Hepatitis B Virus Core Antibody Research Articles

Application of nucleoside analogues to liver transplant recipients with hepatitis B.

Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donors positive for hepatitis B virus (HBV) core antibody (HBcAb) have previously been considered unsuitable for transplants. However, those who test negative for the more serious hepatitis B surface antigen can now be used as liver donors, thereby reducing organ shortages. Remarkable improvements have been made in the treatment against HBV, most notably with the development of nucleoside analogues (NAs), which markedly lessen cirrhosis and reduce post-transplantation HBV recurrence. However, HBV recurrence still occurs in many patients following liver transplantation due to the development of drug resistance and poor compliance with therapy. Optimized prophylactic treatment with appropriate NA usage is crucial prior to liver transplantation, and undetectable HBV DNA at the time of transplantation should be achieved. NA-based and hepatitis B immune globulin-based treatment regimens can differ between patients depending on the patients' condition, virus status, and presence of drug resistance. This review focuses on the current progress in applying NAs during the perioperative period of liver transplantation and the prophylactic strategies using NAs to prevent de novo HBV infection in recipients of HBcAb-positive liver grafts.

Hepatitis B (HBV) Screening in Patients Receiving Rituximab: A Comprehensive Analysis Including Comparison of Adherence By Oncologists and Non-Oncologists

BACKGROUND: It is estimated that >1.4 million people in the US are living with chronic HBV, many of whom are unaware of their infection. Chronic infection is responsible for the majority of HBV-related morbidity and mortality ranging from hepatitis to fulminant hepatic failure. The monoclonal anti-CD20 antibody, rituximab, is used to treat a variety of malignant and non-malignant conditions. Its use is associated with reactivation of HBV (HBV-R), including in historically low risk populations (i.e., HBV core antibody (HBcAb) positivity) and HBV-R may occur >8-10 months after completion of therapy. Professional societies such as the CDC and Infectious Diseases Society of America (IDSA) recommend screening all persons receiving cytotoxic or immunosuppressive therapy for HBV infection, although not all guidelines surrounding this topic are consistent. The primary aim of this study was to determine the rate of rituximab-related HBV screening and HBV-R over a recent time period across multiple medical specialties and disease conditions.METHODS: We completed a single center, retrospective cohort study at an urban, academic medical center reviewing all patients (pts) ≥ 18 years of age who received rituximab 1/1/06 to 7/31/13 who had at least 12 months of follow-up following the final rituximab dose. Eligible pts were queried using an electronic pharmacy database and reviewed by 3 physicians. Detailed data included demographics, indication for rituximab, number of rituximab doses, HBV screening serology, vaccination status, and comorbidities and risk factors for HBV-R.RESULTS: We identified 407 pts; of these, 10 were excluded due inadequate follow-up, 7 for incomplete records, and 1 was due to age <18 years with 389 pts meeting inclusion criteria. 47% of pts were female and the median age was 63 years (range, 19-94 years). The median number of rituximab doses received was 5 (1-35) and 86% of pts had a hematologic or oncologic diagnosis (most common: DLBCL n=84, CLL n=49, follicular lymphoma n=35, marginal zone lymphoma n=17, mantle cell lymphoma n=15, acute leukemia n=14, myeloma/amyloid n=13, ITP n=12, hemolytic anemia, n=10 and Burkitt’s n=9) and 14% of pts had a non-oncology indication (most common: rheumatoid arthritis n=20, lupus n=5, vasculitits n=4, scleritis n=3, Wegner’s n=3, Sjogren’s n=3, and dermatomyositis n=3) for rituximab therapy. Overall, 32% of pts were screened for HBV <6 months prior to the 1st rituximab dose. Among hematology/oncology pts, 31% had HBV screening prior to rituximab with 24% occurring within 6 months prior to the 1st dose (3% 6-12 months, 3% 12-24 months, and 1% >24 months prior). For non-oncology pts, 40% had HBV screening with 26% occurring within 6 months prior to the 1st dose (6% 6-12 months, 2%, 12-24 months, and 6% >24 months prior). Interestingly, the type of HBV screening tests varied widely with no consistent panel of serologies tested, although the majority of pts who had screening had testing for HBV surface antigen (90.7%). HBcAb was not checked as often (66%), which represents a subset of pts at risk for developing HBV-R. Of pts screened for HBcAb, 15/88 (17%) were found to be positive for HBV (n=14 HBcAb and n=1 pt was positive for HBV surface antigen). 8/15 pts had no known or obvious risk factors for HBV infection. Of the 14 pts testing positive for HBcAb prior to rituximab, only 1 pt received anti-HBV prophylactic therapy. 3 of 14 pts without HBV prophylaxis experienced HBV-R (all HBcAb+ lymphoma pts treated with rituximab/chemotherapy), one of who died due to multiorgan failure.CONCLUSION: At our academic center, we identified a relatively low rate of HBV screening amongst pts receiving rituximab irrespective of disease specialist or diagnostic condition. In addition, among pts who were screened, testing panels were inconsistent and a significant minority of pts did not have testing for HBcAb. Furthermore, we identified a relatively high rate of occult positivity for HBcAb including in a significant fraction of pts without known risk factors. It is advocated that a National unified guideline be instituted towards rituximab-related HBV screening and institutions implement and adhere to these guidelines. Likewise, a standardized panel of HBV serology is essential, both for initial testing and follow up. This is especially important given the increasing number of FDA approvals of other anti-CD20 and related monoclonal antibodies that carry similar risks of HBV-R. DisclosuresEvens:Genentech: Honoraria, Speakers Bureau.

