Profiling the repertoire of T-cell receptor beta-chain variable genes in peripheral blood lymphocytes from subjects who have recovered from acute hepatitis B virus infection

The profile of T-cell receptor beta-chain variable （TRBV） genes usually skews in subjects with virus infection or cancer. The gene melting spectral pattern （GMSP） can be used to determine the profile of the TRBV gene family. To explore the portrait of the TRBV family in peripheral blood lymphocytes from subjects who have recovered from acute hepatitis B virus infection （AHI）, peripheral blood mononuclear cells （PBMCs） were separated and further sorted into CD4^＋ and CD8^＋ T-cell subsets. The molecular features of the TRBV complementary determining region 3 （CDR3） motifs were determined using GMSP analysis. When a GMSP profile showed a single peak, the monoclonally expanded TRBV gene was cloned and sequenced. Skewed expansions of multiple TRBV genes were observed among the CD4^＋ and CD8^＋ T-cell subsets and the PBMCs. The frequency of monoclonally expanded TRBV genes in the CD8^＋ T-cell subset was significantly higher than that of the CD4^＋ T-cell subset and the PBMCs. Compared to other members of the TRBV gene family, TRBV11, BV15 and BV20 were predominantly expressed in the repertoire of peripheral blood lymphocytes in recovered AHI subjects. The relatively conserved amino acid motifs of TRBV5.1 and BV20 CDR3 were also detected in the CD4^＋ and CD8^＋ T-cell subsets. These results demonstrate the presence of multiple biased TRBV families in recovered AHI subjects. TRBV11, BV15 and BV20, especially from the CD8＋ T-cell subset, may be relevant to the pathogenesis of subjects with AHh The preferentially selected TRBV5.1 and BV20 with the relatively conserved CDR3 motif may be potential targets for personalized treatments of chronic HBV infection.

Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy

The spread of hepatitis B virus(HBV)infection has gradually decreased in Italy in the last 5 decades as shown by the steady reduction in the incidence rates of acute hepatitis B,from 10/100000 inhabitants in1984 to 0.85/100000 in 2012,and by the reduced prevalence of hepatitis B surface antigen(HBsAg)-positive cases among chronic hepatitis patients with different etiologies,from 60%in 1975 to about 10%in 2001.The prevalence of HBsAg chronic carriers in the general population also decreased from nearly 3%in the 1980s to 1%in 2010.Linked to HBV by its characteristics of defective virus,the hepatitis delta virus(HDV)has shown a similar epidemiological impact on the Italian population over time.The incidence of acute HDV infection decreased from 3.2/100000 inhabitants in 1987 to 0.8/100000 in 2010 and the prevalence of HDV infection in HBsAg chronic carriers decreased from24%in 1990 to 8.5%in 2006.Before the beneficial effects of HBV mass vaccination introduced in 1991,the decreased endemicity of HBV and HDV infection in Italy paralleled the improvement in screening blood donations,the higher standard of living and impressive reduction in the birth rate associated with a marked reduction in the family size.A further contribution to the decline in HBV and HDV infections most probably came from the media campaigns to prevent the spread of human immunodeficiency virus infection by focusing the attention of the general population on the same routes of transmission of viral infections such as unsafe sexual intercourse and parenteral exposures of different kinds.

Risk factors of acute hepatitis B through blood and sexual contact transmitted in Beijing

Objective To investigate the risk factors of acute hepatitis B virus through blood and sexual contact transmission in Beijing.Methods A population-based 1∶2matched case-control study was used in our survey.Three hundred and one acute hepatitis B cases living

The Pathogenesis of Acute on Chronic Hepatitis B liver Failure

Acute-on-chronic liver failure is a characteristic clinical liver syndrome, which should be differentiated from acute liver failure, acute decompensated liver cirrhosis and chronic liver failure. The pathogenesis of ACLF is not fully understood yet. Viral factors and immune injury have been reported to be the two major pathogenesis. This paper reviewed the researches on the pathogenesis of acute on chronic hepatitis B liver failure in recent years, to provide theoretical basis for prompt and accurate diagnosis and treatment of this syndrome. This would benefit for the prognosis and raise the survival rate of patients.

Epidemiological and clinical aspects of hepatitis B virus infection in Italy over the last 50 years

A relevant gradual reduction of both the incidence rate of acute hepatitis B(AHB)and prevalence of chronic hepatitis B has occurred in Italy in the last 50 years,due to substantial epidemiological changes:Improvement in socioeconomic and hygienic conditions,reduction of the family unit,accurate screening of blood donations,abolition of re-usable glass syringes,hepatitis B virus(HBV)-universal vaccination started in 1991,use of effective well tolerated nucleo(t)side analogues able to suppress HBV replication available from 1998,and educational mediatic campaigns against human immunodeficiency virus infection focusing on the prevention of sexual and parenteral transmission of infections.As an example,AHB incidence has gradually decreased from 10/100000 inhabitants in 1985 to 0.21 in 2020.Unfortunately,the coronavirus disease 2019(COVID-19)pandemic has interrupted the trend towards HBV eradication.In fact,several HBV chronic carriers living in the countryside have become unable to access healthcare facilities for screening,diagnosis,clinical management,and nucleo(t)side analogue therapy in the COVID-19 pandemic,mainly for anxiety of becoming infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),movement restrictions,and reduced gains from job loss.In addition,one-third of healthcare facilities and personnel for HBV patients have been devolved to the COVID-19 assistance.

