Quantitative hepatitis B core antibody and quantitative hepatitis B surface antigen:Novel viral biomarkers for chronic hepatitis B management

The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment response.Traditional HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic effectiveness.Quantitation of HBV core antibodies(qAnti-HBc)is a novel non-invasive biomarker that may help with a variety of diagnostic issues.It was shown to correlate strongly with infection stages,hepatic inflammation and fibrosis,chronic infection exacerbations,and the presence of occult infection.Furthermore,qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance,relapse after medication termination,re-infection following liver transplantation,and viral reactivation in the presence of immunosuppression.qAnti-HBc,on the other hand,cannot be relied on as a single diagnostic test to address all problems,and its diagnostic and prognostic potential may be greatly increased when paired with qHBsAg.Commercial qAnti-HBc diagnostic kits are currently not widely available.Because many methodologies are only semi-quantitative,comparing data from various studies and defining universal cut-off values remains difficult.This review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.

Transformation of hepatitis B serologic markers in babies born to hepatitis B surface antigen positive mothers

AIM:To better understand the clinical significance of hepatitis B seroiogic markers in babies born to hepatitis B surface antigen (HBsAg) positive mothers, the incidence of maternal seroiogic markers of hepatitis B via placenta and its transformation in these babies were investigated. METHODS: Mothers with positive HBsAg were selected in the third trimester of pregnancy. Their babies received immunoprophylaxis with hepatitis B immunoglobulin and hepatitis B vaccine after birth, and were consecutively followed up for hepatitis B seroiogic markers and HBV DNA at birth, mo 1, 4, 7, 12, and 24. RESULTS: Forty-two babies entered the study, including 16 born to hepatitis B e antigen (HBeAg)-positive HBsAg carrier mothers and 26 to HBeAg-negative HBsAg carrier mothers. Apart from four babies born to HBeAg-positive carrier mothers and demonstrated persistent positive HBeAg eventually became HBV carriers, all other babies developed anti-HBs before 12 mo of age. Among the other 12 babies born to HBeAg-positive carrier mothers, HBeAg was detected in 7 at birth, in 4 at mo 1, and in none of them thereafter. No antibody response to the transplacental HBeAg was detected. Among the babies born to HBeAg-negative carrier mothers, anti-HBe was detected 100% at birth and mo 1, in 88.5% at mo 4, in 46.2% at mo 7, in 4.2% at mo 12 and none in mo 24. Among all the immunoprophylaxis-protected babies born to either HBeAg-positive or HBeAg-negative carrier mothers, anti-HBc was detected in 100% at birth, mo 1 and mo 4, in 78.9% at mo 7, in 36.1% at mo 12 and in none at mo 24. CONCLUSION: HBeAg can pass through human placenta from mother to fetus and become undetectable before 4 mo of age, but no antibodies response to the transplacental HBeAg can be detected till mo 24 in the immunoprophylaxis-protected babies. The sole existence of anti-HBe before 1 year of age or anti-HBc before 2 years of age in babies born to HBsAg carrier mothers may simply represent the transplacental maternal antibodies, instead of indicators of HBV infection status.

Immunogenicity and reactogenicity of a recombinant hepatitis B vaccine in subjects over age of forty years and response of a booster dose among nonresponders

AIM:The study was initiated to evaluate the reactogenicity and immunogenicity of a recombinant hepatitis B vaccine in age group >40 years and to study the response of a single booster dose in primary non-responders to the hepatitis B vaccination. METHODS:A total of 102 volunteers without markers of hepatitis B infection (negative for HBsAg,anti-HBc antibody, HBeAg and anti-HBs antibody) received 20μg of recombinant HB vaccine intramuscularly at 0,1,and 6 months.Anti HBs titers were evaluated by a quantitative Elisa kit at 90 and 210 days.A booster dose of 20μg HB vaccine was given after 6 months of the 3^(rd) vaccine dose to the 15 non- responders and anti-HBs titers were measured after i month. RESULTS:Seroprotection (anti-HBs GMT^3 10 IU/L) was achieved in 85.3 % (87/102) volunteers.The mean GMT titers of the vaccine responders was 136.1 IU/L.Of the seroprotected individuals,there were 32.4% (33/102) hyporesponders (anti- HBs titers <10-99 mIU/ml) and 52.9% (54/102) were responders (anti-HBs titers >100 IU/L).All the non-responders (15/15) responded to a single dose of the booster dose of recombinant HB vaccine and their mean anti-HBs antibody titers were more than 100.5 mIU/ml after the booster dose. CONCLUSION:Recombinant hepatitis B vaccine offers good seroprotection in the age group >40 years and has a good safety profile.A single booster dose after 6 months in primary non-responders leads to good seroprotective anti-HBs antibody titers.However,larger population based studies are needed to evaluate the role of a booster dose in selected group of non-responders and whether such an approach will be cost effective.

