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.

Derivatives of Thiohydrazides as Effective Antibacterial Remedies for Chlamydial Infection Treatment at Chronic Stages of Infections

Hydrazones of poorly studied fluorine-containing oxamic acid thiohydrazides were synthesized by the reaction with salicylaldehydes. Tests showed that the newly synthesized compounds were effective low-toxic inhibitors of type III secretion system in Chlamydia trachomatis.

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.

Peripheral T-lymphocyte subpopulations in different clinical stages of chronic HBV infection correlate with HBV load

AIM： To characterize the peripheral T-cell subpopulation profiles and their correlation with hepatitis B virus （HBV） replication in different dinical stages of chronic HBV infection. METHODS： A total of 422 patients with chronic HBV infection were enrolled in this study. The patients were divided into three stages： immune-tolerant stage, immune active stage, and immune-inactive carrier stage. Composition of peripheral T-cell subpopulations was determined by flow cytometry. HBV markers were detected by enzyme-linked immunosorbent assay. Serum HBV DNA load was assessed by quantitative real-time poiymerase chain reaction.RESULTS： CD8^＋ T-cells were significantly higher in patients at the immune-tolerant stage than in patients at the immune-active and -inactive carrier stages （36.87 ± 7.58 vs 34.37 ± 9.07, 36.87 ± 7.58 vs 28.09 ± 5.64, P 〈 0.001）. The peripheral blood in patients at the immune-tolerant and immune active stages contained more CD8^＋ T-cells than CD4^＋ T-cells （36.87 ± 7.58 vs 30.23 ± 6.35, 34.37 ± 9.07 vs 30.92 ± 7.40, P 〈 0.01）, whereas the peripheral blood in patients at the immune- inactive carrier stage and in normal controls contained less CD8^＋ T-cells than CD4^＋ T-cells （28.09 ± 5.64 vs 36.85 ±6.06, 24.02 ± 4.35 vs 38.94 ± 3.39, P 〈 0.01）. ANOVA linear trend test showed that CD8^＋ T-cells were significantly increased in patients with a high viral load （39.41 ± 7.36, 33.83 ± 7.50, 31.81 ± 5.95 and 26.89 ± 5.71, P 〈 0.001）, while CD4^＋ T-cells were significantly increased in patients with a low HBV DNA load （37.45 ± 6.24, 33.33 ± 5.61, 31.58 ± 6.99 and 27.56 ± 5.49, P 〈 0.001）. Nultiple regression analysis displayed that log copies of HBV DNA still maintained its highly significant coefficients for T-cell subpopulations, and was the strongest predictors for variations in CD3^＋, CD4^＋ and CD8^＋ cells and CD4^＋/CD8^＋ ratio after adjustment for age at HBV-infection, maternal HBV-infection status, presence of hepatitis B e antigen and HBV mutation.CONCLUSION： Differences in peripheral T-cell subpopulation profiles can be found in different clinical stages of chronic HBV infection. T-cell impairment is significantly associated with HBV load.

Efficiency and safety of lamivudine therapy in patients with chronic HBV infection, dialysis or after kidney transplantation

AIM: To analyze the effectiveness and safety of lamivudine treatment in patients with chronic HBV infection undergoing hemodialysis or after kidney transplantation, and to study the frequency of tyrosine - methionine - aspartate - aspartate (YMDD) mutation occurrence after lamivudine treatment. METHODS: We analyzed 91 patients with chronic hepatitis B, among whom, 16 patients underwent hemodialysis, 7 patients had kidney transplantation and 68 patients had normal function of kidney. The hemodialysis patients were treated by lamivudine 300 mg/wk. patients after kidney transplantation and patiente with normal function of kidney were treated with lamivudine 100 mg/d. Therapy lasted for 12 mo. HBV-DNA, HBsAg, HBeAg and anti-HBe, and anti-HCV antibodies were assessed in sera of patients. The analysis was performed before and 6 mo after the end of lamivudine treatment. Before, during and after the lamivudine therapy, the number of erythrocytes, leukocytes, platelets and hemoglobin concentration, ALT and AST activity, as well as bilirubin, urea and creatinine concentrations were analyzed in sera from patients. RESULTS: After the 12-mo lamivudine treatment, elimination of HBV - DNA was observed in 56% patients undergoing hemodialysis and in 53% patients with normal kidney function. Only 1 from 7 (14%) kidney-transplanted patients eliminated HBV-DNA. Furthermore, HBeAg elimination was observed in 36% hemodialysis patients, in 51% patients with normal function of kidneys and in 43% kidney transplanted patients. Among the patients undergoing dialysis, no YMDD mutation was found after 12 mo of therapy, while it was detected in 9 patients (13%) with normal function of kidney and in 2 kidney-transplanted patients (29%, P<0.006). We did not observe significant side effecte of lamivudine treatment in studied patiente. CONCLUSION: Effectiveness of lamivudine therapy in dialysis patients is comparable with that in patiente with normal function of kidney. Lamivudine treatment is well tolerated and safe in patiente with renal insufficiency undergoing hemodialysis and kidney-transplantation. However, in the latter group, high incidence of YMDD mutation after lamivudine treatment was observed.

