Acute Hepatitis B Virus Infection Research Articles

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

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

Hepatitis B virus nucleic acid amplification testing of Australian blood donors highlights the complexity of confirming occult hepatitis B virus infection

We present an analysis of the first 2 years of hepatitis B virus (HBV) nucleic acid testing (NAT) of the Australian donor population. Between July 5, 2010, and July 4, 2012, all blood donations were screened for HBV DNA and hepatitis B surface antigen (HBsAg). Donors who tested HBsAg negative but HBV NAT positive were assessed as occult hepatitis B infections (OBI) if reactive for antibodies to HBV core antigen (anti-HBc). Donors who were anti-HBc reactive but with nonrepeatable or nondiscriminated NAT results were assessed as HBV inconclusive pending follow-up testing. During the study period a total of 2,673,521 donations were screened for HBV. Forty-two chronic OBI infections (5.55/100,000 donors) were identified compared to eight acute serologic window period infections (1.06/100,000 donors). Of the 42 OBI cases, 23 (54.8%) were detected the first time they were screened for HBV DNA while 19 (45.2%) gave one or more HBV NAT-nonreactive results before detection. Of 68 donors initially assessed as HBV inconclusive and available for follow-up, 10 later confirmed as OBI cases while 51 were NAT nonreactive but remained anti-HBc reactive and OBI could not be excluded. This study demonstrated a substantially higher prevalence of OBI compared to acute serologic window period HBV infections in Australian blood donors. Follow-up testing of OBI cases indicates that HBV DNA is often only intermittently detectable in OBI, highlighting the importance of including anti-HBc to optimize the HBV testing algorithm.

Seroprevalence of hepatitis B virus infection among antenatal clinic attendees at a tertiary hospital in Dar es Salaam, Tanzania.

Hepatitis B virus (HBV) infection is a serious public health problem in sub-Saharan Africa. The risk of vertical transmission increases if the mother is hepatitis B surface antigen (HBsAg) positive and more so when she is also hepatitis B envelope antigen (HBeAg) positive. Since 2000, the World Health Organization recommends screening of pregnant women for HBV infection. However, this is not currently practiced in Tanzania. The objective of this study was to determine seroprevalence and associated factors of HBV infection among pregnant women attending antenatal clinic at the Muhimbili National Hospital, in Dar es Salaam, Tanzania. This cross-sectional study was conducted from August-September 2010. Data on socio-demographic characteristics, obstetric and risk factors such as history of blood transfusion, and risky sexual practices was collected. Blood samples were tested for HBsAg, HBeAg, antibodies to HBsAg (Anti-HBs), IgM antibodies to hepatitis B core antigen (Anti-HBc) and anti-HIV antibodies. A total of 310 pregnant women (28.5 ± 5.4 years) were enrolled in the study. Thirty-one percent (96) of the women were primigravidae. Most of studied women were of low educational status and married. The seroprevalence of HBsAg was 3.9% (12/310) and none had detectable anti-HBs. None had IgM HBcAb, thus excluding acute HBV infection. All women tested negative for HBeAg. The overall seroprevalence of HIV infection was 9.7%. Three of 12 (25%) women had HBV-HIV co-infection. None of the assessed associated factors were significantly related to HBV infection. In conclusion, the seroprevalence of HBsAg among women attending antenatal care at Muhimbili National Hospital is moderate. It is recommended to introduce routine antenatal screening for HBV and "at birth dose" vaccination to new born babies of mothers found to be HBsAg positive.

Management of hepatitis B virus-related acute liver failure.

