Presence Of HBeAg Research Articles

Presence of entry receptors and viral markers suggest a low level of placental replication of hepatitis B virus in a proportion of pregnant women infected with chronic hepatitis B

The transplacental route of vertical transmission of Hepatitis B Virus (HBV) has been known for over a decade. Here we present evidence which suggest HBV can replicate in placenta. Forty-one HBsAg positive and 10 control pregnant women were enrolled in the study after obtaining informed consent. HBV positives were further divided in the High Viral Load (HVL) Group and Low Viral Load (LVL) Group according to INASL guidelines 2018. The Presence of the HBV DNA and expression of NTCP in the placenta was analyzed by qPCR/RT-qPCR and/or immunohistochemistry (IHC). The presence of cccDNA was assessed using Digital Droplet PCR while the presence of pre-genomic (pg) RNA was assessed through qRT-PCR and sequencing. The presence of HBeAg and HBcAg in the placenta was assessed by IHC. Immunostaining of NTCP, HBeAg and HBcAg on trophoblasts along with the presence of total HBV DNA, cccDNA and pgRNA indicated, that these cells are not only susceptible to HBV infection but may also support viral replication. This is further supported by the finding that trophoblasts of the several HBeAg seronegative samples harbored the HBeAg. Although, we did not find any correlation in NTCP expression and viral markers with viral load indicates placental replication may not aping hepatocytes. The presence of the HBV receptor, NTCP along with the presence of cccDNA, pgRNA, and HBeAg in placenta of HBV infected females without circulating HBeAg suggest that placenta act as a replication host.

THU409 - Presence of HbeAg, HBV DNA in cord blood and down regulation of TLR9 may act as predictive marker for HBV mother to child transmission

THU409 - Presence of HbeAg, HBV DNA in cord blood and down regulation of TLR9 may act as predictive marker for HBV mother to child transmission

Hepatitis B elimination in children of Slovenian origin born in Slovenia after the introduction of preventive strategies: The results of a national study

IntroductionIn Slovenia national strategies to prevent hepatitis B virus (HBV) infection in children were introduced in the mid-nineties. The aim of the present study was to analyze the epidemiological characteristics of chronic hepatitis B infection in children in Slovenia after the introduction of mandatory HBV vaccination of children and mandatory screening of pregnant women for HBV surface antigen (HBsAg) with consecutive active and passive immunization of newborns of HBsAg-positive mothers.MethodsChildren from all regions of Slovenia whose blood samples tested positive for HBsAg at the national reference laboratory for viral hepatitis between January 1997 and December 2010 were included. Demographic, epidemiological and virological data were reviewed retrospectively. Statistical evaluation of the patients’ characteristics was performed and possible trends during the observation period determined.ResultsAmong 52 HBsAg-positive children, there were 22 (42.3%) girls and 30 (57.7%) boys. Among 40 children tested for HBeAg, 17 were positive (42.5%). The most frequent risk factor for acquiring HBV infection was “presence of HBV infection within the family” (24/35; 68.8%). A significant association between the presence of HBeAg and a viral load of >20,000 IU/ml was found (p=0.001). The difference in the proportion of children of Slovenian origin born before 1994 and after was statistically significant (p=0.039). A statistically significant negative linear trend of the number of diagnosed children in the observed period was found (p=0.006).ConclusionsPrevention strategies adopted in the mid-nineties have resulted in the elimination of chronic hepatitis B in children of Slovenian origin born in Slovenia.

