anti-HB Antibodies Research Articles

Detekcija dobrovoljnog darivatelja krvi s preboljelom infekcijom hepatitisa Bprikaz bolesnice

Introduction: Hepatitis B is liver inflammation caused by the hepatitis B virus, with more than 250 million documented cases worldwide in the chronic form of infection. Markers of hepatitis B infection can be measured in the blood during or after infection and may be present in the form of specific hepatitis B surface antigen (HBsAg) or antibodies to hepatitis B surface (HBs), core (HBc), or envelope (HBe) antigens. Case report: A 42-year-old female, who successfully donated blood for the first time, underwent mandatory serological and molecular testing along with additional testing for other hepatitis B markers. Standard screening showed the absence of HBsAg in the blood, but additional serological testing confirmed the presence of total antibody to hepatitis B core antigen (anti-HBc). Upon repeated reactive results, the sample was sent for confirmatory testing to a reference center. After obtaining all the results, it was determined that the voluntary blood donor had the presence of anti-HB cand HBs antibodies, indicating a prior contact with the hepatitis B virus. While serological tests suggested a resolved hepatitis B infection, the possibility of a persistent liver infection could not be ruled out, despite the absence of detectable hepatitis B virus DNA in the blood. Therefore, the individual has been permanently excluded from the list of potential blood donors. Conclusion: Mandatory serological and molecular testing of blood donors for the hepatitis B virus successfully detects potentially infected individuals and carriers of hepatitis B markers. However, additional testing further enhances the safety of both recipients and blood donors. This case study highlights the importance of comprehensive screening for hepatitis B markers, as relying solely on HBsAg screening would not have identified the voluntary blood donor as a resolved hepatitis B case. Thus, comprehensive screening ensures a higher level of safety in blood transfusion and contributes to overall healthcare protection.

Serodiagnosis of Hepatitis B Surface Antigen and Anti Hepatitis C Virus among Hemodialysis Patients in Khartoum State- Sudan

Background: Hepatitis B virus (HBV) is a hepatotropic virus that can establish a persistent and chronic infection in humans through immune energy. Hepatitis C virus (HCV) is a hepatotropic RNA virus that causes progressive liver damage. In hemodialysis (HD), blood is removed from the patient with needles and plastic tubing and pumped past the dialysis membrane. Poisons and toxins cross the dialysis membrane into the dialysate, which is then discarded, and the blood is returned to the patient. Objectives: The study aimed to detect HBsAg and anti-HCV in HD patients and the control group. Methods: A retrospective case-control, a hospital-based study was carried out on 110 participants 60 HD patients and 50 control, 60 males and 50 females, ages between 20 -39 years 27 participants and ages between 40-59 years 32 participants and ages more than 60 51 participants, ELISA method was used to detect HBsAg and anti-HCV in HD patients and control sera, the study was carried out during the period from August 2021 to January 2022. Results: In this study, the overall prevalence of HBV infection among HD patients and the control group was 26.3% (2/110), and among HD patients was 45 % (27/60), while it was 4% (2/50) among the control group any non – HD patient, co-patient, hospital staff and the overall prevalence of HCV was 1,8 % (2/110) and it was 3.3% (2/60) among the HD patients, 0% (0/50) among the control group. There was a significant association between HBV infection and HD (P value 0.019). Conclusions: The prevalence of HBV among HD patients was very high (45%). The results emphasize the need to carry out proactive tasks for early diagnosis by using highly sensitive and specific methods such as PCR technique, treatment of infected individuals, and vaccinating those with non-protective anti-HB antibodies to reduce morbidity and mortality in HD patients.

