anti-HB Core Antibody Research Articles

Non Invasive Evaluation of Hepatic Iron Concentration By Fibroscan in Transfusion-Dependent Egyptian Patients with Chronic Hemolytic Anemia

Background: Transient elastography (Fibroscan®) is an ultrasound technique used to measure liver stiffness (LS), and thus assess for liver fibrosis, in patients with various chronic hepatic disorders. It can also be used to predict severity in multiple other diseases that might affect LS such as amyloidosis and possibly conditions associated with iron overload.Objectives: To assess the frequency of liver fibrosis in patients with chronic hemolytic anemia using Transient elastography (Fibroscan®), and to determine the reliability of this tool as a non-invasive method to predict hepatic iron content as compared to liver iron concentration (LIC) measured by magnetic resonance imaging (MRI).Patients and methods: Seventy-five transfusion dependent patients (50 β-thalassemia major;25 sickle cell disease) with a mean age of 13.4±5.2 years in addition to 75 -age and sex matched- healthy children were recruited. All subjects underwent assessment of LS in kilopascals (kPa), by Transient elastography measurement using FibroScan (Echosens, Paris, France І). Steady state serum ferritin (SF), and hepatitis B serologies (HBsAg and antiHB core antibodies) were assessed by enzyme linked immunoassay (ELISA). LIC values, within 6 months' duration, as identified by quantitative MRI of hepatic iron stores as a signal intensity ratio method based on T1 and T2* contrast imaging without gadolinium were retrieved. Informed consent was obtained from patients' legal guardians prior to enrollment in the study.Results: The median SF was 2280 ng/ml (84% had values exceeding 1000 ng/ml). The median LIC was 13.86 mg/g dw (78.7% patients showed LIC above 7 mg/g dw). The median cardiac T2* was 30.8 ms (3 patients had values below 20). Fifty-two (69.3%) patients were categorized as F0-1 and 21 (28%) were stage F2, 2 (1.3%) were stage F3, and 2 patients had severe fibrosis. The mean and median fibroscan (FS) values were 6.19 ±1.76 kPa and 5.9 kPa (range 3 to 14.1) respectively. Patients had significantly higher mean FS compared to control group (p ˂0.001). Patients with no or mild fibrosis (F0-1) had lower FS values (5.3kPa) compared to patients with fibrosis grades 2-4 (p ˂0.001). FS values were not affected by disease type (thalassemia or sickle cell disease), age (above 12 years), or HCV sero-positivity. FS values correlated with SF (r=0.410, p˂ 0.001). Simple regression analysis of the two variables suggested that changes in SF were associated with minimal but significant changes in FS values (p=0.04) with good agreement (kappa =0.324, p=0.003). LIC did not differ in relation to grade of fibrosis (p>0.05), did not correlate with FS values (r= 0.014, p=0.908), and no changes in FS were expected with LIC changes on regression analysis (p=0.466) with low agreement between LIC and FS at cutoff value 5.3 kPa (kappa = 0.015, p=0.9). Sensitivity and specificity of FS values to predict LIC were high at cutoff values ranging between 3.2 to 3.75 kPa but decreased markedly at higher cutoff values. On comparing sensitivity and specificity of FS values in prediction of iron overload at different cutoff values by ROC curve, it could not significantly predict iron overload (p=0.7). No correlations were found between LIC and other variables including SF (r=0.2), and changes in SF were not significantly associated with changes in LIC values (p =0.089). However, sensitivity and specificity of SF in predicting LIC were good at cutoff 1003.85 ng/ml but decreased markedly at higher cutoff values. Comparing its sensitivity and specificity to that of SF in the prediction of iron overload at different cutoff values by ROC curve, FS could not predict iron overload accurately (p=0.9) and the degree of agreement between these two variables as indicators of iron overload was low (kappa=0.063, p=0.478).Conclusion: Fibroscan could be a valuable tool to assess the degree of liver fibrosis in patients with elevated SF, but it does not appear to reliably predict LIC in such group of patients especially with severe iron overload. FS values were not affected by disease type, age above 12 years, or HCV sero-positivity. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

PREVALENCE OF OCCULT HEPATITIS B INFECTION IN IRANIAN CANCER PATIENTS BEFORE CHEMOTHERAPY TREATMENT.

