HBeAg Positive Rate Research Articles

Ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China: a CR-HepB-based real-world study

Objective: To understand ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China. Methods: Patients with chronic HBV infection:demographic, virologic, hematologic, blood biochemistry, and antiviral treatment data were extracted from the China Registry of Hepatitis B (CR-HepB) database between 2012 and 2022 for descriptive statistics and change trend analysis. Multiple group comparisons were conducted using the Kruskal Wallis H test, while counting data was compared between groups using χ (2) test. Results: A total of 180 012 patients with chronic HBV infection were included, with a median age of 40 years old, and a male proportion accounting for 60.2%. The HBeAg positive rate was 43.3%. Over time, the median age of new patients each year increased from 39 to 47 years, while the HBeAg positive rate decreased from 51.3% to 32.8%. The initial diagnosis of patients was mainly CHB (71.4%), followed by hepatitis B cirrhosis (11.8%), inactive HBsAg carrier status (10.6%), and chronic HBV carrier status (6.2%). Among the newly registered patients every year from 2012 to 2022, the proportion of hepatitis B cirrhosis remained stable, but after 2019, the proportion of CHB increased and the proportion of other diagnoses decreased. The proportion of patients with cirrhosis increased with age in different age groups, with 3.5%, 19.3%, and 30.4% in the < 40, 40-69, and≥70 age groups, respectively. The proportion of women in patients with cirrhosis also increased with age, from 16.1% in those < 30 years old to 44.3% in those≥80 years old. From 2012 to 2022, the proportion of patients receiving first-line nucleos(t)ide analog antiviral treatment increased year by year, from 51.0% in 2012-2013 to 99.8% in 2022. Conclusion: The CR-HepB registration data reflect the changes in clinical characteristics and antiviral treatment patterns in patients with chronic HBV infection in China over the past ten years and can thus provide a reference to promote hepatitis B diagnosis and treatment practice, as well as scientific research.

The relationship of maternal hepatitis B e antigen and response to vaccination of infants born to women with chronic infection

BackgroundThe relationship of maternal HBeAg and infants’ response to hepatitis B vaccine remains controversial. This study aims to observe the dynamic changes in infant birth HBV markers and study the time-varying effects of maternal HBeAg on vaccination response of infants born to women with chronic HBV infection.Methods3163 infants born to HBsAg positive mothers including 1737 with maternal HBeAg positive in group A and 1426 negative in group B were enrolled eventually. Demographic information and laboratory tests were collected at birth, 7-12th and 24th month. The dynamic changes of infant HBV markers and HBsAb titers at different time points were compared between the two groups.ResultsThe infant HBV markers at birth displayed different modes. During the follow-up, we observed a significant downward trend in the positive rates of HBsAg, HBeAg, HBeAb and HBcAb. The HBsAg of two groups switched to negative at 7–12 months and HBeAg in Group A became negative at 24 months. The HBsAb titers of the infants in the two groups were 576.91(192.8–1000.0) vs 719.67(208.1–1000.0) at 7–12 months (Z = -3.049, P = 0.002) and 783.5(227.8–1000.0) vs 891.4(234.0–1000.0) at 24 months (Z = -0.853, P = 0.394). High HBV DNA viral load (OR 1.260, 95% CI 1.139–1.395, P < 0.001) and maternal HBeAg level (OR 1.003, 95% CI 1.002–1.003, P < 0.001) were associated with the higher HBeAg positive rate of infants.ConclusionsMaternal HBeAg did affect the infants’ immune response to vaccination and reduce the anti-response at 7-12th month temporarily, but these influences were negligible by 24th months after birth, which proved that the maternal HBeAg would not induce immune tolerance of infants from a long-term perspective.

Analysis of characteristics of drug resistance gene mutation in HBV RT region of hepatitis B infected patients