Viral Hepatitis in pregnancy

The global prevalence of viral hepatitis is very high and seems to be rising over the years. The infection can profoundly affect pregnant women causing significant maternal and perinatal morbidity and mortality with some strains much worse than others.Hepatitis A (HAV) and E (HEV) which are transmitted mainly through the faecal-oral route present as acute hepatitis during pregnancy and are responsible for most local epidemic outbreaks. HAV infection remains self-limiting during pregnancy, while HEV has a higher prevalence and causes significant morbidity. It is also associated with a very high maternal mortality rate (20 %) and requires special attention in endemic areas. HEV vaccines do exist, but the WHO has yet to approve them for general use. Hepatitis B is the most prevalent form and is part of the ante-natal screening program. The presence of HBeAg is associated with high viral loads and infectivity. Antiviral therapy, preferably tenofovir (TDF), is recommended for mothers with viral load ≥ 200,000 IU/mL2), with the neonates receiving both active and passive immunisations. Hepatitis C and D are usually found as chronic infections in the pregnant and non-pregnant populations. Screening for hepatitis C during pregnancy and its subsequent management is still unsettled, but the introduction of direct-acting antiviral (DAA) drugs will change the picture if their safety is established in pregnancy. HDV is an incomplete virus linked to HBV and cannot establish an infection on its own. Controlling HBV is paramount to controlling HDV. HEV is quite prevalent and looked upon as hepatotropic. It seems to be quite prevalent in some blood donor populations and has a high co-infection rate with HCV. It has a high Mother-to-Child-Transmission (MTCT) but causes little or no illness in infected infants, and antenatal screening is not justified.This review summarises the prevalence, clinical picture, maternal, perinatal effects, and the management and prevention of hepatitis A, B, C, D, E and G viral infections during pregnancy.

Estimating the proportion of people with chronic hepatitis B virus infection eligible for hepatitis B antiviral treatment worldwide: a systematic review and meta-analysis

SummaryBackgroundIn 2016, of the estimated 257 million people living with chronic hepatitis B virus (HBV) infection worldwide, only a small proportion was diagnosed and treated. The insufficiency of information on the proportion of people infected with HBV who are eligible for treatment limits the interpretation of global treatment coverage. We aimed to estimate the proportion of people with chronic HBV infection who were eligible for antiviral treatment worldwide, based on the WHO 2015 guidelines.MethodsIn this systematic review and meta-analysis, we searched Medline, EMBASE, and the Cochrane databases from Jan 1, 2007, to Jan 31, 2018, for studies describing HBsAg-positive people in the population or health-care facilities. We extracted information from published studies using a standardised form to estimate the frequency of cirrhosis, abnormal alanine aminotransferase (ALT), HBV DNA exceeding 2000 IU/mL or 20 000 IU/mL, presence of HBeAg, and eligibility for treatment as per WHO and other guidelines as reported in the studies. We pooled proportions through meta-analysis with random effects. The study was registered with PROSPERO, CRD42020132345.FindingsOf the 13 497 studies, 162 were eligible and included in our analysis. These studies included 145 789 participants. The pooled estimate of the proportion of cirrhosis was 9% (95% CI 8–10), ranging from 6% (4–8) in community settings to 10% (9–11) in clinic settings. Examining the proportion of participants who had characteristics used to determine eligibility in the WHO guidelines, 1750 (10·1%) of 17 394 had HBV DNA exceeding 20 000 IU/mL, and 20 425 (30·8%) of 66 235 had ALT above the upper limit of normal. 32 studies reported eligibility for treatment according to WHO or any other guidelines, with a pooled estimate of eligibility at 19% (95% CI 18–20), ranging from 12% (6–18) for studies in community settings to 25% (19–30) in clinic settings.InterpretationMany studies described people with HBV infection, but few reported information in a way that allowed assessment of eligibility for treatment. Although about one in ten of the 257 million people with HBV infection (26 million) might be in urgent need of treatment because of cirrhosis, a larger proportion (12–25%) is eligible for treatment in accordance with different guidelines. Future studies describing people with HBV infection should report on treatment eligibility, according to broadly agreed definitions.FundingWHO and US Centers for Disease Control and Prevention.

Placental infection of hepatitis B virus among Thai pregnant women: Clinical risk factors and its association with fetal infection.

