metabolic syndrome(MetS)worldwide.A disproportionate co-burden of human immunodeficiency virus(HIV)infection is also reported in sub-Saharan Africa,which poses a further risk of liver-related morbidity and mortality in the region.We reviewed the existing evidence base to improve current understanding of the effect of underlying MetS on the development and progression of chronic liver disease during CHB and HIV co-infection.While the mechanistic association between CHB and MetS remains poorly resolved,the evidence suggests that MetS may have an additive effect on the liver damage caused by CHB.Among HIV infected individuals,MetS-associated liver disease is emerging as an important cause of non-AIDS related morbidity and mortality despite antiretroviral therapy(ART).It is plausible that underlying MetS may lead to adverse outcomes among those with concomitant CHB and HIV co-infection.However,this remains to be explored through rigorous longitudinal studies,especially in sub-Saharan Africa.Ultimately,there is a need for a comprehensive package of care that integrates ART programs with routine screening for MetS and promotion of lifestyle modification to ensure an improved quality of life among CHB and HIV coinfected individuals.

Non-initiation of hepatitis C virus antiviral therapy in patients with human immunodeficiency virus/hepatitis C virus co-infection

AIM: To assess whether reasons for hepatitis C virus(HCV) therapy non-initiation differentially affect racial and ethnic minorities with human immunodeficiency virus(HIV)/HCV co-infection.METHODS: Analysis included co-infected HCV treatment-na?ve patients in the University of North Carolina CFAR HIV Clinical Cohort(January 1, 2004 and December31, 2011). Medical records were abstracted to document non-modifiable medical(e.g., hepatic decompensation, advanced immunosuppression), potentially modifiable medical(e.g., substance abuse, severe depression, psychiatric illness), and non-medical(e.g., personal,social, and economic factors) reasons for non-initiation. Statistical differences in the prevalence of reasons for non-treatment between racial/ethnic groups were assessed using the two-tailed Fisher's exact test. Three separate regression models were fit for each reason category. Odds ratios and their 95%CIs(Wald's) were computed.RESULTS: One hundred and seventy-one patients with HIV/HCV co-infection within the cohort met study inclusion. The study sample was racially and ethnically diverse; most patients were African-American(74%), followed by Caucasian(19%), and Hispanic/other(7%). The median age was 46 years(interquartile range = 39-50) and most patients were male(74%). Among the 171 patients, reasons for non-treatment were common among all patients, regardless of race/ethnicity(50% with ≥ 1 non-modifiable medical reason, 66% with ≥1 potentially modifiable medical reason, and 66% with ≥ 1 non-medical reason). There were no significant differences by race/ethnicity. Compared to Caucasians, African-Americans did not have increased odds of nonmodifiable [adjusted odds ratio(a OR) = 1.47, 95%CI: 0.57-3.80], potentially modifiable(a OR = 0.72, 95%CI: 0.25-2.09) or non-medical(a OR = 0.90, 95%CI: 0.32-2.52) reasons for non-initiation.CONCLUSION: Race/ethnicity alone is not predictive of reasons for HCV therapy non-initiation. Targeted interventions are needed to improve access to therapy for all co-infected patients, including minorities.

Transfusion-transmitted virus co-infection in other types of hepatitis and its genotypes

OBJECTIVE: To identify the influence of transfusion transmitted virus (TTV) co-infection in other virus infected patients and its genotypes. METHODS: A conservative sequence of ORFl in the TTV genome was selected as primers and TTV DNA was measured in students and other hepatitis patients by using microplate nucleic acid hybridization and ELISA. The results were statistically analyzed. Nucleotide sequence of divergence >50% was used as color probe for distinguishing TTV genotypesⅠorⅡ. RESULTS: TTV DNA was detected in the sera from 2 (3.3%) of 60 students, 2 (14.3%) of 14 patients with non A-non E hepatitis, 6 (12%) of 50 patients with chronic hepatitis B, and 4 (16%) of 25 patients with liver cirrhosis, respectively. Statistical difference was observed between the patient group and the student group (P<0.05), but no significant difference in age, gender, serum ALT levels and TBiL between TTV DNA positive and negative patients (P>0.05). TTV genotype Type Ⅰ was by far the most frequent viral genotype (66.7%), followed by type Ⅱ (25%), and mixed infection (8.3%). CONCLUSIONS: These results suggest that the routes of TTV infection may be similar to those of HBV and HCV, and concurrent infection with HBV, HCV are common. TTV co-infection could not affect the clinical features of patients with liver diseases and the pathological process. TTV is not a main causative factor for patients with non A-non E hepatitis. Further study is needed to clarify the role of TTV in patients with non A-non E hepatitis.