Objective: This article investigated the clinical characteristics and distribution of drug resistance mutation sites in HBV RT region of hepatitis B infected patients. Methods: Retrospective analysis was made on 1 948 patients with HBV infection, who had been tested for NAs resistance mutation and had a medical history of NAs in the Laboratory Department of the Fifth Medical Center of the PLA General Hospital from January 2020 to December 2021. Basic clinical information and drug resistance related mutation information were recorded. Meanwhile, the serological index data of hepatitis B were collected. Drug resistance gene mutant group and non-mutated group were grouped according to whether the drug resistance genes had a mutation in HBV RT region, and the clinical characteristics and genotype distribution of the two groups were statistically analyzed. The pattern of drug resistance gene mutation, number of mutation sites, drug resistance type and mutation of NAs resistance-related sites were analyzed in 917 patients with drug resistance gene mutation in HBV RT region. χ2 Inspection was used for counting data. Meanwhile, two independent samples t-test and Wilcoxon rank sum test were used for measurement data. Results: Among the 1 948 patients with chronic HBV infection, 917 patients had drug resistance gene mutation in RT region (47.07%). The proportion of patients with acute hepatitis B and CHB in HBV RT resistance gene mutant group was lower than that in the non-mutated group, while the proportion of patients with HBV-related cirrhosis was higher than that in the non-mutated group, these differences were statistically significant. Compared with the non-mutated group in HBV RT region, the age, the positive rates of HBeAg and HBV DNA, and HBV DNA load of these patients were increased in drug resistance gene mutant group, these differences were statistically significant. Genotypes of patients in both groups were dominated by C, followed by B and D. The proportion of patients with genotype C in HBV RT drug resistance gene mutant group was higher than that of non-mutated group, the difference was statistically significant. There were 53 gene mutation patterns in 917 patients with drug resistance gene mutation in HBV RT region, and the main pattern was rtL180M+rtM204V+rtS202G (9.70%). The mutation sites were dominated by 3 (20.74%). There were 5 types of drug resistance, LAM+Ldt (21.25%) was the most. Among the 18 sites that were clearly associated with LAM, ADV, ETV and Ldt resistance in the HBV RT region, 14 sites were mutated, and the most common mutation sites were rtL180M, rtM204V, rtM204 and rtS202G. what's more, the proportion of patients with NAs drug resistance was LAM>Ldt>ETV>ADV. Conclusion: In order to prevent adverse consequences of this study such as disease recurrence or disease progression caused by HBV drug resistance, HBV infected patients, who have long-term use of NAs antiviral therapy, should monitor the level of HBV DNA and drug resistance genes in HBV RT region in order to optimize the treatment plan in time or guide individualized treatment.

Mitochondrial DNA haplogroup F confers genetic susceptibility to chronic HBV infection for the Yi nationality in Lijiang, China.

Mitochondria are essential for hepatitis B virus (HBV) infection. Moreover, the findings of our previous study indicate that host mitochondrial genetic factors are associated with chronic hepatitis B (CHB) for the Han Chinese. However, in terms of genetic heterogeneity, the impact of mitochondria on host susceptibility to HBV infection in ethnic minorities in China remains unclear. Here, a total of 7070 subjects who had visited the hospital between June 1, 2019, and April 31, 2020, were enrolled for seroprevalence of HBV infection investigation. A total of 220 individuals with CHB (CHBs) and 223 individuals with a trace of HBV infection (spontaneously recovered subjects, SRs) were analyzed for mitochondrial DNA (mtDNA) sequence variations and classified into respective haplogroups. Haplogroup frequencies were compared between CHBs and SRs. Among eight nationalities, Yi nationality patients had the highest HBsAg prevalence rate (27.9% [95% CI: 25.3%-30.5%]) and the lowest vaccination rate (4.9% [95% CI: 3.7%-6.2%]). After adjustment for age and gender, haplogroup F was a risk factor for CHB infection (P=0.049, OR=2.079, 95% CI=1.002-4.31), while D4 had a significant negative correlation with the HBeAg-positive rate (P=0.024, OR=0.215, 95% CI=0.057-0.816). Together with our previous study, the findings indicate that different nationalities have different genetic susceptibility to HBV infection.

Hepatitis B Infection Among Pregnant Women in China: A Systematic Review and Meta-Analysis.

BackgroundA study of the current situation and characteristics of hepatitis B virus (HBV) infection among Chinese pregnant women is meaningful to provide baseline information for future research and policy making, with an aim to eliminate HBV in China.ObjectivesTo provide the epidemiological status of HBV infection among pregnant women in China.MethodsPubMed, EMbase, The Cochrane Library, and three Chinese databases were searched. Cohort studies and cross-sectional studies on HBV prevalence in Chinese pregnant women, published after 2016, were retrieved. In addition, combined HBV prevalence and 95% confidence interval (CI) were calculated. This research was registered in PROSPERO (CRD42021289123).Main ResultsA total of 42 studies were included in the study, with a sample size of 4,007,518 cases, and 20 provinces in China. The prevalence of HBV in Chinese pregnant women was 6.64% (95% CI: 5.72–7.57%) during the period between 2016 and 2021. Among HBsAg positive pregnant women, the HBeAg positive rate was 25.80% (95% CI: 22.26–29.69%). Moreover, geographic regions with HBV prevalence ranking from high to low were in western China, eastern China, and central China, successively.ConclusionThe prevalence of HBV in Chinese pregnant women is intermediate endemic, although disparities exist between different regions. Among pregnant women with HBV infection, a high proportion of the patients have strong infectivity. Factors affecting HBV prevalence remain controversial, which demands further studies.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021289123.

Seroepidemiology of Hepatitis B Virus Infection in Native and Immigrant Pregnant Women: A 20-Year Retrospective Study in Taiwan.