Hepatitis B virus (HBV) is the most important cause of acute liver failure (ALF) in Eastern countries. HBV-related ALF may occur after acute HBV infection (A-ALF) or during acute exacerbation (flare) of chronic HBV infection (C-ALF). C-ALF may occur spontaneously or as a result of the effect of immunosuppression due to chemotherapeutic or immunosuppressive agents. The definition of HBV-related ALF is uncertain, because different diagnostic criteria are used in C-ALF, which may present as acute-on-chronic liver failure. Although the pathogenesis differs in the two subgroups of ALF, the symptoms and biochemical parameters can be similar. High titers of immunoglobulin M hepatitis B core antibody and lower viral loads are frequent in A-ALF as compared with C-ALF. The prognosis of C-ALF is significantly poor as compared with that of A-ALF. In C-ALF, most immunosuppression-mediated reactivation of hepatitis B results in fatality. Many case series or case-control studies have not demonstrated the survival benefit of nucleos(t)ide treatment. This treatment failure is probably related to delayed initiation of nucleos(t)ide treatment and viral suppression. Treatment with nucleos(t)ide analogs should be started immediately and should be continued regardless of subgroups of HBV-related ALF. Liver transplantation is the only treatment option that improves the prognosis of HBV-related ALF. Patients under consideration for transplantation should be given nucleos(t)ide analogs as prophylaxis to reduce the likelihood of post-transplant HBV recurrence.

Clinical features of adult patients with acute hepatitis B virus infection progressing to chronic infection.

Background. Information regarding the progression of acute hepatitis B virus (HBV) infection to chronic infection in adults is scarce. Methods. Twenty-five adult patients with acute HBV infection (14 men and 11 women, 18–84 years old), whose clinical features progressed to those of chronic infection (group A) or did not (group B), were studied retrospectively. Results. There were 3 and 22 patients in groups A and B, respectively. Two of the 3 patients of group A lacked the typical symptoms of acute hepatitis. No differences were found between groups with respect to age, sex, or HBV genotypes. However, total bilirubin and alanine aminotransaminase levels were significantly lower in group A. Conclusions. Three of the 25 adult patients with acute HBV infection progressed to chronic infection. Hepatitis was mild in these patients. Patients with mild acute hepatitis B or unapparent HBV infection may have a higher risk of progressing to chronic infection.

Current Information Concerning Association of IL-12 and Hepatitis B Infection

Hepatitis B is one of the most prevalent infectious diseases and is induced by hepatitis B virus (HBV). The chronic, asymptomatic, and occult forms of hepatitis B are long-term infections that can lead to various hepatic cancers and cirrhosis in the carrier. IL-12 is one of the main cytokines involved in inducing appropriate immune responses against viral infections, especially HBV. Therefore, the aim of the present review was to address the most recent information within the database regarding the status and association between IL-12 and hepatitis B infection and its complications including cirrhosis and hepatocellular carcinoma. The data presented was collected by searching the following keywords in the Pubmed and Scopous databases: Hepatitis B, occult HBV infection, chronic HBV infection, asymptomathic HBV infection, acute HBV infection, fulminant HBV infection, IL-12, and all the papers regarding the relation between IL-12 and hepatitis B were used. These data were presented in the current review article. Results showed that IL-12 plays important roles in Hepatitis B infection and patients infected with the long-term form of hepatitis B are unable to produce sufficient amount of this cytokine. Our research provided mechanistic insights into the immunoprotective roles of IL-12 and proposed that it can be considered as an important molecule for immunotherapy of HBV infected infection.

Clinical impact of occult hepatitis B virus infection in immunosuppressed patients.

Occult hepatitis B infection (OBI), is characterized by low level hepatitis B virus (HBV) DNA in circulating blood and/or liver tissue. In clinical practice the presence of antibody to hepatitis B core antigen in hepatitis B surface antigen (HBsAg)-/anti-HBs-negative subjects is considered indicative of OBI. OBI is mostly observed in the window period of acute HBV infection in blood donors and in recipients of blood and blood products, in hepatitis C virus chronic carriers, in patients under pharmacological immunosuppression, and in those with immunodepression due to HIV infection or cancer. Reactivation of OBI mostly occurs in anti-HIV-positive subjects, in patients treated with immunosuppressive therapy in onco-hematological settings, in patients who undergo hematopoietic stem cell transplantation, in those treated with anti-CD20 or anti-CD52 monoclonal antibody, or anti-tumor necrosis factors antibody for rheumatological diseases, or chemotherapy for solid tumors. Under these conditions the mortality rate for hepatic failure or progression of the underlying disease due to discontinuation of specific treatment can reach 20%. For patients with OBI, prophylaxis with nucleot(s)ide analogues should be based on the HBV serological markers, the underlying diseases and the type of immunosuppressive treatment. Lamivudine prophylaxis is indicated in hemopoietic stem cell transplantation and in onco-hematological diseases when high dose corticosteroids and rituximab are used; monitoring may be indicated when rituximab-sparing schedules are used, but early treatment should be applied as soon as HBsAg becomes detectable. This review article presents an up-to-date evaluation of the current knowledge on OBI.

