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Sudan is a highly endemic area for hepatitis B virus (HBV), and >5% of blood donors are chronically infected. To examine potential strategies to improve HBV blood safety, 404 replacement donor samples previously screened for HBV surface antigen (HBsAg) were tested for antibody to HBV core (anti-HBc), anti-surface antigen (anti-HBs), and HBV DNA. Of 145 anti-HBc-containing samples (36%) identified, 16 retested were HBsAg positive (11%). Anti-HBs was detected in 43/77 (56%) anti-HBc-reactive samples. Six samples were HBsAg−/anti-HBc+/anti-HBs+ and contained HBV DNA, meeting the definition of occult HBV infection (OBI). OBIs had low HBV DNA loads (<10 IU/ml) and were genotype B (n = 1) or genotype D (n = 5). Pre-S/S and/or whole genome sequences were obtained from 47 randomly selected HBsAg-positive donors added to the previous 16. Genotype E was identified in 27 strains (57.5%), genotype D in 19 strains (40.5%), and genotype A2 in 1 strain (2%). Two outlier strains within genotype D ultimately were identified as recombinants of genotypes D and E with identical recombination points, suggesting circulating, infectious, recombinant strains. Anti-HBc screening does not appear to be a sustainable blood safety strategy because of the cost and the negative impact on the Sudanese blood supply, even when reduced by anti-HBs testing. Being at the junction between two main African HBV genotypes, genetic recombination occurred and became part of the molecular epidemiology of HBV in Sudan.

AIM: To study the seroprevalence of antibody to hepatitis B core antigen (anti-HBc) in healthy blood donors negative for HBsAg and to evaluate whether anti-HBc detection could be adopted in India as a screening assay for HBV in addition to HBsAg.

METHODS: A total of 1700 serum samples collected from HBsAg-negative healthy blood donors were tested for the presence of anti-HBc antibody (IgM + IgG). All samples reactive for anti-HBc antibody were then investigated for presence of anti-HBs and for liver function tests (LFTs). One hundred serum samples reactive for anti-HBc were tested for HBV DNA by PCR method.

RESULTS: Out of 1700 samples tested, 142 (8.4%) blood samples were found to be reactive for anti-HBc. It was significantly lower in voluntary (6.9%) as compared to replacement donors (10.4%, P = 0.011). Seventy-two (50.7%) anti-HBc reactive samples were also reactive for anti-HBs with levels > 10 mIU/mL and 70 (49.3%) samples were non-reactive for anti-HBs, these units were labeled as anti-HBc-only. These 142 anti-HBc reactive units were also tested for liver function test. HBV DNA was detected in only 1 of 100 samples tested.

CONCLUSION: Keeping in view that 8%-18% of donor population in India is anti-HBc reactive, inclusion of anti-HBc testing will lead to high discard rate. Anti-HBs as proposed previously does not seem to predict clearance of the virus. Cost effectiveness of introducing universal anti-HBc screening and discarding large number of blood units versus considering ID NAT (Individual donor nuclic acid testing) needs to be assessed.

Background

Occult hepatitis B virus (HBV) infection might transmit viremic units into the public blood supply if only hepatitis B surface antigen (HBsAg) testing is used for donor screening. Our aim was to evaluate the prevalence of occult HBV infection among the HBsAg negative/antiHBc positive donations from a highly HIV prevalent region of India.

Methods

A total of 729 HBsAg negative donor units were included in this study. Surface gene and precore region were amplified by in house nucleic acid test (NAT) for detection of occult HBV infection and surface gene was analyzed after direct sequencing.

Results

A total of 220 (30.1%) HBsAg negative donors were antiHBc positive, of them 66 (30%) were HBV DNA positive by NAT. HBV DNA positivity among 164 antiHBc only group, was 27.1% and among 40 antiHBs positive group was 30.0%. HBV/D (93.3%) was predominant and prevalence of both HBV/C and HBV/A was 3.3%. Single or multiple amino acids substitutions were found in 95% samples.