Universal immunoprophylaxis against hepatitis B virus (HBV) is regarded as a key element to prevent perinatal HBV infection. The aim of the present study was to investigate the changes in the hepatitis B surface antigen (HBsAg)- and hepatitis B envelope antigen (HBeAg)-positive rates in native and immigrant pregnant women, to realize the impact of immigrants, and to identify any weaknesses 30 years after the implementation of hepatitis B vaccination in Taiwan. A total of 20,020 test results of HBsAg and HBeAg in pregnant women-2,915 (14.6%) immigrant women and 17,105 native Taiwanese-from 1996 to 2015 were analyzed for changes during this 20-year retrospective cohort study. Native Taiwanese have a higher HBsAg-positive rate than immigrant women (P < 0.001). However, the HBsAg-positive rates decreased by 0.6% per year among native women, but did not decrease significantly (only by 0.18% per year) among immigrant women. The overall HBsAg-positive rate remained at high levels, 4.8% in the year 2015. The HBeAg-positive rate decreased significantly, by 0.22% per year, in the total women as well as by 0.23% per year in the native women (all P < 0.001); by contrast, the HBeAg-positive rate in immigrants decreased at a slower rate (0.10% per year), without a significant decreasing trend (P = 0.300). Higher HBeAg (+)/HBsAg (+) rate was found for the immigrants than for the native women (P < 0.001). To quickly and effectively lower the risk of vertical transmission, new approaches combined with vaccination may be needed in the post-immunization era.

Qualitative pathological assessment of liver fibrosis regression after antiviral therapy in patients with chronic hepatitis B

Objective: To investigate the methods for qualitative pathological assessment of dynamic changes in liver fibrosis/cirrhosis after antiviral therapy in patients with chronic hepatitis B (CHB), since antiviral therapy can partially reverse liver fibrosis and cirrhosis caused by hepatitis B and semi-quantitative, rather than qualitative, pathological assessment is often used for the research on liver fibrosis regression. Methods: Previously untreated CHB patients with liver fibrosis and cirrhosis were enrolled, and liver biopsy was performed before treatment and at 78 weeks after the antiviral therapy based on entecavir. The follow-up assessment was performed once every half a year. Based on the proportion of different types of fibrous septum, we put forward the new qualitative criteria called P-I-R classification (predominantly progressive, predominantly regressive, and indeterminate) for evaluating dynamic changes in liver fibrosis. This classification or Ishak fibrosis stage was used to evaluate the change in liver fibrosis after treatment and Ishak liver inflammation score was used to evaluate the change in liver inflammation after treatment. Results: A total of 112 CHB patients who underwent liver biopsy before and after treatment were enrolled, and among these patients, 71 with an Ishak stage of ≥3 and qualified results of live biopsy were included in the final analysis. Based on the P-I-R classification, 58% (41/71) were classified as predominantly progressive, 29% (21/71) were classified as indeterminate, and 13% (9/71) were classified as predominantly regressive; there were no significant differences between the three groups in alanine aminotransferase, aspartate aminotransferase, albumin, HBeAg positive rate, HBV DNA, and liver stiffness (P < 0.05). After treatment, the proportion of predominantly progressive, indeterminate, or predominantly regressive patients changed to 11% (8/71), 11% (8/71), and 78% (55/71), respectively. Among the 35 patients who had no change in Ishak stage after treatment, 72% (25/35) were classified as predominantly regressive and had certain reductions in the Laennec score, percentage of collagen area, and liver stiffness. Conclusion: This new P-I-R classification can be used to assess the dynamic changes in liver fibrosis after antiviral therapy in CHB patients.

Analysis of the relationship between serum HBV-DNA quantitative detection level and liver function markers and hepatitis B markers in patients with chronic hepatitis B virus

Objective To investigate the relationship between serum HBV-DNA quantitative detection level and liver function markers and hepatitis B markers in patients with chronic hepatitis B virus. Methods The clinical data of 80 patients with chronic hepatitis B virus infection were retrospectively analyzed, and the HBV-DNA load, the serum hepatitis B markers and liver function indicators of the patients were detected and recorded.Another 80 cases received normal physical examination were selected as the control group.The serum markers were detected in both two groups. Results Of 80 patients with chronic hepatitis B virus infection, the positive rate of HBV-DNA was 45.0% (36/80) and the detection rate of HBeAg was 30.0% (24/80). The positive rate of HBV-DNA was positively correlated with HBeAg positive rate(χ2=12.46, P=0.00). The levels of alanine aminotransferase (ALT), α-L-fucosidase (AFU), aspartate aminotransferase (AST) and plasma prothrombin time (PT) in HBV-DNA positive patients were significantly higher than those in HBV-DNA negative group(F=42.693, 18.752, 32.692, 48.225, all P=0.000); and with the increase of the amount of virus, the level of the patients' index continued to increase. Conclusion For patients with chronic hepatitis B, the HBV-DNA level and the viral replication should be detected, and the liver function should be evaluated to observe the liver damage timely, thus to provide reference for clinical effective intervention. Key words: Hepatitis B, chronic; DNA; Liver function tests