Prevalence of hepatitis B and C markers among refugees in Athens

AIM: To assess the prevalence of hepatitis B and C serological markers in a population of refugees living in Athens.METHODS: One hundred and thirty refugees (81 males and 49 females, mean age ±SD: 31.7±8 years) were included in the study. The hepatitis B virus surface antigen (HBsAg),the hepatitis B virus core antibody (anti-HBc) and the hepatitis C virus antibody (anti-HCV) were detected using a third-generation immunoassay.RESULTS: Twenty individuals (15.4%) were HBsAg positive and 69 (53.1%) were anti-HBc positive. The prevalence of HBsAg and anti-HBc was higher among refugees from Albania and Asia (statistical significant difference, P＜0.008 and P＜0.001 respectively). The prevalence of these markers was found irrelevant to age or sex. Anti-HCV was detected in the serum of 3 individuals (2.3 %). No differences among age, sex or ethnicity regarding anti-HCV prevalence were found.CONCLUSION: It can be concluded that refugees living in Athens are an immigrant population characterized by a high incidence of HBV infection. The prevalence of HBV markers is higher among refugees from Albania and Asia. It is therefore believed that the adherence to general precautions and the initiation of HBV vaccination programs will be necessary in the future, especially in these communities.Although the prevalence of HCV infection seems to be relatively low, extended epidemiological surveys are needed to provide valid results.

Association of core promoter mutations of hepatitis B virus and viral load is different in HBeAg(+) and HBeAg(-) patients

AIM:To identify the prevalence of hepatitis B e antigen (HBeAg) and to assess the association of hepatitis B virus (HBV) core promoter mutations and viral load in Indonesian patients.METHODS:Sixty-four patients with chronic hepatitis,65 with liver cirrhosis and 50 with hepatocellular carcinoma were included in this study.HBeAg and hepatitis B e antibody (HBeAb) tests were performed using enzyme-linked immunosorbent assay and the mutations were analyzed by sequencing.Viral load was measured by real-time polymerase chain reaction.RESULTS:Of 179 patients,108 (60.3%) were HBeAg(-) and 86 (79.6%) of these HBeAg(-) patients had been seroconverted.The A1896 mutation was not found in HBeAg(+) patients,however,this mutation was detected in 70.7% of HBeAg(-) patients.This mutation was frequently found when HBeAg was not expressed (87.7%),compared to that found in HBeAg seroconverted patients (65.1%).The A1899 mutation was also more prevalent in HBeAg(-) than in HBeAg(+) patients (P=0.004).The T1762/A1764 mutation was frequently found in both HBeAg(+) and HBeAg(-) patients,however,the prevalence of this mutation did not significantly differ among the two groups (P=0.054).In HBeAg(+) patients,the T1762/A1764 mutation was correlated with lower HBV DNA (P < 0.001).The A1899 mutation did not correlate with HBV DNA (P=0.609).In HBeAg(-) patients,the T1762/A1764 mutation alone was not correlated with HBV DNA (P=0.095),however,the presence of either the T1762/A1764 or A1896 mutations was associated with increased HBV DNA (P < 0.001).CONCLUSION:The percentage of HBeAg(-) patients is high in Indonesia,and most of the HBeAg(-) patients had been seroconverted.The A1896 mutation was most likely the major cause of HBeAg loss.The T1762/A1764 mutation alone was associated with lower viral loads in HBeAg(+) patients,but not in HBeAg(-) patients.