Conclusion

Thus, a considerable number of HBV infected donors remain undiagnosed, if only HBsAg is used for screening. Addition of antiHBc testing for donor screening, although will lead to rejection of a large number of donor units, will definitely eliminate HBV infected donations and help in reducing HBV transmission with its potential consequences, especially among the immunocompromised population. The HBV genetic diversity found in this donor population are in accordance with other parts of India.

Rapid counter-immunoelectrophoresis (CIE) and radioimmunoassay (RIA) methods for detecting antibody to hepatitis B core antigen (anti-HBc) were used to screen nearly 8000 blood donors, including 919 prisoners. The prevalence of anti-HBc in prisoner donors (3.4%) was significantly higher than that in other donors (0.7%). The three HBsAg positive donors in the series were all anti-HBc positive and, of the other 73 anti-HBc positive donors, 62 had antibody to HBsAg (anti-HBs). Two panels of control sera, including 155 HBsAg positive samples, were tested by CIE for anti-HBc: 149 of the 155 were anti-HBc positive. Of the six negative samples, four were HBsAg positive only by RIA. One of the panels, containing 16 weakly HBsAg positive samples, was available for anti-HBc testing by RIA. Fifteen of the samples were positive and the other was slightly reactive. Donor sera that gave unconfirmable reactions in initial CIE tests were invariably negative when tested by RIA. The RIA was a more sensitive and specific test for anti-HBc than CIE. The ways in which anti-HBc screening could meet the needs of blood transfusion centres are discussed. We suggest that, in areas of low prevalence, it has a role as a rapid confirmatory test of HBV infection and as a means of identifying those potentially infectious donations in which HBsAg cannot be detected.

Background and Aims

Occult hepatitis B infected (OBI) patients can not completely eradicate hepatitis B virus-DNA (HBV-DNA) from their liver and peripheral blood. The main aim of this study was to investigate the Interleukin (IL)-10and IL-17A serum levels in patients suffering from OBI.

Material and Methods

In this observational study, plasma samples of 3700 blood donors were tested for hepatitis Bsurface antigen (HBsAg) and antibodies to the hepatitis B core antigen (anti-HBc), using enzyme-linked immunosorbent assay (ELISA). The HBsAg-/anti-HBc+ samples were selected and screened for HBV-DNA, using the polymerase chain reaction (PCR). HBV-DNA positive samples were assigned as OBI cases and IL-10 and IL-17 serum levels were detected using ELISA.

Results

The results demonstrated that, 352 (9.5%) out of 3700 blood samples were HBsAg-/anti-HBc+ and HBV-DNA was detected in 57/352 (16.1%) of the HBsAg-/anti-HBc+ samples. Our results showed that the IL-10 and IL-17A serum levels increased significantly in the OBI cases in comparison to the controls (P < 0.001).

Conclusions

According to the results of this study the higher level of IL-10 production may suppress the functioning of the immune system against HBV in OBI patients. The elevated IL-17A serum level also indicates a long period of infection in the patients observed.

Anti-hepatitis B core antigen (HBcAg)-positive hepatitis B surface antigen (HBsAg)-negative plasma samples from blood donors were tested by nested PCR. DNA positivity was more significantly associated with high levels of anti-HBcAg than with low levels of anti-HBsAg antibodies. Analysis of a dilution of anti-HBcAg antibodies might result in a more rational exclusion of anti-HBcAg-positive HBsAg-negative samples, reducing the number of donations discarded and enabling more countries to incorporate anti-HBcAg testing.

Background

Transfusion-associated hepatitis B viral infection continues to be a major problem in India even after adoption of mandatory screening for HBsAg by ELISA method. The high incidence of TAHBV is reported in patients receiving multiple transfusions.

Objective

To study the seroprevalence of hepatitis B core antibody among healthy voluntary blood donors

Subjects and Methods

The study was conducted in the department of Transfusion Medicine of a tertiary care referral hospital. A total of 12,232 volunteers after passing through the stringent criteria were selected for blood donation. Donor samples were tested for all mandatory transfusion transmissible infections and anti HBc IgM (Monolisa HBc IgM PLUS:BIO-RAD, France). Reactive results were confirmed by repeat testing in duplicate. Donor data was analyzed using SPSS software and Chi-square test was used to calculate the significance of difference between the groups.