Occult hepatitis B infection is characterized by negative hepatitis B surface antigen (HBsAg) and also detectable hepatitis B virus (HBV) -DNA, with or without hepatitis B core antibody (anti-HBc). HBV reactivation in individuals under immunosuppressive therapy is critical, occurring in occult HBV. In this study, we aimed to determine the prevalence of occult HBV infection among hepatitis B surface antigen negative in cancer patients before receiving chemotherapy. Sera from 204 cancer patients who were negative for HBsAg, were tested for anti-HBc antibodies. The samples that were negative for HBsAg but positive for anti-HBc also examined for HBV-DNA by polymerase chain reaction (PCR). Of the 204 HBsAg negative blood samples, 11 (5.4%) samples were positive for anti-HBc antibodies. HBV-DNA was detected in 9/11 (81%) of anti-HBc positive samples. Occult HBV infection in hematological cancers was more than solid cancers, 4.8% and 4.3% respectively. There was no significant difference in HBc antibody positivity based on vaccination, previous blood transfusions, history of familial hepatitis or biochemical parameters (ALT, AST, total and direct bilirubin levels) (P>0.05). Screening of occult HBV infection by HBsAg, HBV DNA and anti HB core antibody should be suggested as a routine investigation in cancer patients before receiving chemotherapy.

Transfusion transmittable infections - Seroprevalence among blood donors in a tertiary care hospital of Delhi

Context:Transfusion transmittable infections (TTI) continue to be a major threat to safe transfusion practices. Blood is one of the major sources of transmission of infectious diseases viz. human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, malaria, and many other infections in India. Screening assays for the infectious diseases with excellent sensitivity and specificity helps to enhance the safety of the blood transfusions reducing the diagnostic window period as much as possible.Aims:The present study was designed to determine the seroprevalence of TTIs viz., HIV, HCV, and HBV, among the blood donors in Max Super Specialty Hospital, New Delhi, India based on dual testing strategy using high sensitive screening assays such as enhanced chemiluminescence assay and nucleic acid testing (NAT).Materials and Methods:A total of 41207 blood units collected from the donors (both voluntary and replacement donors) were screened for the TTI s, viz., anti HIV 1 and 2 antibody, anti HCV antibody, anti HBcore antibody, and HBsAg by enhanced chemiluminescence assay on VITROS® ECiQ immunodiagnostics system. NAT was performed using Roche Cobas® TaqScreen MPX assay, which can detect simultaneously HIV 1 (groups M and O), HIV-2, HCV, and HBV on Roche Cobas® s201 system.Results:The seroprevalence of HIV, HBsAg, anti HBcore antibody, and HCV based on enhanced chemiluminescence assay was found to be 0.25, 0.2, 7.06, and 0.7%, respectively. A total number of 6587 samples from July 2010 to December 2010 were tested on NAT, of which 3 samples were reactive for HBV in NAT; this was missed by enhanced chemiluminescence assay.Conclusions:Based on the seroprevalence study of infectious diseases viz., HIV, HBV, and HCV, we conclude that screening of blood and blood components by dual testing strategy using high sensitivity serological assay like enhanced chemiluminescence technology and NAT helps in detecting the potentially infectious blood units in all phases of infection, which aids in enhancing the safety of blood transfusion and reducing the potential risk of post-transfusion infection.

Hepatitis B virus reactivation induced by infliximab administration in a patient with Crohn's disease.