Hepatitis B in men who have sex with men and HIV-infected individuals: missed opportunities and future challenges

Hepatitis B transmission in priority populations continues to occur in Australia despite the availability of a safe, effective vaccine for over 30 years. In this edition of Sexual Health, Body et al. report an incidence of 1.8 hepatitis B virus (HBV) infections per 1000 person years in the Victorian HIV database (VHIVSD), a cohort of HIV-infected individuals receiving care at a tertiary referral hospital in Melbourne. A similar incidence of infection (1.98 per 1000 person-years) was found by Gamagedara et al. among men who have sex with men (MSM) attending a community sexual health centre, also in Melbourne. This incidence of infection is more than 10 times the estimated incidence in the general population and is evidence of ongoing transmission in these priority populations despite being part of clinical cohorts and therefore occurring in people linked to care. Both of these recent studies highlighted missed opportunities for screening, vaccination and follow-up testing to ensure the protection of individuals at particular risk of HBV infection. This new evidence reinforces the need for a greater focus on comprehensive testing and vaccination of priority populations, including HIV-infected individuals and MSM – particularly given recent reports of increasing sexual risk practices in MSM and corresponding increases in sexually transmissible infections, including HIV. With an estimated 218,00 people (1.0% of the population) living with chronic hepatitis B (CHB) in 2011, Australia is generally a low-prevalence country, with the main burden of disease experienced by those born overseas in endemic areas, and by Aboriginal and Torres Strait Islander people. MSM are estimated to account for ~4.4% (around 9700 individuals) of those living with CHB and are identified as a priority population for prevention of infection in the First National Hepatitis B Strategy 2010–2013. The higher incidence of acute HBV infection and prevalence of CHB in HIV-infected individuals and MSM is multifactorial. The increased incidence of infection relates to shared modes of transmission, including sexual, injecting drug use or both. Globally, areas with a high or increasing population prevalence of HIV are often also endemic for CHB, making coinfection with HBV more common in HIV-infected individuals born in these countries who now reside in Australia. HIV infection is associated with both an increased risk of developing CHB if exposed to HBV and an increased risk of complications, including cirrhosis and liver cancer. In the retrospective cohort reported by Body and colleagues, 23% of patients with incident HBVinfection went onto to develop CHB – far greater than the expected 5% progression observed in immunocompetent adults. Both studies highlight the need for further improvements in access to HBV testing. In the study reported by Gamagedara et al., ascertainment of immunity status was high but markers of infection were less commonly tested: hepatitis B surface antibody (anti-HBs) was tested in 96% of patients, compared with testing for core antibody (anti-HBc) in 79% and surface antigen (HBsAg) in 26% of patients. As the authors comment, incomplete testing raises the possibility of missed incident and chronic infections. Similarly, Body et al. report that HBsAg and anti-HBc testing were not performed in 32% of HIV-positive individuals. The National Hepatitis B Testing Policy released in 2012 recommends testing for all three markers of HBV infection in those at higher risk of CHB, including MSM and HIVinfected individuals. The use of alternative screening algorithms can lead to missing chronic infections, and creates the need for unnecessary vaccination, recall and repeat testing of individual patients. The panel of three tests (HBsAg, anti-HBs and anti-HBc) is Medicare rebatable and is advised for any person at risk of having CHB. For individuals in the VHIVSD in whom HBV infection was documented, the median estimated time between HIV diagnosis and HBV infection was 4.6 years (range: 4 months to 17 years). These results indicate missed opportunities for prevention through vaccination, and suggest infrequent routine testing to determine anti-HBs status and promote vaccination. Together, they suggest that the prevention of HBV infection in HIVinfected individuals needs greater attention. Vaccination is recommended for susceptible MSM and HIVinfected individuals. However, eligibility for a funded CSIRO PUBLISHING

