Epidemiological and Diagnostic Profile of Patients with Chronic Hepatitis B Virus from 2017 to 2021 in Parakou, Republic of Benin

Introduction: Viral hepatitis B is a public health problem worldwide. The objective of this study was to determine the epidemiological and diagnostic profile of chronic carriers of hepatitis B virus seen for gastroenterology consultations in Parakou, Republic of Benin. Patients and Methods: This was a cross-sectional and descriptive study with retrospective data collection. Patients seen for gastroenterology consultations from January 1, 2017 to June 30, 2021 at the Regional Teaching Hospital of Borgou/Alibori (CHUD-B/A) and having been diagnosed as chronic carriers of hepatitis B virus were included. A minimum initial assessment was required to be included. The minimum sample size was calculated with Schwartz formula. The variable of interest was the detection of HBsAg twice and at least 6 months apart. The other variables studied were sociodemographic, clinical and paraclinical data. The data collected were analyzed using SPSS 17 software. Results: A total of 2786 patients were seen for gastroenterology consultations, including 1126 (40.4%) HBsAg-positive patients. Among them, 417 patients met the inclusion criteria and were the subject of the present study. The average age of the patients was 34.8 ± 10.5 years. Two hundred and forty-seven patients (65.7%) were male, representing a sex ratio of 1.9. The discovery of positive HBsAg status was made during systematic screening in 231 patients (55.4%). Scarifications were noted in 373 patients (89.4%). Asthenia was reported in 184 patients (44.1%). Co-infections with human immunodeficiency virus, hepatitis C and D viruses were 0% (0 in 92), 2.8% (4 in 146) and 14.3% (2 in 146), respectively. During the initial assessment, 274 patients (65.7%) were sero-negative for chronic HBeAg infection, 21 (5%) had clinically significant fibrosis including 16 (3.8%) at the stage of cirrhosis and 7 patients (5.4%) had hepatocellular carcinoma. Conclusion: In Parakou, chronic hepatitis B virus infection is common and affects young people with a male predominance. Asthenia is a non-specific symptom and the most reported by the patients. Around 5 out of 100 patients are seen for consultations at the stage of complication. Emphasis must be placed on early detection and subsidy for pre-therapeutic assessment.

Establishment and validation of a nomogram for predicting the risk of liver inflammation in chronic HBV infection

Objective:To establish a non-invasive quantitative and visual predictive model for assessing the occurrence of significant inflammation in chronic HBV infection,and to present nomogram to validate the efficacy.Methods:A total of 180 patients with chronic HBV infection that were admitted to the Department of Infectious Liver Diseases of the First Affiliated Hospital of Hainan Medical College from January 2019 to December 2021 with informed consent and underwent liver biopsy puncture were selected,and to prevent overfitting of the model,131 patients and 49 patients were randomly divided into a model group and a validation group according to randomization,to collect the clinic information,serological examination,liver elastography and liver histopathology results.The patients were divided into non-significant inflammation and significant inflammation groups in the modeling group.The R 4.1.1 package and the rms package were used to build the column line graph model,while the Bootstrap method was applied to repeat the sampling 1000 times for internal and external validation,and the H-L goodness of fit test and ROC curve were used to assess the calibration and discrimination of the column line graph model respectively.Results:A total of 180 patients with chronic HBV infection were included,and 92 patients(51.1%)had significant inflammation.In the modeling set,67 patients(51.1%)had significant inflammation.In the modeled group,comparison of HBV DNA,PLT,ALT,AST,ALP,GGT,PAB,H.A,PⅢP,CⅣ,L.N,IL-6,LSM and HBeAg for non-significant inflammation and significant inflammation showed statistically significant differences(P<0.05).Nomogram were obtained using stepwise regression analysis to establish a predictive model for the risk of significant inflammation following chronic HBV infection.The χ^(2) values of the H-L goodness-of-fit test for the modelling and validation groups were 0.279 and 2.098,respectively,corresponding to P values of 0.87 and 0.35,suggesting that the nomogram has good predictive accuracy;the area under the ROC curve of the column line plot predicting the occurrence of significant inflammation after HBV infection for the modelling and validation groups was 0.895[95%CI(0.843-0.948)]and 0.760[95%CI(0.622-0.897)],suggesting that the column line plot model has good discrimination.Conclusion:After stepwise regression analysis,it was established that PLT,Ln(HBV-DNA),AST,C桇and LSM were more closely associated with the occurrence of significant inflammation after HBV infection,and a visualization of the occurrence of significant inflammation nomogram was established by comprehensive assessment,and the effectiveness was good.