A 47-year-old man diagnosed with Crohn's disease was treated with infliximab. He tested negative for hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) but positive for anti-HB core antibody (anti-HBc). He tested positive for hepatitis B virus (HBV-) DNA 3 months after treatment and was administered entecavir. HBV-DNA test showed negative results 1 month later. ALT was persistently within the normal range, and HBV-DNA was persistently negative thereafter despite the continuation of infliximab every 8 weeks. In our hospital, 14 patients with inflammatory bowel disease, who tested negative for HBsAg, were treated with infliximab; 2 of them tested positive for anti-HBs and/or anti-HBc, and HBV reactivation was observed in 1 patient (the present patient). The present case and these findings highlight that careful follow-up is needed in patients with inflammatory bowel disease treated with infliximab who test positive for anti-HBc and/or anti-HBs.

Long-Term Surveillance of Allogeneic and Autologous Hemopoietic Stem Cell Transplant Recipients Affected by Primary Occult Hepatitis B Virus Infection

AbstractAbstract 3350 Introduction:In the absence of serum hepatitis B (HB) surface antigen (HBsAg) and clinical evidence of HB, an occult HB virus (HBV) infection (OBI) is defined as the existence of HBV DNA in the serum, in the peripheral blood mononuclear cells (PBMC), and/or in the liver. Most frequently, OBI follows the resolution of acute hepatitis and continues indefinitely after HBsAg clearance and liver function improvement. Usually, this form of infection, termed secondary OBI (sOBI), is associated with the presence of serum anti-HB core antibodies (anti-HBc). Up to 20% of individuals with OBI do not react for either anti-HBc or any other serological indicator of HBV exposure. Consistent with the woodchuck model, this form of infection, termed primary OBI (pOBI), is characterized by the presence of DNA in both serum and PBMC, but not in the liver. Although reactivation of sOBI has been reported in a high proportion of hemopoietic stem cell transplant (HSCT) recipients, pOBI reactivation risk has not yet been fully investigated in the transplant setting. We followed up 9 long term surviving HSCT recipients with pOBI, in order to define its clinical significance in immune suppressed patients. Patients and Methods:A total of 75 consecutive patients with hematological disease, receiving autologous or allogeneic HSCT between April 2006 and March 2007, were included in a database and retrospectively examined. As a prerequisite for inclusion in the study, each of the following was needed: (i) negative serological indicators of HBV exposure and absence of clinical signs/symptoms of hepatitis at the time of HSCT, (ii) positive HBV DNA, as detected by polymerase chain reaction (PCR), in both serum and PBMC samples drawn within 6 months before transplant, and (iii) availability of stocked frozen serum/PBMC samples collected after HSCT from each patient. Following these criteria, 9 patients (7 males, 2 females) were selected for the analysis. Five patients (1 Hodgkin disease, 3 non-Hodgkin lymphomas, and 1 B-cell chronic lymphocytic leukemia) received autologous HSCT, and 4 patients (1 acute myeloid leukemia, 1 multiple myeloma, 1 myelodysplastic syndrome, and 1 acute lymphoblastic leukemia) received allogeneic HSCT. Median age at transplant was 49 (range: 33–63) years. No patient received lamivudine prophylaxis. Serum and PBMC samples collected after HSCT were analyzed for HBV serology and DNA detection. The latter was performed by in-house PCR amplification by nested primers (detection limit 50 copies/ml) from highly conserved S region encompassing a-determinant of HBV. Direct sequencing of all HBV DNA amplified products was used to confirm the specificity of the reaction. Results:In 8 cases, one serum/PBMC sample per patient was available, at a median of 27 (range: 21–34) months after HSCT; in 1 case, three serum/PBMC samples were available, at 17, 22, and 28 months after HSCT, respectively. During follow-up, positive HBV DNA was found, both in the serum and in the PBMC. All patients were confirmed to be infected with HBV subgenotype D1, with mutations known to impair HBsAg antigenicity. Three patients were confirmed to be further infected with HBV subgenotype A2. So far, 41 to 52 months after transplant (median: 46 months), neither patients showed seroconversion nor developed clinical hepatitis, suggesting pOBI persistence. Conclusions:Although the virus persisting in pOBI remains biologically competent, it is likely neither to reach liver-pathogenic doses nor to induce “classical” HBV reactivation during PBMC-restricted replication. However, prospective studies with large sample size and long-term follow-up are warranted, to define the actual clinical relevance of HBV occult infection. Indeed, OBI with low viremia could induce DNA damage, cellular demise, immune hypo-responsiveness, and oxidative stress in peripheral blood lymphocytes. Disclosures:No relevant conflicts of interest to declare.