Prevalence of Plasmodia and hepatitis B virus co-infection in blood donors at Bishop Murray Medical Centre,Makurdi,Benue State,Nigeria

Objective:To evaluate the prevalence of co-infection of hepatitis B and Plasmodia among potential blood donors in Benue State,and Nigeria at large and offer suggestions and containment methods.Methods:Three hundred and thirty seven(337) potential blood donors,comprising 229(67.95%) Males and 108(32.05%) Females were screened for co-infection with hepatitis B virus(HBV) and Plasmodia between the months of July and December,2009 using standard laboratory methods.Results:An overall co-infection rate of 137(40.67%) was observed among the donors.The month of December showed highest co-infection rates 59(17.51%).Highest rates of infection was observed in males at 129(38.30%) to 8(2.37%) in females.Statistical analysis showed significant difference in infection rates between males and females(P【0.05).The more youthful age groups 18-22,23-27 and 28-32 had higher prevalence of infection at 11.90%,13.05% and 6.53%,respectively.Irrespective of age group,males showed higher rates of infections than females in corresponding age groups.Conclusions:The high rates of co-infection imply that these infections are threats the health of citizens and should be adequately addressed by adoption of strategies to combat and control them.Further,blood should be rigorously screened before transfusion to safeguard the health of recipients.

Advances in the Treatment of Human Immunodeficiency Virus and Hepatitis B Virus Co-infection

Hepatitis B virus(HBV) and human immunodeficiency virus(HIV) are transmitted through the same pathways.Therefore,the incidence of HBV in the HIV-infected population is higher than that in the healthy population,and is more obvious in China given the high HBV prevalence in the country.HIV and HBV co-infection can accelerate the disease process of HBV.Moreover,the incidence of cirrhosis and endstage liver disease is higher in patients co-infected with HIV and HBV than in patients infected HBV alone.When treating patients co-infected with HIV and HBV for HBV infection alone,care should be taken to avoid the induction of HIV resistance.HBV should be considered during drug selection for anti-retroviral treatment.Furthermore,the effective HBV treatment should be retained if anti-retrov iral dr ugs require changing.

Hepatitis B Virus Co-Infection: Yet Another Reason for Early Initiation of Treatment in HIV Infected Individuals

Background: Hepatitis B virus (HBV) co-infection with HIV is becoming a major challenge due to shared routes of transmission. The burden is apparent in regions with widespread use of antiretroviral treatment, which led to the enhanced emergence of liver-related diseases and mortality. Though there are conflicting results about the effect of chronic HBV infection on response to highly active antiretroviral therapy (HAART) (CD4+ cell count and HIV viral load, HIV RNA copies/ml), HAART is known to cause immune mediated HBV specific liver damage after it reconstitutes cell-mediated immunity. The relationship of different HAART regimes with immune recovery is an area of research interest. Objective: It is in order to determine the changes in immune recovery during HBV infection in the setting of HAART among HIV positive individuals attending care and treatment services. Methods: Two cohorts of co-infected patients were analyzed from data of one to seven months retrospectively. The first group (n = 380) was antiretroviral drug naive and the second cohort (n = 380) was on HAART for the entire period. The study was conducted in one referral hospital and six health centers. Data were gathered from 760 patients using their intake form, their follow-up form and their medical records supplemented by data from a structured questionnaire. HBV infection was determined by using HBsAg rapid and confirmatory tests and CD4 cells were enumerated by using laboratory registers and patient cards. Bivariate and multivariate logistic regressions were done by using SPSS Version 18 and Epi info Version 3.5. Results: Poor immune recovery due to HBV infection was improved after initiation of HAART. Before the initiation of HAART, the mean CD4 cell count of HBV infected individuals was lower than that of non-HBV infected ones, 234/mm3 and 384/mm3, respectively (p 0.05). Individuals co-infected with HBV had experienced delayed recovery of immune cells (CD4 cell count). However, after, on average, more than two years of therapy, the association is reversed. In addition to HBV infection, CD4 cell count of patients on chronic HIV care/pre-ART was decreased by older age, living in rural areas and previous opportunistic infections. Conclusion: HBV infection has different outcomes between pre-ART and ART-initiated individuals. In the former cohort, HBV infection causes significant delays in immune recovery which is reversed after initiation of anti-HIV treatment. HBV co-infection has a significant and immediate negative effect on CD4 cell counts and immune recovery before HAART but such effects slowly subside after initiation of the treatment. As a result, HBV infection is another issue to consider for swift initiating of HAART for HIV infected individuals in long-term care.

Effects of Hepatitis B Virus Co-Infection and Antiretroviral Therapy on Disease Progression among HIV Patients Treated at the Buea Regional Hospital, Southwest Region, Cameroon: A Case-Control Study