Results

A total of 12,232 healthy voluntary blood donors were recruited. Majority (93.4%) were males. Median age of donor population was 26 years (range: 18–60 years). Eighty six (0.7%) were positive for HBsAg, which comes under “low prevalence (<2%) zone” as per WHO. On screening for HBcAg Ig M, 15 (0.1%) were found to be positive and none were HBsAg reactive. There was no significance of difference in the mean age between reactive and non-reactive donors.

Conclusion

Evaluating the usefulness of anti-HBc screening is critical. Anti HBcAg IgM screening may be included in routine screening of donors as it is an indicator of occult HBV during window period. The cost and the unnecessary wastage of the blood units when they are positive for anti HBsAg along with the core antibody need to be studied.

Background and aims

Occult hepatitis B virus infection (OBI) poses a challenge to the safety of blood donation. The prevalence of OBI is not well documented in Indonesia, although this information in such an endemic country is needed. This study was aimed to evaluate the prevalence of occult hepatitis B in blood donors from two cities of Indonesia, and to study the genetic variation and its effect on the predicted antigenicity of HBsAg.

Methods

Serum samples of 309 regular blood donors negative for HBsAg were tested for anti-HBs and anti-HBc. Hepatitis B virus (HBV) DNA isolated from anti-HBc-positive samples were analyzed by polymerase chain reaction, cloned and sequenced. Antigenic properties of identified HBsAg mutants were predicted by calculation of the antigenic index.

Results

Of the 309 HBsAg-negative samples, anti-HBc was positive in 134 (43.4%) and HBV DNA was detected in 25 (8.1%). Seven of the viremic samples had nucleotide substitutions (A521G, A551T, C582T, and A562G) in the S gene, causing amino acid mutations (T123A, M133L, and T143M) in the ‘a’ determinant of HBsAg that resulted in changes in the predicted antigenicity.

Conclusions

OBI was detected in blood donors’ samples in Indonesia. Anti-HBc was shown to be a better screening parameter than HBsAg, however, it might result in the loss of donors particularly in endemic countries. HBsAg detection failure in this study might be due to mutations altering the protein antigenicity and/or the low-level carriage of HBV.

The value of testing for core antibody (anti HBc) in acute hepatitis was assessed in 503 patients. All hepatitis B surface antigen (HBsAg) positive patients tested were also anti HBc positive. Of the 110 HBsAg negative, anti HBc positive patients, 32 were found to have surface antibody, indicating previous infection with hepatitis B virus (HBV). Of the remaining 78 patients in whom anti HBc alone was detectable, follow-up specimens were received from 28 and, of these, 21 were then found to be anti HBc negative. Thus in acute hepatitis non-specific transient reactions to core antigen may appear, and the presence of anti HBc alone cannot be considered adequate evidence for a diagnosis of HBV infection.

Background/Aim:

Occult hepatitis B infection (OBI) is identified as a form of hepatitis in which despite the absence of detectable HBsAg, HBV-DNA is observed in peripheral blood of patients. The main aim of this study has been to investigate the association between polymorphisms in +874 of IFN-γ and +1188 of IL-12 with their serum level in patients suffering from OBI.

Materials and Methods:

In this experimental study, plasma samples of 3700 blood donors were tested for the presence of hepatitis B surface antigen (HBsAg) and anti-HBc by ELISA. The HBsAg-/anti-HBc+ samples were selected and screened for HBV-DNA by PCR. HBV-DNA positive samples were assigned as OBI cases and ARMS-PCR techniques were performed to examine the two known polymorphisms within IL-12 and IFN-γ. In addition, the serum levels of IL-12 and IFN-γ were also determined by ELISA.

Results:

Results of this study demonstrated that, 352 (9.5%) out of 3700 blood samples were HBsAg-/anti-HBc+ and HBV-DNA was detected in 57/352 (16.1%) of HBsAg-/anti-HBc+ samples. Our results showed that groups showed significant difference in CC allele of +1188 region of IL-12 and no difference was observed in the other evaluated genes. Our results also showed that the alleles of +1188 region of IL-12 and alleles of +874 of IFN-γ were also not associated with serum level of cytokines.