Spirochetes as an Almost Forgotten Cause of Hepatitis

A 47-year-old man who has sex with men (MSM) with a history of chronic hepatitis B virus (HBV) presented with fever and a diffuse non-pruritic rash involving his trunk and extremities, including palms and soles. On examination, he had tender inguinal lymphadenopathy but no hepatosplenomegaly or jaundice. His liver enzymes were elevated from his baseline: aspartate aminotransferase 524 U/L, alanine aminotransferase 510 U/L, alkaline phosphatase 278 U/L, and total bilirubin 1.4 mg/dL. An acute flare of HBV was considered initially; however, it was believed to be less likely when serology testing returned negative for HBV core antibody immunoglobulin M.

Arsenic Exposure and the Seroprevalence of Hepatitis a and B Antibodies in the US Population

Background: Data from in vitro and in vivo studies demonstrate that arsenic alters IgM and IgG antibody formation and inhibits antigen-driven T-cell proliferation. Aim: Evaluate the relationship between urinary arsenic and the seroprevalence of the Hepatitis A (HAV) and Hepatitis B (HBV) viruses in the US population. Methods: Cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) from 2003-2012. Arsenic exposure was defined as the sum of arsenite, arsenate, monomethylarsonate and dimethylarsinate. Serological markers of Hepatitis included: total HAV antibodies (anti-HAV), HBV antigen (HBsAg), HBV antibodies (anti-HBs) and HBV core antibody (anti-HBc). Hepatitis A and B serology were evaluated in 9615 and 11301 participants, respectively. Effect modification was evaluated by self-reported immunization status. All models were adjusted for creatinine, gender, race, age, ratio of family income to poverty, BMI, country of birth, survey year and self reported immunization. Results: An overall association was observed for urinary arsenic and total anti-HAV (OR=1.24, 95% CI: 1.08-1.43). In stratified analysis, the association remained significant among fully vaccinated individuals (OR=1.41, 95% CI: 1.07-1.87) but not significant for non vaccinated participants (OR=0.96, 95% CI: 0.79-1.14). Urinary arsenic was associated with an increase in the seroprevalence of anti-HBs (OR=1.21, 95% CI: 1.03-1.41) and anti-HBc (OR=1.83, 95% CI: 1.53-2.19), but no association was observed with HBsAg. The stratified association with anti-HBs was significant among non-immunized participants (OR=1.61, 95% CI: 1.29-2.01) and non-significant for immunized participants (OR=1.02, 95% CI: 0.82-1.25). The association with anti-HBc remained significant regardless of immunization status. Conclusion: These findings support the hypothesis that arsenic exposure affects immunity to Hepatitis A and B. Prospective studies are needed to evaluate if the association is causal.

Hepatitis B Serology in the U.S. Population: Results From the National Health and Nutrition Examination Survey (NHANES) 2003-2012

