Immunohistochemical Expression of Surviving in Viral Hepatitis and Hepatocellular Carcinoma, a Comparative Study

Hepatocellular carcinoma (HCC) is the fifth most common neoplasm, the major cause of death in patients with cirrhosis, and the third most common cause of cancer-related death in the world. In Egypt, hepatocellular carcinoma (HCC) is the second most common cancer in men and the 6th most common cancers in women. Egypt has the highest prevalence of HCV in the world and the prevalence of HCC is increasing in the last years. Nowadays, HCV infection and its complications are among the leading public health challenges in Egypt with 13.8% of population infected and, in these patients, the risk of HCC is increased 17-fold. Glypican-3 (GPC3) is a member of heparin sulfate proteoglycan family which is linked to cell surface. It plays an important role in regulation of cell growth, differentiation, and migration. It is normally expressed in fetal liver and placenta but not in normal adult liver tissue. 8-Hydroxydeoxyguanosine (8-OHdG) is an oxidatively modified promutagenic DNA that is produced by oxygen radicals and is recognized as a useful marker in estimating DNA damage induced by oxidative stress. The present work is a retrospective, cross-sectional, study performed on 150 liver paraffin blocks that included 100 cases of chronic hepatitis C and 50 cases of hepatocellular carcinoma. These cases were collected from the Pathology Department. The 100 cases of chronic hepatitis C were graded into low grade chronic hepatitis (58) cases and high-grade chronic hepatitis (42) cases, 30 patients had cirrhosis, all in the high-grade group. The 50 cases of hepatocellular carcinoma (HCC) included 18 cases of well-differentiated HCC (grade I), 22 cases of moderately differentiated HCC (grade II) and 10 cases of poorly differentiated HCC (grade III). Among 50 cases of HCC, 44 cases showed cirrhosis in the non-neoplastic liver tissue. There was a statistically significant difference in 8-OHdG index between chronic hepatitis and hepatocellular carcinoma (P = 0.006).

A Stochastic Model to Assess the Epidemiological Impact of Vaccine Booster Doses on COVID-19 and Viral Hepatitis B Co-Dynamics with Real Data

A patient co-infected with COVID-19 and viral hepatitis B can be atmore risk of severe complications than the one infected with a single infection.This study develops a comprehensive stochastic model to assess the epidemiological impact of vaccine booster doses on the co-dynamics of viral hepatitis B and COVID-19.The model is fitted to real COVID-19 data from Pakistan.The proposed model incorporates logistic growth and saturated incidence functions.Rigorous analyses using the tools of stochastic calculus,are performed to study appropriate conditions for the existence of unique global solutions,stationary distribution in the sense of ergodicity and disease extinction.The stochastic threshold estimated from the data fitting is given by:R_(0)^(S)=3.0651.Numerical assessments are implemented to illustrate the impact of double-dose vaccination and saturated incidence functions on the dynamics of both diseases.The effects of stochastic white noise intensities are also highlighted.

Effect of viral hepatitis on type 2 diabetes:A Mendelian randomization study

BACKGROUND The effects of viral hepatitis(VH)on type 2 diabetes(T2D)remain controversial.AIM To analyze the causal correlation between different types of VH and T2D using Mendelian randomization(MR).METHODS Single nucleotide polymorphisms of VH,chronic hepatitis B(CHB),chronic hepatitis C(CHC)and T2D were obtained from the BioBank Japan Project,European Bioinformatics Institute,and FinnGen.Inverse variance weighted,MREgger,and weighted median were used to test exposure-outcome associations.The MR-Egger intercept analysis and Cochran’s Q test were used to assess horizontal pleiotropy and heterogeneity,respectively.Leave-one-out sensitivity analysis was used to evaluate the robustness of the MR analysis results.RESULTS The MR analysis showed no significant causal relationship between VH and T2D in Europeans[odds ratio(OR)=1.028;95%confidence interval(CI):0.995-1.062,P=0.101].There was a negative causal association between CHB and T2D among East Asians(OR=0.949;95%CI:0.931-0.968,P<0.001),while there was no significant causal association between CHC and T2D among East Asians(OR=1.018;95%CI:0.959-1.081,P=0.551).Intercept analysis and Cochran’s Q test showed no horizontal pleiotropy or heterogeneity(P>0.05).Sensitivity analysis showed that the results were robust.CONCLUSION Among East Asians,CHB is associated with a reduced T2D risk,but this association is limited by HBV load and cirrhosis.Although VH among Europeans and CHC among East Asians are not associated with the risk of T2D,focusing on blood glucose in patients with CHC is still relevant for the early detection of T2D induced by CHCmediated pathways of hepatic steatosis,liver fibrosis,and cirrhosis.