To identify the risk factors of placental and fetal infections among HBsAg-positive women. A prospective cohort study involving HBsAg-positive pregnant women was conducted. Maternal risk factors, including serum HBeAg status, anti-HBcIgM, and HBV-DNA levels, were determined. Placental infection was identified by PCR and confirmed by DNA sequencing. Fetal infection was defined as a positive umbilical cord blood HBV-DNA at birth. A total of 96 HBsAg-positive women were enrolled in the study. The prevalence of placental infection was high (44 of 96; 45.8%) among HBsAg-positive women. The major risk factors for placental infection were high maternal viral load and the presence of HBeAg. Fetal infection was detected in one quarter of HBsAg-positive women (25 of 95; 25.3%). The risk of fetal infection was strongly associated with placental infection (78.3%), high maternal viral load, and the presence of HBeAg. There was no significant difference in perinatal outcomes between the groups with and without placental infection. Data on rates of chronic HBV infection in infants after fetal infection were not available. A significant association between maternal measures of viral replication and placental and fetal infection was demonstrated. These findings suggest that transplacental infection prior to birth may be a mechanism contributing to the higher rates of newborn prophylaxis failure in women with a high viral load.

Serum HBV pregenomic RNA is correlated with Th1/Th2 immunity in treatment‐naïve chronic hepatitis B patients

Background and AimHepatitis B virus (HBV) load and antigens are related to the innate and adaptive immunity of chronic hepatitis B (CHB) patients. As a new HBV biomarker, the role of pregenomic RNA (pgRNA) in host immunity is not known. This study aimed to identify the relationship between serum HBV pgRNA and host immunity in CHB patients.MethodsTwo hundred twenty‐five treatment‐naïve CHB patients were enrolled. Serum cytokines were measured by cytokine antibody array (Luminex multiplex platform). Th1 (T‐helper cell, Th) and Th2 cells were tested by flow cytometry. Serum HBV pgRNA was detected by a reverse transcription‐polymerase chain reaction.ResultsSerum HBV pgRNA was significantly different among patients in different disease phases and significantly associated with both HBV antigens and antibodies. Serum HBV pgRNA was positively correlated with the HBsAg level (P < .001) and the presence of HBeAg (P < .001). Patients with higher HBcAb levels showed lower serum HBV pgRNA levels (P = .003). Notably, HBsAb positivity was associated with higher levels of serum HBV pgRNA in HBeAg(−) patients (P = .049). Serum HBV pgRNA was positively associated with ALT level, Th2 cell frequency, and related cytokine sCD30 (P < .001, P < .001, and P = .003, respectively), but negatively associated with Th1‐related cytokine interleukin (IL)‐12P70 and cytotoxic lymphocytes (CTLs) (P = .017 and P < .001, respectively).ConclusionOur study confirmed the relationship between serum HBV pgRNA and host immunity. The results demonstrated that serum HBV pgRNA is positively correlated with Th2 immunity but negatively correlated with Th1 immunity, indicating that it might have a relationship with HBV antigen conversion and CTL immunodeficiency in CHB patients.

Maternal HBeAg positivity and viremia associated with umbilical cord blood hepatitis B viremia

Hepatitis B (HBV) transmission may result from in utero transmission. We aimed to determine the correlation between maternal serum and umbilical cord blood HBV DNA levels in infants delivered by chronic HBV-infected mothers and to describe the effect of cord blood viremia on vertical transmission. A prospective cohort of 92 chronic HBV-infected mother-and-child pairs recruited over three years was analyzed. Maternal and cord blood were tested for HBV DNA by real-time PCR. Standard immunoprophylaxis with both active and passive immunization was administered to all infants. Serological testing was performed on all infants at 9 months of age. Moderate positive correlation of the maternal HBV DNA with cord blood HBV DNA was demonstrated (r2=0.521, p=<0.001). HBeAg+ve mothers were younger with higher HBV and cord viremia. At 9 months of age, one infant was infected. Infants delivered by HBeAg positive mothers and mothers with high HBV DNA of more than 6LOG IU/mL (1 x 106 IU/mL) have increased relative risk of cord blood viremia. Maternal HBV DNA and presence of HBeAg were positively correlated to cord blood HBV DNA in infants delivered by chronic HBV-infected mothers. Our data suggest that reducing maternal viremia during the antenatal period may help to reduce cord blood viremia.