Management of chronic hepatitis B infection: Current treatment guidelines, challenges, and new developments

Chronic hepatitis B(CHB)virus infection is a global public health problem,affecting more than 400 million people worldwide.The clinical spectrum is wide,ranging from a subclinical inactive carrier state,to progressive chronic hepatitis,cirrhosis,decompensation,and hepatocellular carcinoma.However,complications of hepatitis B virus(HBV)-related chronic liver disease may be reduced by viral suppression.Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon,entecavir,or tenofovir,but the optimal treatment for an individualpatient is controversial.The indications for treatment are contentious,and increasing evidence suggests that HBV genotyping,as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response.The likelihood of achieving a sustained virological response is also increased by extending treatment duration,and using combination therapy.Hence the paradigm for treatment of CHB is constantly evolving.This article summarizes the different indications for treatment,and systematically reviews the evidence for the efficacy of various antiviral agents.It further discusses the shortcomings of current guidelines,use of rescue therapy in drug-resistant strains of HBV,and highlights the promising clinical trials for emerging therapies in the pipeline.This concise overview presents an updated practical approach to guide the clinical management of CHB.

Intervention effect and mechanism of curcumin in chronic urinary tract infection in rats

Objective: To analyze the invention effect of curcumin on chronic urinary tract infection in rats and explore its possible mechanism of action. Methods: The experimental animals were randomly divided into three groups, normal, model and curcumin group. Chronic urinary tract infection models were built for model group and curcumin group by injecting coliform fluid into the cavity of bladder. From the first day of modeling, rats in the curcumin group were injected with 150 mg/kg curcumin, while rats in normal group and model group were given no other treatment. The treatment lasted for 14 d. The white blood cell counts in blood and urine, bacterial colony count in urine and renal tubular functional indexes of rats in all groups at day I, 7, and 14 after treatment were detected. Urine beta 2-microglobulin (beta 2-MG), urinary N-acetyl-D glucosaminidase (NAG) levels were used to detected the inflammatory cytokines in serum after treatment including the contents of IL-6, IL-8, IL-10 and monocyte chemoattractant protein-I(MCP-1), and real-time PCR was employed to determine the expression of mRNA of toll-like receptor 2(TLR-2) and TLR-4 in renal tissues and bladder tissues of all groups after treatment. Results: The white blood cell counts at day I and 7 after treatment in rats of model group and curcumin group were significantly higher than those of normal group at the same time points, while the white blood cell counts of the curcumin group were significantly lower than those of model group (P < 0.05). The urine white blood cell counts in rats of model group at day 1, 7 and 14 were all significantly higher than those of normal group at the same time points: those in the curcumin group were significantly lower than those of the model group at day I, 7 and 14 at the same time points (p < 0.05). The bacterial colony counts of urine in rats of model group and curcumin group at day I. 7 and 14 were all significantly higher than those of normal group at the same time points, while the counts of curcumin group were significantly lower than those of model group at the same time points (P < 0.05). Levels of urine beta 2-MG, NAG, IL-6, IL-8, IL-10, MCP-1 and expression of TLR2 mRNA and TLR4 mRNA in renal and bladder tissues in rats of model group were significantly higher than those of the normal group, while these variables of the cercumin group were significantly higher than those of the normal group but lower than those of model group (P < 0.05). Conclusions: Curcumin can significantly improve the symptoms of chronic urinary tract infections. protect renal tubular function, and also decline inflammatory responses by influencing the expressions of TLR2 mRNA and TLR4 mRNA so as to exert its curative effect on chronic urinary tract infections.

Different effects of a CD14 gene polymorphism on disease outcome in patients with alcoholic liver disease and chronic hepatitis C infection