Novel exosome-targeted T-cell-based vaccine counteracts T-cell anergy and converts CTL exhaustion in chronic infection via CD40L signaling through the mTORC1 pathway

CD8＋ cytotoxic T lymphocyte （CTL） exhaustion is a chief issue for ineffective virus elimination in chronic infectious diseases. We generated novel ovalbumin （OVA）-specific OVA-Texo and HIV-specific Gag-Texo vaccines inducing therapeutic immunity. To assess their therapeutic effect in chronic infection, we developed a new chronic infection model by i.v. infecting C57BL/6 mice with the OVA-expressing adenovirus AdVova. During chronic AdVova infection, mouse CTLs were found to express the inhibitory molecules programmed cell-death protein-1 （PD-1） and lymphocyte-activation gene-3 （LAG-3） and to be functionally exhausted, showing a significant deficiency in T-cell proliferation, IFN-7 production and cytolytic effects. Naive CD8＋ T cells upregulated inhibitory PD-ligand 1 （PD-L1）, B- and T-lymphocyte attenuator and T-cell anergy-associated molecules （Grail and Itch） while down-regulating the proliferative response upon stimulation in mice with chronic infection. Remarkably, the OVA-Texo vaccine counteracted T-cell anergy and converted CTL exhaustion. The latter was associated with （i） the upregulation of a marker for CTL functionality, diacetylated histone-H3 （diAcH3）, （ii） a fourfold increase in CTLs, occurring independent of host DCs or CD4＋ T cells, and （iii） the restoration of CTL IFN-7 production and cytotoxicity. In vivo OVA-Texo-stimulated CTLs upregulated the activities of the mTORC1 pathway-related molecules Akt, S6, elF4E and T-bet, and treatment of the CTLs with an mTORC1 inhibitor, rapamycin, significantly reduced the OVA-Texo- induced increase in CTLs. Interestingly, OVA-Texo-mediated CD40L signaling played a critical role in the observed immunological effects. Importantly, the Gag-Texo vaccine induced Gag-specific therapeutic immunity in chronic infection. Therefore, this study should have a serious impact on the development of new therapeutic vaccines for human immunodeficiency virus （HIV-1） infection.

Associations of content and gene polymorphism of macrophage inhibitory factor-1 and chronic hepatitis C virus infection

BACKGROUND The expression of macrophage inhibitory factor-1(MIC-1) is increased in peripheral blood of patients with chronic hepatitis and liver cirrhosis. However, whether MIC-1 gene polymorphism is correlated with relevant diseases is not yet reported.AIM To explore the correlation between gene polymorphism in MIC-1 exon region and chronic hepatitis C virus(HCV) infection.METHODS This case-control study enrolled 178 patients with chronic hepatitis C(CHC) in the case group, and 82 healthy subjects from the same region who had passed the screening examination comprised the control group. The genotypes of rs1059369 and rs1059519 loci in the MIC-1 gene exon were detected by DNA sequencing. Also, the MIC-1 level, liver function metrics, liver fibrosis metrics, and HCV RNA load were determined. Univariate analysis was used to compare the differences and correlations between the two groups with respect to these parameters. Multivariate logistic regression was used to analyze the independent relevant factors of CHC.RESULTS The plasma MIC-1 level in the CHC group was higher than that in the control group(P < 0.05), and it was significantly positively correlated with alanine aminotransferase, aspartate aminotransferase(AST), type III procollagen N-terminal peptide(known as PIIINP), type IV collagen, and HCV RNA(P < 0.05), whereas negatively correlated with total protein and albumin(P < 0.05). The genotype and allele frequency distribution at the rs1059519 locus differed between the two groups(P < 0.05). The allele frequency maintained significant difference after Bonferroni correction(Pc < 0.05). Logistic multiple regression showed that AST, PIIINP, MIC-1, and genotype GG at the rs1059519 locus were independent relevant factors of CHC(P < 0.05). Linkage disequilibrium(LD) was found between rs1059369 and rs1059519 loci, and significant difference was detected in the distribution of haplotype A-C between the CHC and control groups(P < 0.05). Meanwhile, we found the MIC-1 level trend to increase among rs1059519 genotypes(P = 0.006) and the level of MIC-1 in GG genotype to be significantly higher than CC genotype(P = 0.009, after Bonferroni correction).CONCLUSION Plasma MIC-1 level was increased in CHC patients and correlated with liver cell damage, liver fibrosis metrics, and viral load. The polymorphism at the MIC-1 gene rs1059519 locus was correlated with HCV infection, and associated with the plasma MIC-1 level. G allele and GG genotype may be an important susceptible factor for CHC.