Evaluation of Biochemical and Molecular Parameters of Patients Suffering from Chronic Viral Hepatitis B Treated by a Medicinal Plant Recipe of a Health Care Practitioner in Burkina Faso

Chronic viral hepatitis B (HBV) remains a major public health problem in Burkina Faso. Since access to diagnostic tests and treatments is limited because of their high cost, the majority of the population turn to traditional herbal treatments. This study aimed to evaluate the effectiveness of a plant recipe called Hepatib tiben. It consisted of comparing certain biochemical and molecular parameters of patients infected with HBV that were supported by the recipe. The patients were recruited in Ouagadougou by the traditional health practitioner according to the requirements of the study. Thus 44 patients aged 20 to 61 years and carrier of HBsAg for at least 06 months were treated with Hepatib tiben. The tests were performed in the laboratory before and three months after the treatment. ELISA tests were used to confirm the presence of HBsAg and search for anti-HCV antibodies;transaminases, creatinine were quantified by the “Chem 400” automaton and the viral load of HBV by Real-time PCR. The analysis of the results reveals an improvement of the biochemical and molecular parameters of the patients with the following means (ASAT: 21.02 ± 9.97;ALAT: 21.11 ± 13.27;DNA: 1571.82 ± 3990.97 with p = 0.01 for each). As for HBsAg, its disappearance was observed in 4.55% of patients after treatment. The evaluation of the creatinine parameter explained that the recipe of plants has a tolerated effect on the kidneys of treated patients. These results, while encouraging, need to be complemented by further research for the development of effective phytomedicine to treat and eliminate this viral hepatitis B virus.

Prevalence of Children Vaccinated against Viral Hepatitis B in Brazzaville

Introduction: Viral hepatitis B (VHL) is a public health problem, particularly in sub-Sahara Africa. The aim of this study was to assess vaccination coverage against HBV in children in Brazzaville. Patients and Methods: This was a cross-sectional analytical study conducted in Brazzaville health centres from January to September 2019. It involved children aged between six months and six years who received a vaccination against HBV. Sampling was exhaustive and based on stratified sampling. Results: The overall prevalence of children vaccinated against HBV in Brazzaville was 96.2%. It was insufficient in the Talangai health district (79%). The pentavalent vaccine was administered to 97.7% of children, 85% of whom had received all three doses. The reasons for incomplete vaccination were parents’ ignorance of HVB (85.6%) and of vaccination (14.3%). Conclusion: Although the prevalence of vaccinated children is high in Brazzaville, it is still insufficient in some health districts, particularly Talangai, because parents are unaware of the disease and of vaccination. Pentavalent is the only vaccine available in the national vaccination programme, which is why an effective national vaccination policy needs to be put in place. .

Plant-based vaccines against viral hepatitis: A panoptic review

The traditional vaccines against hepatitis have been instrumental in reducing the incidence of some types of viral hepatitis;however,the need for cost-effective,easily distributable,and needle-free vaccine alternatives has led to the exploration of plant-based vaccines.Plant-based techniques offer a promising avenue for producing viral hepatitis vaccines due to their low-cost cultivation,scalability,and the potential for oral administration.This review highlights the successful expression of hepatitis B surface antigens in plants and the subsequent formation of virus-like particles,which have shown immunogenicity in preclinical and clinical trials.The challenges such as achieving sufficient antigen expression levels,ensuring consistent dosing,and navigating regulatory frameworks,are addressed.The review considers the potential of plant-based vaccines to meet the demands of rapid vaccine deployment in response to outbreaks and their role in global immunization strategies,particularly in resource-limited settings.This review underscores the significant strides made in plant molecular farming and the potential of plant-based vaccines to complement existing immunization methods against viral hepatitis.