AIM： Clinical and experimental data suggest that gut-derived endotoxins are an important pathogenic factors for progression of chronic liver disease. Recently, a C-T （-159） polymorphism in the promoter region of the CD14 gene was detected and found to confer increased CD14 expression and to be associated with advanced alcoholic liver damage. Here, we investigated this polymorphism in patients with less advanced alcoholic liver disease （ALD） and chronic hepatitis C virus （HCV） infection. METHODS： CD14 genotyping was performed by PCR-RFLP analysis in （a） 121 HCV patients, （b） 62 patients with alcohol-associated cirrhosis （AIc-Ci）, （c） 118 individuals with heavy alcohol abuse without evidence of advanced liver damage （Alc-w/o Ci）, and （d） 247 healthy controls. Furthermore, serum levels of soluble CD14 （sCD14） and transaminases were determined. RESULTS： The TT genotype was significantly more frequent in Alc-Ci compared to Alc-w/o Ci or controls （40.3% vs 23.7% or 24.0%, respectively）. In Alc-w/o Ci, serum levels of transaminases did not differ significantly between patients with different CD14 genotypes. In HCV patients, TT-homozygotes had significantly higher sCD14 levels and sCD14 serum levels were significantly higher in patients with advanced fibrosis or cirrhosis. However, no association was found between CD14 genotypes and histological staging or grading. CONCLUSION： Considering serum transaminases as surrogate markers for alcoholic liver damage, the CD14 polymorphism seems to exhibit different effects during the course of ALD. Differences in genotype distribution between cirrhotic HCV patients and alcoholics and the known functional impact of this polymorphism on CD14 expression levels further indicate differences in the pathophysiological role of CD14 and CD14-mediated lipopolysaccharides signal transduction with regard to the stage as well as the type of the underlying liver disease.

Hepatic flares in chronic hepatitis C: Spontaneous exacerbation vs hepatotropic viruses superinfection

The hepatitis C virus(HCV)causes an acute infection that is frequently asymptomatic,but a spontaneous eradication of HCV infection occurs only in one-third of patients.The remaining two-thirds develop a chronic infection that,in most cases,shows an indolent course and a slow progression to the more advanced stagesof the illness.Nearly a quarter of cases with chronic hepatitis C(CHC)develop liver cirrhosis with or without hepatocellular carcinoma.The indolent course of the illness may be troubled by the occurrence of a hepatic flare,i.e.,a spontaneous acute exacerbation of CHC due to changes in the immune response,immunosuppression and subsequent restoration,and is characterized by an increase in serum aminotransferase values,a frequent deterioration in liver fibrosis and necroinflammation but also a high frequency of sustained viral response to pegylated interferon plus ribavirin treatment.A substantial increase in serum aminotransferase values during the clinical course of CHC may also be a consequence of a superinfection by other hepatotropic viruses,namely hepatitis B virus(HBV),HBV plus hepatitis D virus,hepatitis E virus,cytomegalovirus,particularly in geographical areas with high endemicity levels.The etiology of a hepatic flare in patients with CHC should always be defined to optimize follow-up procedures and clinical and therapeutic decisions.

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.

Chronic hepatitis C infection in a patient with bone marrow hypoplasia

Chronic hepatitis C virus(HCV) infection is associated with multifarious extra-hepatic manifestations;the most described and discussed being mixed cryoglob-ulinemia which is strongly related to B-cell lympho-proliferative disorders(LPDs).We present a case of chronic HCV infection and mixed cryoglobulinemia,with minimal liver involvement.The case is a 53-year-old patient who was diagnosed as having bone marrow hypoplasia at the age of three.She received several blood transfusions to normalize her haemoglobin.At the age of 31,she was diagnosed with rheumatoid ar-thritis on account of her diffuse joint pain and inflam-mation,elevated rheumatoid factor(RF) and Raynaud's phenomenon.Twenty years later,monoclonal gam-mopathy of IgG Lambda(one year later,changed to IgM Kappa) was detected during a routine examina-tion.A bone marrow biopsy showed hypoplasia,Kappa positive B-lymphocytes and low-grade malignant lym-phoma cells.PCR of the bone marrow aspirate was not contributory.No treatment was initiated owing to herpoor bone marrow function and she is under regular follow-up.

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.

Mucosal T-cell responses to chronic viral infections:Implications for vaccine design

Mucosal surfaces that line the respiratory,gastrointestinal and genitourinary tracts are the major interfaces between the immune system and the environment.Their unique immunological landscape is characterized by the necessity of balancing tolerance to commensal microorganisms and other innocuous exposures against protection from pathogenic threats such as viruses.Numerous pathogenic viruses,including herpesviruses and retroviruses,exploit this environment to establish chronic infection.Effector and regulatory T-cell populations,including effector and resident memory T cells,play instrumental roles in mediating the transition from acute to chronic infection,where a degree of viral replication is tolerated to minimize immunopathology.Persistent antigen exposure during chronic viral infection leads to the evolution and divergence of these responses.In this review,we discuss advances in the understanding of mucosal T-cell immunity during chronic viral infections and how features of T-cell responses develop in different chronic viral infections of the mucosa.We consider how insights into T-cell immunity at mucosal surfaces could inform vaccine strategies:not only to protect hosts from chronic viral infections but also to exploit viruses that can persist within mucosal surfaces as vaccine vectors.