Mutations in surface and polymerase gene of chronic hepatitis B patients with coexisting HBsAg and anti-HBs

AIM： To investigate the clinical significance and presence of mutations in the surface （S） and overlapping polymerase gene of hepatitis B patients with coexisting HBsAg and anti-HBs. METHODS： Twenty-three patients with chronic hepatitis B were studied. Of the 23 patients, i i were both positive for hepatitis B virus （HBV） surface antigen （HBsAg） and antibody to HBV surface antigen （anti-HBs）, 12 were negative for anti-HBs while positive for HBsAg. DNA was extracted from 200 μL serum of the patients. Nucleotide of the surface and overlapping polymerase gene from HBV-infected patients was amplified by PCR, and the PCR products were sequenced. RESULTS： Forty-one mutations were found within the surface gene protein of HBV in 15 patients （10 with coexisting HBsAg and anti-HBs）. Six （14.6%） out of 41 mutations were located at ＂α＂ determinant region in 5 patients （4 positive for HBsAg and anti-HBs）. Eleven mutations （26.8%） occurred in the downstream or upstream of ＂α＂ determinant region. Lamivudine （LMV）- selected mutations were found in three patients who developed anti-HBs, which occurred in amino acid positions （196, 198, 199） of the surface protein and in YMDD motif （M204I/V） of the polymerase protein simultaneously. Presence of these mutations did not relate to changes in ALT and HBV DNA levels.CONCLUSION： Besides mutations in the ＂α＂ determinant region, mutations at downstream or upstream of the ＂α＂ determinant region may contribute to the development of anti-HBs. These mutations do not block the replicating competency of HBV in the presence of high titer of anti-HBs.

Prevention of de novo HBV infection by the presence of anti-HBs in transplanted patients receiving core antibody-positive livers

AIM： To analyze whether the presence of anti-HBs in liver transplant recipients is effective in preventing HBV infection. METHODS： Twenty-three patients receiving anti-HBc positive liver were studied. Nine recipients were anti-HBc positive as a result of previous HBV infection. Of them, one also received HBV vaccine during the pre-liver transplantation period. Fourteen recipients were anti-HBs positive due to HBV vaccine administered during the pretransplant period. Liver biopsy was obtained in 10/14 anti-HBc negative/anti-HBs positive recipients and in 4/9 anti-HBc positive recipients. RESULTS： After a mean foUow-up period of 46 months, 1 recipient with protective serum anti-HBs levels developed de novo HBV infection as a consequence of immune escape HBV mutants. Among the 14 vaccinated anti-HBc negative/anti-HBs positive recipients, 1/10 patients with available liver biopsy （10%） had liver HBV-DNA at 13 mo post-liver transplantation without serum viral markers and did not develop de novo HBV infection.The vaccinated anti-HBc positive recipient without HBV vaccine response was HBV-DNA positive in serum and liver, viral DNA was continuously negative in the following tests, so a spontaneous seroconversion was diagnosed. CONCLUSION： The presence of anti-HBs as a result of HBV vaccine or past HBV infection seems to be effective at protecting patients receiving livers from anti-HBc positive donors. However, the emergence of immune escape HBV mutants, which can evade the anti-HBs protection, should be considered as a risk of HBV infection.

Prediction of hepatic inflammation in chronic hepatitis B patients with a random forest-backward feature elimination algorithm