Conclusion:

According to the results of this study, it may be concluded that the polymorphisms in +1188 region of IL-12 and +874 region of IFN-γ would not affect the expression of both cytokines at serum level in OBI patients.

Background & objectives:

Safe blood and blood products should be offered to all patients in need for blood transfusion. The objectives of the present study were to establish prevalence estimates for hepatitis B and hepatitis C virus infections as a foundation for safe blood transfusion in rural Vietnam, and to check the accuracy of the laboratory analysis used for hepatitis testing of blood donors in Vietnam.

Methods:

A cross-sectional study was conducted in two rural communities in Quang Tri, Vietnam. A total of 1,200 blood samples collected from potential blood donors were tested by an enzyme immunoassay technique (EIA) for detection of hepatitis surface antigen (HBsAg), antibodies to hepatitis B core antigen (anti-HBc), and antibodies to hepatitis C antigen (anti-HCV). The EIA test outcome was validated by a chemiluminescent micro particle immunoassay technique (CMIA).

Results:

The prevalence of HBsAg and anti-HBc in the study population was 11.4 per cent (95% CI 9.6 - 13.2) and 51.7 per cent (95% CI 48.8 - 54.5), respectively, the prevalences being higher in males than females. The prevalence of anti-HCV was 0.17 per cent. The test agreement between the EIA and CMIA techniques was high both for HBsAg detection (κ = 0.91; 95% CI: 0.83 - 0.99) and for anti-HBc detection (κ = 0.89; 95% CI 0.81 - 0.97). Compared to CMIA results, the positive and negative predictive values of the EIA tests were found to be 94.9 per cent (95% CI 87.5 - 98.6) and 97.5 per cent (95% CI 86.8 - 99.9) for HBsAg, and 92.4 per cent (95% CI 84.2 - 97.2) and 100 per cent (95% CI 91.2 - 100) for anti-HBc.

Interpretation & conclusions:

The study shows that hepatitis B virus infection is endemic in rural areas of Vietnam and that almost half of the population is or has been infected. Hepatitis C infection is rare, but false negative test results cannot be ruled out. Also, the results indicate that the EIA performance in blood donor screening in Vietnam may be sub-optimal, missing 2.5 per cent of hepatitis B virus carriers and falsely excluding more than 7 per cent of blood donors. As the prevalence of hepatitis B infection is high, occult hepatitis B infection may represent a threat to safe blood transfusion. Therefore, nucleic acid amplification testing for HBV should be considered for blood donor screening in Vietnam.

Hepatitis B core antigen (HBcAg) was prepared from human liver tissue and used in an immunoelectro-osmophoresis screening test to detect antibody to HBcAg (anti-HBc) in patients with evidence of liver disease and in blood donors. With the exception of two immunosuppressed HBsAg carriers, anti-HBc was found in all cases of hepatitis B infection even when HBsAg was detectable only by radioimmunoassay. Non-specific reactions were observed in 'non-B' hepatitis but, in spite of this problem, antib-HBc screening was considered a useful addition to routine tests in the clinical hepatitis laboratory.

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A total of 284 Lancashire police officers each with a minimum of 5 years experience was tested for evidence of hepatitis B infection. None was hepatitis B surface antigen positive (HBsAg). Three were positive for both antibody to hepatitis B core antigen (anti-HBc) and HBsAg (anti-HBs). Five were positive for anti-HBc alone. Thus the overall prevalence was 2.8% which is within the range reported for blood donors in the UK. There was no association with working in the drug squad or custody office but there was a higher prevalence in those who had worked in the scene-of-crime's squad. However, the numbers were small, and of this group of 28 officers, 2 of the 3 with detectable hepatitis B markers were positive for anti-HBc alone. Therefore for police officers in mixed rural/urban areas of the UK, routine administration of hepatitis B vaccine is not justified although special consideration should be given to those working in selected groups. Further studies are required to ascertain whether there may be an increased risk for police officers working in conurbations.