Cytokine and Chemokine Responses in the Acute Phase of Hepatitis B Virus Replication in Naive and Previously Vaccinated Blood and Plasma Donors

Blood and plasma donor screening for hepatitis B virus (HBV) DNA, HBV surface antigen (HBsAg), and antibodies to surface (anti-HBs) and core (anti-HBc) antigens allows identification of individuals who acquired HBV despite previous HBV vaccination. Of 14 HBV acute infection donor panels (HBV-DNA-positive/anti-HBc-negative), 6 donors were previously vaccinated (anti-HBs+). We investigated the differences in viral kinetics and immune responses in vaccinated and nonvaccinated individuals. Serial specimens were characterized for HBV DNA and serological markers and 39 cytokines. The rate of viral load increase was blunted, and virus was cleared more rapidly in vaccinated individuals (P = .004). In unvaccinated individuals, induced protein 10 (IP-10), interleukin 10 (IL-10), macrophage inflammatory protein 1β (MIP-1β), and soluble interleukin 2Rα (sIL-2Rα) levels were commonly elevated at the time of peak viremia. In contrast, vaccinated individuals had earlier peaks in IL-10 and IP-10 responses that occurred at much lower viral loads and coincided with anamnestic anti-hepatitis B surface (HBs) responses and clearance of viremia. There is earlier engagement of innate and adaptive immunity in infected subjects with previous vaccination, possibly explaining suppressed viremia in vaccine breakthrough infections. Although breakthrough infections occur in partially protected vaccine recipients, vaccination likely contributes to early control of replication, limiting immune activation and preventing development of clinically significant acute and chronic HBV infection.

Hepatitis B screening and vaccination strategies for newly arrived adult Canadian immigrants and refugees: a cost-effectiveness analysis.

BackgroundImmigrants have increased mortality from hepatocellular carcinoma as compared to the host populations, primarily due to undetected chronic hepatitis B virus (HBV) infection. Despite this, there are no systematic programs in most immigrant-receiving countries to screen for chronic HBV infection and immigrants are not routinely offered HBV vaccination outside of the universal childhood vaccination program.Methods and findingsA cost-effective analysis was performed to compare four HBV screening and vaccination strategies with no intervention in a hypothetical cohort of newly-arriving adult Canadian immigrants. The strategies considered were a) universal vaccination, b) screening for prior immunity and vaccination, c) chronic HBV screening and treatment, and d) combined screening for chronic HBV and prior immunity, treatment and vaccination. The analysis was performed from a societal perspective, using a Markov model. Seroprevalence estimates, annual transition probabilities, health-care costs (in Canadian dollars), and utilities were obtained from the published literature. Acute HBV infection, mortality from chronic HBV, quality-adjusted life years (QALYs), and costs were modeled over the lifetime of the cohort of immigrants. Costs and QALYs were discounted at a rate of 3% per year. Screening for chronic HBV infection, and offering treatment if indicated, was found to be the most cost-effective intervention and was estimated to cost $40,880 per additional QALY gained, relative to no intervention. This strategy was most cost-effective for immigrants < 55 years of age and would cost < $50,000 per additional QALY gained for immigrants from areas where HBV seroprevalence is ≥ 3%. Strategies that included HBV vaccination were either prohibitively expensive or dominated by the chronic HBV screening strategy.ConclusionsScreening for chronic HBV infection from regions where most Canadian immigrants originate, except for Latin America and the Middle East, was found to be reasonably cost-effective and has the potential to reduce HBV-associated morbidity and mortality.

Hepatitis B virus transmissions associated with a portable dental clinic, West Virginia, 2009