Studies on Mutual Relationship between Anti-HBx and sFas, IL-10 or IL-12 in Sera of Cases with Chronic Hepatitis B Infection

Objective To study the mutual relationship between anti-HBx and IL-10, IL-12 or soluble Fas(s Fas) in sera of patients with chronic HBV infection and to explore the importance of anti-HBx detection as well as its role in the development of chronic HBV infection.Methods Total of 90 cases with chronic HBV infection were randomly selected, including 10 of asymptomatic carriers(ASC), 28 of chronic hepatitis B(CHB), 26 of liver cirrhosis(LC) and 26 patients of hepatocellular carcinoma(HCC). Their clinical data and blood samples were collected, and serum was prepared and stored at-73℃. Anti-HBx was detected with an indirect ELISA established in our earlier research, and levels of IL-10, IL-12 and Fas were determined with commercial double-antibody sandwich ELISA kits. The mutual relationship between anti-HBx and IL-10, IL-12 or s Fas in serum were analyzed with the software SPSS 20.0. Results All levels of IL-10, IL-12 and s Fas in peripheral blood showed a rising trend with development of chronic HBV infection. The levels of IL-10 in ASC, CHB, LC and HCC groups were 13.93 ± 14.40 ng/L, 39.38 ± 20.77 ng/L, 69.06 ± 46.37 ng/L and 62.82 ± 23.42 ng/L, respectively, levels of IL-12 in the 4 groups were 15.64 ± 23.04 ng/L, 68.50 ± 23.14 ng/L, 76.83 ± 12.82 ng/L and 83.74 ± 24.88 ng/L, respectively, and levels of s Fas were 58.17 ± 77.42 ng/L, 179.88 ± 104.36 ng/L, 249.22 ± 107.80 ng/L and 252.98 ± 87.65 ng/L, respectively. Twenty-seven out of 90 patients showed a positive result for anti-HBx detection, including 1 in ASC, 4 in CHB, 12 in LC and 10 in HCC group. The levels of IL-10, IL-12 and sF as were higher in anti-HBx positive group than in negative group. Statistical analysis demonstrated significant differences of IL-10 and IL-12 between the two groups(P < 0.05), but the differences of s Fas had no statistical significance(P = 0.094). Conclusions Anti-HBx antibody is not protective, and is closely related to IL-10, IL-12 and s Fas. It may be an important serum indicator for aggravation from chronic hepatitis B to liver cirrhosis or hepatocellular carcinoma in patients with chronic HBV infection.

Prevalence of chronic infections and susceptibility to measles and varicellazoster virus in Latin American immigrants