Exploring different strategies to express Dengue virus envelope protein in a plant system

Dengue virus envelope glycoprotein (E-protein) is the main protein associated with immunity induction. To produce a candidate for subunit vaccines and to provide an antigen for diagnostic kits, it was expressed in a novel plant system using deconstructed viral modules. A truncated version of the E-protein was designed to be expressed alone and co-expressed with Dengue virus structural proteins. As well, the critical domain III of E-protein was fused to hepatitis B core antigen (HBcore). The recombinant proteins were produced in Nicotiana benthamiana plants and were reactive with the anti-E antibody. The fusion was reactive with both anti-E and anti-HBcore antibodies.

Hepatocellular carcinoma (HCC) recurring 10 years after clearance of hepatitis B surface antigen and 20 years after resection of hepatitis B virus-related HCC

A 62-year-old man had been followed up for chronic hepatitis B (HB) since 1973. Hepatocellular carcinoma (HCC) was detected in 1985, at the age of 42 years. Serum HB surface antigen and anti-HB envelope antibody were positive at that time. A right hepatic lobectomy was performed. In 1995, serum HB surface antigen had cleared spontaneously and liver function had normalized. In March 2005, at the age of 62 years, a 1.5-cm diameter hepatic mass was detected in the left lateral segment. At that time, he was seropositive only for anti-HB core antibody. A diagnosis of recurrent HCC was made, and partial hepatectomy was performed. Covalently closed circular HBV DNA was detected in both cancerous and noncancerous tissues by nested polymerase chain reaction (PCR). Cassette-ligation-mediated PCR showed that HBV DNA was integrated into the telomerase reverse transcriptase gene located on chromosome 5p15.

Analysis of risk factors for hepatocellular carcinoma in patients with HBs antigen- and anti-HCV antibody-negative alcoholic cirrhosis: clinical significance of prior hepatitis B virus infection.

The hepatitis B virus (HBV) or hepatitis C virus (HCV) markers frequently are detected in alcoholic patients with hepatocellular carcinoma (HCC). However, risk factors for the development of HCC in patients with HBs antigen (Ag)- and anti-HCV antibody (anti-HCV)-negative alcoholic cirrhosis have not been clearly documented. The present study was conducted to elucidate the occurrence rates of HCC in HBs Ag- and anti-HCV-negative male alcoholic cirrhosis and to assess the risk factors for hepatocellular carcinogenesis. We prospectively studied 91 consecutive patients with HBs Ag- and anti-HCV-negative alcoholic cirrhosis for 0.5 to 12.5 years (median 5.9 years). Potential risk factors assessed for liver carcinogenesis included the following six variables: age, total alcohol intake, association of continuing alcohol intake after diagnosis, indocyanine green retention rate at 15 min, anti-HB core antibodies (anti-HBc), and association of diabetes mellitus. Cumulative occurrence rates of HCC were 6.4%, 18.9%, and 28.7% at the end of the 5th, 7th and 10th years, respectively. When classified by anti-HBc, the occurrence rates of HCC in 31 patients with anti-HBc and 60 patients without anti-HBc were 15.6% and 2.9% at the 5th year, 28.4% and 13.5% at the 7th year, and 40.4% and 22.1% at the 10th year, respectively. The occurrence rates of HCC were also significantly related to the cumulative alcohol intake. Cox proportional hazard model identified that cumulative alcohol intake (p = 0.0047) and positive anti-HBc antibodies (p = 0.0598) were independently associated with the occurrence rates of HCC. These epidemiologic results suggest that heavy cumulative alcohol intake and prior exposure to HBV infection are risk factors for the development of HCC in patients with HBs Ag- and anti-HCV-negative alcoholic cirrhosis.

