Relevance of hepatitis B surface antigen levels in patients with chronic hepatitis B during 5 year of tenofovir treatment

The role of quantitative hepatitis B surface antigen (HBsAg) levels in patients receiving highly potent oral antiviral therapy is controversial, and here, we determined the HBsAg response in 121 chronic hepatitis B patients treated with tenofovir 300 mg daily. During tenofovir treatment, HBsAg decline of ≥1.0 log from baseline was seen in 16.1%, 16.3%, 18.4%, 34.6%, 36.4% and 11.8%, 15.2%, 14.8%, 28.6%, 20% at years 1, 2, 3, 4, 5 for HBeAg‐positive and HBeAg‐negative patients, respectively. Early decline in HBsAg levels at week 4 was predictive of subsequent significant HBsAg level decline. HBeAg seroconversion occurred in 29.9% of HBeAg‐positive patients. On multinomial logistic regression, HBsAg level decline from baseline at week 4 and week 12 or any time subsequently did not correlate with HBeAg seroconversion and HBV DNA level decline from baseline at week 4 and week 12 (OR = 3.704; 95% CI = 1.511–9.076; P = 0.006 and OR = 1.732; 95% CI = 1.032–2.867; P = 0.037, respectively) was significantly predictive of seroconversion. A small proportion of chronic HBV‐infected patients treated with tenofovir exhibit a significant (≥1.0 log) decline in HBsAg levels. Early decline in HBsAg levels at week 4 was predictive of subsequent and significant HBsAg level decline. The HBsAg decline did not correlate with HBeAg seroconversion in HBeAg‐positive patients. Reduction in HBV DNA levels at week 4 and 12 correlated with seroconversion.     

Maternal hepatitis B virus (HBV) DNA positivity and sexual intercourse are associated with HBV intrauterine transmission in China: a prospective case-control study

BACKGROUND AND AIM: Hepatitis B virus (HBV) intrauterine transmission from infected mothers contributes significantly to the persistence of the high number of HBV carriers. The aim of this study was to identify potential risk factors for HBV intrauterine transmission. METHODS: A case-control study was performed on pregnant women tested positive for HBsAg at Shaanxi Maternal and Neonatal Health Hospital, Xi'an, China, from September 2002 to October 2004. Serum samples were taken from infected women and their newborn infants and used for the detection of HBsAg. A structured standard questionnaire was used to collect demographic, medical and maternal data, and maternal HBV DNA, HBeAg, anti-hepatitis C virus and anti-hepatitis D virus were also assessed. Ten neonates validated as having HBV intrauterine transmission were selected as cases and others as controls. RESULTS: The univariate analysis indicated that maternal HBeAg positivity (odds ratio [OR] = 5.96, 95% confidence interval [CI]: 1.61-22.12), HBV DNA positivity (OR = 12.09, 95% CI: 2.97-40.17) and sexual intercourse in the second trimester (OR = 9.15, 95% CI: 1.08-202.99) were significantly associated with an increased risk for HBV intrauterine transmission, whereas contraceptive measures before pregnancy (OR = 0.21, 95%CI: 0.04-0.99) were associated with a decreased risk. The multivariate analysis, however, identified maternal HBV DNA positivity (OR = 19.18, 95%: CI: 3.26-118.73) and sexual intercourse in the second trimester (OR = 1.29, 95%: CI: 1.00-1.66) as the only independent risk factors for HBV intrauterine transmission. CONCLUSIONS: The risk of HBV intrauterine transmission increased with increased frequency of sexual intercourse. Therefore, it is concluded that maternal HBV DNA positivity and sexual intercourse in the second trimester are independent risk factors for HBV intrauterine transmission.     

The role of caesarean section and nonbreastfeeding in preventing mother‐to‐child transmission of hepatitis B virus in HBsAg‐and HBeAg‐positive mothers: results from a prospective cohort study and a meta‐analysis