Introduction: To provide updated data on hepatitis B (HB) serology from a large sample of the U.S. population. Methods: Data from the last 5 cycles of NHANES from 2003-2012 were analyzed. The NHANES is a nationally representative survey of non-institutionalized participants with oversampling of certain minorities. To account for missing data and sampling variation and over-representation, weighted frequencies were used to calculate and report prevalence estimates. Results: Testing for HBV surface antibody (HBsAb), surface antigen (HBsAg), and core antibody (HBcAb) was performed on the sera of 39,461 participants over the 10-year period from 2003-2012. The prevalence of HBsAb has remained relatively stable over the past 5 cycles and ranged from 27.6-30.0% with an average of 28.6%. The prevalence of HBsAg ranged from 0.24-0.39% with an average of 0.31%. The prevalence of HBcAb ranged form 3.7-5.2% with an average of 4.24%. The prevalence of HBcAb appeared to be trending down through the 5 cycles: 5.2% in 2003-2004, 4.3% in 2005-2006, 3.8% in 2007-2008, 4.2% in 2009-2010, and 3.7% in 2011-2012. Conclusion: 28.6% of the U.S. population exhibit evidence of immunity against HBV (natural or due to vaccine), while 0.31% exhibit evidence of chronic infection. In addition, 4.24% of the population has positive HBcAb, which can be an indicator of chronic infection, immunity after resolved HBV, or marker of infection in window phase of acute HBV. Noteworthy, the survey sample did not include participants with potentially higher risk for HBV such as prison and homeless populations, and therefore it might have underestimated the true prevalence of chronic HBV.

Positive hepatitis B virus core antibody in HIV infection--false positive or evidence of previous infection?

Isolated HBV core antibody (anti-HBc) is defined as the presence of anti-HBc with a negative HBV surface antigen (HBsAg) and HBV surface antibody (anti-HBs <10 IU/l). In patients infected with HIV with isolated anti-HBc, the aim was to determine: The prevalence of isolated positive anti-HBc; The most effective method of identifying which patients have had previous Hepatitis B Virus (HBV) infection; The prevalence of false positive anti-HBc. HBV serology results were identified from 539 patients infected with HIV sampled between January 2010 and December 2012. In those with an isolated anti-HBc and negative anti-HBe, a second anti-HBc test was carried out using a different assay. Samples were also screened for HBV DNA. The anti-retroviral regimens at time of screening were documented. 101/539 had an isolated anti-HBc. Of these, 32 (32%) had a positive anti-HBe (including 1 equivocal) and 69(68%) were anti-HBe negative. Of those negative for anti-HBe, 32 were tested for both DNA and a second anti-HBc. Of these 26 (81%) were on cART at time of HBV testing, with 25 (78%) on ART with anti-HBV activity. The prevalence of isolated anti-HBc was 19%. Only 32% were also anti-HBe positive, whereas 97% of those anti-HBe negative were positive on a second anti-HBc assay suggesting lack of utility of anti-HBe in resolving serological quandaries. One subject (3%) had a false positive anti-HBc. There was no evidence of chronic HBV but 78% patients were on HBV-suppressive combination anti-retroviral therapy.

Hepatitis B core antibody-positive donors in cardiac transplantation: a single-center experience.

Hepatitis B virus (HBV) core antibody (HBcAb)-positive donors are increasingly utilized in solid organ transplantation. We report a single center's experience in cardiac transplantation with 18 HBcAb-positive donors. Available follow-up on recipients of cardiac allografts from HBcAb-positive donors, including 2 donors with low-level serum HBV DNA at the time of transplantation, demonstrated no documented donor-derived HBV transmission.

CpG oligodeoxynucleotide inhibits HBV replication in a hydrodynamic injection murine model.

Chronic HBV infection is a significant public health problem and one major cause of liver cirrhosis and hepatocellular carcinoma (HCC). HBV impairs the host immune system and results in immunotolerance, which is a major obstacle to HBV therapy. CpG oligodeoxynucleotide (ODN) is a strong immunostimulant which activates the innate immune response rapidly and has been shown to be an efficient therapy agent in viral infection treatment. Here, we report the anti-HBV activity of CpG-1826 in a hydrodynamic injection murine model. CpG-1826 was administrated intraperitoneally every other day in HBV carrier mice established by tail vein hydrodynamic injection of HBV plasmids. The serum concentrations of HBV surface antigen (HBsAg), HBV e antigen (HBeAg), HBV surface antibody (HBsAb), HBV core antibody (HBcAb), interferon-α (IFN-α) and interferon-γ (IFN-γ) were measured by enzyme-linked immunosorbent assay (ELISA). The activities of alanine aminotransferase (ALT) were determined by ALT kit using a Spectramax Plus spectrophotometer. Hepatic HBV DNA was quantified by quantitative real-time PCR. The expression of HBV core antigen (HBcAg) in liver was detected by immunohistochemistry. Drug toxicity of CpG-1826 was evaluated by body weighting and liver histopathology confirmation. CpG-1826 administration inhibited HBV replication efficiently with significant reduction of serum HBsAg and HBeAg, hepatic HBcAg and HBV DNA levels. The serum levels of IFN-α, IFN-γ and HBsAb increased but the HBcAb level declined in the CpG-1826 group compared to CpG-1982 and PBS control groups. Results of ALT activity indicated no significant difference among CpG-1826 group, CpG-1982 and PBS control groups. Body weighting and histopathology examination showed no obvious toxicity. Given the stimulation activity of a host immune system, CpG ODN is a promising strategy for HBV therapy with more relevant research needed.