Proximity hybridization-induced competitive rolling circle amplification to construct fluorescent dual-sensor for simultaneous evaluation of glycated and total hemoglobin

The glycated hemoglobin (HbA1c) level, defined as the ratio of HbA1c to total hemoglobin (tHb), has been considered as a standard index for diabetes mellitus diagnosis, avoiding any short-term fluctuation of the blood glucose level. However, it is still a key challenge that some complicated separation procedures are required to detect HbA1c and tHb in a single experiment. Herein, we developed a dual-sensing fluorescent assay for HbA1c and tHb based on proximity hybridization-induced rolling circle amplification (RCA) and T7 exonuclease aided signal cycle to calculate the HbAlc level in one single experiment. Typically, four DNA-tagged probes were used for immunoreactions of anti-HbA1c antibodies (Ab1) and anti-Hb antibodies (Ab2) with HbA1c and Hb, respectively. The RCA1 and RCA2 were induced by the complexes of assistant DNAs and the products of proximity hybridization with anti-HbA1c-DNA1 (2) and anti-Hb-DNA3 (4), respectively. Meanwhile, the tHb in solution could prevent the existing RCA2 based on its competing with Hb-DNA3 for Ab2-DNA4. Thus, RCA1 and RCA2 routes create “signal-on” and “signal-off” readouts, respectively. After the hybridization of signal probes and RCA products, the quenched fluorescence was recovered by the digestion of T7 exonuclease. Under optimized conditions, the method displayed high sensitivity with a limit of detection 2.17 ng/mL and 33.4 ng/mL for HbA1c and tHb, respectively, and the real sample analysis results were found to match well with the theoretical data, holding feasibility for rapid, homogeneous, and easy HbA1c level evaluation and great promise as a potential alternative tool to analyze HbA1c level clinically.

Polymeric microsphere enhanced surface plasmon resonance imaging immunosensor for occult blood monitoring

Occult blood testing is a routine screening method for evaluating the function of the urinary system and digestive tract. The hemoglobin (Hb) content in human excreta is an important indicator of the presence of occult blood. In this study, a surface plasmon resonance imaging (SPRi)-based immunosensor with high sensitivity was developed for the detection of Hb. The immunosensor was constructed by physically immobilizing anti-Hb antibodies on the detection channels. Samples for evaluation were pre-incubated with the polymeric microsphere-antibody conjugate. The shift in resonance wavelength induced by the specific binding of microsphere-antibody-antigen and immobilized antibodies was monitored in real time. Owing to the amplification effect of microspheres, the detection limit of the immunosensor was reduced 42-fold to 4.8 ng/mL under the optimized concentration of immobilized antibody (10 μg/mL) with microsphere-antibody conjugate dilution ratio of 1:200 and incubation time of the microsphere-antibody conjugate and samples (10 min). The immunosensor displayed a good linear response to Hb ranging from 10 ng/mL to 500 ng/mL in both test solutions and in 1:30 urine sample, as well as a good specificity toward Hb and an acceptable recovery rate for spiked Hb solution in urine sample. The immunosensor was also exploited to detect the Hb concentration in 50 clinical urine samples. Therefore, the proposed SPRi immunosensor developed in this study provides a simple, rapid, high-throughput, and sensitive immunology strategy for the detection of occult blood.

Discrete cis-acting element regulates developmentally timed gene-lamina relocation and neural progenitor competence invivo.

SUMMARYThe nuclear lamina is typically associated with transcriptional silencing, and peripheral relocation of genes highly correlates with repression. However, the DNA sequences and proteins regulating gene-lamina interactions are largely unknown. Exploiting the developmentally timed hunchback gene movement to the lamina in Drosophila neuroblasts, we identified a 250 bp intronic element (IE) both necessary and sufficient for relocation. The IE can target a reporter transgene to the lamina and silence it. Endogenously, however, hunchback is already repressed prior to relocation. Instead, IE-mediated relocation confers a heritably silenced gene state refractory to activation in descendent neurons, which terminates neuroblast competence to specify early-born identity. Surprisingly, we found that the Polycomb group chromatin factors bind the IE and are required for lamina relocation, revealing a nuclear architectural role distinct from their well-known function in transcriptional repression. Together, our results uncover in vivo mechanisms underlying neuroblast competence and lamina association in heritable gene silencing.