We studied the epidemiologic features of hepatitis B virus (HBV) infection in northern Labrador to determine the prevalence of the infection and to obtain a database to develop a vaccination strategy. The study population included seven communities in which five ethnic groups were represented: Inuit, Innu, mixed Inuit and European ancestry ("settler"), nonnative/nonsettler transient population ("white") and people of Innu-white or Innu-Inuit origin ("mixed"). Blood samples from 2156 people (62% of the area residents) were tested for antibody to HBV core antigen (anti-HBc), HBV surface antigen (HBsAg), HBV e antigen (HBeAg), anti-HBc IgM and antibody to the surface antigen (anti-HBs). The overall crude prevalence rate of HBV seromarkers was 14.7% and the HBsAg carrier rate at least 3.2%; the rates were highest for Inuit (26.4% and 6.9% respectively), followed by settler (10.0% and 1.9% respectively) and Innu (7.6% and 0.4% respectively); the white and mixed groups had the lowest overall rates (2.5% and 3.3% respectively). Although the overall prevalence rates were about the same for the two sexes, the HBsAg carrier rate was higher in males (male:female ratio 1.6:1.0). No HBV carriers were positive for HBeAg or anti-HBc IgM antibody. The rate of exposure to HBV was 4% for those below the age of 20 years and reached a peak for those aged 45 to 54 years (85% for Inuit, 40% for settlers and 37% for Innu). There was also a wide variation in the age-standardized prevalence rates (0% to 27.9%) among the ethnic groups in the seven communities surveyed.

Background and aims: Liver donors with serological evidence of resolved hepatitis B virus (HBV) infection (HBV surface antigen (HBsAg) negative, anti-HBV core (HBc) positive) can transmit HBV infection to recipients. In the context of organ shortage, we investigated the efficacy of hepatitis B immunoglobulin (HBIG) to prevent HBV infection, and assessed the infectious risk by polymerase chain reaction (PCR) testing for HBV DNA on serum and liver tissue of anti-HBc positive donors.

Patients: Between 1997 and 2000, 22 of 315 patients were transplanted with liver allografts from anti-HBc positive donors. Long term HBIG therapy was administered to 16 recipients. Four naive and two vaccinated patients received no prophylaxis.

Results: Hepatitis B developed in the four HBV naive recipients without prophylaxis and in none of the vaccinated subjects. Among the 16 recipients receiving HBIG, one patient with residual anti-HBs titres below 50 UI/ml became HBsAg positive. The remaining 15 remained HBsAg negative and HBV DNA negative by PCR testing throughout a 20 month (range 4–39) follow up period. HBV DNA was detected by PCR in 1/22 donor serum, and in 11/21 liver grafts with normal histology. A mean of 12 months post-transplantation (range 1–23) HBV DNA was no longer detectable in graft biopsies from patients remaining HBsAg negative.

Conclusion: Anti-HBs antibodies may control HBV replication in liver grafts from anti-HBc positive donors, without additional antiviral drugs. These grafts are thus suitable either to effectively vaccinated recipients or to those who are given HBIG to prevent HBV recurrence.

Background

Occult hepatitis B infection (OBI) is a form of hepatitis in which there is an absence of detectable HBsAg, despite the presence of HBV-DNA in the peripheral blood of patients. It seems that non-effective or attenuated immune system responses against HBV lead to the development of OBI. Previous studies showed that the Fas/Fas ligand (FasL) system is an important death signaling pathway that is used by cytotoxic T lymphocytes to eradicate HBV from the liver.

Objectives

To investigate polymorphisms in the -670 region of the Fas gene in those with OBI.

Patients and Methods

The plasma samples from 3700 blood donors were tested for HBsAg and anti-HBs by ELISA. The HBsAg-/anti-HBc(+) samples were selected and screened for HBV-DNA by PCR. Those with HBV-DNA were diagnosed as OBI and PCR-RFLP technique was performed to examine polymorphisms within their Fas gene.