BACKGROUND Persistent liver inflammatory damage is the main risk factor for developing liver fibrosis,cirrhosis,and even hepatocellular carcinoma in chronic hepatitis B(CHB)patients.Thus,accurate prediction of the degree of liver inflammation is a high priority and a growing medical need.AIM To build an effective and robust non-invasive model for predicting hepatitis Brelated hepatic inflammation.METHODS A total of 650 treatment-naïve CHB(402 HBeAg-positive and 248 HBeAgnegative)patients who underwent liver biopsy were enrolled in this study.Histological inflammation grading was assessed by the Ishak scoring system.Serum quantitative hepatitis B core antibody(qAnti-HBc)levels and 21 immunerelated inflammatory factors were measured quantitatively using a chemiluminescent microparticle immunoassay.A backward feature elimination(BFE)algorithm utilizing random forest(RF)was used to select optional features and construct a combined model.The diagnostic abilities of the model or variables were evaluated based on the estimated area under the receiver operating characteristics curve(AUROC)and compared using the DeLong test.RESULTS Four features were selected to predict moderate-to-severe inflammation in CHB patients using the RF-BFE method.These predictive features included qAnti-HBc,ALT,AST,and CXCL11.Spearman’s correlation analysis indicated that serum qAnti-HBc,ALT,AST,and CXCL11 levels were positively correlated with the histology activity index(HAI)score.These selected features were incorporated into the model to establish a novel model named I-3A index.The AUROC[0.822;95%confidence interval(CI):0.790-0.851]of the I-3A index was significantly increased compared with qAnti-HBc alone(0.760,95%CI:0.724-0.792,P<0.0001)in all CHB patients.The use of an I-3A index cutoff value of 0.41 produced a sensitivity of 69.17%,specificity of 81.44%,and accuracy of 73.8%.Additionally,the I-3A index showed significantly improved diagnostic performance for predicting moderate-to-severe inflammation in HBeAg-positive and HBeAgnegative CHB patients(0.829,95%CI:0.789-0.865 and 0.810,95%CI:0.755-0.857,respectively).CONCLUSION The selected features of the I-3A index constructed using the RF-BFE algorithm can effectively predict moderate-to-severe liver inflammation in CHB patients.

EFFECTS OF ACUPUNCTURE ON THE IMMUNOLOGICAL FUNCTIONS IN HEPATITIS B VIRUS CARRIERS

A contrast study on the effects of manual acupuncture and electroacupuncture wasconducted in 60 cases of chronic hepatitis B carriers.The results demonstrated that theimmunological functions,both cellular and humoral,were markedly regulated asevidenced by the negative turnover rates of HBsAg,HBeAg,anti-HBc and HBcAg,as wellas the positive turnover rate of anti-HBe.

Risk factors for de novo hepatitis B during solid cancer treatment

BACKGROUND Reactivation of hepatitis B virus(HBV)during anticancer treatment is a critical issue.When treating patients with solid tumors,it is unclear whether specific cancer types or treatments affect HBV reactivation in hepatitis B surface antigen(HBsAg)-negative and hepatitis B core antibody(HBcAb)-positive patients,socalled de novo hepatitis B patients.The risk of de novo hepatitis B may vary based on different background factors.AIM To determine the frequency and risk factors for de novo hepatitis B during solid tumor treatment.METHODS This retrospective cohort study comprised 1040 patients without HBsAgs and with HBcAbs and/or hepatitis B surface antibodies(HBsAbs).The patients were treated for solid cancer from 2008 to 2018 at the National Kyushu Cancer Center and underwent HBV DNA measurements.Patient characteristics and disease and treatment information were investigated.HBV DNA measurements were performed using TaqMan polymerase chain reaction(PCR).To identify the risk factors associated with HBV DNA expression,the age,sex,original disease,pathology,treatment method,presence or absence of hepatitis C virus(HCV),and HBsAb and/or HBcAb titers of all subjects were investigated.In patients with HBV DNA,the time of appearance,presence of HBsAgs and HBsAbs at the time of appearance,and course of the subsequent fluctuations in virus levels were also investigated.RESULTS Among the 1040 patients,938 were HBcAb positive,and 102 were HBcAb negative and HBsAb positive.HBV DNA expression was observed before the onset of treatment in nine patients(0.9%)and after treatment in 35 patients(3.7%),all of whom were HBcAb positive.The HBV reactivation group showed significantly higher median HBcAb values[9.00(8.12-9.89)vs 7.22(7.02-7.43),P=0.0001]and significantly lower HBsAb values(14 vs 46,P=0.0342)than the group without reactivation.Notably,the reactivated group showed a significantly higher proportion of cancers in organs related to digestion and absorption(79.0%vs 58.7%,P=0.0051).A high HBcAb titer and cancers in organs involved in digestion and absorption were identified as independent factors for HBV reactivation(multivariate analysis,P=0.0002 and P=0.0095).The group without HBsAbs tended to have a shorter time to reactivation(day 43 vs day 193),and the frequency of reactivation within 6 mo was significantly higher in this group(P=0.0459)than in the other group.CONCLUSION A high HBcAb titer and cancers in organs involved in digestion and absorption are independent factors that contribute to HBV reactivation during solid tumor treatment.