Surface Modification of Hemoglobin-Based Oxygen Carriers Reduces Recognition by Haptoglobin, Immunoglobulin, and Hemoglobin Antibodies

Hemoglobin-based oxygen carriers (HBOCs) represent a propitious type of blood substitute to transport oxygen throughout the body while acting as a carrier in biomedical applications. However, HBOCs in blood are recognized and rapidly scavenged by the body’s innate immune systems. To overcome this problem, HBOCs require a surface modification that provides protection against detection and elimination in order to prolong their circulation time after administration. In this study, we investigated different surface modifications of hemoglobin submicron particles (HbMPs) by double/triple precipitation, as well as by adsorption of human serum albumin (HSA), hyaluronic acid (HA), and pluronic (Plu) to discover how diverse surface modifications influence the oxygen binding capacity and the binding of anti-hemoglobin (Hb) antibodies, immunoglobulin G (IgG), and haptoglobin (HP) to HbMPs. The particle size and zeta potential of the six types of HbMP modifications were analyzed by zeta sizer, confocal laser scanning microscopy, and transmission electron microscopy (TEM), and were compared to the unmodified HbMPs. The results revealed that all surface-modified HbMPs had a submicron size with a negative charge. A slight decrease in the oxygen binding capacity was noticed. The specific binding of anti-Hb antibodies, IgG, and HP to all surface-modified HbMPs was reduced. This indicates a coating design able to protect the particles from detection and elimination processes by the immune system, and should lead to a delayed clearance and the required and essential increase in half-life in circulation of these particles in order to fulfill their purpose. Our surface modification method reflects a promising strategy for submicron particle design, and can lead the way toward novel biomedical applications.

Direct detection for concentration ratio of HbA1c to total hemoglobin by using potentiometric immunosensor with simple process of denaturing HbA1c

A direct measurement method for HbA1c (%), which is the concentration ratio of HbA1c to total hemoglobin (Hb), was investigate with a potentiometric immunosensor. The direct measurement method is based on sandwich immunoassay that combines anti-Hb and enzyme-labeled anti-HbA1c antibodies. While the anti-Hb antibodies capture both Hb and HbA1c maintaining HbA1c (%) in blood sample, the enzyme-labeled anti-HbA1c antibodies bind only to HbA1c in the total captured Hb. Though we tried the direct detection of HbA1c (%) with a combination of four anti-Hb antibodies and two anti-HbA1c antibodies, the obtained result showed lower sensitivity and reproducibility. We presumed that the binding site of HbA1c for anti-HbA1c antibody hides inside the folding structure of HbA1c and anti-HbA1c antibody is not able to bind to HbA1c efficiently resulting in lower sensitivity. As a result of examination of both the type and concentration of the surfactant, it was found that the process of denaturing HbA1c with 0.2% dodecyltrimethylammonium bromide was added to enable it to be accessible to anti-HbA1c antibodies and could enhance the sensitivity. By adding the simple process of denaturing HbA1c, the direct measurement of HbA1c (%) was successfully performed with this immunosensor. The results showed a good correlation (correlation efficiency, r2 = 0.975) between the certified and experimental values of HbA1c (%) in the clinically relevant range (from 5.6% to 10.6%).

Oxidized Hemoglobin Is Antigenic and Immunogenic in Lupus.

Hemolysis-associated anemia is characteristic of diseases such as atherosclerosis, lupus, malaria, and leishmaniasis; the toxic effects of free hemoglobin (Hb) have been extensively described. This study was based on the premise that release of this sequestered, inflammatory molecule can result in deleterious immunological consequences, particularly in the context of pre-existing lupus. IgG anti-Hb responses were detected in the sera of lupus patients. Lupus-prone mice exhibited heightened plasma Hb levels, and ferric (Fe3+) Hb triggered preferential release of lupus-associated cytokines from splenocytes derived from aging lupus-prone mice. Anti-Hb B cell precursor frequencies were heightened in such mice, which also expressed increased titers of anti-Hb antibodies in serum and in kidney eluates. Fe3+ Hb preferentially increased the functional maturation of bone marrow-derived dendritic cells (BMDCs) from lupus-prone mice, effects abrogated upon the inhibition of Stat3. Hb interacted with lupus-associated autoantigens extruded during apoptosis and coincubation of Hb and apoptotic blebs had additional maturation-inducing effects on lupus BMDCs. Immunization with Hb in lupus-prone mice induced antigen spreading to lupus-associated moieties; Hb-interacting autoantigens were preferentially targeted and increased complement deposition and glomerulosclerosis were observed. Hb therefore demonstrates both antigenicity and immunogenicity and triggers specific immuno-pathological effects in a lupus milieu.