Background:Large numbers of Latin American immigrants recently arrived in Western Europe.Curative and preventive programmes need to take account of their risk of suffering and transmitting imported chronic infections and of their susceptibility to cosmopolitan infections.We aimed to assess the prevalence and co-occurrence of imported chronic infections among Latin American immigrants,and their susceptibility to highly prevalent cosmopolitan infections.Methods:Adult participants were recruited in the community and in a primary health centre in Geneva in 2008.Serological tests were performed on stored sera for HIV,HBV,syphilis,Strongyloides stercoralis,Trypanosoma cruzi,varicella and measles.We considered only chronic active infections in the analysis.Results and discussion:The 1012 participants,aged 37.2(SD 11.3)years,were mostly female(82.5%)and Bolivians(48%).Overall,209(20.7%)had at least one and 27(2.7%)two or more chronic infections.T.cruzi(12.8%)and S.stercoralis(8.4%)were the most prevalent chronic active infections compared to syphilis(0.4%),HBV(0.4%)and HIV(1.4%).Concomitant infections affected 28.2 and 18.5%of T.cruzi and S.stercoralis infected cases.Bolivian origin(aOR:13.6;95%CI:3.2–57.9)was associated with risk of multiple infections.Susceptibilities for VZV and measles were 0.7 and 1.4%,respectively.Latin American immigrants are at risk of complications and possible reactivation of chronic parasitic infections but have overall low risks of chronic viral and syphilitic active infections.Conclusions:Systematic screening for chronic active parasitic infections is therefore necessary especially among Bolivians.The high protection rate against measles and VZV doesn’t require specific preventive interventions.

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

Chronic hepatitis B virus(HBV)infection(CHB)is a public health concern worldwide.Current therapies utilizing nucleos(t)ide analogs(NA)have not resulted in a complete cure for CHB.Furthermore,patients on long-term NA treatment often develop low-level viremia(LLV).Persistent LLV,in addition to causing the progression of liver disease or hepatocellular carcinoma,may shed light on the current plight of NA therapy.Here,we review the literature on LLV,NA treatment,and various doses of entecavir to find a strategy for improving the efficacy of this antiviral agent.For LLV patients,three therapeutic options are available,switching to another antiviral monotherapy,interferon-αswitching therapy,and continuing monotherapy.In real-world clinical practice,entecavir overdose has been used in antiviral therapy for CHB patients with NA refractory and persistent LLV,which encouraged us to conduct further in-depth literature survey on dosage and duration related entecavir studies.The studies of pharmacodynamics and pharmacokinetics show that entecavir has the maximal selected index for safety,and has great potential in inhibiting HBV replication,in all of the NAs.In the particular section of the drug approval package published by the United States Food and Drug Administration,entecavir doses 2.5-20 mg/d do not increase adverse events,and entecavir doses higher than 1.0 mg/d might improve the antiviral efficacy.The literature survey led us to two suggestions:(1)Increasing entecavir dose to 1.0 mg/d for the treatment of NA naïve patients with HBV DNA>2×106 IU/mL is feasible and would provide better prognosis;and(2)Further research is needed to assess the long-term toxic effects of higher entecavir doses(2.5 and 5.0 mg/d),which may prove beneficial in treating patients with prior NA treatment,partial virological response,or LLV state.

Chronic active Epstein-Barr virus infection treated with PEGaspargase: A case report

BACKGROUND Chronic active Epstein-Barr virus infection(EBV)is a systemic EBV-positive lymphoproliferative disease,which may lead to fatal illness.There is currently no standard treatment regimen for chronic active EBV(CAEBV),and hematopoietic stem cell transplantation is the only effective treatment.We here report a CAEBV patient treated with PEG-aspargase,who achieved negative EBV-DNA.CASE SUMMARY A 33-year-old female Chinese patient who had fever for approximately 3 mo was admitted to our hospital in December 2017.EBV-DNA was positive with a high copy number.She was diagnosed with chronic active EB virus infection.PEGaspargase was administered at a dose of 1500 U/m2 at a 14-d interval,resulting in eradication of EBV for more than 6 mo.The effect of PEG-aspargase in this patient was excellent.CONCLUSION A chemotherapy regimen containing PEG-aspargase for CAEBV may be further considered.