Prognostic factors of hepatic decompensation and hepatocellular carcinoma in patients with transfusion‐acquired HCV infection

Aim of this study was to assess if host (immunogenetic traits, age, sex), exogenous (alcohol) or viral factors (viral type, past HBV infection) might affect the progression of chronic hepatitis C to liver decompensation or the development of HCC in a cohort of patients exposed to a single blood transfusion prior to the introduction of anti-HCV screening. Two hundred and forty-eight patients with a history of a single exposure to blood or blood products prior to 1990 were retrospectively considered. Patients were devoid of other risk factors of liver disease or immunosuppression and naïve to antiviral therapies. Eight baseline variables were assessed: age at transfusion, sex, HBV core antibody, immunogenetic profile (DRB1*11, DRB1*1104, DRB1*07), HCV genotype and alcohol consumption. The follow-up was 22 (SD: 11) years. Sixty-eight patients (27%) progressed to hepatic decompensation over a median period of 22.5 years (IQR: 14-30) and 41 patients (16%) developed HCC over a median period of 31 years (IQR: 24-38). The cumulative incidence of liver failure was 0.4% (95% CI: 0.1-3.1), 4.9% (95% CI: 2.6-9.3) and 16.2% (95% CI: 10.4-24.7) at 10, 20 and 30 years after blood transfusion respectively. By univariate analysis, only age at transfusion was correlated with the risk of decompensation. Stratifying the age of transfusion by tertiles, the incidence of hepatic decompensation was 0.7% per year in patients transfused at ≤24 years of age as compared to 1.2% and 1.9% per year in those transfused at 25-35 and >36 years of age respectively (HR: 5.5, 95% CI: 2.78-10.7, P<0.001). The risk of HCC development was correlated by univariate analysis with age at transfusion (as continuous variable, HR: 1.12, 95% CI: 1.08-1.16 per year of age, P<0.001, >36 compared to ≤24 years, HR: 10.3, 95% CI: 3.9-26.9, P<0.001) and male sex (HR: 4.2, 95% CI: 1.7-10, P=0.001). Multivariate analysis confirmed age at transfusion and male sex as independent predictors of HCC development [HR: 1.12 per year (95% CI: 1.08-1.16), P<0.001 and HR: 5.4 (95% CI: 2.2-13.2), P<0.001 respectively]. In patients with transfusion-acquired HCV infection, age at transfusion affects the risk for hepatic decompensation. Age at transfusion and male sex are independent risk factors for HCC development.

Surface antigen-negative hepatitis B virus infection in Dutch blood donors

Hepatitis B virus (HBV) surface antigen (HBsAg) is a reliable marker for HBV infection, but HBsAg-negative forms of HBV infection occur. The introduction of HBV DNA screening of Dutch blood donors, which were not preselected for absence of HBV core antibodies, enabled the characterization of HBsAg-negative HBV infection in healthy persons and a comparison of the HBV genomes involved. The screening of 4.4 million Dutch blood donations identified 23 HBsAg-negative, HBV DNA-positive persons. Serological testing of the index donations, follow-up samples and archived earlier samples was performed to determine the nature of each HBV DNA-only case. Despite low viral loads HBV DNA could be sequenced in 14 out of 23 donors, allowing HBV genotyping and the analysis of mutations in the HBV surface gene. Four types of HBsAg-negative HBV infection were detected: infection in the early stage before occurrence of HBsAg; suppressed infection after vaccination; HBV genotype G infection with decreased HBsAg production; and chronic occult (HBsAg negative) HBV infection. In the donors with occult HBV genotype D infection the HBV surface gene showed multiple "escape" mutations in the HBsAg a-determinant and CTL epitopes, while in an occult genotype A case the surface gene showed no mutations. HBsAg-negative forms of HBV infection in healthy blood donors explain the ongoing transmission of HBV via blood transfusion, if donor screening is limited to HBsAg. The screening of blood donors for HBV DNA and HBV core antibodies seems to cover all stages and variants of HBV infection.