Filaments with Affinity Binding and Wet Strength Can Be Achieved by Spinning Bifunctional Cellulose Nanofibrils.

We demonstrate benzophenone (BP) conjugation via amine-reactive esters onto oxidized cellulosic fibers that were used as precursors, after microfluidization, of photoactive cellulose nanofibrils (CNF). From these fibrils, cellulose I filaments were synthesized by hydrogel spinning in an antisolvent followed by fast biradical UV cross-linking. As a result, the wet BP-CNF filaments retained extensively the original dry strength (a remarkable ∼80% retention). Thus, the principal limitation of these emerging materials was overcome (the wet tensile strength is typically <0.5% of the value measured in dry conditions). Subsequently, antihuman hemoglobin (anti-Hb) antibodies were conjugated onto residual surface carboxyl groups, making the filaments bifunctional for their active groups and properties (wet strength and bioactivity). Optical (surface plasmon resonance) and electroacoustic (quartz crystal microgravimetry) measurements conducted with the bifunctional CNF indicated effective anti-Hb conjugation (2.4 mg m-2), endowing an excellent sensitivity toward Hb targets (1.7 ± 0.12 mg m-2) and negligible nonspecific binding. Thus, the anti-Hb biointerface was deployed on filaments that captured Hb efficiently from aqueous matrices (confocal laser microscopy of FITC-labeled antibodies). Significantly, the anti-Hb biointerface was suitable for regeneration, while its sensitivity and selectivity in affinity binding can be tailored by application of blocking copolymers. The developed bifunctional filaments based on nanocellulose offer great promise in detection and affinity binding built upon 1D systems, which can be engineered into other structures for rational use of material and space.

Effect of birth weight on immunogenicity of hepatitis B vaccine among Neonatal Intensive Care Unit graduates

Objective: The objective of this study was to compare the immunogenicity of hepatitis B vaccine between infants aged 9 and 12 months who were delivered with a birth weight 10 IU/mL) of anti-HB antibodies. Conclusions: There was no effect of birth weight on the development of protective anti-HB antibody titers (>10 IU/mL) in infancy.

Detection of Total and A1c-Glycosylated Hemoglobin in Human Whole Blood Using Sandwich Immunoassays on Polydimethylsiloxane-Based Antibody Microarrays

The percentage of glycosylated hemoglobin A1c (%GHbA1c) in human whole blood indicates the average plasma glucose concentration over a prolonged period of time and is used to diagnose diabetes. However, detecting GHbA1c in the whole blood using immunoassays has limited detection sensitivity due to its low percentage in total hemoglobin (tHb) and interference from various glycan moieties in the sample. We have developed a sandwich immunoassay using an antibody microarray on a polydimethylsiloxane (PDMS) substrate modified with fluorinated compounds to detect tHb and glycosylated hemoglobin A1c (GHbA1c) in human whole blood without sample pretreatment. A polyclonal antibody against hemoglobin (Hb) immobilized on PDMS is used as a common capture probe to enrich all forms of Hb followed by detection via monoclonal anti-Hb and specific monoclonal anti-GHbA1c antibodies for tHb and GHbA1c detection, respectively. This method prevents the use of glycan binding molecules and dramatically reduces the background interference, yielding a detection limit of 3.58 ng/mL for tHb and 0.20 ng/mL for GHbA1c. The fluorinated modification on PDMS is superior to the glass substrate and eliminates the need for the blocking step which is required in commercial enzyme linked immunosorbent assay (ELISA) kits. Moreover, the detection sensitivity for GHbA1c is 4-5 orders of magnitude higher, but the required sample amount is 25 times less than the commercial method. On the basis of patient sample data, a good linear correlation between %GHbA1c values determined by our method and the certified high performance liquid chromatography (HPLC) standard method is shown with R(2) > 0.98, indicating the great promise of the developed method for clinical applications.