Subclinical hepatitis E virus genotype 1 infection:The concept of“dynamic human reservoir”

Hepatitis E virus(HEV)is hyperendemic in South Asia and Africa accounting for half of total Global HEV burden.There are eight genotypes of HEV.Among them,the four common ones known to infect humans,genotypes 1 and 2 are prevalent in the developing world and genotypes 3 and 4 are causing challenge in the industrialized world.Asymptomatic HEV viremia in the general population,especially among blood donors,has been reported in the literature worldwide.The clinical implications related to this asymptomatic viremia are unclear and need further exploration.Detection of viremia due to HEV genotype 1 infection,apparently among healthy blood donors is also reported without much knowledge about its infection rate.Similarly,while HEV genotype 3 is known to be transmitted via blood transfusion in humans and has been subjected to screening in many European nations,instances of transmission have also been documented albeit without significant clinical consequences.Epidemiology of HEV genotype 1 in endemic areas often show waxing and waning pattern.Occasional sporadic occurrence of HEV infection interrupted by outbreaks have been frequently seen.In absence of known animal reservoir,where HEV exists in between outbreak is a mystery that needs further exploration.However,occurrence of asymptomatic HEV viremia due to HEV genotype 1 during epidemiologically quiescent period may explain that this phenomenon may act as a dynamic reservoir.Since HEV genotype 1 infection cannot cause chronicity,subclinical transient infection and transmission of virus might be the reason it sustains in interepidemic period.This might be the similar phenomenon with SARS COVID-19 corona virus infection which is circulating worldwide in distinct phases with peaks and plateaus despite vaccination against it.In view of existing evidence,we propose the concept of“Dynamic Human Reservoir.”Quiescent subclinical infection of HEV without any clinical consequences and subsequent transmission may contribute to the existence of the virus in a community.The potential for transmitting HEV infection by asymptomatic HEV infected individuals by fecal shedding of virus has not been reported in literature.This missing link may be a key to Pandora's box in understanding epidemiology of HEV infection in genotype 1 predominant region.

State of the HIV, Hepatitis B and C Virus Pandemic from 2003 to 2022 in Burkina Faso: Evolution of Prevalence Trends and Strategic Recommendations to Achieve the WHO’s Goal for Their Eradication by 2030

Background: The World Health Organization (WHO) has set a goal to eradicate or at least significantly reduce the prevalence the human immunodeficiency virus (HIV), hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) by 2030. The main objective was to provide an evolving overview of the prevalence of HIV, HBV and HCV infection between 2003 and 2022 in Burkina Faso. Methods: It was a retrospective cross-sectional study based on data from 2003 to 2022. The data were collected using information available in the databases of the HOSCO and CERBA laboratories and included all individuals who underwent HIV and/or HBV and/or HCV testing. Data analysis was performed using SPSS version 20.0, EpiInfo 7, and R version 4.1.0. Results were considered statistically significant if p Results: The study recorded 7432 samples and the mean age of the subjects was 27.98 ± 8.50 years. During this period, the respective prevalence of HIV, HBV, and HCV were 4.66% (346/7432), 8.77% (582/6636) and 5.54% (322/5816). However, from 2003 to 2022, there was a significant decrease (P y=−1.75x+12.59;y=−0.24x+10.01and y=−0.11x+6.02, with “y” corresponding to prevalence and “x” to the years. Conclusion: Burkina Faso needs to rigorously apply prevention and control strategies recommended by the WHO by 2030.

Chronic Hepatitis B Virus Infection: Biological Parameters in Patients Treated with Tenofovir Disoproxil Fumarate

Chronic hepatitis B causes a liver disease characterized by inflammation of the liver parenchyma. The aim of this study was to investigate the evolution of biological parameters in patients treated with Tenofovir for chronic B infection at the Commune V referral health center in Bamako. We obtained a prevalence of 14.15%. The most represented age group was 31 - 40 years, with 36.8%. The sex ratio was 1.44 in favour of men. Viral load was undetectable after 18 months of treatment in 25 patients (42.37%). Tenofovir, the 1st-line drug in Mali, is effective on the biological parameters monitored in patients.

Viral etiologies of acute liver failure

Acute liver failure(ALF)is a rare cause of liver-related mortality worldwide,with an estimated annual global incidence of more than one million cases.While drug-induced liver injury,including acetaminophen toxicity,is the leading cause of ALF in the Western world,viral infections remain a significant cause of ALF and the most common cause in many developing nations.Given the high mortality rates associated with ALF,healthcare providers should be aware of the broad range of viral infections that have been implicated to enable early diagnosis,rapid treatment initiation when possible,and optimal management,which may include liver transplantation.This review aims to provide a summary of viral causes of ALF,diagnostic approaches,treatment options,and expected outcomes.