Although hepatitis B virus (HBV) transmission in dental settings is rare, in 2009 a cluster of acute HBV infections was reported among attendees of a two-day portable dental clinic in West Virginia. The authors conducted a retrospective investigation by using treatment records and volunteer logs, interviews of patients and volunteers with acute HBV infection as well as of other clinic volunteers, and molecular sequencing of the virus from those acutely infected. The clinic was held under the auspices of a charitable organization in a gymnasium staffed by 750 volunteers, including dental care providers who treated 1,137 adults. Five acute HBV infections-involving three patients and two volunteers-were identified by the local and state health departments. Of four viral isolates available for testing, all were genotype D. Three case patients underwent extractions; one received restorations and one a dental prophylaxis. None shared a treatment provider with any of the others. One case volunteer worked in maintenance; the other directed patients from triage to the treatment waiting area. Case patients reported no behavioral risk factors for HBV infection. The investigation revealed numerous infection control breaches. Transmission of HBV to three patients and two volunteers is likely to have occurred at a portable dental clinic. Specific breaches in infection control could not be linked to these HBV transmissions. All dental settings should adhere to recommended infection control practices, including oversight; training in prevention of bloodborne pathogens transmission; receipt of HBV vaccination for staff who may come into contact with blood or body fluids; use of appropriate personal protective equipment, sterilization and disinfection procedures; and use of measures, such as high-volume suction, to minimize the spread of blood.

Acute Hepatitis B in an Urban Tertiary Care Hospital in the United States

The incidence of acute hepatitis B virus (HBV) infection in the United States is declining, and precise epidemiology for newly acquired infection remains obscure. We sought to clarify the clinical presentation and management of acute symptomatic HBV infection at a hepatology referral center. We prospectively evaluated the demographic, epidemiological, clinical, and treatment data of 32 patients with acute symptomatic HBV who were referred to a single urban tertiary care hospital in the United States. Slightly more than half of the patients were male (53%) or belonged to the black race (53%) and slightly fewer than half of the patients (47%) were unemployed. The median patient age was 41.9 years, and 20 (63%) patients were unmarried. The most common HBV risk factor was a new sexual partner over the previous months (34%). Fifteen percent of the patients reported no known risk factors. Four (13%) patients were diabetic. Presenting symptoms included jaundice (75%), abdominal pain (63%), and marked fatigue (59%). The mean peak for aspartate aminotransferase/alanine aminotransferase was 1822/2109 IU/L, for total bilirubin was 12.6 mg/dL, and for International Normalized Ratio was 1.53. Eight patients (25%) were started on oral nucleot(s)ide therapy. One diabetic patient underwent liver transplantation. In a sample of patients from a US urban tertiary hepatology center, common epidemiological features of acute symptomatic hepatitis B were being middle aged and unmarried and having acquired the infection through a new sexual contact. Antiviral therapy was sometimes but not commonly started. These data reinforce the need for HBV vaccination of individuals at risk, including those not traditionally targeted.

Selective Hepatitis B Virus Vaccination Has Reduced Hepatitis B Virus Transmission in The Netherlands

Background & AimsIn the Netherlands, a selective hepatitis B virus (HBV) vaccination programme started in 2002 for men having sex with men, drug users, commercial sex workers and heterosexuals with frequent partner changes. We assessed the programme's effectiveness to guide policy on HBV prevention.MethodsWe analysed reports of acute HBV infection in the Netherlands between 2004 and 2010 requesting serum from patients for HBV-genome S- and C-region sequencing. We used coalescence analyses to assess genetic diversity of nonimported genotype-A cases over time.Results1687 patients with acute HBV infection were reported between 2004 and 2010. The incidence of reported acute HBV infection decreased from 1.8 to 1.2 per 100,000 inhabitants, mostly due to a reduction in the number of cases in men who have sex with men. Men were overrepresented among cases with an unknown route of transmission, especially among genotype A2 cases mainly associated with transmission through male homosexual contact. The genetic diversity of nonimported genotype-A strains obtained from men who have sex with men decreased from 2006 onwards, suggesting HBV incidence in this group decreased.ConclusionsThe selective HBV-vaccination programme for behavioural high-risk groups very likely reduced the incidence of HBV infection in the Netherlands mainly by preventing HBV infections in men who have sex with men. A considerable proportion of cases in men who did not report risk behaviour was probably acquired through homosexual contact. Our findings support continuation of the programme, and adopting similar approaches in other countries where HBV transmission is focused in high-risk adults.

Acute hepatitis B outbreaks in 2 skilled nursing facilities and possible sources of transmission: North Carolina, 2009-2010.