Establishment and Validation of a nomogram for Predicting the Risk of Liver Fibrosis in Chronic HBV Infection

Objective:To establish a non-invasive quantitative and visual predictive model for assessing the occurrence of significant fibrosis in chronic HBV infection,and to present nomogram to validate the efficacy.Methods:A total of 180 patients with chronic HBV infection that were admitted to the Department of Infectious Liver Diseases of the First Affiliated Hospital of Hainan Medical University from January 2019 to December 2021 with informed consent and underwent liver biopsy puncture were selected.131 patients and 49 patients were randomly divided into a model group and a validation group according to randomization.The patients were divided into non-significant fibrosis and significant fibrosis groups in the modeling group.To collect the clinic information,serological examination,liver elastography and liver histopathology results and to establish a rosette model to predict the risk of chronic HBV infection with significant fibrosis.Results:A total of 180 patients with chronic HBV infection were included,and 113 patients(62.7%)had significant fibrosis.In the modeling set,84 patients(64.1%)had significant fibrosis.In the modeled group,comparison of HBV DNA,PLT,ALT,AST,ALP,ALB,PAB,IL-6,HA,PⅢP,CIV,L.N and LSM for non-significant fibrosis and significant fibrosis showed statistically significant differences.The χ^(2) values of the H-L goodness-of-fit test for the modelling and validation groups were 4.988 and 0.527,respectively,corresponding to P values of 0.08 and 0.77,suggesting that the nomogram has good predictive accuracy;the area under the ROC curve of the column line plot predicting the occurrence of significant fibrosis after HBV infection for the modelling and validation groups was 0.843[95%CI(0.775-0.910)]and 0.776[95%CI(0.714-0.838)],suggesting that the column line plot model has good discrimination.Conclusion:After stepwise regression analysis,it was established that ALB,HA,PⅢP,LSM and IL-6 were more closely associated with the occurrence of significant fibrosis after HBV infection,and a visualization of the occurrence of significant fibrosis column line graph model was established by comprehensive assessment,and validation was given that all were superior to the traditional models FIB-4 and APRI.

Chronic Active Epstein–Barr Virus Infection

Chronic active Epstein-Barr virus(CAEBV)infection is a systemic Epstein–Barr virus(EBV)positive lymphoprolifetative disease characterized by fever,lymphadenopathy,splenomegaly,unusual pattern of antiEBV antibodies,and/or increased EBV genomes in affected tissues.Most cases are from Asia.So far,there is hardly any adult case reported from mainland of China.We herein presented a 33-year-old man with fever,facial erythema and rash,lymphadenopathy,lower limbs weakness,splenomegaly and liver lesion.EBV VCA,EA and EBNA were all positive.EBV DNA could be found in serum and PBMC.In situ hybridization of EBV encoded RNA in skin and liver biopsy was positive.Viral load in serum decreased under interferon alpha therapy.To our knowledge,it’s the first adult case reported from mainland of China.

Baseline hepatocyte ballooning is a risk factor for adverse events in patients with chronic hepatitis B complicated with nonalcoholic fatty liver disease

BACKGROUND Although many studies have investigated the impact of chronic hepatitis B virus(HBV)infection and nonalcoholic fatty liver disease(NAFLD)on liver disease,few have investigated the relationship between nonalcoholic steatohepatitis(NASH)defined by liver pathology and the prognosis of chronic HBV infection.Most patients were followed up for a short time.This study aimed to further explore the impact of NAFLD and the pathological changes confirmed by liver pathology in patients with chronic HBV infection.AIM To study the effect of NAFLD confirmed using liver pathology on the outcomes of long-term serious adverse events[cirrhosis,hepatocellular carcinoma(HCC),and death]in patients with chronic hepatitis B(CHB)virus infection.METHODS We enrolled patients with chronic hepatitis B virus(HBV)infection who underwent liver biopsy at the Third People’s Hospital of Zhenjaing Affiliated Jiangsu University between January 2005 and September 2020.Baseline clinical and pathological data on liver pathology and clinical data at the end of follow-up were collected.Propensity score matching(PSM)was used to balance baseline parameters,Kaplan-Meier(K-M)survival analysis was used to evaluate the risk of clinical events,and Cox regression was used to analyze the risk factors of events.RESULTS Overall,456 patients with chronic HBV infection were included in the study,of whom 152(33.3%)had histologically confirmed NAFLD.The median follow-up time of the entire cohort was 70.5 mo.Thirty-four patients developed cirrhosis,which was diagnosed using ultrasound during the follow-up period.K-M survival analysis showed that NAFLD was not significantly associated with the risk of cirrhosis(log-rank test,P>0.05).Patients with CHB with fibrosis at baseline were more prone to cirrhosis(log-rank test,P=0.046).After PSM,multivariate analysis showed that diabetes mellitus,ballooning deformation(BD),and platelet(PLT)were independent risk factors for cirrhosis diagnosed using ultrasound(P<0.05).A total of 10 patients(2.2%)developed HCC,and six of these patients were in the combined NAFLD group.K-M survival analysis showed that the cumulative risk of HCC in the NAFLD group was significantly higher(log-rank test,P<0.05).Hepatocyte ballooning,and severe liver fibrosis were also associated with an increased risk of HCC(log-rank test,all P<0.05).Cox multivariate analysis revealed that hepatocyte ballooning,liver fibrosis,and diabetes mellitus were independent risk factors for HCC.CONCLUSION There was no significant correlation between chronic HBV infection and the risk of cirrhosis in patients with NAFLD.Diabetes mellitus,BD,and PLT were independent risk factors for liver cirrhosis.Patients with chronic HBV infection and NASH have an increased risk of HCC.BD,liver fibrosis,and diabetes mellitus are independent risk factors for HCC.