Programmed death-1 expression is associated with the disease status in hepatitis B virus infection

AIM： TO define the potential role of programmed death-i/programmed death-ligand （PD-1/PD-L） pathway in different hepatitis B virus （HBV） infection disease status; we examined the expression of PD-1 on antigen specific CD8＋T cells in peripheral blood of patients with chronic hepatitis B （CriB） and acute exacerbation of hepatitis B （AEHB） infection. METHODS： The PD-1 level on CD8＋ T lymphocytes and the number of HBV specific CD8＋ T lymphocytes in patients and healthy controls （HCs） were analyzed by staining with pentameric peptide-human leukocyte antigen2 （HLA2） complexes combined with flow cytometry. Real-time quantitative polymerase chain reaction （PCR） was used to measure the serum HBV- DNA levels. RESULTS： The level of PD-1 expression on total CD8＋ T cells in CHB patients （13.86% ± 3.38%） was significantly higher than that in AEHB patients （6.80%± 2.19%, P 〈 0.01） and healthy individuals （4.63% ± 1.23%, P 〈 0.01）. Compared to AEHB patients （0.81% ± 0.73%）, lower frequency of HBV-specific CD8＋ T cells was detected in chronic hepatitis B patients （0.37% ± 0.43%, P 〈 0.05）. There was an inverse correlation between the strength of HBV-specific CD8＋ T-cell response and the level of PD-1 expression. Besides, there was a significant positive correlation between HBV viral load and the percentage of PD-1 expression on CD8＋ T cells in CriB and AEHB subjects （R = 0.541, P 〈 0.01）. However, PD-1 expression was not associated with disease flare-ups as indicated by alanine aminotransferase （ALT） levels （R = 0.066, P 〉 0.05）. CONCLUSION： Our results confirm previous reports that HBV specific CD8＋T-cell response in the peripheral blood is more intense in patients with AEHB than in chronic hepatitis B wlth persistent viral infection. Moreover, there is a negative correlation between the level of PD-1 and the intensity of virus specific CD8＋ T cell response.

Plasmacytoid Dendritic Cell Function and Cytokine Network Profiles in Patients with Acute or Chronic Hepatitis B Virus Infection

Background： Plasmacytoid dendritic cells （pDCs） and cytokines play an important role in occurrence and recovery of hepatitis B virus （HBV） infection. The aim of this study was to explore the frequency and function ofpDC and serum cytokine network profiles in patients with acute or chronic HBV infection. Methods： The healthy individuals （HI group）, hepatitis B envelope antigen （HBeAg）-positive chronic HBV patients in immune tolerance （IT） phase （IT group）, HBeAg-positive chronic HBV patients （CHB group）, and acute HBV patients （AHB group） were enrolled in this study. The frequency of cluster of differentiation antigen 86 （CD86） ＋ pDC and the counts of CD86 molecular expressed on surface ofpDC were tested by flow cytometer. The quantitative determinations ofcytokines, including Fins-like tyrosine kinase 3 ligand （FIt-3L）, interferon （1FN）-α2, IFN-γ, interleukin （IL）-17A, IL-6, IL-10, transforming growth factor （TGF）-β1 and TGF-β2, were performed using Luminex multiplex technology. Results： In this study, there were 13 patients in HI group, 30 in IT group, 50 in CHB group, and 32 in AHB group. Compared with HI group, HBV infected group （including all patients in IT, CHB and AHB groups） had significantly higher counts of CD86 molecular expressed on the surface ofpDC （4596.5 ± 896.5 vs. 7097.7 ± 3124.6; P 〈 0.001）. The counts of CD86 molecular expressed on the surface of pDC in CriB group （7739.2 ±4125.4） was significantly higher than that of IT group （6393.4 ± 1653.6, P=0.043）. Compared with IT group, the profile of cytokines of FIt-3L, IFN-γ, and IL-17A was decreased, IFN-α2 was significantly increased （P =0.012） in CH B group. The contents of IL-10, TGF-{31, and TGF-132 in AHB group were significantly increased compared with IT and CHB groups （all P 〈 0.05）. Conclusions： This study demonstrated that the function of pDC was unaffected in HBV infection. The enhanced function of pDC and IFN-α2 might involve triggering the immune response from IT to hepatitis active phase in H BV infection. Acute patients mainly presented as down-regulation of the immune response by enhanced IL-10 and TGF-β.