The study aimed to assess whether caesarean section and nonbreastfeeding can prevent mother‐to‐child transmission (MTCT) in HBsAg‐ and HBeAg‐positive mothers via a cohort study and a meta‐analysis. (1) Pregnant women who were positive for HBsAg and HBeAg and did not receive antiviral treatment during pregnancy were recruited from the First Hospital of Jilin University, Maternal and Child Health Care Center of Jiangsu and Henan from August 2009 to June 2015. Infants received active and passive immunity. (2) In addition, a systematic literature search was performed in the PubMed, Embase, Cochrane, China National Knowledge Infrastructure and Wanfang Chinese databases. The retrieval strategy was [(“HBV” or “hepatitis b” or “hepatitis b virus”) and (“mother‐to‐infant transmission” or “vertical transmission”)]. Studies were screened, and data were extracted. The fixed‐effect model was used to analyse the studies. A total of 852 mothers and 857 newborns were enrolled. At the age of 7 months, 41 infants (4.78%) were positive for HBsAg. Multivariate analysis showed that mothers with higher HBV DNA levels (>10⁸ IU/mL; RR = 3.03, 95% CI: 1.41‐6.52) were associated with an increased risk of infection. Although there was no statistical significance, caesarean section (RR = 0.61) and nonbreastfeeding (RR = 0.88) showed a tendency to reduce the risk of infection. (2) A total of 5726 studies were identified. Together with our study, 13 were included in the analysis of delivery mode, and 12 were included in the analysis of feeding mode. The risk of infection in the caesarean section group was lower than that in the vaginal delivery group (RR = 0.58, 95% CI: 0.46‐0.74). In the analysis of feeding mode, the risk in the nonbreastfeeding group was significantly lower (RR = 0.74, 95% CI: 0.56‐0.98). In conclusion, caesarean section and nonbreastfeeding reduced the risk of MTCT in infants of HBsAg‐ and HBeAg‐positive mothers who did not receive antiviral therapy during pregnancy.     

Maternal HBsAg carriers and adverse pregnancy outcomes: A hospital‐based prospective cohort analysis

It is not clear whether chronic hepatitis B virus (HBV) infection during pregnancy can increase the risk of adverse pregnancy outcomes for both mothers and neonates. We conducted a hospital‐based prospective cohort study on pregnant women (PW) and used an analysis strategy that was guided by directed acyclic graphs (DAGs). Maternal characteristics and major adverse pregnancy outcomes were collected both from questionnaires and hospital‐based electronic medical records. Serum hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) status were determined. In total, 3329 of the 3416 pregnant women who received routine antenatal care in a hospital setting at baseline, including 346 HBsAg carriers, were available for analysis. Maternal HBsAg carrier status was associated with an increased risk of intrahepatic cholestasis pregnancy [aOR (adjusting odds ratio) = 1.70; 95% CI (confidence interval) = 1.16‐2.49], premature rupture of the membranes (aOR = 1.38; 95% CI = 1.00‐1.89) and large for gestational age birth aOR = 1.67; 95% CI = 1.17‐2.39). The risk of intrahepatic cholestasis remained in pregnant women with either HBeAg‐positive (aOR = 2.96; 95% CI = 1.33‐6.62) or HBeAg‐negative (aOR = 1.52; 95% CI =1.00‐2.32)] status; notably, only maternal HBeAg‐negative status was associated with a higher risk of large for gestational age birth (aOR = 1.91; 95% CI = 1.33‐2.76). Our results implied that chronic HBV infection during pregnancy may increase the risk of intrahepatic cholestasis of pregnancy, premature rupture of membranes and large for gestational age pregnancies.     

Serum HBcrAg is better than HBV RNA and HBsAg in reflecting intrahepatic covalently closed circular DNA

The correlation between serum HBcrAg and HBV RNA is unclear, and correlations of intrahepatic cccDNA with HBcrAg, HBV RNA and HBsAg are rarely reported in the same cohort. This study aimed to assess the correlation of HBcrAg with HBV RNA and HBsAg, and investigate whether serum HBcrAg is superior to serum HBV RNA and HBsAg in reflecting intrahepatic HBV cccDNA in HBeAg‐positive and HBeAg‐negative CHB patients. In this study, 85 HBeAg‐positive and 25 HBeAg‐negative patients who have never received antiviral therapy were included. Among HBeAg‐positive patients, HBcrAg was correlated positively with HBsAg (r = 0.564, P < 0.001) and HBV RNA (r = 0.445, P < 0.001), and HBV RNA was also correlated positively with HBsAg (r = 0.323, P = 0.003). Among HBeAg‐negative patients, no significant correlation was observed between HBcrAg, HBsAg and HBV RNA. By multivariable linear regression, HBcrAg (β = ?0.563, P < 0.001), HBsAg (β = ?0.328, P < 0.001) and HBV RNA (β = 0.180, P = 0.003) were all associated with cccDNA levels among HBeAg‐positive patients, but only serum HBcrAg was associated with cccDNA level (β = 0.774, P = 0.000) among HBeAg‐negative patients. HBcrAg was better correlated with cccDNA as compared to HBsAg and HBV RNA, irrespective of HBeAg status. Among HBeAg‐positive patients, though HBcrAg level was influenced by hepatic inflammatory activity and HBV DNA levels, the good correlations of HBcrAg with cccDNA persisted after stratification by inflammatory activity and HBV DNA levels. In conclusion, correlations of serum HBcrAg, HBV RNA and HBsAg levels differ significantly between HBeAg‐positive and HBeAg‐negative patients, but serum HbcrAg correlates with cccDNA levels better than HBV RNA and HBsAg, irrespective of HBeAg status.     