Acute hepatitis B virus (HBV) infections have been reported in long-term care facilities (LTCFs), primarily associated with infection control breaks during assisted blood glucose monitoring. We investigated HBV outbreaks that occurred in separate skilled nursing facilities (SNFs) to determine factors associated with transmission. Outbreak investigation with case-control studies. Two SNFs (facilities A and B) in Durham, North Carolina, during 2009-2010. Residents with acute HBV infection and controls randomly selected from HBV-susceptible residents during the outbreak period. After initial cases were identified, screening was offered to all residents, with repeat testing 3 months later for HBV-susceptible residents. Molecular testing was performed to assess viral relatedness. Infection control practices were observed. Case-control studies were conducted to evaluate associations between exposures and acute HBV infection in each facility. Six acute HBV cases were identified in each SNF. Viral phylogenetic analysis revealed a high degree of HBV relatedness within, but not between, facilities. No evaluated exposures were significantly associated with acute HBV infection in facility A; those associated with infection in facility B (all odds ratios >20) included injections, hospital or emergency room visits, and daily blood glucose monitoring. Observations revealed absence of trained infection control staff at facility A and suboptimal hand hygiene practices during blood glucose monitoring and insulin injections at facility B. These outbreaks underscore the vulnerability of LTCF residents to acute HBV infection, the importance of surveillance and prompt investigation of incident cases, and the need for improved infection control education to prevent transmission.

High Levels of Hepatitis B Virus After the Onset of Disease Lead to Chronic Infection in Patients With Acute Hepatitis B

Some patients with acute hepatitis B virus (HBV) infection develop chronic infection. However, the method for identifying these patients has not been established. We followed 215 Japanese patients with acute HBV infection until the clearance of hepatitis B surface antigen (HBsAg) or the development of chronic infection. Levels of HBsAg and HBV DNA were serially monitored from the onset. Of the 215 patients, 113 (52.5%) possessed HBV genotype A, 26 (12.0%) genotype B, and 73 (34.0%) genotype C. Twenty-one of the 215 (9.8%) developed chronic infection, with the persistence of HBsAg for >6 months. The rate of chronicity of genotype A, B, and C was 12.4%, 3.8%, and 8.2%. Of the 21 patients, only 6 (2.8%) patients, including 5 with genotype A, failed to clear HBsAg within 12 months. Levels of HBsAg at 12 weeks and HBV DNA at 4 weeks were useful for distinguishing the patients who became chronic from those who did not (P < .001 and P < .001, respectively). Likewise, the levels of HBsAg at 12 weeks and HBV DNA at 8 weeks were useful for discriminating between the patients who lost HBsAg within 12 months and those who did not (P < .01 and P < .05, respectively). In acute HBV infection, clearance of HBV may happen between 6 and 12 months from the onset. Only those who fail to clear HBV within 12 months from the onset may develop chronic infection.

969 COST-EFFECTIVE STRATEGY FOR THE DIAGNOSIS OF HEPATITIS C INFECTION WITH VIREMIA: UTILITY OF THE HIGH ANTIBODY LEVEL IN LOW PREVALENCE POPULATION

Background: In the French adult population, an estimated proportion of 0.65% of HBs Antigen (HBsAg) carriers, of whom 55% ignore their status, constitutes Hepatitis B virus (HBV) reservoir. In addition, anti-HBV vaccination coverage is low (<60% in children aged of two years in 2009) although vaccination has been recommended for toddlers and pre-teenagers since 1995. Vaccination is also targeted to populations at-risk of HBV infection. To assess the impact of vaccination strategy, we estimated the incidence and described the modes of transmission of acute HBV infection. Methods: Acute HBV infection was defined as the first detection of 1) anti-HBc IgM or 2) HBsAg and total anti-HBc with elevated ALT. Chronic HBV infections were excluded. The modes of transmission were analysed based on mandatory notifications of HBV acute infection during 2003–2011. As the annual number of reported cases was underestimated, we conducted a national survey among a random sample of 1,412 laboratories to estimate the 2010’ incidence of acute infection. Multiple imputation was applied to estimate missing data. Results: Overall, the estimated incidence of acute infection in 2010 was 2.5 per 100,000 (=1,622 cases), higher in men than in women (3.0 versus 2.1/100,000). It ranged from 1.1/100,000 in the 0–19 to 3.6/100,000 in the 20–39 years age groups. Estimates of total acute infections (symptomatic and asymptomatic) and chronic infections will be presented. Among the 1,218 notified cases in 2003–2011, 71% were men, older than women (median age: 40 vs. 34 years). At least one HBV at-risk exposure (in the six months preceding the diagnosis) was reported in 63% of cases (multiple sexual partners: 35%, travel to high endemic countries: 31%; men who have sex with men: 21%, HBsAg carrier sexual partner: 13%; family exposure: 12%; intravenous drug use: 4%...). Among them, at least 53% should have been vaccinated. A fulminant hepatitis was reported in 45 patients (4%), leading to liver transplantation (n =18) and death (=14). Among these 45 cases, at least 56% corresponded to a vaccine indication. Conclusions: In France, incidence of acute HBV infection is low. However, it should be definitively even lower if vaccine recommendations were better applied.