Results

352 (9.5%) of 3700 blood samples were HBsAg-/anti-HBc(+). HBV-DNA was detected in 57 (16.1%) of 352 HBsAg-/anti-HBc(+) samples. Therefore, 57 HBsAg-/anti-HBc+/HBV-DNA(+) patients were diagnosed as OBI. Patient and control groups had no significant differences in terms of the studied polymorphisms.

Conclusions

The functional polymorphisms in the promoter region of Fas gene are not associated with OBI. Therefore, it may be concluded that polymorphisms at the -670 position of the Fas gene do not have any critical effects on the immune response against HBV in OBI.

Background

Isolated antibody to hepatitis B core antigen (anti-HBc) is a common serologic finding in persons infected with human immunodeficiency virus (HIV), but the outcome and clinical significance are uncertain.

Methods

We performed repeated hepatitis B virus (HBV) serologic tests on women who participated in the Women’s Interagency HIV Study and who had isolated anti-HBc at study entry.

Results

Repeated serologic tests were performed for 322 women (282 HIV-infected and 40 HIV-uninfected) at a median of 7.5 years after study entry. Seventy-one percent of women retained isolated anti-HBc serologic status, 20% acquired antibody to hepatitis B surface antigen (anti-HBs), and 2% acquired hepatitis B surface antigen (HBsAg). In unadjusted analysis, increasing age, injection drug use, and hepatitis C viremia were negatively associated with acquisition of anti-HBs. For HIV-infected women, predictors of acquisition of anti-HBs were an increase in CD4 cell count and the use of highly active antiretroviral therapy (HAART). Receipt of drugs with activity against HBV and self-reported HBV vaccination did not predict anti-HBs acquisition. In the multivariable regression model, HAART use remained a significant predictor of anti-HBs acquisition, whereas women with hepatitis C viremia were more likely to retain isolated anti-HBc serologic status.

Conclusions

Isolated anti-HBc status remained stable over time for the majority of women, especially women with chronic hepatitis C virus infection. Development of anti-HBs was predicted by HAART use and an increase in CD4 cell count. We conclude that a proportion of HIV-infected women with isolated anti-HBc have prior natural HBV infection with anti-HBs that is at an undetectable level because of immune dysfunction. Isolated anti-HBc in the presence of chronic hepatitis C virus infection may be attributable to a different phenomenon, such as dysfunctional antibody production.

Background

The clinical significance of occult hepatitis B virus (HBV) infection, defined as the presence of HBV DNA in individuals with HBV core antibodies (anti-HBc) in the absence of HBV surface antigen (HBsAg), is unclear in HIV-infected patients. This information is needed to determine the importance of detecting and treating occult HBV in this population.

Objective

To determine if HIV-infected patients with occult HBV infection have an increased incidence of transaminitis.

Study Design

We performed a cohort study among randomly-selected HBsAg−/anti-HBc+ HIV-infected patients in the Penn CFAR Database and Specimen Repository. HBV DNA was qualitatively detected using a transcription-mediated amplification assay. Hepatic transaminase levels, the main study outcome, were collected at 6-month intervals from the time of occult HBV determination.

Results

Among 97 randomly-selected subjects without baseline transaminitis, 13 (13%) had occult HBV. These subjects more frequently had detectable HIV RNA. The two-year incidence of transaminitis among HIV-infected subjects with occult HBV (50 events/100 person-years) was not significantly different from those without occult HBV (38 events/100 person-years; adjusted incidence rate ratio=1.36 [95% CI, 0.72-2.59]).

Conclusions

Occult HBV did not increase the incidence of hepatic transaminitis over two years. Future studies should determine whether occult HBV is associated with other clinically important outcomes, particularly hepatocellular carcinoma.