Serum and organ‐associated anti‐hemoglobin humoral autoreactivity: Association with anti‐Sm responses and inflammation

The release of hemoglobin (Hb) occurs in some infectious and autoimmune diseases characterized by inflammation. As levels of haptoglobin (Hp) fall, free Hb can cause pathology. Humoral autoreactivity to human Hb was demonstrated in the sera of systemic lupus erythematosus (SLE), leishmania and malaria patients. Serum anti-murine Hb antibody levels in lupus-prone mice also exhibited an age-dependent increase, with progressive organ sequestration; significant isotypic correlation was observed with anti-dsDNA antibodies. A suggestive link between anti-Hb and anti-Sm responses was observed: Human lupus sera expressing anti-Sm antibody reactivity preferentially contained heightened levels of anti-Hb autoantibodies, and immunization of lupus-prone mice with Sm led to enhanced anti-murine Hb reactivity. Human and murine anti-Hb monoclonal antibodies were generated, some of which were preferentially reactive toward disease-associated methemoglobin. Epitope-mapping studies revealed evidence of intra-molecular cross-reactivity. One such autoantibody synergized with Hb to enhance the secretion of pro-inflammatory cytokines while eliciting the increased production of monocyte migratory signals from endothelial cells. Preferential usage of specific variable region gene segments was not observed, although somatic mutations were documented. These studies reveal that, while the etiology, specificity and sequences of anti-Hb autoreactive antibodies can vary, they occur quite frequently and can have inflammatory consequences.

The Amino Acid Residues at Positions 120 to 123 Are Crucial for the Antigenicity of Hepatitis B Surface Antigen

The major hydrophilic region (MHR) of hepatitis B surface antigen (HBsAg) harbors conformational B-cell epitopes and is the major target of neutralizing antibodies to HBsAg (anti-HBs). Mutant HBsAg (mtHBsAg) with amino acid substitutions such as G145R is known to affect the binding of specific anti-HB antibodies and their detection by conventional diagnostic assays. In the present study, we focused on the role of the amino acid positions 120 to 123, which are around MHR 2 according to the spectrum of recently identified, naturally occurring mtHBsAg. Strikingly, the amino acid substitution K122I abolished the reactivity of HBsAg in all immunoassays tested so far. Also, mtHBsAg G145R could be clearly detected with four different enzyme-linked immunosorbent assays that were based on monoclonal anti-HB antibodies (MAbs) with high affinity. Positive immunofluorescence staining of mtHBsAg K122I was achieved only by polyclonal anti-HBs, while all MAbs tested failed. mtHBsAg T123N showed a low reactivity in immunoassays and appeared to be secretion defective. The amino acid substitution P120T reduced the binding of anti-HBs but did not completely prevent the detection of mtHBsAg by anti-HB MAbs. The testing of naturally occurring mtHBsAg confirmed that the presence of amino acid substitutions within the region of 120 to 123 is strongly associated with impaired detection in immunoassays. In conclusion, MHR 2 is essential for HBsAg antigenicity, a fact that has not been recognized before.

Immunogenicity and Reactogenicity of Two Recombinant Hepatitis B Vaccines in Small Infants: A Randomized, Double-Blind Comparative Study