Relationship between HBeAg from HBsAg positive mothers and regulatory T cells in neonates and its influence on HBV intrauterine transmission

Objective: To explore the relationship between HBeAg in HBsAg positive mothers and CD(4)(+)CD(25)(+)Foxp3(+)regulatory T cells (Treg) in newborns, as well as how they would influence the increasing risk on HBV intrauterine transmission. Methods: We collected information on general demographic characteristics and delivery on 270 HBsAg positive mothers and their newborns from the Third People's Hospital of Taiyuan. Fluorescence quantitative polymerase chain reaction (FQ-PCR) and chemiluminescence immunoassay (CLIA) were used to detect HBV DNA and HBV serological markers in peripheral blood from both mothers and neonates. The expression of Treg and other immune cells in peripheral blood of neonates were detected with flow cytometry (FCM). Results: Maternal HBeAg positive rates were associated with an increased risk of intrauterine transmission (OR=4.08, 95%CI: 1.89-8.82). Rates of Treg in newborns born to HBsAg-positive mothers were higher than that of the negative group (Z=2.29, P=0.022). Each pair of the subjects was assigned to five different groups according to the HBeAg titers of mothers. Frequencies of both Treg and HBeAg in newborns and HBV DNA in mothers between the above said 5 groups showed similar trends of changing patterns and the differences between groups were statistically significant(χ(2)=18.73, P<0.001; χ(2)=181.60, P<0.001; χ(2)=183.09, P<0.001). Results from partial correlation analysis showed that after adjusting for neonatal HBeAg and maternal HBV DNA, mother's HBeAg titers were positively related to the percentage of Treg in their newborns (r(s)=0.19, P=0.039). In addition, the frequencies of Treg were negatively correlated with pDC and CD(4)(+) T cell in their newborns (r(s)=-0.21, P=0.017; r(s)=-0.23, P=0.009). Conclusion: HBeAg from HBsAg positive mothers might have inhibited the function of neonatal DC cells and T cells to reduce the immune response to HBV by up-regulating the proportion of Treg and finally increased the risk of HBV intrauterine transmission.

Entecavir Combined With Adefovir Ameliorates Patients With Chronic Hepatitis B Who Fail to Respond to Nucleotide (Acid) Analog Monotherapy.

The aim of this study was to evaluate the efficacy and safety of entecavir (ETV) combined treatment with adefovir (ADV) on chronic hepatitic B (CHB) patients who failed to respond to nucleotide (acid) analog (NA) treatment. On this basis, the possible factors in the combined treatment of these patients will be analyzed. The safety, biochemical index, and the possible factors that might affect the ETV and ADV combined treatment at different points in time were retrospectively analyzed. The biochemical index included the following: virological response, hepatitis B virus (HBV) DNA decline, primary nonresponse, biochemical response, and the hepatitis B virus E antigen/hepatitis B virus E antibody seroconversion rate. There were 94 CHB patients and compensated liver cirrhosis patients who received ETV plus ADV treatment for over 12 weeks after failure of treatment with NAs. The authors have also investigated 76 CHB patients (80.9%) and 18 hepatitis B cirrhosis patients (19.1%) in this study. The HBV DNA baseline was 4.4 ± 1.4 log10 IU/mL, and the positive rate of HBeAg before salvage treatment was 78.7% (74/94). The sample sizes were 94, 78, 42, 10, 6, and 1 for follow-up of 24, 48, 96, 144, 192, and 240 weeks, respectively. The virological responses (HBV DNA < 2 log10 IU/mL) and biochemical responses were 52.1%, 74.3%, and 90.4% and 63.1%, 61.6%, and 81.1%, respectively, at 24, 48, and 96 weeks, which showed significant differences (P < 0.001 and P < 0.005, respectively). The HBV DNA decline was presented as mean ± SEM, which were 1.53 ± 1.23, 1.75 ± 1.37, 2.07 ± 1.54, and 2.39 ± 1.77 log10 IU/mL at 12, 24, 48, and 96 weeks, respectively. They showed significant differences compared with the baseline (χ = 8.084, P < 0.05). The rate of primary nonresponse was 30.9% (29/94), and the primary treatment failure rates were 26.6% (25/94), 24.4% (19/78), and 4.8% (2/42) at 24, 48, and 96 weeks, respectively. They all have statistical difference (P = 0.011 < 0.05). There were 23 patients who experienced virological breakthrough after the HBV DNA levels were undetectable, whereas after follow-up for 12-24 weeks, the HBV DNA levels were back to undetectable again. ETV plus ADV treatment is an efficient and safe treatment for CHB and compensated liver cirrhosis patients who experienced NA treatment failure. The high quantity of baseline HBV DNA level is a risk factor for poor efficacy of salvage treatment.