Chronic hepatitis B:New potential therapeutic drugs target

liverrelated morbidity and mortality worldwide.It impacts nearly 300 million people.The current treatment for chronic infection with the hepatitis B virus(HBV)is complex and lacks a durable treatment response,especially hepatitis B surface antigen(HBsAg)loss,necessitating indefinite treatment in most CHB patients due to the persistence of HBV covalently closed circular DNA(cccDNA).New drugs that target distinct steps of the HBV life cycle have been investigated,which comprise inhibiting the entry of HBV into hepatocytes,disrupting or silencing HBV cccDNA,modulating nucleocapsid assembly,interfering HBV transcription,and inhibiting HBsAg release.The achievement of a functional cure or sustained HBsAg loss in CHB patients represents the following approach towards HBV eradication.This review will explore the up-to-date advances in the development of new direct-acting anti-HBV drugs.Hopefully,with the combination of the current antiviral drugs and the newly developed direct-acting antiviral drugs targeting the different steps of the HBV life cycle,the ultimate eradication of CHB infection will soon be achieved.

Vaccination Coverage and the Risk of Hepatitis B Virus Infection amongst Medical and Paramedical Students Practicing at the Bamenda Regional Hospital in Cameroon Sub-Saharan Africa

Introduction: The endemic nature of hepatitis B virus (HBV) in Sub-Saharan Africa is a significant public health problem that places health care providers (medical students inclusive) at increased risk of occupational exposure. However, vaccination against HBV is not systematic among medical students in Cameroon. Thus, we sought to evaluate awareness and HBV vaccine coverage amongst medical students in Cameroon. Aim: The present study was aimed at determining the proportion of Medical and Paramedical students on internship at the Bamenda Regional Hospital (BRH) who are vaccinated and immune to hepatitis B virus (HBV). Methods: This was a hospital-based cross sectional study carried out at the BRH in Cameroon. Questionnaires were administered to 120 participants who signed an informed consent form and venous blood samples collected in dry tubes for the HBV-5 PANEL test. Data were collected within a period of two weeks. HBV vaccine status was defined as complete (3 doses), partial (1 or 2 doses), and unvaccinated. Results: Of 120 participants (87 females and 33 males), 56 (46.7%) were vaccinated at least once against HBV;15 (12.5%) were partially vaccinated and 41 (34.2%) completely vaccinated. Out of the 56 vaccinated individuals, only 13 (23.2%) were confirmed immunized against HBV by testing positive for hepatitis B surface antibodies. Only 3 (5.4%) students had done post-vaccination serologic test to confirm their immunized status. There was high exposure to potentially infected body fluids like blood (97.5%) and urine (87.5%). There was equally poor practice of adequate preventive measures like regular hand washing and the proper use of personal protective equipment. A prevalence of 3.1% of HBV amongst the unvaccinated group was recorded. Conclusion: Only 1 in 3 medical students had completed the HBV vaccination series and only 26.8% of this cohort was confirmed immunized against HBV. This highlights the need for improved health policies aimed at increasing access and coverage of HBV immunization in high risk groups such as health workers.

Extremely high titer of hepatitis B surface antigen antibodies in a primary hepatocellular carcinoma patient:A case report