Parents’s knowledge and awareness about hepatitis B can influence the vaccination of their children

BACKGROUND Birth-dose(Hep-BD)followed by three additional doses(Hep-B3)of hepatitis B virus(HBV)vaccine are key to eliminating HBV by 2030.Unfortunately,Hep-BD and Hep-B3 coverage in our country is poor.AIM To studied the parent’s knowledge and awareness about HBV infection,its prevention,consequences and vaccination.METHODS Parents of 6 months to 8 years old children were interviewed to assess their knowledge&awareness about hepatitis B,its transmission,prevention,illness caused by this,and vaccination.Eighteen close-ended questions were admini-stered,and responses were recorded as‘yes’,‘no’,or‘not sure’.HBV knowledge score was calculated based on the sum of correct answers.Each correct response scored one point and incorrect,missing or‘not sure’responses received no points.Categorical data are presented as number(%)and numerical data are expressed as median.Data were compared using Chi2 tests and level of significance was kept as P<0.05.RESULTS Parents(58.3%mothers)of 384 children(89.9%age<5 years;82%age-appropriately vaccinated)were included.Three hundred and twenty-two(83.9%)children were Hep-B3 vaccinated.94.3%,87.5%,and 29.2%parents knew about polio,tetanus,and hepatitis B vaccine.Overall,41.2%,15.8%,and 23%parents knew about hepatitis B transmission,consequences of infection,and prevention respectively.Only 7.6%parents knew about three-dose schedule of hepatitis B vaccination.Only 23%parents believed that vaccine could prevent HBV,15.7%knew that HBV affects liver.Parents of Hep-B3 vaccinated children were significantly more aware about HBV than the parents of unvaccinated children(P<0.05 for 17/18 questions).CONCLUSION The knowledge and awareness among the parents about hepatitis B is poor.The Increasing knowledge/awareness about HBV among parents may improve Hep-B3 vaccination coverage.

Evaluation of the diagnostic efficacy of noninvasive diagnosis in patients with chronic viral hepatitis B complicated with nonalcoholic fatty liver disease and significant liver fibrosis

Objective:To evaluate the diagnostic efficacy of chronic viral hepatitis B(CHB)with significant liver fibrosis(S2)in patients with nonalcoholic fatty liver disease(NAFLD)by using noninvasive diagnosis and their combined models,and to explore their clinical features.Methods:A total of 104 inpatients with CHB diagnosed and complicated with NAFLD(hepatic steatosis suggested by liver biopsy)were retrospectively collected from January 2018 to January 2023 in the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University.Liver biopsy was performed in all patients.General data,laboratory test results,liver hardness(LSM),FIB-4,APRI,GGT/PLT,AST/PLT and other results of patients were collected and grouped according to different fibrosis stages(S)to explore the clinical and pathological characteristics of patients with<S2 and S2 stages.Receiver operating characteristic curve was used to evaluate the diagnostic value of LSM,FIB-4,APRI,GGT/PLT,AST/PLT and their combined models in patients with significant liver fibrosis in CHB patients with NAFLD.Results:Among the 104 patients,there were 55 patients had S1 fibrosis,32 patients had S2 fibrosis,11 patients had S3 fibrosis and 6 patients had S4 fibrosis.Patients had<S2 fibrosis,ALT 33.75±17.15 U/L,AST 24.00(19.77,29.00)U/L,inflammation above G2 stage accounted for 92.72%,GGT/PLT 0.07(0.10,0.15),AST/PLT 0.09(0.10,0.15),LSM 8.70(6.80,10.10)kPa,FIB-41.07±0.51,APRI 0.26(0.22,0.28).In patients S2 fibrosis,ALT 42.14±21.39 U/L,AST 29.04(24.00,40.32)U/L,inflammation above G2 stage accounted for 97.95%,GGT/PLT 0.15(0.10,0.28),AST/PLT 0.14(0.10,0.26),GGT/PLT 0.15(0.10,0.28),AST/PLT 0.14(0.10,0.26).LSM 11.80(8.50,16.65)kPa,FIB-41.39±0.72,APRI 0.35(0.26,0.66),the difference between the two groups was statistically significant(P<0.05).The area under the receiver operator characteristic curves of the subjects of LSM,FIB-4,APRI,GGT/PLT and AST/PLT were 0.716,0.623,0.669,0.644 and 0.669(P<0.05),respectively.In the combined model,the area under the receiver operator characteristic curves of LSM combined with FIB-4,LSM combined with APRI,LSM combined with GGT/PLT and LSM combined with AST/PLT were 0.712,0.719,0.715 and 0.719,respectively(P<0.05).Conclusion:Although the currently commonly used Noninvasive diagnosis of liver fibrosis has certain diagnostic efficacy for significant liver fibrosis in CHB complicated with NAFLD,it cannot replace liver biopsy.Noninvasive Diagnosis can be used as an auxiliary method for regular clinical evaluation of liver biopsy.