Changes in the Prevalence of HBsAg and HBeAg: a Study of 8696 Parturients in a Well Vaccinated Area

To elucidate the impact of a hepatitis B (HB) vaccination program on the prevalence of HB surface antigen (HBsAg) and HB envelope antigen (HBeAg) as well as the success rate of HBeAg clearance among parturients, we collected data on parturients who gave birth between 2000 and 2010, and recorded the HB status postpartum of those with positive HBeAg before birth. A total of 8696 parturients were enrolled, of whom 113 with prenatal positive HBeAg were invited back. The prevalence of HBsAg decreased over the study period, particularly in the vaccinated cohort, while there was no change in the prevalence of HBeAg. Foreign parturients had a higher HBeAg-positive rate and delayed HBeAg clearance, and those with a higher body mass index (>24 kg/m2) had earlier HBeAg clearance (51.9% vs. 23.9%, p = 0.005). Only 30% of the subjects who were positive for HBeAg before birth became negative 5 years after delivery. In conclusion, the downward trend in HB infection with more significance among vaccinated parturients reflects effective prevention and the impact of universal HB immunization. Nonetheless, aggressive follow-up is necessary for parturients who are persistently positive for HBeAg postpartum, as well as developing different public health policies for foreign parturients from endemic areas.

Characterization of Novel Hepatitis B Virus B/C Intergenotypic Recombinants in 3′-terminal Reverse Transcriptase Sequences among Chronic Hepatitis B Patients

Background Chronic hepatitis B (CHB) remains a severe global public health concern. Hepatitis B virus (HBV) can be divided into 8 genotypes with different geographical distribution and virological features. We demonstrated genotypes B and C prevalent in southern and northern China, respectively, had divergent genotype-dependent amino acid polymorphisms and variations in reverse transcriptase (RT) gene, a target of anti-HBV therapy. Recently B/C intergenotypic recombination was reported in RT but its prevalence and clinical implications are elusive. This study aimed to characterize novel intergenotypic recombinants in HBV RT and to dissect their association with HBV-related clinical indexes.Methods A total of 220 CHB cases were enrolled in China. Sera were tested for ALT, AST, or HBV serologic markers or DNA. HBV RT sequences were amplified, sequenced and genotyped. Recombination analysis was done with Simplot program.Results29.1% (64/220) of the cases had genotype B while 70.9% genotype C. Though no intergenotypic recombination was detected for genotype C, 37.5% (24/64) of genotype B HBV had recombination with genotype C at 3′ end of RT. No significant difference was found in ALT or AST, or HBeAg positive rate among the cases with the recombinants, or genotype B or C. Remarkably, HBV DNA of the untreated recombinant cases was significantly higher than that of pure genotype B group, though not significantly different from that of genotype C group. The untreated recombinants also had higher mutation rates at 7 residues throughout RT (rt53, 134, 213, 222, 271, 319 and 340) compared with parental genotypes, among which 3–4 substitutions were co-detected for one recombinant. Moreover, a majority of the recombinant HBV carriers were born on the South/North interface of China.Conclusion Novel HBV B/C intergenotypic recombination at the 3’ end of RT is associated with higher HBV DNA, interlinked RT point mutations and birthplace among Chinese patients. Our findings shed new light on the clinical, virological and epidemiological characteristics of novel intergenotypic recombinants. The emergence of new HBV recombinants may contribute to a dramatically enhanced heterogeneity in disease manifestations, treatment response and prognosis among CHB cases.Disclosures All authors: No reported disclosures.

Impact of different feeding patterns on mother-to-child transmission of hepatitis B virus