BACKGROUND Hepatocellular carcinoma(HCC)may be caused by hepatitis B virus(HBV)infection.Post-infection recovery-associated changes of HBV indicators include decreased hepatitis B surface antigen(HBsAg)level and increased anti-HBsAg antibody titer.Testing to detect HBV DNA is conducted rarely but could detect latent HBV infection persisting after acute infection and prompt administration of treatments to clear HBV and prevent subsequent HBV-induced HCC deve-lopment.Here,we present an HCC case with an extremely high anti-HBsAg antibody titer and latent HBV infection.CASE SUMMARY A 57-year-old male patient with abdominal pain who was diagnosed with primary HCC presented with an extremely high level(over 2000 ng/mL)of serum alpha-fetoprotein.Abdominal B-ultrasonography and computed tomography scan results indicated focal liver lesion and mild splenomegaly.Assessments of serological markers revealed a high titer of antibodies against hepatitis B core antigen(anti-HBcAg antibodies),an extremely high titer(1000 mIU/mL)of hepatitis B surface antibodies(anti-HBsAg antibodies,anti-HBs)and absence of detectible HBsAg.Medical records indicated that the patient had reported no history of HBV vaccination,infection or hepatitis.Therefore,to rule out latent HBV infection in this patient,a serum sample was collected then tested to detect HBV DNA,yielding a positive result.Based on the aforementioned information,the final diagnosis was HCC associated with hepatitis B in a compensated stage of liver dysfunction and the patient was hospitalized for surgical treatment.CONCLUSION A rare HCC case with high serum anti-HBsAg antibody titer and detectable HBV DNA resulted from untreated latent HBV infection.

Evaluate the prevalence and trend of hepatitis B and hepatitis C in Nahavand: west of Iran, 2013–2017

Viral hepatitis is a global threat to public health and one of the leading causes of death worldwide.Often,acute viral cases in children and adults are associated with viral hepatitis A,B,C,D and E,or co-infection with two types of hepatitis.Infection with these viruses is a global health problem and continuous efforts are in place to identify infected people through targeted screening,preventing new infections through vaccination,monitoring and treating people at risk for complications of all types of hepatitis.The aim of this study was to determine the evaluate the prevalence and trends of hepatitis B and C infection in the Nahavand city during 5 consecutive years(2013–2017).The total number of patients with hepatitis B and C was 141 persons from March 2013 to March 2017,of these,101 had hepatitis B,and 40 had hepatitis C.The prevalence of hepatitis B and C was higher in men than women.The percentage frequency hepatitis B in the city in the last five years was 0.05 percent.11 cases(10.89%)pregnant women and Six cases(5.9%)receiving blood(blood transfusions)in Hepatitis B was observed.the prevalence of hepatitis C was 0.2%at the end of 2017.The study on the cause of hepatitis C in Nahavand has shown that 21(52.5%)of the total of 40 people were infected with addiction.The interesting point in this report is that according to reports from viral hepatitis testing questionnaires,24 of 101 people with type B hepatitis have 23.7%of people with a history of complete vaccination of hepatitis B and one person(0.9%)had incomplete vaccination.A significant relationship was found between the level of education and the prevalence of hepatitis(P=0.005).

“Anti-HBc alone” in human immunodefi ciency virus-positive and immuno-suppressed lymphoma patients

Hepatitis B virus (HBV) infection is endemic in various parts of the world. A proportion of patients have resolved prior exposure to HBV, as evidenced by the clearance of circulating hepatitis B surface antigen and the appearance of antibody to hepatitis B core antigen (anti-HBc), which could produce protective antibody to hepatitis B surface antigen (anti-HBs). With time, anti-HBs in some patients may become negative. Such patients are described as having occult HBV infection or "anti-HBc alone". In the context of immunodef icient patients, such as HIV patients or lymphoma patients undergoing immunosuppressive immunotherapy, the lack of protective anti-HBs may increase the risk of hepatitis B reactivation. Serum HBV DNA testing may be necessary in "anti-HBc alone" patients, to detect patients at a high risk of developing HBV infection allowing appropriate prophylactic management.

Isolated anti-HBc is an independent risk factor for tumor recurrence in intrahepatic cholangiocarcinoma after curative resection