Hepatitis B virus reactivation in patients treated with monoclonal antibodies

Hepatitis B virus(HBV)reactivation poses a significant clinical challenge,espe-cially in patients undergoing immunosuppressive therapies,including mono-clonal antibody treatments.This manuscript briefly explores the complex rela-tionship between monoclonal antibody therapy and HBV reactivation,drawing upon current literature and clinical case studies.It delves into the mechanisms underlying this phenomenon,highlighting the importance of risk assessment,monitoring,and prophylactic measures for patients at risk.The manuscript aims to enhance the understanding of HBV reactivation in the context of monoclonal antibody therapy,ultimately facilitating informed clinical decision-making and improved patient care.This paper will also briefly review the definition of HBV activation,assess the risks of reactivation,especially in patients treated with monoclonal antibodies,and consider management for patients with regard to screening,prophylaxis,and treatment.A better understanding of patients at risk can help clinicians provide optimum management to ensure successful patient outcomes and prevent morbidity.

Strategies for combating bacterial biofilm infections

Formation of biofilm is a survival strategy for bacteria and fungi to adapt to their living environment, especially in the hostile environment. Under the protection of biofilm, microbial cells in biofilm become tolerant and resistant to antibiotics and the immune responses, which increases the difficulties for the clinical treatment of biofilm infections. Clinical and laboratory investigations demonstrated a perspicuous correlation between biofilm infection and medical foreign bodies or indwelling devices. Clinical observations and experimental studies indicated clearly that antibiotic treatment alone is in most cases insufficient to eradicate biofilm infections. Therefore, to effectively treat biofilm infections with currently available antibiotics and evaluate the outcomes become important and urgent for clinicians. The review summarizes the latest progress in treatment of clinical biofilm infections and scientific investigations, discusses the diagnosis and treatment of different biofilm infections and introduces the promising laboratory progress, which may contribute to prevention or cure of biofilm infections. We conclude that, an efficient treatment of biofilm infections needs a well-established multidisciplinary collaboration, which includes removal of the infected foreign bodies, selection of biofilm-active, sensitive and well-penetrating antibiotics, systemic or topical antibiotic administration in high dosage and combinations, and administration of anti-quorum sensing or biofilm dispersal agents.

Human immune repertoire in hepatitis B virus infection

Hepatitis B virus(HBV)infection is a public health threat that affects 257 million people worldwide and can progress to liver cirrhosis,liver failure,and hepatocellular carcinoma.The HBV antigen-induced adaptive immune response plays an important role in HBV clearance.Immune repertoire sequencing(IRS)has been used to investigate the molecular mechanisms behind the immune system,find novel ways to treat HBV infection,and evaluate the genetic responses and immune characteristics of individuals infected by HBV or immunized by HBV vaccine.This review summarizes the human immune repertoire analysis methodology,and the application of the IRS in the prediction of HBV infection progression,treatment,and vaccination.