Objective To explore the effect of different feeding patterns on mother-to-child transmission of hepatitis B virus (HBV). Methods Chronic HBV-infected puerperae, who gave birth to a single baby at term in Beijing DiTan Hospital from December 18, 2010 to June 26, 2012, were recruited and separated into breast-feeding group and formula-feeding group according to the mother's will. Each group was then divided into three subgroups based on maternal serum HBV-DNA load before delivery: HBV-DNA negative subgroup (<5×102 copies/ml), low viral load subgroup (≥5×102 -<1.0×106 copies/ml) and high viral load subgroup (≥1.0×106 copies/ml). A total of 199 patients in breast-feeding group were divided into three subgroups, separately including 73, 62 and 64 patients, while a total of 210 patients in formula-feeding group into three subgroups, including 74, 62 and 74 patients. Newborns were injected with Hepatitis B hyper-immune globulin (HBIG) within 2 h after birth and at 15 to 30 days, followed by the routine injection of recombinant yeast derived Hepatitis B vaccine in accordance with the scheme of0, 1, 6 months. HBV-DNA was determined by fluorescence quantitative polymerase chain reaction, while serological markers of HBV by microsome chemiluminescence method. Comparisons were made between the breast-feeding and formula-feeding group on maternal background information, immune responses of the infants at one-month and seven-month old, the infectious status when they were between seven-month to two-year old. Statistical analysis was made with independent sample t-test, rank-sum test, χ2 test and Fisher's exact test. Results The HBeAg positive rates of puerperae in the three subgroups (HBV-DNA negative, low viral load and high viral load) among women of the breast-feeding group were 12.3% (9/73), 37.1% (23/62) and 96.9%(62/64), respectively, while 5.4% (4/74), 51.6% (32/62) and 95.9% (71/74) among the formula-feeding group. There was no significant difference between breast-feeding group and formula-feeding group (all P>0.05). Seventy of the 409 infants missed the follow-up at seven-month old, but returned between one to two years old. The anti-HBs positive rates of the three subgroups in infants of the breast-feeding group at seven-month old were 98.4% (61/62), 98.2% (54/55) and 95.7% (44/46), while 100.0% (63/63), 98.2% (56/57) and 92.9% (52/56) in the formula-feeding group (all P>0.05). The infection rate of infants in the breast-feeding group and the formula-feeding group were 3.0% (6/199) and 2.4% (5/210) at seven-month to two-year old. Notably, infected infants was identified in HBV-DNA negative subgroup in neither the breast-feeding group nor the formula-feeding group, while 0.0% (0/62) and 9.4% (6/64) of infection rate were reported in low viral load and high viral load subgroups of the breast-feeding group and 1.6% (1/62) and 5.4% (4/74) of the formula-feeding group (both P>0.05). Conclusion With combined immunization, breast-feeding in chronic HBV infected mothers does not increase the risk of infantile infection. Key words: Hepatitis B, chronic; Infectious disease transmission, vertical; Breast feeding; Feeding methods

Effect of elective cesarean section on the risk of mother-to-child transmission of hepatitis B virus

BackgroundMany clinicians and hepatitis B virus (HBV)-infected pregnant women prefer elective caesarean section (ECS) to prevent mother-to-child transmission of HBV, since some studies found higher transmission of HBV in infants born by vaginal delivery (VD) than by cesarean section. However, other studies showed that ECS does not reduce the risk of being infected with HBV in infants. In this study, we aimed to clarify whether ECS may reduce the risk of mother-to-child transmission of HBV.MethodsTotally 546 children (1–7-year-old) born to 544 HBsAg-positive mothers from 15 cities and rural areas across Jiangsu Province, China, were enrolled. Of these children, 137 (2 pairs of twins) were born to HBeAg-positive mothers; 285 were delivered by ECS and 261 others by VD (one pair of twin in each group). HBV serologic markers were tested by enzyme or microparticle immunoassay.ResultsThe maternal and gestational ages, maternal HBeAg-positive rates, and children’s ages, gender ratios, hepatitis B vaccine coverage and administrations of HBIG were comparable between ECS and VD groups (all p >0.05). The overall prevalence of HBsAg in the 546 children was 2.4%, with 2.5% (7/285) and 2.3% (6/261) in those born by ECS and VD respectively (p = 0.904). Further comparison of chronic HBV infection in the 137 children of HBeAg-positive mothers showed that the HBsAg-positive rates in ECS and VD groups were 10.3% (7/68) and 8.7% (6/69) respectively (p = 0.750), while the mothers had similar HBV DNA levels (2.38 × 106 vs. 2.35 × 106 IU/ml, p = 0.586). Additionally, the overall rate of anti-HBs ≥10 mIU/ml in the children was 71.6%, with 72.3% and 70.9% in those born by ECS and VD respectively (p = 0.717).ConclusionsWith the recommended immunoprophylaxis against hepatitis B, ECS does not reduce the risk of mother-to-child transmission of HBV. Therefore, ECS should not be used in HBsAg-positive pregnant women to prevent mother-to-child transmission of HBV.

Cesarean section does not reduce mother-to-infant transmission of hepatitis B virus