Hepatitis B virus infection is associated with deletion of chromosome 8p in multiple myeloma

Serological analyses within epidemiological cohort and case‐control studies indicate to an association between HBV infection and risk of multiple myeloma (MM). To verify the relationship with an independent approach, we investigated the correlation between HBV positivity and chromosomal aberrations within 680 patients of the National Center for Tumor Diseases Heidelberg for which the serological HBV status (HBsAg and anti‐HBc) and FISH data for five gains (1q21, 9q34, 11q23, 15q22, 19q13), five losses (6q21, 8p21, 13q14, 17p13, 22q11), and three IgH translocations [t(4,14), t(11,14), t(14,16)] were available. Deletion of 8p21 and 13q14 were shown associated with HBV positivity within hepatocellular carcinoma in other investigations. In the present evaluation, the odds ratio for loss of 8p21 was significantly elevated (OR = 2.74, 95% CL = 1.36–5.50, P = 0.0048) and for loss of 13q14 non‐significantly increased (OR = 1.40, 95% CL = 0.74–2.65) in anti‐HBc positive patients. The results provide further support for a role of HBV infection in the pathogenesis of MM.     

Hepatitis D virus infection,cirrhosis and hepatocellular carcinoma in The Gambia

Hepatocellular carcinoma (HCC) incidence is high in The Gambia, and hepatitis B virus (HBV) infection is the main cause. People coinfected with HBV and hepatitis D virus (HDV) have an even greater risk of HCC and cirrhosis. Using a new HDV quantitative microarray antibody capture (Q‐MAC) assay, we evaluated the association between HDV infection and HCC or cirrhosis among participants in The Gambia Liver Cancer Study. In this case‐control study, cases had HCC (n = 312) or cirrhosis (n = 119). Controls (n = 470) had no clinical evidence of liver disease and normal serum alpha‐foetoprotein. Participants were previously tested for hepatitis B surface antigen (HBsAg); we tested HBsAg+ specimens by HDV Q‐MAC, western blot and RNA assays. We evaluated separate cut‐offs of the Q‐MAC assay for predicting anti‐HDV and RNA positivity. Q‐MAC correctly identified 29/29 subjects who were western blot‐positive (sensitivity = 100%, specificity = 99.4%) and 16/17 who were RNA‐positive (sensitivity = 94.1%, specificity = 100%). Compared to controls, cases more often had HBV monoinfection (HBsAg+/HDV RNA?; 54.1% vs 17.0%; odds ratio [OR] = 6.28; P < 0.001) or HBV‐HDV coinfection (HBsAg+/HDV RNA+; 3.9% vs 0%; P < 0.001). Risk estimates (for HCC or cirrhosis) based on HDV antibody status and adjusted for covariates (demographics, alcohol, smoking, body mass index, anti‐HCV and aflatoxin B1 exposure) yielded consistent results for both HBV monoinfection (adjusted OR = 8.29; 95% confidence interval = 5.74‐11.98) and HBV‐HDV coinfection (adjusted OR = 30.66; 95% confidence interval = 6.97‐134.95). In this Gambian population, HDV Q‐MAC had high sensitivity and specificity for both anti‐HDV and HDV RNA. HDV infection contributed to the high risk of HCC in The Gambia.     

Viral determinants predicting hepatitis B surface antigen (HBsAg) seroclearance in HIV‐/HBV‐coinfected patients

The aim of this retrospective study was the identification of clinically useful viral determinants for the prediction of hepatitis B surface antigen (HBsAg) seroclearance and sustained virological response in hepatitis B virus/human immunodeficiency virus (HBV‐/HIV)‐coinfected patients receiving HBV‐active combined antiretroviral therapy (cART). Quantification of HBsAg, HBeAg and HBV DNA before and after initiation of HBV‐active cART in a cohort of 59 HIV‐/HBV‐coinfected patients was performed. Calculations of receiver operating characteristics (ROC) and Kaplan–Meier analysis were used for the identification of predictors of HBsAg seroclearance for HBeAg‐positive [HBeAg(+); n = 36] and HBeAg‐negative [HBeAg(−);n = 23] patients. HBeAg(+) patients with an HBsAg on‐treatment decline ≥1 log IU/mL per year achieved higher HBsAg loss rates (P = 0.0294), whereas the quantification of HBeAg had no predictive value for HBsAg seroclearance. Among HBeAg(−) patients, a pretreatment baseline cut‐off level of HBsAg ≤100 IU/mL was highly predictive for HBsAg seroclearance. No significant influence of the HBV genotype on HBsAg seroclearance was observed among the entire cohort. Quantitative determination of HBsAg provides a clinically useful viral parameter for the prediction of HBsAg seroclearance both in HBeAg(+) and HBeAg(−) HIV‐/HBV‐coinfected patients receiving HBV‐active cART.     

Hepatitis B vaccination with or without hepatitis B immunoglobulin at birth to babies born of HBsAg‐positive mothers prevents overt HBV transmission but may not prevent occult HBV infection in babies: a randomized controlled trial

Vertical transmission of Hepatitis B virus HBV can result in a state of chronic HBV infection and its complications. HBV vaccination with or without hepatitis B immunoglobulin (HBIG) prevents transmission of overt infection to the babies. However, whether it also prevents occult HBV infection in babies is not known. Consecutive pregnant women of any gestation found to be HBsAg positive were followed till delivery, and their babies were included in the study. Immediately after delivery, babies were randomized to receive either HBIG or placebo in addition to recombinant HBV vaccine (at 0, 6, 10 and 14 weeks). The primary end‐point of the study, assessed at 18 weeks of age, was remaining free of any HBV infection (either overt or occult) plus the development of adequate immune response to vaccine. The babies were further followed up for a median of 2 years of age to determine their eventual outcome. Risk factors for HBV transmission and for poor immune response in babies were studied. Of the 283 eligible babies, 259 were included in the trial and randomized to receive either HBIG (n = 128) or placebo (n = 131) in addition to recombinant HBV vaccine. Of the 222 of 259 (86%) babies who completed 18 weeks of follow‐up, only 62/222 (28%) reached primary end‐point. Of the remaining, 6/222 (3%) developed overt HBV infection, 142/222 (64%) developed occult HBV infection, and 12/222 (5%) had no HBV infection but had poor immune response. All 6 overt infections occurred in the placebo group (P = 0.030), while occult HBV infections were more common in the HBIG group (76/106 [72%] vs. 66/116 [57%]; P = 0.025). This may be due to the immune pressure of HBIG. There was no significant difference between the two groups in frequency of babies developing poor immune response or those achieving primary end‐point. The final outcome of these babies at 24 months of age was as follows: overt HBV infection 4%, occult HBV infection 42%, no HBV infection but poor immune response 8% and no HBV infection with good immune response 28%. Women who were anti‐HBe positive were a low‐risk group, and their babies were most likely to remain free of HBV infection (occult or overt) and had good immune response to the vaccine. Maternal HBeAg‐positive status and negativity for anti‐HBe predicted not only overt but also any infection (both overt and occult) in babies. In addition, high maternal HBV DNA and treatment with vaccine alone were significant factors for overt HBV infection in babies. The current practice of administration of vaccine with HBIG at birth to babies born of HBsAg‐positive mothers is not effective in preventing occult HBV infection in babies, which may be up to 40%. Because the most important risk factors for mother‐to‐baby transmission of HBV infection are the replicative status and high HBV DNA level in mothers; it will be worthwhile investigating the role of antivirals and HBIG administration during pregnancy to prevent mother‐to‐child transmission of HBV infection.     

Hepatitis B virus pregenomic RNA status can reveal the long‐term prognoses of chronic hepatitis B patients treated with nucleos(t)ide analogues

We examined whether the hepatitis B virus (HBV) pregenomic RNA (pgRNA) status after nucleos(t)ide (NA) treatment can predict the long‐time prognoses of chronic hepatitis B patients. Patients with chronic hepatitis B (98) who were treatment‐naïve and had begun a 7‐year NA therapy regimen were enrolled in this study. Biochemical indicators and serological markers of HBV infection were performed during therapy. HBV pgRNA was quantified by real‐time quantitative PCR with specific primers. During treatment, HBV DNA undetectable rates increased. The aminotransferase (ALT) normalization (ALT < 50 IU/L) and HBeAg‐negative rates also increased. After 48 weeks’ NA treatment, 48.28% (28/58) of HBV DNA undetectable patients still had HBV pgRNA‐positive. After 7 years of treatment, more HBV pgRNA‐negative patients (n = 35) achieved HBeAg clearance than the patients who were HBV pgRNA‐positive (n = 63) (19/23 vs 19/56, P < .00). HBV pgRNA‐positive patients also had an increased risk of failing to achieve HBeAg clearance (OR = 9.25, 95% CI: 2.75‐31.08). The median time to HBeAg clearance in the HBV pgRNA‐positive patients was longer than that of the HBV pgRNA‐negative patients (152 weeks vs 72 weeks). The HBV pgRNA‐positive patients also required more time to achieve HBV DNA undetectable (124 weeks, 95% CI: 103.33‐144.67 vs 48 weeks, 95% CI: 34.80‐61.20). The HBV pgRNA status after NA treatment can predict the long‐term prognoses of patients with chronic HBV. Patients who remain HBV pgRNA‐positive after 48 weeks of NA treatment have an increased risk of not achieving HBeAg clearance, need more time to achieve HBeAg clearance and undetectable HBV DNA load.     

Hepatitis B reactivation in HBsAg‐negative/HBcAb‐positive patients receiving rituximab for lymphoma: a meta‐analysis

Patients with chronic hepatitis B (HBsAg‐positive) are at risk of viral reactivation if rituximab is administered without antiviral treatment, a potentially fatal complication of treatment. Patients with so‐called ‘resolved hepatitis B virus infection’ (HBsAg‐negative/cAb‐positive) may also be at risk. We performed a systematic review of the English and Chinese language literature to estimate the risk of hepatitis B virus (HBV) reactivation in HBsAg‐negative/cAb‐positive patients receiving rituximab for lymphoma. A pooled risk estimate was calculated for HBV reactivation. The impact of HBsAb status and study design on reactivation rates was explored. Data from 578 patients in 15 studies were included. ‘Clinical HBV reactivation’, (ALT >3 × normal and either an increase in HBV DNA from baseline or HBsAg seroreversion), was estimated at 6.3% (I² = 63%, P = 0.006). Significant heterogeneity was detected. Reactivation rates were higher in prospective vs retrospective studies (14.2% vs 3.8%; OR = 4.39, 95% CI 0.83–23.28). Exploratory analyses found no effect of HBsAb status on reactivation risk (OR = 0.083; P = 0.151). Our meta‐analysis confirms a measurable and potentially substantial risk of HBV reactivation in HBsAg‐negative/cAb‐positive patients exposed to rituximab. However, heterogeneity in the existing literature limits the generalizability of our findings. Large, prospective studies, with uniform definitions of HBV reactivation, are needed to clarify the risk of HBV reactivation in HBsAg‐negative/cAb‐positive patients.     

Seroepidemiology of hepatitis B virus infection: analysis of mass screening in Hawaii

Background  Although hepatitis B seroprevalence has been studied extensively in California and New York, detailed information for other high-risk areas in the United States is lacking. To study current prevalence and risk for hepatitis B virus (HBV) infection in Hawaii, we analyzed cross-sectional data from Hawaii residents screened between July 2003 and April 2006. Methods  We retrospectively reviewed the screening records of 3,989 participants recruited at health fairs and clinics. Prevalence and risk factors for HBV infection were estimated using univariate and multivariate logistic regression models. Results  Total prevalence of hepatitis B surface antigen (HBsAg) was 3.6%. Gender, age, and ethnicity were independently associated with HBsAg seropositivity. In a multivariate logistic regression model, males were at increased risk for HBsAg compared with females (odds ratio [OR] = 1.53, 95% confidence interval [CI]: 1.09–2.16) and persons aged 70 years or older were less likely to test positive than those younger than 30 (OR = 0.25, 95% CI: 0.11–0.61). In addition, multivariate ORs of HBsAg seropositivity were 3.24 (95% CI: 1.04–10.09), 4.13 (95% CI: 1.66–10.29), and 7.47 (95% CI: 2.52–22.11) for Vietnamese, Chinese, and Pacific Islanders, respectively, compared with Whites. Conclusions  This study furthers current knowledge of HBV epidemiology in areas with large populations of high-risk immigrants and demonstrates the relevance of screening programs for hepatitis B.     

Prevalence of HBsAg/HBeAg amongst 1 936 801 couples preparing for pregnancy in rural China: An observational study

There are few extant studies on the prevalence of HBV infection in couples preparing for pregnancy. We assessed the prevalence of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) in couples preparing for pregnancy in rural China, and the association between HBV prevalence and the statuses of HBsAg/HBeAg and ALT in the spouses. We performed a nationwide cross‐sectional study, using data from a health check‐up program for 1 936 801 rural couples from 31 provinces preparing for pregnancy between 2010 and 2012. ELISA was used to test serologic samples, and we defined couples who were either discordant or both positive for HBsAg as “POSITIVE COUPLES” (PC). Amongst the 1 936 801 couples, 202 816 (10.47%; 95% CI, 10.43%‐10.51%) were PC. HBeAg (high infectiousness) was detected in 56 474 (27.84%; 95% CI, 27.65%‐28.04%) of 202 816 HBsAg‐positive couples. Multivariate models showed that the prevalence of HBV infection in wives increased along with the positive statuses for HBsAg/HBeAg and alanine aminotransferase (ALT) of their husbands (adjusted odds ratio increased from 2.31 to 4.98), after adjustment for potential confounders. Similarly, the prevalence of HBV infection in husbands was associated with the positive statuses of HBsAg/HBeAg and ALT of their wives (adjusted odds ratio increased from 2.04 to 4.93). The prevalence of POSITIVE COUPLES in couples preparing for pregnancy in rural China was high, and the prevalence of HBV infection was independently associated with the positive statuses of HBsAg/HBeAg and ALT of the spouses. Instead of solely focussing on mothers prior to becoming pregnant, POSITIVE COUPLES should be taken as an important unit of care.     

Meta‐analysis: Association between hepatitis B virus preS mutation and hepatocellular carcinoma risk

Previous observational studies suggested that hepatitis B virus (HBV) preS mutation plays an important role in the existence of HBV‐related hepatocellular carcinoma (HCC). However, the results are still debatable. With an increasing number of studies about this topic, this study employed a meta‐analysis to identify the association between HBV preS mutation and HCC risk. We searched for eligible studies from PubMed, ProQuest, CINAHL, ScienceDirect and Springer databases to assess the association between HBV mutation and HCC risk. This meta‐analysis was conducted using RevMan 5.3 to provide pooled estimate for odds ratio (ORs) with 95% confidence intervals (95% CIs). Twenty‐one clinical studies were included in this meta‐analysis study which consisted of 1738 participants with HBV‐related HCC and 3740 HBsAg‐positive patients without HCC. All studies used samples of Asian population. PreS deletion was the most common mutation found in all studies. We found that ORs of HBV overall preS deletion was associated with HCC (OR = 3.28; 95% CI = 2.32‐4.65; P < .00001; random‐effects model). Each preS1 and preS2 deletion was associated with increased risk of HCC, with OR 2.42 (95% CI = 1.25‐4.68, P = .008) and 3.36 (95% CI = 2.04‐5.55, P < .00001), respectively. PreS2 start codon mutation was also significantly associated with HCC risk (OR = 2.47; 95% CI: 1.15‐5.27; P = .02; random‐effect model). The result of this meta‐analysis suggested that HBV preS deletion (all, preS1 and preS2) and preS2 start codon mutation might contribute to the increased risk of HBV‐related HCC.     

Inter-method variability of hepatitis B surface antigen quantification in a cohort of Egyptian patients with chronic hepatitis B virus

Background and study aimsHepatitis B (HB) surface antigen (HBsAg) levels can predict clinical and treatment outcomes in chronic HB virus (HBV) infection. We aimed to compare the performance of two different assays [Elecsys® (Roche) and Architect? (Abbott)] for HBsAg quantification and evaluate HBsAg levels in the various immune phases in a cohort of Egyptian patients with chronic HBV.Patients and methodsQuantitative HBsAg by Elecsys® and Architect? assays, measurement of routine biochemical and serological markers, and transient elastography were performed in 92 patients with chronic HBV. Results of the two assays and other tests were compared.ResultsNinety-two treatment-naive patients with chronic HBV, (70% males; mean age, 36.1 ± 10.5 years) were recruited from Cairo Fatemic Hospital. Patients were categorized as HBeAg positive (n = 22) and HBeAg negative (n = 70). The Architect? and Elecsys® assays were significantly correlated (intraclass correlation coefficient: 0.913; 95% CI: 0.870–0.943; p < 0.001). However, Deming regression, Passing and Bablok, and Bland–Altman statistical analyses showed discordance among the assays. HBsAg levels by both assays were significantly higher in the HBeAg positive than patients with HBeAg-negative (p = 0.033 and 0.013, respectively). HBsAg levels in the Architect? and Elecsys® assays were significantly higher in HBeAg-negative chronic hepatitis than in HBeAg-negative chronic infection (p = 0.002 and 0.004, respectively)ConclusionBoth assays for qHBsAg were found to be simple and reproducible tests that could classify patients and provide additional evidence on the natural history of HBV.     

Association between hepatitis B or hepatitis C virus infection and risk of pancreatic adenocarcinoma development: A systematic review and meta-analysis

BackgroundPancreatic adenocarcinoma (PAC) is an aggressive cancer with a poor prognosis. To date, PAC causes are still largely unknown. Antigens and replicative sequences of oncogenic hepatitis B (HBV) and hepatitis C (HCV) virus were detected in different extra-hepatic tissues, including pancreas.Objectivea systematic review and meta-analysis of epidemiological studies assessing PAC risk in patients with HBV/HCV chronic infections.MethodsIn September 2012, we extracted the articles published in Medline, Embase and the Cochrane Library, using the following search terms: “chronic HBV” and “HCV”, “hepatitis”, “PAC”, “risk factors”, “epidemiology”. Only case/control (C/C), prospective/retrospective cohort studies (PCS/RCS) written in English were collected.Resultsfour hospital-based C/C studies and one PCS, in HBV-infected patients and two hospital-based C/C studies and one RCS in HCV-infected subjects met inclusion criteria. In these studies HBsAg positivity enhanced significantly PAC risk (RR = 1.18, 95% CI:1.04–1.33), whereas HBeAg positivity (RR = 1.31, 95% CI:0.85–2.02) as well as HBsAg negative/HBcAb positive/HBsAb positive pattern (RR = 1.12, 95% CI:0.78–1.59) and HBsAg negative/HBcAb positive/HBsAb negative pattern (RR = 1.30, 95% CI:0.93–1.84) did not. Relationship between PAC risk and anti-HCV positivity was not significant, although it reached a borderline value (RR = 1.160, 95% CI:0.99–1.3).ConclusionsHBV/HCV infection may represent a risk factor for PAC, but the small number of available researches, involving mainly populations of Asian ethnicity and the substantial variation between different geographical areas in seroprevalence of HBV/HCV-antigens/antibodies and genotypes are limiting factors to present meta-analysis.     

Maternal immunization promotes the immune response of neonates towards hepatitis B vaccine

Infants infected with hepatitis B virus (HBV) face the risk of developing severe complications. Unfortunately, in spite of universal vaccination programmes, 5% or more of vaccinated newborns still do not achieve protective levels of anti‐hepatitis B virus surface antigen titres (anti‐HBs). The aim of this study was to use animal experiments and population‐based research to determine whether maternal vaccination against HBV affects the outcome of neonatal vaccination. Six sows and 53 newborn piglets were used for this study and randomly assigned to the vaccination group (three 20 μg doses of recombinant HBV vaccine). All the piglets were followed up to 10 weeks of age, and peripheral blood was withdrawn for measurement of anti‐HBs. A cross‐sectional study was also conducted on 449 mothers with infants. A structured questionnaire was used to collect demographic, medical and maternal data, and their peripheral blood was collected for measurement of anti‐HBs. The results of animal experiments demonstrated that nonvaccinated piglets born to vaccinated sows and nonvaccinated piglets born to nonvaccinated sows were negative for anti‐HBs. Repeated measures analysis of variance showed that the titres of anti‐HBs in vaccinated piglets born to vaccinated sows were significantly higher than in vaccinated piglets born to nonvaccinated sows (P < 0.05). In a population‐based study, a cumulative logistic regression analysis showed that the strongest influences on neonatal anti‐HBs titres were delay of the first vaccination dose [OR = 3.02(95% CI: 1.72–5.30)] and maternal anti‐HBs titres [OR = 2.48(95% CI: 2.03–3.04)]. In conclusion, high maternal anti‐HBs titres can enhance the response to HBV vaccination in infants.     

Distribution of ABO/Rh blood groups and their association with hepatitis B virus infection in 3.8 million Chinese adults: A population‐based cross‐sectional study

ABO and Rh blood groups play a vital role in blood transfusion safety and clinical practice and are thought to be linked with disease susceptibility. The results from previous studies that focused on the association between blood groups and HBV infection remain controversial. China has the world's largest burden of HBV infection. We assessed the distribution of ABO/Rh blood groups in Chinese adults and examined the association between these groups and HBV infection. We did a nationwide cross‐sectional study using data from a physical check‐up programme from 31 provinces examined between 2010 and 2012. ELISA was used to test for HBsAg in serologic samples. Multivariable logistic regression was used to estimate aOR of the association between ABO and Rh blood groups and HBV infection. Among 3 827 125 participants, the proportion of participants with blood group A was highest (30.54%), followed by O (30.37%), B (29.42%) and AB (9.66%). A total of 38 907 (1.02%) were Rh‐D negative. The prevalence of HBsAg in blood groups O, A, B and AB were 6.34%, 5.55%, 5.18% and 5.06%, respectively. HBsAg prevalence was 5.65% in Rh‐D‐positive and 3.96% in Rh‐D‐negative participants. After controlling for other potential risk factors, multivariate models showed that participants with blood group O (adjusted OR = 1.22, 95% CI: 1.20‐1.25) were at higher risk of HBV infection compared with group AB. Rh‐D‐positive participants (adjusted OR = 1.44, 95% CI: 1.37‐1.52) were at higher risk of HBV infection than Rh‐D‐negative participants. The associations between ABO/Rh blood groups and HBV infection were similar in subgroup analysis. The proportions of O, A, B and AB blood groups were approximately 3:3:3:1, and nearly 1 in 100 people was Rh‐D negative among Chinese adults. Blood group O and Rh‐D positivity were both associated with increased HBV infection. The risk of HBV infection and blood safety should be taken into consideration in clinical practice, especially when transfusing those with blood group O. Awareness and prevention of HBV infection is of particular importance for individuals with blood group O.     

Evidence on the causal link between homocysteine and hypertension from a meta‐analysis of 40 173 individuals implementing Mendelian randomization

Numerous researchers have investigated the associations among methylenetetrahydrofolate reductase gene (MTHFR) C677T polymorphism, homocysteine (Hcy) concentration, and hypertension. However, the results are controversial. Thus, a meta‐analysis implementing Mendelian randomization approach was conducted to examine the hypothesis that elevated Hcy concentration plausibly contributes to increased risk of hypertension. Based on several inclusion and exclusion criteria, eligible studies were selected to explore the correlation between MTHFR C677T and hypertension risk, MTHFR C677T and Hcy concentration in hypertension, and Hcy concentration and hypertension, and they were evaluated by odds ratios (ORs), effect size (ES), and standard mean difference with their corresponding 95% confidence intervals (95% CIs), respectively. Moreover, Mendelian randomization was implemented to evaluate the relationship between Hcy and hypertension. Consequently, 14 378 cases and 25 795 controls were involved in this study and the results showed that MTHFR C677T led to an elevated risk of hypertension (for T vs C: OR = 1.27, 95% CI = 1.17‐1.37; for TT vs CC: OR = 1.53, 95% CI = 1.30‐1.79). Additionally, in hypertensive subjects, the pooled Hcy concentration in individuals of TT genotype was 7.74 μmol/L (95% CI: 5.25‐10.23) greater than that in individuals of CC genotype. Moreover, the pooled Hcy concentration in hypertensive was 0.69 μmol/L (95% CI: 0.50‐0.87) greater than that in controls. The estimated causal OR associated with hypertension was 1.32 for 5 μmol/L Hcy increment. Via MTHFR C677T polymorphism, the findings in the present study demonstrated that there exists evidence on causal link between Hcy concentration and the risk of hypertension.     

Precore G1896A mutation is associated with reduced rates of HBsAg seroclearance in treated HIV hepatitis B virus co‐infected patients from Western Africa

The nucleotide substitution G1896A on the precore (pc) region has been implicated in virological and serological responses during treatment in hepatitis B virus (HBV)‐infected patients. Whether this mutation affects the therapeutic course of HIV‐HBV co‐infected patients, especially from Western Africa, is unknown. In this prospective cohort study, 86 antiretroviral (ARV)‐naïve HIV‐HBV co‐infected patients from Côte d'Ivoire, initiating ARV‐treatment containing lamivudine (n = 53) or tenofovir (n = 33), had available baseline pc sequences. Association of the pcG1896A mutation with time to undetectable HBV‐DNA, hepatitis B “e” antigen (HBeAg) seroclearance (in HBeAg‐positive patients), and hepatitis B surface antigen (HBsAg) seroclearance was evaluated using Cox proportional hazards regression. At ARV‐initiation, median HBV‐DNA was 6.04 log₁₀ copies/mL (IQR = 3.70‐7.93) with 97.7% harbouring HBV genotype E. Baseline pcG1896A mutation was identified in 51 (59.3%) patients, who were more commonly HBeAg‐negative (P < .001) and had basal core promotor A1762T/G1764A mutations (P < .001). Patients were followed for a median 36 months (IQR = 24‐36). Cumulative proportion of undetectable HBV‐DNA was significantly higher in patients with baseline mutation (pcG1896A = 86.6% vs no pcG1896A = 66.9%, P = .04), but not after adjusting for baseline HBV‐DNA levels and anti‐HBV agent (P = .2). No difference in cumulative proportion of HBeAg seroclearance was observed between mutation groups (pcG1896A = 57.1% vs no pcG1896A = 54.3%, P = .7). Significantly higher cumulative proportion of HBsAg seroclearance was observed in patients without this mutation (pcG1896A = 0% vs no pcG1896A = 36.9%, P < .001), even after adjusting for baseline HBsAg quantification and anti‐HBV agent (P < .001). In conclusion, lacking the pcG1896A mutation before ARV initiation appeared to increase HBsAg seroclearance rates during treatment. The therapeutic implications of this mutation need further exploration in this setting.