Does past exposure to hepatitis B virus effect ART outcomes?

Hepatitis B virus(HBV) has been detected in the semen of infected males, either as free virus in the plasm, or an integrated genome in spermatozoa, and in the ovum or follicular fluid in infected females. There is some evidence that active HBV infection, determined by HBV Surface antigen positivity, can have an effect on ART outcomes. There is a lack of data on the influence of past HBV infection, identified by HBV Core antibody positivity and a negative HBV surface antigen test, on outcomes following IVF or ICSI.

The reliability of HBV core antibody in serological screening for hepatitis B virus

Accurate diagnosis of hepatitis B virus (HBV) infection is essential for infection control, treatment and screening of potential blood, organ and tissue donors. We assessed the sensitivity of the HBsAg and HBcAb as screening assays alone and in combination for detecting HBV infection in a series of Australian patients. The performance of the Architect (Abbott Diagnostics, Germany) and the Elecsys (Roche Diagnostics, Germany) platforms were assessed for detection of HBcAb. There were 2778 blood samples assessed using the COBAS Ampliprep/TaqMan test for HBV DNA, of which 331 sera had concurrent HBV serology testing. This allowed determination of the correlation between HBV DNA and different serological markers. Of the 331 sera, 260 had sufficient residual volume to be retested for HBcAb using both Elecsys and the Architect assays. Of the 331 patients, one (0.3%) was negative by the Architect Anti-HBc II assay, in the presence of HBV DNA and positive HBsAg, consistent with recent infection. Positive HBcAb in the absence of HBV DNA was found in 67 of 331 (20.2%) patients. Of these, 18 of 67 had isolated HBcAb with negative results on all other tests, with 12 of 18 (3.6%) demonstrating low HBcAb signals on chemiluminscent microparticle assay. No cases of detectable HBV DNA in the presence of negative serology were found. When the HBcAb was used as a marker for past exposure or chronic HBV infection, the Architect Anti-HBc II assay demonstrated sensitivity and specificity of 98% and 79.9%, respectively, compared to 90% and 78.9%, respectively, for the Elecsys Anti-HBc assay. The combination of the Architect Anti-HBc II and HBsAg assays, as per conventional solid organ donor and recipient screening protocols, had 90% specificity and 100% sensitivity for determining HBV infection. This study shows that the use of combined HBsAg and HBcAb is sensitive and reliable for screening and predicting HBV nucleic acid test (NAT) positivity, whereas HBcAb alone missed an acute infection in this study population. There were no significant differences detectable between the Architect and the Elecsys HBcAb assays (p=0.001), suggesting laboratories should assess individual assays in the local population before use as screening tests.

Sa1019 Incidence of Hepatitis B Surface Antigen and Hepatitis B Core Antibody in a Screening Population Undergoing Chemotherapy

Background: Reactivation of hepatitis B virus (HBV) infection is a well-recognized complication after immunosuppression from chemotherapeutic agents and can lead to significant morbidity and mortality. We previously reported 23 HBV reactivations in patients of diverse nationalities without association with a particular malignancy or medication. Our institution subsequently initiated a protocol in which all new patients receiving immunosuppressive therapy are screened for HBV and offered anti-viral prophylaxis. The aim of this study is to report the prevalence of HBV surface antigen (HBsAg) and HBV core antibody (HBcAb) positivity since the inception of this screening program.Methods:We conducted a prospective study of all patients at Memorial Sloan-Kettering Cancer Center who were started on immunosuppressive therapy and screened for HBV from May 2009 to November 1, 2012. Patients were screened using tests for HBsAg and HBcAb. If either of these were positive, PCR for HBV DNA was reflexively measured. Patient demographics --including type of malignancy-were recorded. Results: Between May 1 2009 and November 1 2012, 17183 patients met criteria for screening and 12,328 patients (median age 64 years [24-95], 54.4% male) were screened for HBV prior to initiation of immunosuppression (71.75% compliance). Testing revealed 78(0.6%) patients positive for both HbsAg and HbcAb (median age 58, 69.2% male).Of this group, 47/78 (60.26%) had detectable HBV DNA PCR (955766.7 mean, 521 median) .Primary diagnoses of these patients included lymphoma 6.4%, leukemia 2.6%, and myriad solid tumors 91.0%. In addition, 994 patients (8.1%) were negative for HBsAg and positive for HBcAb (median age 58, 53.2% male), Diagnoses among this group included 6.0% lymphoma, 2.0% leukemia and 92.0 % solid tumor. Of this group, 7 (0.7%) had detectable HBV DNA PCR ([41-1,740,000 IU/mL]). Conclusion: In our population screened for HBV prior to initiation of immunosuppression, we report a prevalence of 0.6% for HBsAg positive patients and 8.1% for HBsAg negative, HBcAb positive patients. Screening of these