Hepatitis B Infection and Immunity among Pregnant Women Attending Antenatal Clinics in Health Centers of Mbarara Municipality, Southwestern Uganda

Introduction: Viral hepatitis B (HBV) in pregnancy is a risk for childhood transmission where the majority become chronically infected. In Uganda, HBV is not tested for during antenatal, therefore the number of infected, infectious, immune and none-immune pregnant women is unknown curtailing efforts to prevent mother to child transmission. Methods: We conducted a descriptive cross-sectional study involving 254 pregnant women from four health centers in Mbarara Municipality. HBV status was assessed using an immunochromatographic (COMBO) kit, the type of infection; based on demonstration of anti hepB core IgM (acute infection) and total core IgG antibodies (chronic infection) and infectiousness; based on the presence of HBeAg and/or a quantitative HBV viral load ≥ 20,000 IU/mL. Immunity was determined using the COMBO kit and HBsAb quantification ELISA. One was deemed immune to HBV if HBsAb titers were ≥10 mIU/mL. Results: The prevalence of HBV infection was 1.2%; 33% and 67% with acute and chronic HBV respectively. 33% were infectious based on a high viral load, none had detectable HBeAg. 14% were immune; amongst whom 72% had natural exposure and 18% after vaccination. There was insufficient immunity in 11% with a majority (75%) having acquired immunity following vaccination. Conclusion: The prevalence of HBV is low and most of those are chronically infected. HBeAg and Hepatitis B viral load should be performed when evaluating infectiousness. Further, there is a high transmission of HBV among adults and a low uptake of the HBV vaccine in Mbarara Municipality.

Assessment of Hepatitis B Viral Infection as a Predictor of Hepatic Enzymes and Compounds Alteration among Antenatal Patients.

Worldwide, hepatitis B viral (HBV) infection continues to be a major public health issue. The study was aimed at assessing HBV infection as a predictor of hepatic enzymes and compounds alteration among antenatal patients in Kano State, Nigeria. Sera were screened for HBV markers using immunochromatograhy and ELISA. Serum levels of alkaline phosphatase (ALP), asphatate aminotransferase (AST), alanine aminotransferase (ALT), albumin and bilirubin were also determined. Out of the 160 patients, 6.9% and 31.3% tested positive for HBsAg and HBcAb, respectively. None tested positive for HBeAg. These markers also appeared in other combinations. Of the HBsAg seropositives, 72.7% showed abnormal levels of both AST and ALP, 36.7% showed abnormal levels of both total and direct bilirubin, 9.1% showed abnormal levels of albumin, and none showed abnormal levels of ALT. HBsAg seropositivity shows significant association with ALP elevation (p = 0.02).The study revealed that few subjects (1.3%) that tested positive for HBsAg and HBeAb with normal ALT were in the inactive carrier phase of chronic hepatitisand6.9% that were seronegatives for all HBV markers equally had altered hepatic enzymes. The presence of HBeAg in the serum during HBV infection seems to cause a marked elevation of ALT level, while the reverse happens if HBeAg is absent. HBV infection can alter levels of hepatic enzymes and compounds and thus serve as one of its predictors, however; pregnancy can also lead to some of these alterations, which makes it difficult to establish the origin of these alterations among antenatal patients.