Background:Intrahepatic cholangiocarcinoma(ICC)is a poorly understood and aggressive malignancy with increasing incidence and mortality.Hepatitis B virus(HBV)infection is recognized as one of the important risk factors of ICC.There are few reports focusing on whether isolated antibody to hepatitis B core antigen(isolated anti-HBc,IAHBc)have prognostic role in ICC,while positive hepatitis B surface antigen(HBsAg)has been reported to be associated with the prognosis of ICC.The aim of this study was to investigate the prognostic value of IAHBc in ICC patients after curative resection,in order to identify those who have the high risk of ICC recurrence in the early stage.Methods:We divided 209 ICC patients who underwent curative resection into 4 groups:groupⅠ(n=40),HBsAg(-)/antibody to hepatitis B surface antigen(anti-HBs)(-)/anti-HBc(+);groupⅡ(n=70),HBsAg(+)/anti-HBc(-);groupⅢ(n=55),HBsAg(-)/anti-HBs(+)/anti-HBc(+);and groupⅣ(n=44),HBsAg(-)/anti-HBc(-).We compared the recurrence-free survival(RFS)and overall survival(OS)among these four groups.Results:The median follow-up time was 16.93 months(range 1-34.6 months).The 1-and 2-year RFS and OS rates were 60%and 42%,and 78%and 63%respectively in all patients.Compared to the whole non-IAHBc patients(groupⅡ+groupⅢ+groupⅣ),IAHBc patients(groupⅠ)showed significantly lower RFS at 1 year(39.8%vs.64.4%,P=0.001)and 2 years(20.7%vs.46.7%,P=0.001).When compared to other three individual groups,IAHBc patients(groupⅠ)also had the lowest RFS.We did not find significant difference in OS among the four groups.Further multivariate analysis revealed that IAHBc was an independent risk factor of RFS.Conclusions:IAHBc is an independent poor prognostic factor for tumor recurrence in ICC patients after curative resection.

Effect of delivery mode on maternal-infant transmission of hepatitis B virus by immunoprophylaxis

OBJECTIVE: To study the effect of different delivery modes on immunoprophylaxis efficacy so as to clarify whether or not cesarean section reduces immunoprophylaxis failure. METHODS: Mothers with positive hepatitis B surface antigen (HBsAg) were selected in the third trimester of pregnancy. Their babies were inoculated with hepatitis B immunoglobulin at birth and hepatitis B vaccine at 1, 2 and 7 months of age. HBsAg and its antibodies (anti-HBs) were tested at 1, 4, 7, and 12 months of age, then followed up yearly. RESULTS: A total of 301 babies entered the study, including 144 born by normal spontaneous vaginal delivery, 40 by obstetric forceps or vacuum extraction, and 117 by cesarean section. The incidence of mother's HBeAg positivity or baby's gender constitution was comparable between the three groups. There were no significant differences in the positive rate of anti-HBs or HBsAg at follow-up periods among the three groups. At 12 months of age, anti-HBs could be detected in 78.9% of the babies born by normal vaginal delivery, 84.6% of the babies by forceps or vacuum extraction, and 86.4% of the babies by cesarean section. The positive rate of HBsAg was 8.1%, 7.7%, 9.7%, and chronic HBV infection incidence was 7.3%, 7.7%, 6.8% respectively. CONCLUSIONS: There are no significant effects of delivery mode on the interruption of HBV maternal-baby transmission by immunoprophylaxis. Cesarean section does not reduce the incidence of immunoprophylaxis failure.

B cell dysfunction in chronic hepatitis B virus infection

Chronic hepatitis B(CHB)remains a global health problem.The persistence of hepatitis B surface antigen(HBsAg)in the blood for longer than 6 months after the initial infection is a sign of CHB.The therapeutic goal for the functional cure of CHB is the generation of antibodies against HBsAg.However,the adaptive immune response of patients with CHB cannot generate an efficient antiviral response.Many previous studies have evaluated T cell function and T cell therapy specifically designed to counter hepatitis B virus(HBV)infection.As one of the major components of adaptive immunity,B cells also display dysfunctions in anti-HBsAg antibody(HBsAb)production and antigen presentation.Patients with CHB have amplification of CD19^(+)CD10^(-)CD27^(-)CD21^(-)atypical memory B cell subsets and CD19^(+)CD24^(hi)CD38^(hi) regulatory B cells.Currently,no reviews have summarized specific B cell responses during CHB infection.Thus,in this study,we summarized B cell dysfunction during CHB progression and the potential mechanisms behind these dysfunctions to further our understanding of the mechanisms of adaptive immune response of B cells in the process of CHB development and help provide new methods and ideas for the treatment of CHB.