In the era of “test and treat”, when AIDS-defining events have been drastically reduced, chronic liver disease associated with viral hepatitis and antiretroviral therapy (ART) remains an important cause of non-AIDS morbidity and mortality among HIV-infected patients. Compared to the general population, HIV-infected patients are about 10-times at risk of hepatitis B virus infection. Additionally, several antiretroviral regimens are hepatotoxic. Therefore, effective monitoring and management of ART and HBV co-infection are essential to ending the AIDS epidemic and eliminating viral hepatitis by 2030. This was a hospital-based, matched (age and sex) case-control study. HIV patients (case patients) on ART for at least six months and “healthy” controls aged 18 years and older were enrolled. Blood samples were collected for immuno-hematologic indices and transaminases measurements. Data were presented as counts, percentages, median (IQR) and means (SD), and a p-value 1.5) and mild (0.6 - 1.5) liver fibrosis based on the APRI score was 0.5% and 8%, respectively. Significant fibrosis (>3.25) was 0.9%, while 18.4% had inconclusive fibrosis (1.45 - 3.25) based on the FIB-4 score. HIV/HBV co-infected patients had a higher occurrence of liver fibrosis (APRI: 0.5% vs FIB-4: 0.9%). Co-infections with HBV increase the risk of liver-related morbidity in HIV patients. Therefore, screening for serological markers of chronic HBV infection and hepatic transaminase levels in HIV patients remains crucial in the continuum of care.

Streptococcus pneumoniae and Herpes Simplex Virus-1 Central Nervous System Co-Infection

Co-infections of the central nervous system (CNS) caused by bacterial and viral pathogens are considered to be rare. Herpes simplex virus type-1 (HSV-1) reactivation following Streptococcus pneumoniae infection is well described but most cases are related to oral or cutaneous lesions or in respiratory samples. HSV-1 CNS reactivation after Streptococcus pneumoniae meningitis is a very rare event and may have significant morbidity and mortality. In this case report, we describe a 71-year-old female patient that presented with a history of abdominal pain and confusion/disorientation that had tonic-clonic seizures while in the Emergency Department. The diagnostic work-up confirmed CNS co-infection caused by Streptococcus pneumoniae and HSV-1. Of note, beyond age, the patient had no known risk factors for both entities and recovered fully after antibiotic and antiviral therapy. This case underlines that clinicians must be aware of CNS co-infection despite being a rare diagnosis. This should be suspected particularly in patients who present an unusual clinical course of CNS infection.

Alterations in the gut microbiome after transjugular intrahepatic portosystemic shunt in patients with hepatitis B virus-related portal hypertension

BACKGROUND Gut microbiota(GM)affects the progression and response to treatment in liver diseases.The GM composition is diverse and associated with different etiologies of liver diseases.Notably,alterations in GM alterations are observed in patients with portal hypertension(PH)secondary to cirrhosis,with hepatitis B virus(HBV)infection being a major cause of cirrhosis in China.Thus,understanding the role of GM alterations in patients with HBV infection-related PH is essential.AIM To evaluate GM alterations in patients with HBV-related PH after transjugular intrahepatic portosystemic shunt(TIPS)placement.METHODS This was a prospective,observational clinical study.There were 30 patients(with a 100%technical success rate)recruited in the present study.Patients with esophagogastric variceal bleeding due to HBV infection-associated PH who underwent TIPS were enrolled.Stool samples were obtained before and one month after TIPS treatment,and GM was analyzed using 16S ribosomal RNA amplicon sequencing.RESULTS One month after TIPS placement,8 patients developed hepatic encephalopathy(HE)and were assigned to the HE group;the other 22 patients were assigned to the non-HE group.There was no substantial disparity in the abundance of GM at the phylum level between the two groups,regardless of TIPS treatment(all,P>0.05).However,following TIPS placement,the following results were observed:(1)The abundance of Haemophilus and Eggerthella increased,whereas that of Anaerostipes,Dialister,Butyricicoccus,and Oscillospira declined in the HE group;(2)The richness of Eggerthella,Streptococcus,and Bilophila increased,whereas that of Roseburia and Ruminococcus decreased in the non-HE group;and(3)Members from the pathogenic genus Morganella appeared in the HE group but not in the non-HE group.CONCLUSION Intestinal microbiota-related synergism may predict the risk of HE following TIPS placement in patients with HBVrelated PH.Prophylactic microbiome therapies may be useful for preventing and treating HE after TIPS placement.

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.

Advances in Zika virus vaccines and therapeutics:A systematic review

Zika virus(ZIKV)is the causative agent of a viral infection that causes neurological complications in newborns and adults worldwide.Its wide transmission route and alarming spread rates are of great concern to the scientific community.Numerous trials have been conducted to develop treatment options for ZIKV infection.This review highlights the latest developments in the fields of vaccinology and pharmaceuticals developments for ZIKV infection.A systematic and comprehensive approach was used to gather relevant and up-to-date data so that inferences could be made about the gaps in therapeutic development.The results indicate that several therapeutic interventions are being tested against ZIKV infection,such as DNA vaccines,subunit vaccines,live-attenuated vaccines,virus-vector-based vaccines,inactivated vaccines,virus-like particles,and mRNA-based vaccines.In addition,approved anti-ZIKV drugs that can reduce the global burden are discussed.Although many vaccine candidates for ZIKV are at different stages of development,none of them have received Food and Drug Authority approval for use up to now.The issue of side effects associated with these drugs in vulnerable newborns and pregnant women is a major obstacle in the therapeutic pathway.

Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

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.