Occult hepatitis B virus infection with positive hepatitis B e antigen

BackgroundHepatitis B e antigen (HBeAg) is a marker to indicate active replication of hepatitis B virus (HBV). Occult HBV infection (OBI), referred to persistence of HBV DNA in serum and/or liver without detectable serum hepatitis B surface (HBsAg), usually has low HBV DNA levels. The presence of HBeAg in OBI is unusual. MethodsWe report 2 patients who presented negative for HBsAg but positive for HBeAg and HBV DNA. HBV markers were quantified in the longitudinal sera in a period of 1–2years. The HBV DNA sequences were analyzed in 2 patients' sera and 1 patient's liver. ResultsBoth patients were also positive for total anti-HBs and anti-HBc but negative for anti-HBe and anti-HBc IgM. HBV DNA levels were 234–567IU/ml in case 1 and 42–1130IU/ml in case 2. The alignment analysis of the S gene showed that HBV in both patients was genotype C, serotype adr. Cloning analysis of the a determinant of HBsAg showed that the immune escape mutants were predominant in both patients over the follow-up period. The HBV had double mutations (A1762T and G1764A) in the basal core promoter but had no mutation in the pre C/C gene in both patients. ConclusionsThe patients with negative HBsAg but positive HBeAg may represent a unique type of OBI. Test for HBeAg would be critical to identifying such type of OBI.

High level of IL‐27 positively correlated with Th17 cells may indicate liver injury in patients infected with HBV

Interleukin-6/IL-12 family cytokines play a key role in inflammatory diseases via their effects on the differentiation or regulation of T helper cells. The aim of this study was to determine the role of interleukin-27 (IL-27) and its association with helper T cells in hepatitis B virus (HBV)-infected patients. Samples were assessed from 51 HBV-infected patients [28 chronic hepatitis B (CHB) subjects and 23 acute-on-chronic liver failure (ACLF) subjects] and 18 normal controls (NC). Serum IL-27 levels were examined by enzyme-linked immunosorbent assay. Circulating helper T cells were determined using flow cytometry and associations between IL-27 expression and helper T cells were analysed. Serum IL-27 levels rose in HBV-infected patients (502.88 ± 23.35 pg/ml) compared to (NC, 277.14 ± 23.96 pg/ml, P < 0.0001). Furthermore, it significantly increased in patients with ACLF (587.90 ± 33.08 pg/ml) when compared with CHB (433.04 ± 26.57 pg/ml, P = 0.001). However, no statistically significant differences were observed between IL-27 and the presence of HBeAg. High levels of IL-27 then positively correlated with Tbil levels (r = 0.401, P = 0.004), but negatively associated with prothrombin time activity levels (r = -0.496, P < 0.001), and a slightly negative correlation trend with HBV-DNA loads (r = -0.228, P = 0.107) existed in these HBV-infected subjects. Additionally, frequency of circulating interleukin-17-producing CD4(+) T cells (Th17 cells) increased in HBV-infected patients (ACLF, mean, 5.39%; CHB, median, 3.12%) as compared to NC subjects (median, 2.22%, P < 0.0001). Moreover, correlation analysis showed that serum IL-27 level was positively associated with circulating Th17 cells (r = 0.342, P = 0.036). These results provided evidence that IL-27 was positively correlated with Th17 cells commitment, and may exerted a proinflammatory effect in the development of liver injury in HBV-infected patients.