Hepatitis B virus part 1: risk factors, blood results and nursing care

Chronic hepatitis B virus (HBV) is the most prevalent of the world's blood-borne viral infections. It may lead to liver cirrhosis, end-stage liver disease or hepatocellular carcinoma. HBV is spread via percutaneous and permucosal exposure to infected body fuids. The small numbers of people in the UK who contract acute HBV infection are usually infected in adulthood via unprotected sex or injected drug use using contaminated equipment. Kate Jack, Joanne Cooper and Stephen Ryder discuss HBV infection in terms of defnitions, risk factors, blood testing and immune system responses to infection and vaccination.

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.

Vector-mediated expression of interferon gamma inhibits replication of hepatitis B virus in vitro

Despite the existence of efficient vaccines against hepatitis B virus (HBV) infections, these still represent a serious threat to human health worldwide. Acute HBV infections often become chronic, marked by liver cirrhosis and hepatocellular carcinoma. Promising results with interferons alpha or gamma (IFN-α, γ) or nucleoside/nucleotide analogs in inhibiting HBV replication in vitro have led to therapeutic applications to chronic HBV patients, however, their results so far have not been satisfactory. The treatments were either not effective in all patients or had adverse effects. Certain progress was expected from expression of interferons targeted to liver by adenovirus vectors, however, this approach turned out to be limited by undesired expression of toxic viral genes and high production costs. Therefore, in this study, we attempted to inhibit HBV replication in HepG2.2.15 cells by human IFN-γ expressed through a non-viral vector, an eukaryotic plasmid. The results demonstrated that IFN-γ, targeted to HBV-replicating cells, significantly inhibited the virus growth without inducing apoptosis and indicated that local expression of this kind of cytokine may be a promising strategy of gene therapy.

Hepatitis B reactivation after therapy for non-Hodgkin lymphoma: A case report with review of literature

The natural course of hepatitis B virus (HBV) infection depends on the immune status of the host. In cancer patients, as the consequence of immune suppression due to chemotherapy and malignant disease itself, the balance between replicative potential of the virus and immune response of the host is disrupted leading to acute HBV infection or reactivation. We present a case of HBsAg positive, diffuse large B cell gastric lymphoma patient CD20+ staged IB, treated with six cycles of R-CHOP protocol and two cycles with rituximab monotherapy. Five months after the successful anticancer treatment, patient developed reactivation of chronic HBV infection (ten-fold increase in liver enzymes, HBsAg+, IgM antiHBc+, HBeAg(-), and HBV DNA 5?106 copies/ml). Antiviral therapy with lamivudine was started. Four weeks after the antiviral therapy initiation liver enzymes were in normal ranges. One year after the start of antiviral treatment HBV DNA PCR test did not detect any viral particles. The patient is in complete remission of malignant disease, and still receiving therapy with lamivudine. HBV screening in cancer patients is necessary in order to provide a prompt antiviral therapy and to prevent postponement or even cessation of planned anticancer treatment. HBsAg positive patients should start prophylactic antiviral treatment before the start of immunosuppressive treatment. Chemotherapy protocols consisting rituximab and corticosteroids significantly increase the risk of reactivation. If reactivation is diagnosed in course of chemotherapy, the therapy should be stopped and antiviral treatment should be applied as soon as possible. Treatment with lamivudine is continued at least 6 months after the chemotherapy end.