Hepatitis B “360”

There is an extremely high burden of liver disease owing to viral hepatitis B (HBV); about 2 billion people are infected and 350 million are chronic carriers of HBV worldwide. More effective medical therapy and liver transplantation are available for those with advancing disease. The interaction between the host immune system and the virus influences the rate of development of advanced liver disease or hepatocellular carcinoma (HCC); treatment that successfully reduces viral replication of HBV also reduces the incidence of development of advanced liver disease and HCC. Liver transplantation for HBV has yielded favorable outcomes since the institution of hepatitis B immune globulin and antiviral therapy. The ability to stabilize and rescue some patients with advanced liver disease owing to HBV has resulted in a changing demographic for patients with HBV undergoing liver transplantation. The main indications for transplant owing to HBV are now acute liver failure (both acute and acute reactivation on the background of chronic HBV) and HCC. Use of donor organs exposed to HBV with positive HBV core antibody is now routinely accepted for its good outcomes, and in selected cases with active HBV, HBV surface antigen-positive donors may be utilized to further expand the donor pool. Another indication for antiviral therapy for HBV is to reduce the risk of reactivation of latent virus in some patients previously exposed to HBV who are being treated with chemotherapy. Health care providers with HBV infection have an obligation to appropriately treat or monitor their disease closely to reduce the risk of transmission of disease from provider to patient. In the future, universal vaccination will reduce the overall burden of HBV liver disease, but until then appropriate utilization of available medical and surgical therapeutic options gives excellent clinical outcomes.

Entecavir versus lamivudine for hepatitis B prophylaxis in patients with haematological disease

Hepatitis B reactivation in patients receiving immunosuppressive therapy or chemotherapy may be associated with acute hepatitis, liver failure and/or death. To audit the efficacy of entecavir as compared to lamivudine for the prophylaxis of HBV reactivation in patients with haematological disease receiving immunosuppression or chemotherapy. Patients treated for haematological disease with pretreatment serological evidence of chronic hepatitis B (CHB) (HBV surface antigen, HBsAg positive) or resolved HBV infection (HBsAg negative but HBV core antibody positive) are included in this study. Patients received lamivudine 100 mg or entecavir 0.5 mg daily. Hepatitis B serology, HBV DNA and ALT were audited at baseline, 6 months, year 1, 2 and 3. HBV reactivation was defined as a 1 log increase in HBV DNA from baseline or reversion to sAg positivity. The occurrence of jaundice, symptomatic hepatitis, liver failure or death were audited. Of the 40 patients included in the study, 65% (4 CHB and 22 resolved HBV) received entecavir and 35% (11 CHB and 3 resolved HBV) received lamivudine. One patient with resolved HBV experienced HBV seroreversion related to premature cessation of entecavir. Eight patients with CHB (two from entecavir group and six from lamivudine group) had detectable HBVDNA levels at baseline; one case of HBV reactivation related to probable lamivudine resistance was identified. No HBV related deaths occurred. Lamivudine and entecavir are both efficacious in the prophylaxis of hepatitis B reactivation. Entecavir should be used in preference to lamivudine in patients CHB with detectable baseline HBV DNA levels.

Reactivation of occult hepatitis B virus infection following cytotoxic lymphoma therapy in an anti‐HBc negative patient

Screening hepatitis B virus (HBV) surface antigen (HBsAg) and HBV core antibody (anti-HBc) is recommended prior to cytotoxic or immunosuppressive therapy. This case describes an anti-HBc negative, DNA positive occult HBV infection in a 71-year-old Caucasian male following rituximab-based treatment for follicular lymphoma. Pre-screening serology indicated negative HBsAg and anti-HBc. However, following sequential treatment cycles the patient developed weak HBsAg with a low HBV DNA load (<1,000 IU/ml), but remained anti-HBc negative. The DNA load peaked 5 months later (>1 × 10(6) IU/ml) and he was subsequently treated with Tenofovir. Currently the patient remains anti-HBc negative, and is anti-HBe negative, anti-HBs negative, HBeAg positive. No clinical or biochemical evidence of hepatitis has occurred. Sequencing and phylogenetic analysis identified the HBV genosubtype as D4, most probably acquired some years ago during a stay in Papua New Guinea, in spite of prior hepatitis B vaccination. Four amino acid substitutions were detected within the HBsAg loop yet none in the core protein. This case questions the dependability of anti-HBc testing and highlights the role of HBV DNA testing prior to and throughout cytotoxic or immunosuppressive regimes. As this case exemplifies, vaccination protects against clinical infection but may not exclude seronegative occult infection with the possibility of reactivation.