Addition of reducing agents to competitive assays for antibody to hepatitis B core antigen (anti-HBc) eliminates apparent false reactivity of specimens obtained from individuals with no prior history of hepatitis B virus (HBV) infection and without other serological markers of HBV infection. We have purified and characterized a reduction-sensitive factor (RSF) isolated from the plasma of several volunteer blood donors. Column fractions were assayed fro anti-HBc by using a highly sensitive chemiluminescence assay with a detection of 0.15 Paul Ehrlich Institut units per ml at 50% inhibition. Gel filtration on Sephacryl S-300 indicated that reductant-sensitive samples possessed anti-HBc activity that was associated with immunoglobulin M (IgM), whereas reductant-stable activity was associated with IgG. Gel filtration followed by metal chelate affinity chromatography resulted in a 55-fold purification and demonstrated that RSF activity copurifies with IgM. RSF was recovered from a recombinant hepatitis B core antigen matrix and shown to be an IgM species by immunoblot. In addition, RSF activity coeluted with IgM protein from anti-mu-chain Sepharose. Discrepancies between enzyme immunoassay and radioimmunoassay procedures for anti-HBc (Corzyme and Corab, respectively: Abbott Laboratories, North Chicago, Ill.) appear to be due to the relative sensitivity of the enzyme immunoassay for IgM anti-HBc (sevenfold greater than the radioimmunoassay using a specific panel). The biological basis for the occurrence of low levels of nonspecific IgM anti-HBc reactivity in individuals not previously exposed to HBV remains to be elucidated.

Purpose

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are considered to be hepatotropic and are a major cause of hepatocellular carcinoma. However, little is known about the role of HBV and HCV infection in other malignancies. This study aimed to determine whether HBV and HCV infections increase the risk for pancreatic cancer development.

Patients and Methods

At The University of Texas M. D. Anderson Cancer Center, Houston, TX, we recruited 476 patients with pathologically confirmed adenocarcinoma of the pancreas and 879 age-, sex-, and race-matched healthy controls. Blood samples were tested for the presence of HCV antibodies (anti-HCV), HBV surface antigen (HBsAg), antibodies against HBV core antigen (anti-HBc), and antibodies against HBsAg (anti-HBs). The positive samples were retested by two confirmatory tests. An unconditional multivariable logistic regression analysis was used to estimate adjusted odds ratios (AORs).

Results

Anti-HCV was positive in seven cases (1.5%) and nine controls (1%). Anti-HBc was positive in 36 cases (7.6%) and 28 controls (3.2%). The estimated AORs and 95% CIs were as follows: anti-HCV–positive, 0.9 (95% CI, 0.3 to 2.8), anti-HBc–positive, 2.5 (95% CI, 1.5 to 4.2), anti-HBc–positive/anti-HBs–positive, 2.3 (95% CI, 1.2 to 4.2), and anti-HBc–positive/anti-HBs–negative, 4 (95% CI, 1.4 to 11.1). Risk modification by past exposure to HBV was observed among diabetics (AOR, 7.1; 95% CI, 1.7 to 28.7).

Conclusion

Past exposure to HBV may be associated with pancreatic cancer development. Should such findings be confirmed by other studies, it may offer important insights into the etiology of pancreatic cancer and may suggest the need to consider prevention of HBV reactivation among patients with HBV-related pancreatic cancer during chemotherapy.

Purpose

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are considered to be hepatotropic and are a major cause of hepatocellular carcinoma. However, little is known about the role of HBV and HCV infection in other malignancies. This study aimed to determine whether HBV and HCV infection increase the risk for pancreatic cancer development.

Patients and Methods

At The University of Texas M.D. Anderson Cancer Center, Houston, we recruited 476 patients with pathologically confirmed adenocarcinoma of the pancreas and 879 age-, sex-, and race-matched healthy controls. Blood samples were tested for the presence of HCV antibodies (anti-HCV), HBV surface antigen (HBsAg), antibodies against HBV core antigen (anti-HBc), and antibodies against HBsAg (anti-HBs). The positive samples were retested by two confirmatory tests. An unconditional multivariable logistic regression analysis was used to estimate adjusted odds ratios (AORs).

Results

Anti-HCV was positive in 7 cases (1.5%) and 9 controls (1%). Anti-HBc was positive in 36 cases (7.6%) and 28 controls (3.2%). The estimated AORs and 95% confidence intervals (CIs) were as follows: anti-HCV+, 0.9 (0.3–2.8), anti-HBc+, 2.5 (1.5–4.2), anti-HBc+/anti-HBs+, 2.3 (1.2–4.2), and anti-HBc+/anti-HBs-, 4 (1.4–11.1). Risk modification by past exposure to HBV was observed among diabetics (AOR, 7.1; 95% CI, 1.7–28.7).