Metabolic complications of hepatitis C virus infection

Hepatitis C virus(HCV) infection is a systemic disease that is implicated in multiple extrahepatic organ dysfunction contributing to its protean manifestations. HCV is associated with diverse extrahepatic disorders including atherosclerosis, glucose and lipid metabolic disturbances, alterations in the iron metabolic pathways, and lymphoproliferative diseases over and above the traditional liver manifestations of cirrhosis and hepatocellular carcinoma. The orchestration between HCV major proteins and the liver-muscle-adipose axis, poses a major burden on the global health of human body organs, if not adequately addressed. The close and inseparable associations between chronic HCV infection, metabolic disease, and cardiovascular disorders are specifically important considering the increasing prevalence of obesity and metabolic syndrome, and their economic burden to patients, the healthcare systems, and society. Cellular and molecular mechanisms governing the interplay of these organs and tissues in health and disease are therefore of significant interest. The coexistence of metabolic disorders and chronic hepatitis C infection also enhances the progression to liver fibrosis and hepatocellular carcinoma. The presence of metabolic disorders is believed to influence the chronicity and virulence of HCV leading to liver disease progression. This comprehensive review highlights current knowledge on the metabolic manifestations of hepatitis C and the potential pathways in which these metabolic changes can influence the natural history of the disease.

Distribution of different hepatitis C virus genotypes in patients with hepatitis C virus infection

AIM:To investigate the presence of mixed infection and discrepancy between hepatitis C virus(HCV) genotypes in plasma,peripheral blood mononuclear cells(PBMCs),and liver biopsy specimens.METHODS:From September 2008 up to April 2009,133 patients with chronic hepatitis C referred to Firouzgar Hospital for initiation of an antiviral therapy were recruited in the study.Five milliliters of peripheral blood was collected from each patient and liver biopsy was performed in those who gave consent or had indications.HCV genotyping was done using INNO-LiPATM HCV in serum,PBMCs,and liver biopsy specimens and then conf irmed by sequencing of 5'-UTR fragments.RESULTS:The mean age of patients was 30.3 ± 17.1 years.Multiple transfusion was seen in 124(93.2%) of patients.Multiple HCV genotypes were found in 3(2.3%) of 133 plasma samples,9(6.8%) of 133 PBMC samples,and 8(18.2%) of 44 liver biopsy specimens.It is notable that the different genotypes found in PBMCs were not the same as those found in plasma and liver biopsy specimens.CONCLUSION:Our study shows that a signif icant proportion of patients with chronic hepatitis C are affected by multiple HCV genotypes which may not be detectable only in serum of patients.

Hepatitis B virus infection reactivation in patients under immunosuppressive therapies:Pathogenesis,screening,prevention and treatment

With a 5.3%of the global population involved,hepatitis B virus(HBV)is a major public health challenge requiring an urgent response.After a possible acute phase,the natural history of HBV infection can progress in chronicity.Patients with overt or occult HBV infection can undergo HBV reactivation(HBVr)in course of immunosuppressive treatments that,apart from oncological and hematological diseases,are also used in rheumatologic,gastrointestinal,neurological and dermatological settings,as well as to treat severe acute respiratory syndrome coronavirus 2 infection.The risk of HBV reactivation is related to the immune status of the patient and the baseline HBV infection condition.The aim of the present paper is to investigate the risk of HBVr in those not oncological settings in order to suggest strategies for preventing and treating this occurrence.The main studies about HBVr for patients with occult hepatitis B infection and chronic HBV infection affected by non-oncologic diseases eligible for immunosuppressive treatment have been analyzed.The occurrence of this challenging event can be reduced screening the population eligible for immunosuppressant to assess the best strategies according to any virological status.Further prospective studies are needed to increase data on the risk of HBVr related to newer immunomodulant agents employed in non-oncological setting.