Prevalence and Viral Load Determination of Hepatitis B Virus among Hiv Seropositive Patients Attending Kogi State Specialist Hospital Lokoja, Kogi State

Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV) share common risk factors and HBV occurs in people with HIV resulting in an increased risk for HIV/HBV co-infection. Globally, hepatitis B virus infection is of serious public health causing morbidity and mortality. The increasing incidence of liver diseases caused by HBV is emerging as a significant cause of morbidity and mortality among HIV-infected individuals. A clearer knowledge of HBV prevalence in Kogi State is important in order to educate, inform the population and control epidemics through extensive vaccination and treatment programme. The aim of this study was to determine the seroprevalence of Hepatitis B infection and to evaluate molecularly HBV infection among HIV seropositive individuals. Sera samples were obtained from 218 consented HIV participants and screened for HBsAg using the commercial membrane based rapid qualitative test kit and real-time PCR was performed using Tianlong to assay the virus quantitatively. A structured questionnaire was used to collect information on patient’s demographic variables and risk factors for HBV transmission. Overall, 17 of the participants were seropositive to HBsAg. There was a significant difference between the age distribution with (P-value = 0.006) and marital status with (P-value = 0.044). Type of marriage, occupation, place of residence and risk factors associated with HIV and HBV co-infection do not show significant differences. A total of 17 HBsAg positive samples were subjected to viral load analysis, out of which 7 were highly unsuppressed, 5 were suppressed while the remaining 5 were undetectable. This study confirmed a moderately high HIV/HBV co-infection rate (7.8%). The highly unsuppressed viral load obtained from the study is a potential risk for Hepatocellular carcinoma among the study population. Enlightenment programme on routes of virus acquisition with a view to reducing the morbidity and mortality of HIV/HBV co-infection should be intensified.

Factors Associated with Hepatic Steatosis in Black African Subjects with Chronic Viral Hepatitis B in Côte d’Ivoire

Context/Objectives: With the progression of the global epidemic of obesity and metabolic syndrome, the coexistence of hepatic steatosis in patients with chronic viral hepatitis B (VHB) is becoming significant. The aim of this work was to determine the factors associated with hepatic steatosis assessed by a Fibroscan with Controlled Attenuation Parameter (CAP) in patients with chronic viral hepatitis B in Côte d’Ivoire. Methods: This was a cross-sectional and analytical study. Data was collected from February 15 to July 31, 2020 in a private hospital structure in the city of Abidjan in Côte d’Ivoire. We included 83 patients with chronic viral hepatitis B. These were black patients, having performed a Fibroscan/CAP during the recruitment period and consenting to participate in the study. Patients with significant alcohol consumption, a secondary cause of hepatic steatosis, or other liver disease regardless of the etiology associated with hepatitis B were not included. Results: The frequency of hepatic steatosis in chronic VHB carriers assessed by the CAP in our study population was 48.19% including 24.10% severe steatosis. Obesity and high LDL cholesterol were statistically correlated with the presence of steatosis in our patients. Patients who had steatosis on ultrasound were 5 times more likely to have steatosis on CAP. Significant fibrosis was not significantly associated with steatosis. Conclusion: Obesity and LDL hypercholesterolemia are the main factors associated with hepatic steatosis detected by Fibroscan/CAP in patients with chronic viral hepatitis B.