HBV Infection in Italian and Non-Italian Patients in Northern Italy

Aims: The introduction of HBV vaccination in Italy has reduced the incidence and prevalence of HBV infection. However, increasing immigration from countries in which HBV is endemic has led to a wave of new HBsAg-positive subjects and their clinical impact needs evaluation. We compared the serological, clinical and epidemiological data relating to Italian and non-Italian subjects referred to a hospital in Northern Italy. Study Design: We retrospectively analysed the laboratory and clinical records of 488 subjects, including 107 (21.9%) non-Italians, in order to find data concerning clinical diagnoses, possible routes of infection, anti-HCV and anti-HDV antibodies. Results: The differences in gender distribution and mean age between the non-Italian Research Article British Journal of Medicine & Medical Research, 3(1): 1-12, 2013 2 and Italian patients were statistically significant (p<.001). There were no significant differences in the prevalence of anti-HCV (2.9% vs 4.9%, p=.86) or anti-HDV (4.7% vs 5.0%, p=.89) co-infection, or the presence of HBeAg in chronic infection. There were no differences in the rates of acute (3.3% vs 5.1%; p=.68) or chronic infections (96.7% vs 94.9%; p=.68) infections, but there were statistically significant differences (p<.001) in the rates of prevalent (54.5% vs 85.3%) and incident cases (45.5% vs 14.7%). The differences in the rates of asymptomatic (70.6% vs 34.9%) and symptomatic patients (29.4% vs 65.1%) were also statistically significant (p<.001). The only significant differences in terms of risk factors related to transfusions (0% vs 6.8%; p=.04), and vertical/perinatal transmission (44.1% vs 6.8%; p<.001). Conclusion: The non-Italian HBsAg-positive subjects were mainly women and younger than their Italian counterparts, and had a recent diagnosis. They were predominantly asymptomatic and probably considered themselves healthy and fit to emigrate. Perinatal transmission among non-Italians is still an important risk factor that reflects the epidemiological situation of their countries of origin.

Hepatitis B virus DNA in patients with HBsAg in south western Nigeria

There are about 400 million people with chronic hepatitis B virus (HBV) infection worldwide with a potential of adverse sequelae including hepatocellular carcinoma. Recent data have shown that the level of HBV DNA in serum or plasma of an infected person probably reflects more accurately the replicative activity of the virus and therefore may serve as a better maker for management of the infection. This study was designed to determine the rate of detection of HBV DNA in blood samples of patients with HBsAg positive in Nigeria in comparison with the HBe and anti-HBe used widely as serological markers of infectivity. Plasma samples from 105 patients with HBsAg positive were tested for the presence of HBeAg and anti-HBe using a commercial enzyme-linked immunosorbent assay while plasma HBV DNA was quantified using the COBAS Amplicor HBV Monitor assay. Of the 105 HBsAg samples, 17 (16.2%) and 85 (81%) were positive for HBeAg and anti-HBe, respectively, while 8 (7.6%) were negative for both HBeAg and anti-HBe. HBV DNA was detected in 86 (81.9%) of the samples, out of which 15 (18.1%) and 67 (80.7%) were positive for HBeAg and anti-HBe, respectively. HBV DNA was detected in 78.4% of the HBeAg negative samples and in all the eight samples that were negative for both HBeAg and anti-HBe. The implication of these findings in the management of patients with HBV infection is compelling.

498 DRUG INDUCED LIVER INJURY RESULTING IN ACUTE LIVER FAILURE: AN ASIAN EXPERIENCE

University Hospital during the period from 1999 to 2006 were included. We investigated their alcohol drinking history, DM history, Child-Turcotte-Pugh (CTP) score, development of HCC, and final outcome. Postnecrotic LC (HBV) patients were investigated additionally for HBVDNA value, the presence of HBeAg, and HBeAb. Results: 1. The mean age was 61.5±10.3 years in the alcoholic LC and 51.8±10.7 in the postnecrotic LC(HBV), and the prevalence of DM was 29.2% (192/656) in the alcoholic LC and 17.4% (60/345) in the postnecrotic LC(HBV). 2. In the alcoholic LC, 96 patients (14.6%) developed HCC; 43 patients (43/192, 22.4%) with DM, versus 53 patients (53/464, 11.4%) without DM. The prevalence of HCC was higher in those with DM (P < 0.001). In the postnecrotic LC(HBV), 49 patients (14.2%) developed HCC; 10 patients (10/60, 16.7%) with DM, versus 39 patients (39/285, 13.7%) without DM. The prevalence of HCC was not different according to the presence of DM (P=0.544). 3. Factors showing a correlation with the development of HCC were age (OR, 1.12; 95%CI, 1.03–1.21; P = 0.005) and DM (OR, 11.18; 95%CI, 2.25–55.42; P = 0.003) in the alcoholic LC, and male (OR, 2.17; 95%CI, 1.06–4.44; P = 0.035), age (OR, 1.04; 95%CI, 1.01–1.08; P = 0.008) and HBVDNA (OR, 1.07; 95%CI, 1.03–1.11; P = 0.017) in the postnecrotic LC(HBV). Conclusions: This study suggested that DM is increases the risk of HCC in alcoholic LC patients, but is not considered to be correlated with the development of HCC in postnecrotic LC(HBV) patients. Therefore, closer surveillance is required in alcoholic LC patients accompanied with DM.