Detection of highly prevalent hepatitis B virus co-infection with HIV in Indonesia

The prevalence of hepatitis B virus (HBV) co-infection with HIV is increasing worldwide because of shared transmission routes. This study aimed to assess the prevalence of HBV and HIV co-infection in Indonesia, and its molecular and clinical characteristics. A total of 118 serum samples from HIV-infected patients (age 33.3 ± 8.9 years, 99 male, 19 female) collected in 2009 were serologically examined. HBV DNA was assessed by polymerase chain reaction (PCR) analysis targeting the S region. Overall, 15.3% (18/118) of the patients were hepatitis B surface antigen (HBsAg) positive, whereas 27.1% (32/118) were HBsAg negative but HBV DNA positive, and were considered to have occult HBV infection. HBsAg antibodies and/or HBV core antibodies were detected in 45.6% (31/68) of HBV DNA negative patients. HBV co-infection, including occult HBV infection, was common in Indonesian HIV patients. Hepatic damage by the interaction of host immunity and HBV is still a remaining issue in these immunosuppressive patients, and further study will be needed.

Hepatitis B Virus (HBV) Screening in Hematology/Oncology Patients Who Receive Rituximab: Continued Need for Evidence-Based Standardized Recommendations and Effective Implementation Into Clinical Practice

Abstract 970 Background:The CD20 monoclonal antibody, rituximab, has been implicated in the reactivation of hepatitis B virus (HBV) when given either combined with chemotherapy or as a single-agent. This potentially fatal complication has been documented in patients (pts) with high risk of HBV reactivation (i.e., HBV surface antigen (HBSAg) positive), and in lower risk populations (i.e., HBsAg negative, HBV core antibody (HBcAb) positive), the latter where the risk of reactivation with rituximab-based therapy is approximately 15–20% (Yeo W, et al. J Clin Oncol 2009; Evens AM et al, Ann Onc 2011). Published recommendations on HBV screening and anti-viral prophylaxis related to rituximab vary considerably, leaving practicing clinicians without clear consensus. In addition, HBV screening and prophylaxis have not been universally implemented into clinical practice. We sought to determine our institutional frequency of HBV screening and rates of HBV reactivation in Hematology/Oncology pts treated with rituximab-based therapy who underwent appropriate screening and prophylaxis. METHODS:We completed a single center, retrospective analysis at a large academic center to examine pts >17 years of age who received rituximab for a hematologic or oncologic disorder from January 1, 2005 through August 1, 2011. We reviewed drug administration records to identify pts who received rituximab for a malignancy or other hematological disorder. Pts were evaluated for documented HBV screening, HBV diagnosis, number of doses of rituximab received, vaccination status, baseline characteristics, and relevant past medical history and laboratory values. A ‘cycle' of rituximab was defined as 1 dose given in combination with chemotherapy, 4 consecutive weeks given as a single agent, or 1 dose given q2-4 months as part of maintenance therapy. Data regarding use of prophylactic therapy for HBV were also collected. RESULTS:212 pts were identified as having received rituximab; 109 were excluded as they received rituximab for other indications (n=86 multiple sclerosis, n=11 rheumatoid arthritis, and n=17 other), leaving a total of 103 pts who met study inclusion criteria. The median age was 63 years (19-90), median number of rituximab ‘cycles' received was 3 (1-9); 45% of pts had diffuse large B-cell lymphoma (DLBCL), 15% other high-grade lymphoma, 14% follicular lymphoma (FL), and 26% other hematologic malignancy. Among the 103 pts, a total of 53 (51.4%) were screened for HBV at some point before or after initiation of therapy. Only 6.8% of pts were screened (within 9 months) prior to initiation of treatment, while 18.4% had HBV screening within 30 days of the 1st rituximab dose. Of the pts screened for HBV after 30 days, the median time to screening was 196 days (32-2660) after rituximab initiation. Notably, there were no differences in rates of HBV screening based on the year of therapy. Among the 53 pts screened for HBV prior to or within 30 days of rituximab initiation, eight (15.1%) were positive for HBV infection. Three pts were positive for HBsAg, all of whom received HBV anti-viral prophylaxis. Five pts were negative for HBsAg, but positive for HBcAb (1/5 also with positive HBV surface antibody); one HBcAb+ pt received anti-viral prophylaxis. These four pts received anti-viral prophylaxis for a median time of 17.1 months, which included a median of 7.9 months after the last rituximab dose. Among the 53 pts who underwent HBV screening, there were no cases of HBV reactivation observed with a median follow-up time of 15.6 months (5.9-16.5). CONCLUSION:At our academic institution, we identified an occult HBV infection rate of 15% in Hematology/Oncology pts who received rituximab treatment. A relatively low rate of pre-treatment HBV screening was performed, while approximately 45% of pts had screening after initiation of therapy. Among pts who were screened, appropriate anti-viral prophylaxis was instituted, and there were no cases of HBV reactivation. Altogether, there remains a critical need for standardized recommendations and consensus for screening and prophylaxis of HBV infection in pts who receive rituximab therapy. This is particularly evident given recent data regarding cost effectiveness of this approach (Zurawaska U, et al, J Clin Oncol 2012). In addition, continued efforts are needed to implement evidence-based HBV screening and prophylaxis guidelines in clinical practice. Disclosures:No relevant conflicts of interest to declare.