Conclusion

Past exposure to HBV may be associated with pancreatic cancer development. Should such findings be confirmed by other studies, it may offer important insights on the etiology of the pancreatic cancer and may suggest the need to consider prevention of HBV reactivation among HBV-related pancreatic cancer patients during chemotherapy treatment.

Hepatitis B virus (HBV) infection is endemic in various parts of the world. A proportion of patients have resolved prior exposure to HBV, as evidenced by the clearance of circulating hepatitis B surface antigen and the appearance of antibody to hepatitis B core antigen (anti-HBc), which could produce protective antibody to hepatitis B surface antigen (anti-HBs). With time, anti-HBs in some patients may become negative. Such patients are described as having occult HBV infection or “anti-HBc alone”. In the context of immunodeficient patients, such as HIV patients or lymphoma patients undergoing immunosuppressive immunotherapy, the lack of protective anti-HBs may increase the risk of hepatitis B reactivation. Serum HBV DNA testing may be necessary in “anti-HBc alone” patients, to detect patients at a high risk of developing HBV infection allowing appropriate prophylactic management.

Sera from two blood donors, one of whom was implicated in a case of post-transfusion hepatitis B, were found to be positive for anti-HBc and negative for HBsAg by conventional radioimmunoassay and were retested for HBsAg after concentration (pepsin digestion and polyethylene glycol precipitation). The presence of occult HBsAg was confirmed in both. These observations have implications for blood transfusion, and wider studies of anti-HBc in blood donors are recommended before the introduction of routine screening for anti-HBc and exclusion of the positive donors from blood donation.

Tests by counter-immunoelectrophoresis for antibody to hepatitis B core antigen (anti-HBc) were introduced into a routine testing programme for evidence of hepatitis B virus infection. Samples tested for anti-HBc were selected on the basis of the results of tests for HBsAg and clinical details. The sensitivity and specificity of the test were assessed and correlations made with the presence of HBsAg. The presence of anti-HBc was very useful in the interpretation of a doubtful positive result for HBsAg in the haemagglutination test. With very few exceptions the serum samples positive for HBsAg by routine tests also contained anti-HBc. It is concluded that the test is valuable and merits introduction into routine testing programmes.

BACKGROUND

Fresh-frozen plasma (FFP) may contain antibodies to hepatitis B surface antigen (HBsAg, anti-HBs). These anti-HBs may lead to a misinterpretation of the actual hepatitis B immune status. Furthermore, they may not only confer protection against hepatitis B virus (HBV), but may also favor the selection of HBsAg mutants.

CASE REPORT

We report a case of de novo HBV infection in a HBV-naïve recipient with alcoholic liver disease, who received a liver from a donor with antibodies to hepatitis B core antigen (HBcAg, anti-HBc) and anti-HBs.

RESULTS

A lookback investigation revealed the following: 1) Due to anti-HBs passively acquired through FFP, the recipient was considered immune to HBV and did not receive anti-HBV prophylaxis. 2) Within 1 year after transplantation he developed hepatitis B in absence of any elevated liver enzymes after the anti-HBs by FFP declined. 3) Despite an infection with HBV-containing wild-type HBcAg, the patient did not seroconvert to anti-HBc positivity. 4) The replicating HBV encoded two HBsAg mutations, first sQ129R and 4 months later sP127S. They map to the highly conserved “α” determinant of the HBsAg loop.

CONCLUSION

1) Passive transfer of anti-HBs from FFP led to an erroneous pretransplant diagnosis of HBV immunity when the patient was in fact HBV-naïve. 2) HBsAg mutations might have been selected in escape from donor's actively produced anti-HBs and the recipient's anti-HBs by FFP might have favored this selection. 3) It is doubtful whether hepatitis B immunoglobulin could have prevented the reactivation. 4) Antiviral prophylaxis would have been crucial.