Hepatitis B infection is very common in infants, especially in countries with limited resources. Hepatitis B vaccination is recommended in the routine immunization schedules in many countries, including India. We compared immunogenicity and reactogenicity of two recombinant hepatitis B (HB) vaccines in healthy infants. A total of 262 evaluable Indian infants received three doses of 10 microg of an Indian (GeneVac-B) or European (Engerix-B) HB vaccine in a double-blind, randomized fashion. The first dose, given at birth, was followed by a dose at age 6 and 14 weeks. All the subjects were initially seronegative for HB surface antigen (HBsAg) and anti-HB antibodies (anti-HBs). The post-vaccination anti-HBs titers were assessed by ELISA at the time of second and third dose, and 1 month after the third dose. Seroconversion and seroprotection were defined as anti-HBs titers > or =1 mIU/ml and > or =10 mIU/ml, respectively. After first dose, the seroconversion rates were 20% and 17%, in Indian and European vaccine recipients, respectively. The second and third dose increased the seroconversion to 84% and 80%, and to 98% and 98%, respectively. Correspondingly, the seroprotection rates after the first dose was 11% and 10%, and consequently 54% and 58%, and 97% and 95%. None of the differences between vaccines reached statistically significant proportions. Geometric Mean Titer after third dose was 383 mIU/ml and 285 mIU/ml, respectively, also this difference remaining insignificant. Adverse events were similar in both vaccine groups. Immunogenicity and reactogenicity of the Indian and European Hepatitis B vaccines were comparable, when immunization was started at birth.

Surface acoustic wave immunosensors based on immobilized C60-proteins

Fullerene C60-proteins, C60-hemoglobin (C60-Hb) and C60-myoglobin (C60-Mb), were prepared and applied in surface acoustic wave (SAW) immunosensors to detect the anti-hemoglobin (anti-Hb) and anti-myoglobin (anti-Mb) antibodies, respectively, in aqueous solutions. The immobilizations of Hb and Mb onto fullerene were studied through a C60-coated SAW sensor system in liquid. The partially irreversible responses of these proteins were observed by the desorption study, which implied that fullerene could chemically react with these proteins. Both C60-Hb and C60-Mb coating materials were successfully prepared and identified with an FTIR spectrometer. The C60-protein-coated SAW immunosensors exhibited linear frequency responses to the concentrations of anti-Hb and anti-Mb antibodies with sensitivities of 0.14 and 1.27 kHz/(μg/mL), respectively. Both C60-protein-coated SAW immunosensors showed detection limits of 0.32 and 0.035 μg/mL for anti-Hb and anti-Mb antibodies, respectively. The optimum pH and temperature on the frequency response of the anti-Hb SAW immunosensor were also observed to be at 7.3 and 27 °C, respectively. The interference of various common bio-species in human blood, e.g. urea, ascorbic acid, tyrosine, and metal ions, to the SAW immunosensor coated with C60-Hb was investigated. These common bio-species interferences showed nearly no interference to the SAW immunosensors coated with C60-Hb. The reproducibility and lifetime of these SAW immunosensors immobilized with C60-proteins were also investigated and discussed. Dual-channel SAW immunosensors coated with C60-Hb and C60-Mb were applied to detect anti-Hb and anti-Mb simultaneously.

Development of hepatitis B oral vaccine using B-cell epitope loaded PLG microparticles

Oral hepatitis B vaccine formulation was prepared by successful encapsulation of immunogenic peptide representing residues 127–145 of the immunodominant B-cell epitope of hepatitis B surface antigen (HBsAg) in poly( d, l-lactide co-glycolide) (PLG) microparticles. The smooth, spherical PLG microparticles with a diameter of around 10 μm was prepared by using W/O/W double emulsion solvent evaporation method. The entrapment efficiency of B-cell epitope peptide (BCEP) into PLG microparticles was 64%. In vitro studies showed B-cell epitope loaded PLG microparticles (BCEM) released the peptide in sustained profile and reached 64.9% efficiency by Day 25. Single oral immunization of mice with BCEM led to the significant induction of specific serum IgG and IgM anti-HB antibodies. After the termination of antibody induction, the orally immunized mice were infected with HBsAg, which resulted in the rapid production of antibodies against HBsAg as a result of secondary immune response. PLG microparticles formulation approach may have potential in increasing the efficacy of microparticulate systems for the oral administration of hepatitis B vaccine.

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.

Hepatitis B immunization in low birthweight infants: do they need an additional dose?