Serological survey of viral hepatitis markers among newly diagnosed patients with HIV/AIDS in China

The aim of the study was to determine the seroprevalence and epidemiological features of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection among patients newly diagnosed with HIV/AIDS in China. Two thousand and forty patients newly diagnosed with HIV/AIDS from 10 provinces in China were selected during 2009 to 2010. Serum samples obtained from each individual were screened for HBV and HCV serum markers [HBV surface antigen (HBsAg), HBV surface antibody (HBsAb), HBV envelope antigen (HBeAg), HBV envelope antibody (HBeAb), HBV core antibody (HBcAb) and HCV antibody (HCVAb)]; liver function tests were also performed. Demographics and medical histories were collected. Of the 2040 patients, 741 (36.3%) were positive for at least one HBV and HCV serum marker; 300 (14.71%) were HCVAb positive, and 248 (12.16%) were isolated HCVAb positive; 222 (10.9%) were positive for HBsAg; 19 (0.93%) were positive for both HBsAg and HCVAb. The highest prevalence of HBsAg positivity was found in Guangxi (15.31%), followed by Guangdong (15.19%) and Shanghai (14.36%). The highest prevalence of HCVAb positivity was found in Xinjiang (43.18%), followed by Henan (39.06%) and Yunnan (27.36%). The proportion of patients with abnormal liver function in patients positive for HCVAb and/or HBsAg was significantly higher than that in those who were negative for both HCVAb and HBsAg (P < 0.001). The seroprevalence of HBV and HCV among patients newly diagnosed with HIV/AIDS in China is high. HBsAg and HCVAb positivity prevalences were found to vary significantly in different provinces in China. Patients newly diagnosed with HIV/AIDS and coinfected with HBV and HCV are at higher risk of abnormal liver function. It is necessary to routinely screen for HBV and HCV infection among patients newly diagnosed with HIV/AIDS.

Efficacy of yeast-derived recombinant hepatitis B vaccine after being used for 12 years in highly endemic areas in China

ObjectiveTo evaluate the long-term efficacy and duration of yeast-derived recombinant hepatitis B vaccine in hepatitis B virus (HBV)-endemic areas. MethodA cross-sectional investigation was carried out in five HBV-endemic areas. Children who were born between 1997 and 2008 and vaccinated with yeast-derived recombinant hepatitis B vaccine were selected. Serum samples were taken to test HBV infection markers by microparticle enzyme immunoassay, and the results were compared to those before vaccination. Results7066 subjects were enrolled. The average adjusted hepatitis B surface antigen (HBsAg) prevalence was 1.02%. HBV core antibody (anti-HBc) prevalence was 3.54%. The overall percentage of HBsAg(−)&Anti-HBc(−)&Anti-HBs(+) was 61.34%. With time after immunization, the percentage annually decreases from 86.11% in 2008 to 49.80% in 1997. Geometric mean concentration (GMC) of anti-HBs decreased significantly annually. The portion of GMC=100–999.9mIU/ml was 48.0% in 2008, and decreased to 16.7% in 1997. ConclusionHBsAg prevalence decreased dramatically. This shows that the yeast-derived recombinant hepatitis B vaccine is effective and stable after being used for 12 years in HBV-endemic areas. It is not suggested to carry out booster immunization.