Objective To investigate whether cesarean section on pregnant women with chronic hepatitis B virus (HBV) infection may reduce mother-to-infant transmission risk of HBV.Methods Preserved serum samples of pregnant women at 15-20 weeks of gestation which were collected from July 2002 to August 2004 in 14 counties of Jiangsu Province were analyzed retrospectively.These samples were tested for HBV serologic markers with enzyme immunoassay,and 419 cases of positive hepatitis B surface antigen (HBsAg) were found.HBV DNA level of these HBsAg-positive women were further quantitatively measured with real-time polymerase chain reaction assay.Children of these 419 HBsAg-positive mothers were followed up during October 2009 to March 2010 and 298 of them were contactable (71.1％),among which 281 were enrolled in final analysis as they had complete information and had been vaccinated with three regular doses of HBV vaccine during infantile period.The 281 children were tested for serum HBV markers.The HBV infection rate in these children at age 5-7 was compared between those born by cesarean setion (CS group,n =136) and by vaginal delivery (VD group,n=145).T-test,x2 test or Fisher's exact test was used to analyze relevant parameters.Results(1) Maternal HBeAg-positive rates [25.7％ (35/136) vs 34.5％ (50/145)],HBV DNA levels in HBeAg-positive women [(2.30 × 106) IU/ml vs (2.09× 106) IU/ml],the percentages of HBIG injection after birth [38.2％ (52/136) vs 35.9％ (52/145)],breastfeeding ratios [82.4％ (112/136) vs 75.9％ (110/145)],and children' s ages at the follow-up [(5.9 ± 0.8) vs (6.0±0.6)] were comparable between CS group and VD group (all P＞0.05).(2) Among these 281 children,272 (96.8％) were HBsAg-negative,9 (3.2％) were HBsAg-positive and 163 (58.0％) were anti-HBs-positive.The prevalence of HBsAg-positive [(2.9％ (4/136) vs 3.4％ (5/145)],HBsAg negative and anti HBc positive [0.0％ (0/136) vs 1.4％ (2/145)] and anti-HBs positive [57.4％(78/136) vs 58.6％(85/145)] in CS group were similar to those in VD group.Conclusions Cesarean section does not reduce the risk of mother-to-infant transmission of HBV.In clinical practice,elective cesarean section should not be suggested in order to prevent HBV vertical infection. Key words: Hepatitis B virus; Disease transmission, vertical; Hepatitis B; Casarean section

Breastfeeding Is Not a Risk Factor for Mother-to-Child Transmission of Hepatitis B Virus

BackgroundMany clinicians do not encourage breastfeeding in hepatitis B virus (HBV) carriers, since HBV DNA can be detected in breast milk and breast lesions may increase exposure of infants to HBV. The aim of this study was to determine whether breastfeeding may add risk for perinatal HBV transmission.Methodology/Principal FindingsTotally 546 children (1–7-year-old) of 544 HBV-infected mothers were investigated, with 397 breastfed and 149 formula-fed; 137 were born to HBeAg-positive mothers. All children had been vaccinated against hepatitis B but only 53.3% received hepatitis B immune globulin (HBIG). The overall prevalence of HBsAg+, HBsAg−/anti-HBc+, and anti-HBs (≥10 mIU/ml) in children was 2.4%, 3.1%, and 71.6% respectively. The HBsAg prevalence in breast- and formula-fed children was 1.5% and 4.7% respectively (P = 0.063); the difference was likely due to the higher mothers' HBeAg-positive rate in formula-fed group (formula-fed 49.0% vs. breastfed 15.9%, P<0.001). Further logistic regression analyses showed that breastfeeding was not associated with the HBV infection in the children, adjusting for the effect of maternal HBeAg status and other factors different between the two groups.Conclusions/SignificanceUnder the recommended prophylaxis, breastfeeding is not a risk factor for mother-to-child transmission of HBV. Therefore, clinicians should encourage HBV-infected mothers to breastfeed their infants.

Serolological Profile Among HBsAg-Positive Infections in Southeast China: A Community-Based Study

BackgroundHepatitis B virus (HBV) infection has remained a significant public health problem. Generating a large-scale, community-based profile of HBV infection in China is essential to prevention of the disease.ObjectivesThe current study was designed to investigate HBV-infected individuals at the community level and determine the age distribution, hepatitis B e antigen (HBeAg) positivity and its related risk factors, relationship among serological markers.Patients and MethodsA cross-sectional, community-based survey was carried out without age restriction, in 12 communities of two counties. The study population was selected by random multistage cluster sampling. Serological samples and demographic information were collected from 8439 HB surface antigen (HBsAg)-positive individuals.ResultsThe constituent ratio of individuals with HBsAg-positive infections was lowest among persons aged < 20 years (0.4%) and the highest among persons aged 40-49 years (33.2%). The HBeAg-positive rate among infected individuals was 18.5%, and the constituent ratio decreased with increasing of age. The HBeAg-positive rate in males (21.9%) was significantly higher than in females (14.7%), and was higher among coastland inhabitants (22.9%) than among plains inhabitants (12.9%). Among the 1561 HBeAg-positive individuals, 91.0% were HBV DNA-positive. However, of the 6878 HBeAg-negative individuals, only 45.4% were HBV DNA-positive, and the HBeAg-positive rate was significantly different at different levels of HBV DNA expression. The proportion of detectable HBV DNA levels was significantly higher in individuals with elevated ALT, compared to those with normal ALT, regardless of HBeAg-positivity.ConclusionsThe HBV prevalence remained high in the > 20 age group. The positivity of HBeAg was related to age, region, and sex. Testing HBeAg and serum ALT levels were effective ways to assess HBV infectiousness in community-level hospitals in China.