Hepatitis B and the surgeon

Hepatitis B virus is the most transmissible virus and is very resistant to heat and chemicals, because of its unique structure. Blood has the maximum concentration of the virus among all the body fluids and the risk of transmission is related to the presence of HBeAg and the Hepatitis B virus DNA level in the blood. In India, about 1-10% of the healthcare workers are HBsAg positive. Healthcare workers, especially surgeons, and laboratory technicians are at a high risk of developing Hepatitis B infection. Transmission from Hepatitis B positive surgeons to patients has been well-documented. However, the risk of transmission from a patient to a surgeon is higher - about 30% - following a needle stick injury from an HBeAg positive individual. In India, there is low awareness among healthcare personnel about Hepatitis B vaccination and its related issues, and there is no health policy in this regard. In relation to the healthcare workers, there is an urgent need to formulate guidelines on HBsAg testing, hepatitis B vaccination, restriction of exposure-prone procedures that have to be performed, the extent to which their serological status can be revealed to patients, implementation of universal precautions, and post-exposure prophylaxis.

Three-Year Efficacy and Safety of Tenofovir Disoproxil Fumarate Treatment for Chronic Hepatitis B

Tenofovir disoproxil fumarate (TDF), a nucleotide analogue and potent inhibitor of hepatitis B virus (HBV) polymerase, showed superior efficacy to adefovir dipivoxil in treatment of chronic hepatitis B through 48 weeks. We evaluated long-term efficacy and safety of TDF monotherapy in patients with chronic hepatitis B who were positive or negative for hepatitis B e antigen (HBeAg(+) or HBeAg(-)). After 48 weeks of double-blind comparison of TDF to adefovir dipivoxil, patients who underwent liver biopsy were eligible to continue the study on open-label TDF for 7 additional years; data presented were collected up to 3 years (week 144) from 85% of participants. Primary efficacy end points at week 144 included levels of HBV DNA and alanine aminotransferase, development of resistance mutations, and presence of HBeAg or hepatitis B surface antigen (HBsAg). At week 144, 87% of HBeAg(-) and 72% of HBeAg(+) patients treated with TDF had levels of HBV DNA <400 copies/mL. Among patients who had previously received adefovir dipivoxil and then received TDF, 88% of the HBeAg(-) and 71% of the HBeAg(+) patients had levels of HBV DNA <400 copies/mL; overall, 81% and 74%, respectively, maintained normalized levels of alanine aminotransferase and 34% had lost HBeAg. Amino acid substitutions in HBV DNA polymerase that are associated with resistance to tenofovir were not detected in any patient. Cumulatively, 8% of HBeAg(+) patients lost HBsAg. TDF maintained a favorable safety profile for up to 3 years. TDF was safe and effective in the long-term management of HBeAg(+) and HBeAg(-) patients with chronic hepatitis B.