Evolution of HBV Viral Load during Clinical and Biological Follow-Up of Chronic Hepatitis B Patients at the Saint Camille Hospital in Ouagadougou

Hepatitis B virus (HBV) infection is a major public health problem worldwide. The aim of this study was to document the dynamics of HBV viral load during the follow-up of chronic hepatitis B patients at the Saint Camille Hospital in Ouagadougou (HOSCO) from 2017 to 2021. This descriptive retrospective study was carried out in the Hepato-Gastro-Enterology Department of HOSCO and focused on patients who were undergoing treatment for chronic viral hepatitis B. A total of 260 cases of chronic hepatitis B were included in the study. The most affected age group was 21 to 30 years, accounting for 48.08% of the cases. Lifestyle factors included alcohol consumption (3.08%) and tobacco use (2.69%). Major risk factors for transmission included lack of vaccination (98.46%), family history of HBV infection (68.00%) and engagement in high-risk activities (28.00%). Patients requiring treatment were prescribed Tenofovir 300 mg tablets. FibroScan® showed the presence of stage F3-F4 fibrosis (2.14%) and S3 steatosis (13.33%). After one year of follow-up, 6.92% of patients achieved an undetectable viral load with normalized transaminase levels. The majority of other patients had a detectable viral load but below 20,000 IU/mL. The prevalence of viral hepatitis B remains significant worldwide. Although effective and well-monitored treatment can lead to undetectable viremia, prevention remains the most effective strategy for successful management of this disease.

Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma

Chronic infection with viral hepatitis affects half a billion individuals worldwide and can lead to cirrhosis,cancer,and liver failure.Liver cancer is the third leading cause of cancer-associated mortality,of which hepatocellular carcinoma(HCC)represents 90%of all primary liver cancers.Solid tumors like HCC are complex and have heterogeneous tumor genomic profiles contributing to complexity in diagnosis and management.Chronic infection with hepatitis B virus(HBV),hepatitis delta virus(HDV),and hepatitis C virus(HCV)are the greatest etiological risk factors for HCC.Due to the significant role of chronic viral infection in HCC development,it is important to investigate direct(viral associated)and indirect(immune-associated)mechanisms involved in the pathogenesis of HCC.Common mechanisms used by HBV,HCV,and HDV that drive hepatocarcinogenesis include persistent liver inflammation with an impaired antiviral immune response,immune and viral protein-mediated oxidative stress,and deregulation of cellular signaling pathways by viral proteins.DNA integration to promote genome instability is a feature of HBV infection,and metabolic reprogramming leading to steatosis is driven by HCV infection.The current review aims to provide a brief overview of HBV,HCV and HDV molecular biology,and highlight specific viral-associated oncogenic mechanisms and common molecular pathways deregulated in HCC,and current as well as emerging treatments for HCC.

Fibrinogen-like protein 2 fibroleukin expression and its correlation with disease progression in murine hepatitis virus type 3-induced fulminant hepatitis and in patients with severe viral hepatitis B

AIM： To evaluate the expression of fibrinogenlike protein 2 （fgl2） and its correlation with disease progression in both mice and patients with severe viral hepatitis. METHODS： Balb/cJ or A/J mice were infected intraperitoneally （ip） with 100 PFU of murine hepatitis virus type 3 （MHV-3）, liver and serum were harvested at 24, 48, and 72 h post infection for further use. Liver tissues were obtained from 23 patients with severe acute chronic （AOC） hepatitis B and 13 patients with mild chronic hepatitis B. Fourteen patients with mild chronic hepatitis B with cirrhosis and 4 liver donors served as normal controls. In addition, peripheral blood mononuciear cells （PBMC） were isolated from 30 patients （unpaired） with severe AOC hepatitis B and 10 healthy volunteers as controls. Procoagulant activity representing functional prothrombinase activity in PBMC and white blood cells was also assayed. A polyclonal antibody against fgl2 was used to detect the expression of both mouse and human fgl2 protein in liver samples as well as in PBMC by immunohistochemistry staining in a separate set of studies. Alanine aminotransferase （ALT） and total bilirubin （TBil） in serum were measured to assess the severity of liver injury.RESULTS： Histological changes were found in liver sections 12-24 h post MHV-3 infection in Balb/cJ mice. In association with changes in liver histology, marked elevations in serum ALT and TBil were observed. House fgl2 （mfgl2） protein was detected in the endothelium of intrahepatic veins and hepatic sinusoids within the liver 24 h after MHV-3 infection. Liver tissues from the patients with severe AOC hepatitis B had classical pathological features of acute necroinflammation. Human fgl2 （hfgl2） was detected in 21 of 23 patients （91.30%） with severe AOC hepatitis B, while only 1 of 13 patients （7.69%） with mild chronic hepatitis B and cirrhosis had hfgl2 mRNA or protein expression. Twenty-eight of thirty patients （93.33%） with severe AOC hepatitis B and 1 of 10 with mild chronic hepatitis B had detectable hfgl2 expression in PBMC. No hfgl2 expression was found either in the liver tissue or in the PBMC from normal donors. There was a positive correlation between hfgl2 expression and the severity of the liver disease as indicated by the levels of TBil. PCA significantly increased in PBMC in patients with severe AOC hepatitis B. CONCLUSION： The molecular and cellular results reported here in both mice and patients with severe viral hepatitis suggest that virus-induced hfgl2 prothrombinase/fibroleukin expression and the coagulation activity associated with the encoded fgl2 protein play a pivotal role in initiating severe hepatitis. The measurement of hfgl2/fibroleukin expression in PBMC may serve as a useful marker to monitor the severity of AOC hepatitis B and a target for therapeutic intervention.