Clinical significance of prior hepatitis B virus infection in patients with hepatitis C virus-related hepatocellular carcinoma.

The effect of prior hepatitis B virus (HBV) infection on the clinicopathologic findings for patients with hepatitis C virus (HCV) RNA and hepatocellular carcinoma (HCC) is still unclear. Of 59 patients who underwent liver resection for HCV-related HCC (</=2.0 cm in greatest dimension) without metastases between 1990 and 1997, 38 patients had anti-HB core antibody (anti-HBc) and did not have HB surface antigen in their sera (Group 1). Their clinicopathologic findings and outcomes after surgery were compared with those of the remaining 22 patients without anti-HBc (Group 2). The proportion of well-differentiated HCC was significantly lower in Group 1 than in Group 2 (P = 0.0214). The percentage of patients with cirrhosis was significantly lower in Group 1 than in Group 2 (P = 0.0228). The cumulative survival rate was significantly lower in Group 1 than in Group 2 (P = 0.0224). The risk ratio of anti-HBc for shorter survival time was 3.817. HCC more often developed before cirrhosis in patients with HCV RNA and anti-HBc than in patients positive for HCV RNA alone. Prior HBV infection was a risk factor for poor outcome after liver resection for patients infected with HCV.

Fever, weight loss, and night sweats: infection or malignancy?

Case report (Dr A Winter) A Peruvian man in his 30s was admitted as an emergency with a 3 week history of fluctuating temperatures and rigors, a worsening sore throat,...

Detection of precore/core-mutant hepatitis B virus genome in patients with acute or fulminant hepatitis without serological markers for recent HBV infection

To confirm the possibility that some hepatitis B virus (HBV) variants do not induce HB s antigen (HBsAg), anti-HB core antibody (anti-HBc) and anti-HBc IgM in a transient infection, polymerase chain reaction (PCR) was performed in 20 patients with acute hepatitis and 7 patients with fulminant hepatitis. Patients were diagnosed with non-A, non-B hepatitis by serological markers at admission. PCR successfully amplified the precore/core gene in 5 (25%) of the patients with acute hepatitis and 2 (29%) of the patients with fulminant hepatitis. Subsequent sequencing revealed frequent mutations including precore-defects in the precore/core gene.

Changes of Anti-HB Core Antibody in Children with Positive HB Surface Antigen

To elucidate the clinical courses of children chronically infected with HB virus (HBV), RIA values of anti-HBc were surveyed in 88 cases with positive HBs antigen. Among 56 children with positive HBe antigen, 20 had negative, indefinite or low titers of anti-HBc, and 18 (90%) of them had no liver malfunction. Out of 30 cases with abnormal liver function tests, 28 (93%) had high titers of anti-HBc. Follow-up study for a period of over 12 months reveals that serum HBe antigen disappeared in 10 out of the 40 cases who were positive for this antigen. All of the 10 cases had liver malfunction and high levels of anti-HBc. Among 12 children with initially positive anti-HBe, five had high titers of anti-HBc. Out of 13 children who once had high levels of anti-HBc, 3 showed reduction in titers of anti-HBc during the follow-up period in accordance with decrease in activity of hepatitis. Four out of 16 who initially had HBe antigen and low titers of anti-HBc showed high titers of anti-HBc during the observation period, while only one of 33 who had HBeAg and a high titer of anti-HBc went to the low titer group of anti-HBc, though continuously positive for HBe antigen. We presume that high levels of anti-HBc indicate previous or current liver damage due to HBV infection, while low titers of anti-HBc indicate that HBV-derived liver damage has not yet occurred or that a long time has passed since the last episode of liver damage subsided.