Evolving clinical landscape of chronic hepatitis B: A multicenter Italian study

The aim of the study was to evaluate the characteristics of chronic hepatitis B with special reference to the geographical origin of the patients and to the prevalence of HBeAg and viral and non-viral co-factors of liver disease. A cross-sectional multicenter survey was undertaken, which enrolled 1,386 HBsAg chronic carriers observed consecutively in 21 referral centers over a 6-month period. The prevalence of HBeAg in patients was 11%; the presence of HBeAg was associated independently with a younger age and co-infection with HIV. Anti-HDV, anti-HCV, or anti-HIV antibodies were detected in 8.1%, 6.5%, and 2%, respectively. However, among the patients first diagnosed during the study period (incident cases), 14.3% were anti-HDV positive. Seven percent of the patients were immigrants; they were younger than Italian patients and 18% were HBeAg positive; no difference was observed in the prevalence of anti-HDV, anti-HCV, or anti-HIV antibodies. The presence of cirrhosis was associated independently with an age >52 years, the presence of anti-HDV or anti-HCV, alcohol use >4 drinks/day, and a high BMI. The clinical epidemiology of chronic hepatitis B virus (HBV) infection shows a dynamic profile, with the potential for re-emergence of cases with HBeAg or anti-HDV and an emerging impact of metabolic factors on the evolution of liver disease.

Impact of hepatitis B virus co‐infection on response to highly active antiretroviral treatment and outcome in HIV‐infected individuals: a nationwide cohort study

The impact of chronic hepatitis B virus (HBV) infection on viral suppression, immune recovery and mortality in HIV-1 infected patients on highly active antiretroviral treatment (HAART) is a matter of debate. The impact of HBeAg status is unknown. This prospective cohort study included all adult Danish HIV-1 infected patients who started HAART between 1 January 1995 and 1 December 2006 (3180 patients). Patients were classified as chronic HBV-infected (6%), HBV-negative (87%) or HBV-unknown (7%). HBV-positive patients were divided into HBeAg-positive or -negative (3.0 vs. 2.6%). Study endpoints were viral load, CD4 cell count and mortality. HBV co-infection had no impact on response to HAART regarding viral suppression or immune recovery. HBV co-infection was associated with several outcomes: overall mortality [mortality rate ratio (MRR) 1.5; 95% confidence interval (CI) 1.1-2.1], liver-related mortality (MRR 4.0; 95% CI 1.6-9.9) and AIDS-related deaths (MRR 1.7; 95% CI 1.0-3.0). The presence of HBeAg did not influence patients' response to HAART. In HIV patients, chronic HBV infection has no impact on response to HAART concerning viral load and increase in CD4 cell count. However, co-infected patients have an increased mortality compared to HIV-monoinfected patients.

Rate of YMDD motif mutants in lamivudine-untreated Iranian patients with chronic hepatitis B virus infection

Lamivudine is used for the treatment of chronic hepatitis B patients. Recent studies show that the YMDD motif mutants (resistant hepatitis B virus) occur as natural genome variability in lamivudine-untreated chronic hepatitis B patients. In this study we aimed to determine the rate of YMDD motif mutants in lamivudine-untreated chronic hepatitis B patients in Iran. A total of 77 chronic hepatitis B patients who had not been treated with lamivudine were included in the study. Serum samples from patients were tested by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for detection of YMDD motif mutants. All patients were also tested for liver enzymes, anti-HCV, HBeAg, and anti-HBe. Of the 77 patients enrolled in the study, 73% were male and 27% were female. Mean ALT and AST levels were 124.4+/-73.4 and 103.1+/-81 IU/l, respectively. HBeAg was positive in 40% and anti-HBe in 60% of the patients. Anti-HCV was negative in all of them. YMDD motif mutants were not detected in any of the patients despite the liver enzyme levels and the presence of HBeAg or anti-HBe. Although the natural occurrence of YMDD motif mutants in lamivudine-untreated patients with chronic hepatitis B has been reported, these mutants were not detected in Iranian lamivudine-untreated chronic hepatitis B patients.