Analysis of relationship of HBV PreS1 antigen, anti-HBc IgM, DNA load and genotypes in hepatitis B patients

To explore the relationship of HBV PreS1 antigen, anti-HBc IgM, DNA load and genotypes, and the significance for clinical diagnosis and prognostic. Enzyme linked immune-sorbent assay was used to test the HBV serum markers of HB patients; HBV-DNA copies was detected by time fluorescence quantitative PCR; using nested PCR to amplify the S fragment of HBV genome, then sequence and make blast with HBV standard sequences to ascertain genotypes. Make comprehensive analysis of these indexes. 355 serum specimens of acute or chronic HB patients were collected. The positive rates of HBV PreS1-Ag and HBV-DNA in model I (positive for HBeAg) were 80.2% and 73.7% respectively, which both higher than other models. The abnormal rate of ALT and AST were higher in PreS1-Ag positive group than negative, as well as in anti-HBc IgM positive group. There are 4 samples is genotype B (2.9%), 76 genotype C (55.9%) and 56 genotype D (41.2%). Positive rate of HBeAg and HBV-DNA of genotype C samples were both higher than which of genotype B and D. PreS1-Ag and Anti-HBe-IgM indexes are of great value to viral hepatitis B early diagnosis, HBV replication surveillance and prognostic evaluation; the major HBV genotypes in Henan province are C and D, and the positive rate of HBeAg and HBV-DNA were both higher in genotype C HBV infection population than genotype B and D.

High hepatitis B virus load is associated with hepatocellular carcinomas development in Chinese chronic hepatitis B patients: a case control study

BackgroundPersistent hepatitis B virus (HBV) infection is a risk factor for hepatocellular carcinoma (HCC) development. This study aimed to clarify whether the high HBV DNA level is associated with HCC development by comparing HBV DNA levels between HBV infected patients with and without HCC.ResultsThere were 78 male and 12 female patients in each group and there was no statistical difference between these two group patients' average ages. The HBV DNA level in the HCC patients was 4.73 ± 1.71 Log10 IU/ml while 3.90 ± 2.01 Log10 IU/ml in non-HCC patients (P < 0.01). The HBeAg positive rate was 42.2% (38/90) in the HCC group while 13.3% (12/90) in the non-HCC group (P < 0.001). Compared with patients with HBV DNA level of < 3 Log10 IU/ml, the patients with level of 3 to < 4, 4 to < 5, 5 to < 6, or ≥ 6 Log10 IU/ml had the odds ratio for HCC of 1.380 (95% CI, 0.544-3.499), 3.671 (95% CI, 1.363-9.886), 5.303 (95% CI, 1.847-15.277) or 3.030 (95% CI, 1.143-8.036), respectively.ConclusionsHBV-related HCC patients had higher HBV DNA level than non-HCC counterparts. Our findings imply that active HBV replication is associated with the HCC development.

Pre-core/basal-core promoter and reverse transcriptase mutations in chronic HBV infected-patients.

Some HBV mutations have been shown to have an association with liver disease. The aim of the study was to investigate the incidence of mutations in hepatitis B virus (HBV) pre-core/basal core promoter (BCP) and reverse transcriptase (RT) regions and their relationship with disease progression in chronic HBV-infected patients. A total of 133 patients were enrolled in this study, comprising the acute-on-chronic hepatitis B liver failure (ACLF-HBV) and chronic hepatitis B (CHB) patients. The pre-core/ BCP and RT gene fragments were amplified by high-fidelity PCR. Mutations of pre-core/BCP and RT regions were examined by direct sequencing. There were no significant differences in age, the average level of ALT and course of disease between the ACLF-HBV and CHB groups. The HBeAg positive rate and average values of HBV-DNA loads of the ACLF-HBV patients were lower than that of CHB patients. In HBV pre-core/ BCP region, the point mutations T1753C (39.06% vs. 21.74%, p<0.01), A1762T (26.56% vs. 13.04%, p<0.05), G1764A (31.25% vs. 18.84%, p<0.01), G1896A (29.69% vs. 15.94%, p<0.05) and G1899 (23.44% vs. 10.14%, p<0.05) were significantly more frequent in the ACLFHBV than CHB patients. For combined mutations, A1762T+G1764A (23.43% vs. 11.59 %, p<0.05) and G1896A+ G1899A (21.88% vs. 13.04%, p<0.05) were significantly more frequent in ACLF-HBV than CHB patients. However, there were no significant differences in RT mutations between two groups. ACLFHBV patients had more frequent mutations in HBV precore/ BCP region than that of CHB patients. Some mutations in HBV pre-core/BCP region might be related to the aggravation of chronic HBV infection.