Trends in mortality of liver disease due to hepatitis B in China from 1990 to 2019: findings from the Global Burden of Disease Study

Background::Hepatitis B is a viral infection that attacks the liver and can cause both potentially life-threatening acute and chronic liver disease.China has the world’s largest burden of hepatitis B and is considered to be a major contributor toward the goal of World Health Organization(WHO)of eliminating hepatitis B virus(HBV)as a global health threat by 2030.This study aimed to analyze data from the Global Burden of Diseases,Injuries,and Risk Factors Study(GBD)to determine the trends in mortality of liver disease due to hepatitis B in China between 1990 and 2019 and the gap with the WHO’s goal.Methods::Annual deaths and age-standardized mortality rates(ASMRs)of liver disease due to hepatitis B in China between 1990 and 2019 were collected from GBD 2019.We calculated the percentage changes in deaths and estimated annual percentage changes(EAPCs)of ASMRs of liver disease due to hepatitis B.Results::In China,deaths of total liver disease due to hepatitis B decreased by 29.13%from 229 thousand in 2016 to 162 thousand in 2019,and ASMR decreased by an average of 4.92%(95%confidence interval[CI]:4.45–5.39%)per year in this period.For the spectrum of liver disease due to hepatitis B,deaths decreased by 74.83%,34.71%,and 23.34%for acute hepatitis,cirrhosis and other chronic liver diseases,and liver cancer from 1990 to 2019,respectively,and ASMRs of acute hepatitis(EAPC=–7.63;95%CI:–8.25,–7.00),cirrhosis and other chronic liver diseases(EAPC=–4.15;95%CI:–4.66,–3.65),and liver cancer(EAPC=–5.17;95%CI:–6.00,–4.33)decreased between 1990 and 2019.The proportions of older adults aged≥70 years among all deaths of the spectrum of liver disease due to hepatitis B increased from 1990 to 2019.Deaths of liver cancer due to hepatitis B increased by 7.05%from 2015 to 2019.Conclusions::Although a favorable trend in the mortality of liver disease due to hepatitis B was observed between 1990 and 2019,China still faces challenges in achieving the WHO’s goal of eliminating HBV as a public threat by 2030.Therefore,efforts to increase the coverage of diagnosis and treatment of liver disease due to hepatitis B,especially of liver cancer due to hepatitis B,are warranted in China.

Ratios of T-helper 2 Cells to T-helper 1 Cells and Cytokine Levels in Patients with Hepatitis B

Background：Hepatitis B is an immune response-mediated disease.The aim of this study was to explore the differences of ratios of T-helper （Th） 2 cells to Thl cells and cytokine levels in acute hepatitis B （AHB） patients and chronic hepatitis B virus （HBV）-infected patients in immune-tolerance and immune-active phases.Methods：Thirty chronic HBV-infected patients in the immune-tolerant phase （IT group） and 50 chronic hepatitis B patients in the immuneactive （clearance） phase （IC group）,32 AHB patients （AHB group）,and 13 healthy individuals （HI group） were enrolled in the study.Th cell proportions in peripheral blood,cytokine levels in plasma,and serum levels of HBV DNA,hepatitis B surface antigen,and hepatitis B e antigen were detected.Results：The Th1 cell percentage and Th2/Th1 ratio in the HBV infection group （including IT,IC,and AHB groups） were significantly different from those in HI group （24.10% ± 8.66% and 1.72 ± 0.61 vs.15.16% ± 4.34% and 2.40 ± 0.74,respectively;all P 〈 0.001）.However,there were no differences in the Th1 cell percentages and Th2/Th1 ratios among the IT,IC,and AHB groups.In HBV infection group,the median levels of Flt3 ligand （Flt3L）,interferon （IFN）-γ,and interleukin （IL）-17A were significantly lower than those in HI group （29.26 pg/ml,33.72 pg/ml,and 12.27 pg/ml vs.108.54 pg/ml,66.48 pg/ml,and 35.96 pg/ml,respectively;all P 〈 0.05）.IFN-α2,IL-10,and transforming growth factor （TGF）-β2 median levels in hepatitis group （including patients in AHB and IC groups） were significantly higher than those in IT group （40.14 pg/ml,13.58 pg/ml,and 557.41 pg/ml vs.16.74 pg/ml,6.80 pg/ml,and 419.01 pg/ml,respectively;all P 〈 0.05）,while patients in hepatitis group had significant lower Flt3L level than IT patients （30.77 vs.59.96 pg/ml,P =0.021）.Compared with IC group,patients in AHB group had significant higher median level s of IL-1 0,TGF-β 1,and TGF-β2 （22.77 pg/ml,10,447.00 pg/ml,and 782.28 pg/ml vs.8.66 pg/ml,3755.50 pg/ml,and 482.87 pg/ml,respectively;all P 〈 0.05）.Conclusions：Compared with chronic HBV-infected patients in immune-tolerance phase,chronic HBV-infected patients in immune-active phase and AHB patients had similar Th2/Th 1 ratios,significantly higher levels of IFN-α2,IL-10,and TGF-β.AHB patients had significantly higher IL-10 and TGF-β levels than chronic HBV-infected patients in immune-active phase.