Viral hepatitis update: Progress and perspectives

Viral hepatitis,secondary to infection with hepatitis A,B,C,D,and E viruses,are a major public health problem and an important cause of morbidity and mortality.Despite the huge medical advances achieved in recent years,there are still points of conflict concerning the pathogenesis,immune response,development of new and more effective vaccines,therapies,and treatment.This review focuses on the most important research topics that deal with issues that are currently being solved,those that remain to be solved,and future research directions.For hepatitis A virus we will address epidemiology,molecular surveillance,new susceptible populations as well as environmental and food detections.In the case of hepatitis B virus,we will discuss host factors related to disease,diagnosis,therapy,and vaccine improvement.On hepatitis C virus,we will focus on pathogenesis,immune response,direct action antivirals treatment in the context of solid organ transplantation,issues related to hepatocellular carcinoma development,direct action antivirals resistance due to selection of resistanceassociated variants,and vaccination.Regarding hepatitis D virus,we describe diagnostic methodology,pathogenesis,and therapy.Finally,for hepatitis E virus,we will address epidemiology(including new emerging species),diagnosis,clinical aspects,treatment,the development of a vaccine,and environmental surveillance.

Specific CD8^+ T cell response immunotherapy for hepatocellular carcinoma and viral hepatitis

Hepatocellular carcinoma (HCC), chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are characterized by exhaustion of the specific CD8+ T cell response. This process involves enhancement of negative co-stimulatory molecules, such as programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), 2B4, Tim-3, CD160 and LAG-3, which is linked to intrahepatic overexpression of some of the cognate ligands, such as PD-L1, on antigen presenting cells and thereby favouring a tolerogenic environment. Therapies that disrupt these negative signalling mechanisms represent promising therapeutic tools with the potential to restore reactivity of the specific CD8+ T cell response. In this review we discuss the impressive in vitro and in vivo results that have been recently achieved in HCC, CHB and CHC by blocking these negative receptors with monoclonal antibodies against these immune checkpoint modulators. The article mainly focuses on the role of CTLA-4 and PD-1 blocking monoclonal antibodies, the first ones to have reached clinical practice. The humanized monoclonal antibodies against CTLA-4 (tremelimumab and ipilimumab) and PD-1 (nivolumab and pembrolizumab) have yielded good results in testing of HCC and chronic viral hepatitis patients. Trelimumab, in particular, has shown a significant increase in the time to progression in HCC, while nivolumab has shown a remarkable effect on hepatitis C viral load reduction. The research on the role of ipilimumab, nivolumab and pembrolizumab on HCC is currently underway.

Role of chemokines and their receptors in viral persistence and liver damage during chronic hepatitis C virus infection

Chemokines produced in the liver during hepatitis C virus(HCV) infection induce migration of activated T cells from the periphery to infected parenchyma.The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper cell/Tc1 T cell(Th1/Tc1) response.These chemokines consist of CCL3(macrophage inflammatory protein-1α;MIP-1α),CCL4(MIP-1β),CCL5(regulated on activation normal T cell expressed and secreted;RANTES),CXCL10(interferon-γ-inducible protein-10;IP-10),CXCL11(interferon-inducible T-cell α chemoattractant;I-TAC),and CXCL9(monokine induced by interferon γ;Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors.Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C.The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection.When the adaptive immune response fails in this task,non-specific T cells without the capacity to control the infection are also recruited to the liver,and these are ultimately responsible for the persistent hepatic damage.The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection,and to maintain liver viability during the chronic phase,by impairing non-specific T cell migration.Some chemokines and their receptors correlate with liver damage,and CXCL10(IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome.The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver.