Chronic Hepatitis B Virus Carriers Research Articles

Hepatitis B virus surface antigen (HBsAg) mutations are rare but clustered in immune epitopes in chronic carriers from Sistan-Balouchestan Province, Iran.

Hepatitis B virus (HBV) gene and protein variations have frequently been observed in chronic patients. The aims of this study were to determine the genotypes as well as the patterns of HBsAg variations in chronically-infected patients from the south-eastern part of Iran. Twenty- one chronic inactive HBV carriers from Sistan-Balouchestan Province (an area with a low prevalence of HBV complications such as cirrhosis and hepatocellular carcinoma [HCC]) were enrolled. The surface genes were amplified, sequenced, and subsequently aligned using international and national Iranian database. All strains belonged to genotype D, subgenotype D1, and subtype ayw2. Of all 39 mutations occurred at 31 nucleotide positions, 15 (38.5%) were missense (amino acid altering) and 24 (61.5%) were silent (no amino acid changing). At the amino acid level, 15 substitutions occurred; 10 (66.67%) were distributed in different immune epitopes, five of which (33.33%) were in B cell epitopes; four (36.27%) were distributed in T helper epitopes, and one (6.67%) occurred inside CTL epitopes. A narrowly-focused immune pressure has been on the surface proteins, especially at the B cell level, led to the emergence of escape mutants in these patients that might be related to the pathogenicity of HBV chronic infection. Also, due to the negative selection imposed on HBV genome and the uniqueness of genotype D in this ethnic group, complications (cirrhosis and HCC) are lower than other published studies.

Predictability of Liver-Related Seromarkers for the Risk of Hepatocellular Carcinoma in Chronic Hepatitis B Patients

BackgroundHepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is a major global health problem. A few risk calculators have been developed using mainly HBV seromarkers as predictors. However, serum HBV DNA level, HBV genotype, and mutants are not routinely checked in regular health examinations. This study aimed to assess the predictability of HCC risk in chronic hepatitis B patients, using a combination of liver-related seromarkers combined with or without HBV seromarkers.MethodsA prospective cohort of 1,822 anti-HCV-seronegative chronic HBV carriers was included in this study. Liver-related seromarkers including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alpha-fetoprotein (AFP), gamma-glutamyltransferase (GGT), total bilirubin, total protein, albumin, serum globulins, apolipoprotein A1, and apolipoprotein B were examined. Hazard ratios of HCC with 95% confidence intervals were estimated using Cox proportional hazards regression models. Regression coefficients of seromarkers significantly associated with HCC risk in multivariate analyses were used to create integer risk scores. The predictability of various risk models were assessed by area under receiver operating characteristic curves (AUROCs).ResultsDuring a median follow-up of 5.9 years, 48 newly-developed HCC cases were ascertained. Elevated serum levels of ALT (≥28 U/L), AFP (≥5 ng/mL), and GGT (≥41 U/L), an increased AST/ALT ratio (AAR, ≥1), and lowered serum levels of albumin (≤4.1 g/dL) and alpha-1 globulin (≤0.2 g/dL) were significantly associated with an increased HCC risk (P<0.05) in multivariate analysis. The risk model incorporating age, gender, AAR, and serum levels of ALT, AFP, GGT, albumin, and alpha-1 globulin had an AUROC of 0.89 for predicting 6-year HCC incidence. The AUROC was 0.91 after the addition of HBV seromarkers into the model, and 0.83 for the model without liver-related seromarkers, with the exception of ALT.ConclusionLiver-related seromarkers may be combined into useful risk models for predicting HBV-related HCC risk.

Chronic HBV Carrier’s acceptance of regular surveilling program in China

Long-term compliance with regular surveillance is important for the prevention and timely management of chronic hepatitis B (CHB). However, there are no researches focusing on the compliance of hepatitis B virus infected patients in regular surveillance so far. The purpose of our study was to investigate the outpatient compliance with long-term regular surveillance in China. Data of 3257 CHB outpatients was pooled and analyzed to assess the outpatient's compliance with the long-term regular surveillance plan. In all outpatients, the non-follow-up and the follow-up group accounted for 73.2% and 26.8%, respectively. Among the follow-up outpatient's, only 48.9% received ongoing-follow-up and 51.1% were finally lost to follow-up; the median length of visiting duration was 25 months; and the predictive 1-, 2-, 3-, 4- and 5-year ongoing follow-up rate was 72.7%, 52.5%, 42.4%, 33.8%, and 26.3%, respectively. In conclusion, our survey proved that the regular long-term surveillance on Chinese chronic HBV carrier is difficult to be fully implemented. A large proportion of outpatients do not receive routine follow-up and are at risk of treatment delay due to various social reasons.

433 QUANTIFICATION OF LARGE, MIDDLE AND SMALL HEPATITIS B VIRUS (HBV) SURFACE PROTEIN (HBsAg) FRACTIONS IN PATIENTS WITH ACUTE HEPATITIS B

Methods: 315 HBsAg positive mothers and their offspring received combined immunoprophylaxis (hepatitis B immune globulin and hepatitis B vaccine) were recruited in this study. The venous blood of 315 mothers and infants (315 at birth, 262 at 1-month-old and 251 at 7-month-old) was collected for tests of HBVDNA load and HBV markers titer. Result: The positive rates of HBVDNA, HBsAg and HBeAg in the newborns at birth were 17.8% (56/315), 25.1% (79/315) and 25.4% (80/315), respectively. Maternal HBVDNA load, HBsAg and HBeAg titer were associated with neonatal HBVDNA load, HBsAg and HBeAg titer at birth respectively. In the neonatus born to the pregnant mothers with HBVDNA>10 IU/ml, HBsAg>10 IU/ml and HBeAg>1 s/co, the probability of HBVDNA-, HBsAgand HBeAgpositive at birth significantly increased (areas under ORC curve were the largest, 0.770, 0.697 and 0.944, respectively). During the follow-up, the positive rates of HBVDNA, HBsAg and HBeAg in infants reduced gradually and HBVDNA (83.9%), HBsAg (87.3%) and HBeAg (87.5%) in the majority of infants turned to be negative at 7 months after birth, while 3.6% (9/251) infants became chronic HBV carriers (HBVDNAand HBsAg-positive from birth to 7-monthold) and 8.6% (18/242) were non-responders (anti-HBs <10mIU/ml at 7-month-old). High levels of HBsAg titer and HBVDNA load of newborns at birth were associated with chronic HBV infection, while the relevance between HBsAg, HBeAg and HBVDNA from mother to infant and the non-response to HB vaccination was uncertain. Conclusion: HBsAg and HBVDNA, as HBeAg, could cross the human placenta from mother to infant and lead to short-term antigenemia or virusemia in newborns, while HBsAgand HBVDNA-positive at birth may not be indication for HBV infection of infants. HBVDNA, HBsAg and HBeAg from mother to infant did not contribute to the non-response to HB vaccination, while further follow-up was still in need.

Association of polymorphism in MicroRNA 219‐1 with clearance of hepatitis B virus infection

Polymorphisms in the primary microRNA region may be associated with natural course of hepatitis B virus (HBV) infection. This study evaluated if the mircoRNA 219-1 (miR-219-1) polymorphism can influence the susceptibility towards persistence of HBV infection and the progression to hepatocellular carcinoma (HCC) in patients with chronic HBV infection. A total of 1,439 individuals having either past or present evidence of HBV infection were enrolled for the study. The subjects were divided into four groups; (1) spontaneous recovery (n = 404), (2) chronic HBV carrier (n = 313), (3) chronic HBV carrier with cirrhosis (n = 305), and (4) hepatocellular carcinoma (n = 417). Genotyping was performed at three polymorphic variants (rs421446, rs107822, and rs213210) in the pri-miRNA region of miR-219-1. The rs421446 T allele was found to be strongly associated with HBV clearance (OR = 0.73, P = 0.0005 in a codominant model and OR = 0.67, P = 0.0009 in a dominant model, OR = 0.69, P = 0.04 in a recessive model, respectively). The rs107822 G allele was also found to be associated with HBV clearance (OR = 0.79, P = 0.008 in a codominant model and OR = 0.72, P = 0.01 in a dominant model, respectively). In haplotype analysis, ht2 (T-G-T) and ht1 (C-A-C) were found to be in significant association with the clearance of HBV. However, no significant association was observed between miR-219-1 polymorphism and the risk of HCC occurrence. This result suggests that polymorphisms in the pri-miRNA region of miR-219-1 might be a genetic factor for HBV clearance after infection.

A pregnant woman with acute hepatitis B in whom vertical transmission was prevented by tenofovir disoproxil fumarate.

The optimal management of acute hepatitis B in pregnant women remains to be fully evaluated. A case of hepatitis B virus (HBV) infection in a 20-year-old pregnant woman who initially presented with jaundice is reported. Serum samples were positive for anti-HBc IgM and HBe antigen. Her husband was infected with HBV genotype A and received entecavir because of prolonged hepatitis and a high viral load. The HBV DNA sequence of the wife completely matched that of her husband, indicating that he was the source of HBV infection. In accordance with guidelines for the treatment of chronic HBV carriers, the wife started to receive tenofovir disoproxil fumarate (TDF) in her third trimester. After 4months of treatment, the HBV DNA load decreased from 7.6 to 3.5log copies/ml. At delivery, the serum was found negative for the HBe antigen. Seven months after treatment began, the HBs antigens also disappeared. The baby, totally healthy, received passive-active immunoprophylaxis. At 3months, the baby remained free of HBV infection. TDF thus prevented exacerbation and prolongation of acute HBV infection in a pregnant woman. Subsequent treatment also prevented mother-to-infant transmission of HBV. The clinical course of her husband, who had HBV infection and received entecavir, is also reported.

Hepatitis B virus among Saudi National Guard Personnel: Seroprevalence and risk of exposure

Data on HBV prevalence among active military personnel in Saudi Arabia (SA) are lacking. In addition, the work-related risk of exposure is unclear. The objective of this study was to estimate the seroprevalence of HBV and the risk of HBV exposure among SA National Guard (SANG) soldiers. A cross-sectional study was performed and included 400 male SANG soldiers working in Jeddah during January 2009. All soldiers completed a questionnaire to assess their risk of exposure and gave a blood sample to test for hepatitis serology markers. A total of 16 (4.0%) soldiers were positive for HbsAg, 53 (13.2%) were positive for anti-HBc, and 230 (57.5%) were positive for anti-HBs. None of the soldiers had acute HBV infection, but 15 (3.8%) were chronic HBV carriers. A total of 152 (38.0%) soldiers were susceptible to HBV infection, and 230 (57.5%) were immune to HBV infection, primarily (84.3%) due to HBV vaccination. Compared with those who were negative for anti-HBc (never exposed), soldiers who were positive for anti-HBc were more likely to be older, have a lower education level, have a higher income, have a longer service duration, have a household member with HBV disease, have undergone surgery, or have undergone endoscopy. In the multivariate logistic regression model, older age, presence of a household member with HBV disease and previous endoscopy were independent predictors of HBV exposure. We report a 4% prevalence of HBsAg in the Saudi military population. This HBV prevalence was higher than those in the general Saudi population and military populations from Western countries. Both work-related and community-related risk factors for exposure are suggested.

Epidemiology of viral hepatitis B and C in Iraq: a national survey 2005-2006

Background and objective: Viral Hepatitis Type B&C is serious public health challenge throughout the world.Hepatitis B and C viruses still remain to be the major causes of chronic hepatitis.It is estimated that around 350-400 million people in the world are chronic carriers of HBV, which represents approximately 7% of the total populationwhereas infection with HCV is found in approximately 3% of the world population, which represents 160 million people. Hepatitis B infection has a wide range of seroprevalence in the Mediterranean countries ranging from intermediate (=>2% ) to high prevalence ( =>7%). World Health Organization estimated a prevalence rate for HCV infection of about 4.6% in Eastern Mediterranean in 1999. During the eightieths years of the last century, Iraq was considered to be of intermediate endemicity with hepatitis B as reflected by 3% seroprevalence of HBsAg in normal population. Hepatitis C was found to be of low endemicity among blood donors 0.5%. There were no national wide epidemiological studies regarding the prevalence of hepatitis B&C accordingly we conduct this study to determine the prevalence of both types all over the Iraq. Methods: From the 1 st of January 2005 to 31 st of December 2006, a community based cross-sectional study was conducted all over Iraqi governorates. A total of 9610 persons, recruited by surveying a nationally representative random sample of households were analyzed. A stratified random sample proportional to size of each of the 18 Iraqi governorates, both urban and rural areas were included. Prevalence estimates were therefore weighted and age-adjusted. Five (5ml) of blood samples were taken from the study subjects, and tested for hepatitis B surface antigen, antibody to hepatitis B core antigen antibody to hepatitis B surface antigen and hepatitis C antibodies . Results: The national prevalence rate of HBs Ag was 1.6% and correlated positively with age. The prevalence rate of anti-HBs antibodies was 17%. The prevalence of anti-HBc was 9.7%. The prevalence of anti-HCV was low (0.4%). The prevalence rate of anti-HBs antibodies in <10 years children is only 32.2%, which raise the issue of incomplete coverage of hepatitis B vaccine during the years preceding the study years. Conclusion: The findings revealed that Iraq is of low prevalence with HBsAg.On the other

Longitudinal cohort study on the spontaneous HBeAg seroconversion among chronic HBV carriers

Objective To study the HBeAg spontaneous seroconversion among chronic HBV infection.Methods A chronic HBV infection cohort with 172 HBsAg/HBeAg positive carriers was set up through the cross-sectional serological survey in 8 villages of Zhengding county,Hebei province in 1999,2005 and 2006.Serum specimens were collected from all carriers during the follow-up at 2010 and 2012,and were tested for anti-HBs,HBsAg,anti-HBe,HBeAg,HBV DNA,as well as ALT.Results Loss of HBeAg were detected from 32 carriers,the annual rate was 2％ (95％ CI:1.4％-2.8％).Of these,HBeAg seroconversion occurred in 26 carriers,the annual spontaneous HBeAg seroconversion rate was 1.6％ (95％CI:1.1％-2.4％).Conclusion Spontaneous HBeAg seroconversion could be observed in rare cases among chronic HBV carriers,coming along with the significant decrease of HBV DNA and HBsAg level. Key words: Hepatitis B virus; Carrier; HBeAg; Spontaneous seroconversion

Drug-Related Mutational Patterns in Hepatitis B Virus (HBV) Reverse Transcriptase Proteins From Iranian Treatment-Naïve Chronic HBV Patients

BackgroundImmunomodulators and Nucleotide analogues have been used globally for the dealing of chronic hepatitis B virus (HBV) infection. However, the development of drug resistance is a major limitation to their long-term effectiveness.ObjectivesThe aim of this study was to characterize the hepatitis B virus reverse transcriptase (RT) protein variations among Iranian chronic HBV carriers who did not receive any antiviral treatments.Materials and MethodsHepatitis B virus partial RT genes from 325 chronic in active carrier patients were amplified and directly sequenced. Nucleotide/amino acid substitutions were identified compared to the sequences obtained from the database.ResultsAll strains belonging to genotype D.365 amino-acid substitutions were found. Mutations related to lamivudine, adefovir, telbivudine, and entecavir occurred in (YMDD) 4% (n = 13), (SVQ) 17.23% (n = 56), (M204I/V + L180M) 2.45% (n = 8) and (M204I) 2.76% (n = 9) of patients, respectively.ConclusionsRT mutants do occur naturally and could be found in HBV carriers who have never received antiviral therapy. However, mutations related to drug resistance in Iranian treatment-naïve chronic HBV patients were found to be higher than other studies published formerly. Chronic HBV patients should be monitored closely prior the commencement of therapy to achieve the best regimen option.

Prevalence of Hepatitis B e Antigen in Chronic HBV Carriers in North-central Nigeria

Hepatitis B virus (HBV) is an important clinical problem due to its worldwide distribution and potential of adverse sequelae, including hepatocellular carcinoma (HCC). We studied the prevalence of hepatitis B virus e antigen (HBeAg) among individuals determined to be HBV surface antigen-positive (HBsAg+) and analyzed the gender/age category associated with more active HBV infection. A total of 572 HBsAg+ individuals, as determined by a double antibody sandwich ELISA method, participated in the study. They were tested for HbeAg, using a lateral flow chromatographic immunoassay. One hundred and ten individuals were found to be HBeAg-positive giving an overall prevalence of 19.2%. Of these 110 individuals, 20 (18.2%) were females, and 90 (81.8%) were males. Thus, the prevalence of HBeAg appears to be higher in males than in females (p < 0.05). Our data also revealed that the prevalence of HBeAg was higher in patients between the age-group of 0-10 years and 11-20 years and appeared to decrease with increase in age. Taken together, our data show that approximately 1/5 of HBV-infected individuals are HBeAg+, suggesting that the virus is actively replicating and infecting liver-cells thereby ensuring an HBV-transmission pool within the Nigerian population. We suggest strengthening of the childhood HBV vaccination programmes, massive intervention activities, and treatment programmes, especially among young people to reverse the possible devastating effect of HBV infection. The success of these efforts will depend on our resolution to make the elimination of HBV infection a top priority on the public-health agenda as we start the second decade of this new century.

Host Genetic Factors Affecting Spontaneous HBsAg Seroclearance in Chronic Hepatitis B Patients

Spontaneous clearance of hepatitis B surface antigen (HBsAg) in chronic hepatitis B (CHB) patients usually indicates a remission of hepatitis activity and a favorable outcome. Two single nucleotide polymorphisms (SNP), rs3077 near HLA-DPA1 region and rs9277535 near HLA-DPB1 region, have been shown to be associated with HBV persistence after acute HBV infection. However, little is known about the impact of these 2 SNPs on spontaneous HBsAg clearance in CHB patients. In this case-control study, a total of 100 male HBeAg-negative chronic HBV carriers who cleared HBsAg spontaneously (case group) and 100 age-matched HBeAg-negative male patients with persistent HBsAg positivity (control group) were enrolled. We investigated the relationship between these 2 SNPs and HBsAg clearance. There was a higher frequency of rs9277535 non-GG genotype in the case group (57% vs. 42%). Patients with rs9277535 non-GG genotype had a higher chance to clear HBsAg [Odds ratio (OR): 1.83, 95% confidence interval (CI): 1.04∼3.21, P = 0.034]. Compared to GG haplotype of rs3077 and rs9277535, GA haplotype had a higher chance of achieving spontaneous HBsAg loss (OR: 2.17, 95% CI: 1.14∼4.16, P = 0.030). In conclusion, rs9277535 non-GG genotype is associated with a higher likelihood of spontaneous HBsAg seroclearance in CHB patients.

HBV infection increases the risk of pancreatic cancer: a meta-analysis

Hepatitis B virus (HBV) infection is reported to be associated with an increased risk of pancreatic cancer (PaC), but it remains controversial whether this is a causal relationship. In addition, it is unclear whether the status of HBV infection also affects PaC risk. Therefore, we conducted a meta-analysis to more closely examine the association between HBV infection and PaC. The studies included in the meta-analysis were identified and retrieved from PubMed and several other databases. The literature search was conducted up until August 2012. We adopted the Cochrane Collaboration's RevMan 5.1 in a combined analysis of pooled relative risk (RR) with their corresponding 95% confidence intervals (CIs) using a random-effects and a fixed-effects model. Nine studies including 6 case-control and 3 cohort studies met eligibility criteria. The meta-analysis showed that the PaC risk was positively correlated with HBV infection when comparing with 'never exposed to HBV' subgroup, the pooled RR was 1.39 (95% CI 1.22-1.59, p<0.00001) in chronic HBV carriers, 1.41 (95% CI 1.06-1.87, p=0.02) in past exposure to HBV, and 3.83 (95% CI 1.76-8.36, p=0.0007) in active HBV infection. Using a stratified analysis, we also found that the risk of PaC was independent of smoking, alcohol drinking, and diabetes. Findings from this meta-analysis strongly support that HBV infection is associated with an increased risk of PaC.

Optimal management of HBV infection during pregnancy

Chronic hepatitis B virus (HBV) infection in pregnancy presents a unique and important challenge. Over 50% of chronic HBV carriers in endemic areas acquire infection vertically from their mothers. More importantly, over 90% of perinatally acquired infections progress to chronic HBV infection. Thus, management of chronic HBV during pregnancy and strategies to prevent mother-to-child transmission is an important step in eradicating or reducing the global burden of chronic hepatitis B. In addition, chronic HBV infection in pregnancy presents a unique clinical challenge because of the complex relationship between the physiological changes of pregnancy and the pathophysiological response to HBV. This review will present the current knowledge and a practical approach to management of HBV in pregnancy.

A clinical study on hepatitisi B vaccine triple-therapy in chronic hepatitis B virus infection

Event Abstract Back to Event A clinical study on hepatitisi B vaccine triple-therapy in chronic hepatitis B virus infection Bang-FU Wu1, 2* and Jiang-Ying Yang2 1 Southern Medical University Renkang Hospital, Gastroenterology and Hepatology Center, China 2 Guangzhou Pubang Bio-Immunological Tech Research Institute, China Aims: To observe the clinical efficacy of the admixture of hepatitis B vaccine, rhGM-CSF and BCG polysaccharide ucleic acid(for short: hepatitis B vaccine triple-therapy) combined with adefovir dipivoxil in the patients of chronic hepatitis B virus(HBV) infection. Methods: 18 HBeAg positive chronic hepatitis B(CHB) patients, 11 HBeAg positive chronic HBV carriers, 5 HBeAg negative CHB patients, 2 HBeAg negative chronic HBV carriers and 12 inactive HBsAg carriers were recruited in the study. Hepatitis B vaccine containing 20µg HBsAg, rhGM-CSF 100µg and BCG polysaccharide nucleic acid 2ml were mixed. And then the admixture injected hypodermically to the patient once every two weeks for 12 practices applications totally. Adefovir dipivoxil was taken 10mg daily for 33 patients those HBVDNA>10000 copy/ml. Quantitative HBVM(TRFIA) and HBVDNA were evaluated at week 0, 12, and 24. Results: At week 12 and 24, HBeAg seroconversion rate were 13.79%(4/29) and 27.59%(8/29) respectively, HBVDNA negative conversion rate were 37.14%(13/35), and 60.00%(21/35), HBsAg negative conversion rate were 2.08%(1/48) and 6.25%(3/48), HBsAb positive conversion rate were 16.67%(8/48) and 37.50%(18/48), HBsAg seroconversion rate were 2.08%(1/48) and 6.25%(3/48). The rate of adverse effect was 50.17%. The adverse effect include fever, headache, ache all over, bellyache, urticaria and hives, dyspnea, and tumefaction ache in the injection site after injected the admixture. Conclusions: The hepatitis B vaccine triple-therapy in combination with adefovir dipivoxil can be considered as a efficient approach for patients of chronic HBV infection, which may effectively inhibit the viral replication, improve the production of HBsAb and HBeAb, and increase HBeAg seroconversion rate. Keywords: Hepatitis B virus (HBV), Chronic hepatitis B (CHB), Hepatitis B vaccine, Chronic HBV carriers, rhGM-CSF Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Translational immunology and immune intervention Citation: Wu B and Yang J (2013). A clinical study on hepatitisi B vaccine triple-therapy in chronic hepatitis B virus infection. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00895 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 20 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Prof. Bang-FU Wu, Southern Medical University Renkang Hospital, Gastroenterology and Hepatology Center, Dongguan, Guangdong, 523952, China, bangfu.wu@163.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Bang-FU Wu Jiang-Ying Yang Google Bang-FU Wu Jiang-Ying Yang Google Scholar Bang-FU Wu Jiang-Ying Yang PubMed Bang-FU Wu Jiang-Ying Yang Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Efficacy and Safety of a Chinese Herbal Formula (Invigorating Kidney and Strengthening Spleen) in Chronic Hepatitis B Virus Carrier: Results from a Multicenter, Randomized, Double-Blind, and Placebo-Controlled Trial

A Chinese Herbal Formula (CHF) has acquired a certain therapeutic effect on chronic HBV infection. To assess the efficacy and safety of CHF on HBV replication in chronic HBV carriers, we performed a randomized, double-blind, and placebo-controlled trial involving patients from 16 centers. A total of 300 confirmed chronic HBV carriers were randomized at baseline in a ratio of 2 : 1 to receive either CHF or placebo for 52 weeks. The results showed that a greater proportion of CHF than placebo treated patients achieved virological response at week 52; the mean decline of serum HBsAg levels in the CHF group dropped more obviously than that in the control group at all stages of the treatment; however, the rates of HBeAg loss and seroconversion had no difference between the two groups. Meanwhile, were presented significant increases in IFN-γ; IL-2 levels and reductions in IL-4 and IL-10 levels in the treatment group compared to the control group at week 52. There were no drug-related serious adverse events. In conclusion, the treatment with 52-week CHF is safe and effective in inhibiting HBV replication in chronic HBV carriers. The ability of the compound to modulate host immune function probably contributed to this effect.

Hepatitis B: An Overlooked STI, a Silent Threat, a Global Disease

In the Western world, exposure to hepatitis B virus (HBV) occurs in adulthood via sexual or percutaneous transmission. One-third develop acute hepatitis, while half undergo a subclinical course. Both groups acquire antibodies. The remaining 5-10% of adults develop chronic HBV, the majority of whom are immunocompromised (HIV, chronic renal dialysis or immunosuppression). In endemic regions, primary infection occurs perinatally. Nearly 90% of neonates become chronic HBV carriers. While neonates are at high risk in endemic regions, sexual exposure remains the most common risk factor in the United States. Populations at risk are those with infected partners, multiple partners, or same-sex male partners. Untreated, 25-40% of chronically infected individuals develop cirrhosis and hepatocellular carcinoma (HCC). Following the discovery of HBV, Blumberg also developed an HBV vaccine using HBV-infected human plasma. Produced during the AIDS epidemic, while highly efficacious, recombinant vaccine replaced plasma because of concern the plasma could be coinfected. The 1980s yielded another triumph in the fight against HBV. Again, as HIV came to the forefront of public and political attention, research began in the field of anti-HIV drugs. The anti-HBV drugs used today, starting in 1998, were actually discovered to be efficacious in trials developed for HIV patients. HIV-patients coinfected with HBV showed regression of HBV while on HIV therapy. Currently, these therapies delay disease progression and reduce the incidence of HCC. Now armed with both preventative and therapeutic measures for HBV, coupled with increased awareness and education, the eradication of HBV as we move into the 21 st century seems within grasp.

Genetic variants in pseudogene E2F3P1 confer risk for HBV-related hepatocellular carcinoma in a Chinese population

Recent studies showed that pseudogenes can regulate the expression of their coding gene partners by competing for miRNAs. The E2F family plays a crucial role in the control of cell cycle checkpoint. E2F3P1 is a pseudogene of E2F3. Few studies focused on genetic variations on pseudogenes. In this study, we performed a case-control study to assess the association between single nucleotide polymorphisms (SNPs) in E2F3P1 and hepatocellular carcinoma (HCC) risk in 1050 hepatitis B virus (HBV)-positive HCC cases and 1050 chronic HBV carriers. Logistic regression analysis was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between genotypes and HCC risk. We found that the variant CT/TT genotypes of rs1838149 were associated with a significantly decreased risk of HCC (adjusted OR = 0.66, 95% CIs = 0.51-0.86, P = 0.002) compared to those with wildtype CC homozygote. Furthermore, the AA genotype of rs9909601 had an increased HCC risk with an adjusted OR of 1.41 (95% CIs = 1.07-1.86), and the A allele of rs9909601 was significantly associated with HCC risk compared to those with the G allele (adjusted OR = 1.17, 95% CIs = 1.03-1.33, P = 0.017). These results indicate that genetic variations in the pseudogene E2F3P1 may confer HCC risk.

Polymorphic APOBEC3 modulates chronic hepatitis B in Moroccan population

The cytidine deaminase apolipoprotein B mRNA editing catalytic subunit-3 (APOBEC3) induces G-to-A hypermutation in hepatitis B virus (HBV) genomes and operates as part of the innate antiviral immune system. We investigated the associations between the presence of APOBEC3 variants and HBV carriage in a case-control study in the Moroccan population. A polymorphic deletion affecting the APOBEC3B gene and the H186R variant of APOBEC3G were genotyped in 179 HBV chronic carriers and 216 healthy control subjects. In addition, to assess the overall impact of APOBEC3 deaminases on circulating HBV, we looked for hyperedited forms of the viral genome using the 3DPCR technique and analysed editing context. Data analysis showed that there was no significant difference in the frequencies of deleted APOBEC3B alleles (P = 0.261) or genotypes (P = 0.333) between patients with chronic hepatitis B and control subjects. By contrast, subjects bearing deleted genotype had a faster progression of liver disease than those with the insertion genotype (adjusted OR, 3.72; 95% CI, 0.38-36.12). The analysis of the APOBEC3G H186R polymorphism revealed that R/R genotype frequencies were not significantly different in HBV infected patients and in healthy subjects. 3DPCR was positive in 26 samples (14%) among 179. Amplified viral segments displayed monomorphic G>A transitions highly reminiscent of APOBEC3G activity. Most intriguingly, hemi/homozygous carriers of the APOBEC3B deletion had significantly lower virus loads than patients with the wild type (median 539 vs. 2213 IU/mL, P = 0.0023). This result suggests that genetic variations in APOBEC3 cytidine deaminases do not predispose to chronicity but may modulate the course of persistent HBV infection.

Role of T follicular helper cells and their associated molecules in the pathogenesis of chronic hepatitis B virus infection

In this study, we investigated the roles of T follicular helper (TFH) cells and related molecules in the pathogenesis of chronic hepatitis B virus (HBV) infection. The levels of circulating TFH cells and their surface CD40 ligand (CD40L), as well as CD19+ B cells and their surface CD40 expression were detected by flow cytometry. Peripheral blood plasma interleukin (IL)-21 levels were detected by enzyme-linked immunosorbent assay (ELISA). Compared with hepatitis B surface antibody (HBsAb)− and HBsAb+ healthy controls, the percentage of TFH cells and their surface CD40L expression significantly increased in patients with chronic HBV infection, particularly those with chronic hepatitis B (P<0.05). The percentage of CD19+ B cells significantly increased in chronic hepatitis B patients and CD40 expression levels on the CD19+ B cell surface in chronic HBV infection decreased compared with those in the healthy controls (P<0.05). Compared with the healthy controls, the plasma IL-21 level in chronic hepatitis B patients was significantly increased in chronic HBV carriers and decreased in inactive hepatitis B surface antigen (HBsAg) carriers (P<0.05). The TFH cell percentage, B cell percentage and IL-21 expression did not significantly differ between the hepatitis B e-antigen (HBeAg)− and HBeAg+ chronic hepatitis B groups (P>0.05). The abnormal expression of TFH cells and IL-21 is related to the dysfunction of immune response during chronic HBV infection. The interaction of CD19+ B cells with TFH cells via their CD40 and CD40L molecules may also play an important role in this process.