Natural killer/T-cell lymphoma with intracranial infiltration and Epstein-Barr virus infection: A case report

BACKGROUND Because of atypical clinical symptoms,lymphoma is easily confused with infectious diseases.Extranodal nasal-type natural killer/T-cell lymphoma(NKTL)is more common,and there are few cases of eyelid site onset and intracranial infiltration,which increases the difficulty of diagnosis.This disease usually has a very poor prognosis and there are few reports of recovery.CASE SUMMARY A 3-year-old boy was admitted to our hospital due to an initial misdiagnosis of"eyelid cellulitis"and failed antibiotic treatment.He was characterized by fever,right eyeball bulging,convulsions,and abnormal liver function.His blood Epstein-Barr virus(EBV)DNA was positive(8.798×10^4 copies/mL),and remained positive for about half a year.The cranial imaging examination suggested a space-occupying lesion in the right eyelid,with the right temporal lobe and meninges involved.The boy underwent ocular mass resection.The pathological diagnosis was NKTL.He was diagnosed as having NKTL with intracranial infiltration,combined with chronic active EBV infection(CAEBV).Then he underwent systemic chemotherapy and intrathecal injection.The boy suffered from abnormal blood coagulation,oral mucositis,diarrhea,liver damage,and severe bone marrow suppression but survived.Finally,the tumor was completely relieved and his blood EBV-DNA level turned negative.The current follow-up has been more than 2 years and his condition is stable.CONCLUSION This case suggests that chemotherapy combined with intrathecal injection may have a good effect on intracranial infiltrating lymphoma and CAEBV,which deserves further study and discussion.

Decoy receptor 3: Its role as biomarker for chronic inflammatory diseases

Members of the tumor-necrosis factor-α(TNF-α) and TNF-α receptor(TNFR) superfamilies of proteins(TNFSF and TNFRSF, respectively) play important roles in the function of the immune system. Decoy receptor 3(Dc R3, TNFRSF6b) is a decoy receptor that binds to three TNFSF ligands, Fas L, LIGHT and TL1 A. Association to these ligands competes with the corresponding functional receptors and blocks downstream signaling, leading to immunomodulatory effects, including the prevention of apoptosis. Dc R3 lacks a transmembrane region and exists only as a secreted protein, which is detectable in biological fluids. Recent studies have shown that Dc R3 is upregulated and may be pathogenetically implicated in several and diverse chronic inflammatory diseases. The strongest associations have been described for rheumatological diseases, mainly systemic lupus erythematosus and rheumatoid arthritis, inflammatory bowel disease, and serious infectious conditions, including systemic inflammatory response syndrome. In the majority of these conditions, Dc R3 m RNA and protein expression is elevated both at the target tissues as well as in the systemic circulation. Dc R3 concentration in the serum is untraceable in the majority of healthy individuals but can be detected in patients with various inflammatory diseases. In mostsuch cases, soluble Dc R3 correlates with disease severity, as patients with severe forms of disease have significantly higher levels than patients with milder or no activity. In addition, effective anti-inflammatory treatment leads to the disappearance of soluble Dc R3 from the circulation. Taken together, current evidence suggests that serum Dc R3 may become a useful biomarker for chronic inflammatory disorders, as it is upregulated in response to inflammatory stimuli, and may serve both as a prognostic marker for disease severity and as a surrogate indicator of response to treatment.

The role of periodontal disease in atherosclerotic cardiovascular disease

Atherosclerotic cardiovascular disease(ASCVD)includes a group of disorders of the heart and blood vessels and accounts for major morbidity and premature death worldwide.Periodontitis is a chronic inflammatory disease with the gradual destruction of supporting tissues around the teeth,including gingiva,periodontal ligament,alveolar bone,and cementum.Periodontitis has been found to potentially increase the risk of ASCVD.Generally,oral microorganisms and inflammation are the major factors for periodontitis to the incidence of ASCVD.Recently,evidence has shown that the loss of masticatory function is another important factor of periodontitis to the incidence of ASCVD.In this review,we illustrate the recent finding of the relationship between periodontitis and ASCVD,from a microscale perspective-oral microorganisms,inflammation,and tooth loss.With the high prevalence of periodontitis,it is important to add oral therapy as a regular ASCVD prevention strategy.Regular dental visits could be a helpful strategy for ASCVD patients or general medical practitioners.