Aim: To determine the influence of gestation and weight on the development of protective anti‐HB levels and geometric mean titres after three doses of HBV vaccine and to ascertain the need for a fourth dose in low birthweight infants. Methods: Hepatitis B vaccine (Enivac HB, Panacea Biotec Ltd., India) was given to 82 preterm (PT) and 60 term intrauterine growth‐retarded (T‐IUGR) infants at birth and at 6, 10 and 14 wk of life. Results: Protective anti‐HB levels (&gt;10 mIU/ml) were reached in 86.6% (71/82) of PT infants and 96.7% (58/60) of T‐IUGR infants after three doses of HBV vaccine (p= 0.044). The odds of having a protective response after the third dose of HBV vaccine was 1.25 (95% CI 1.02–1.53) with every one‐week increase in gestation (p= 0.032). Birthweight was not associated with the development of a protective immune response. After the third dose, only 66.7% (8/12) of the PT infants whose mothers had anti‐HB antibodies, developed protective anti‐HB levels compared with 90% (63/70) of those with no maternal antibodies (p= 0.028). In PT infants after the fourth dose, there was a significant increase in the proportion of infants with protective antibody levels (8.6%, 95% CI 0.6–16.6%) among those with no maternal antibodies and 12.2% overall (95% CI 6.0–21.3) (p= 0.031 to 0.002) over that reached with the third dose. Administration of the fourth dose to T‐IUGR infants did not confer such a benefit. Conclusion: In HBV‐endemic areas, PT infants, irrespective of their birthweights, may benefit from an additional dose of hepatitis B vaccine in a schedule starting at birth. This approach will prevent vertical transmission and bring their immune response up to par with term infants. Term intrauterine growth‐retarded infants should be vaccinated as per the schedule recommended for normal term infants. However, studies in other settings with different vaccine formulations and a longer follow‐up period will be required before this strategy can be practised more widely.

Antibodies directed against rubella virus induce demyelination in aggregating rat brain cell cultures.

To link the presence of intrathecal virus-specific oligoclonal immunoglobulin G (IgG) in multiple sclerosis patients to a demyelinating activity, aggregating rat brain cell cultures were treated with antibodies directed against two viruses, namely, rubella (RV) and hepatitis B (HB). Anti-RV antibodies in the presence of complement decreased myelin basic protein concentrations in a dose-dependent manner, whereas anti-HB antibodies had no effect. A similar but less pronounced effect was observed on the enzymatic activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase, which is enriched in noncompact membranes of oligodendrocytes. These effects were comparable to those in cultures treated with antibodies directed against myelin oligodendrocyte glycoprotein (MOG), previously found to be myelinotoxic both in vitro and in vivo. Sequence homologies were found between structural glycoprotein E(2) of RV and MOG, suggesting that demyelination was due to molecular mimicry. To support the hypothesis that demyelination was caused by anti-RV IgG that recognized an MOG epitope, we found that anti-RV antibodies depleted MOG in a dose-dependent manner. Further evidence came from the demonstration that anti-RV and anti-MOG IgG colocalized on oligodendrocyte processes and that both revealed by Western blot a 28 kDa protein in CNS myelin, a molecular weight corresponding to MOG. These findings suggest that a virus such as RV exhibiting molecular mimicry with MOG can trigger an autoimmune demyelination.

Recurrent hepatitis B, hepatitis C, and combined hepatitis B and C in liver allografts: A comparative pathological study

Although recurrence of viral hepatitis in liver transplants is common, data comparing recurrent hepatitis B (HB), hepatitis C (HC), and co-existing dual hepatitis B and C (HB&C) are sparse. Posttransplantation liver biopsies, along with molecular, serological, immunohistochemical, and clinical data from 27 patients with pretransplantation diagnosis of chronic viral hepatitis, were reviewed. The patients were placed into 4 groups: Group I, with pretransplantation HB (n = 8); group II, with pretransplantation HC (n = 10); group III with pretransplantation HC and anti-HB surface or core antibody (n = 4); and group IV, with pretransplantation HB&C (n = 5). The histopathologic findings and patient outcome were compared in the 4 groups. A high rate of recurrence of viral hepatitis was seen for all 4 groups: Group I = 100%, group II = 90%, Group III = 100%, and group IV = 80%, with the mean (median) recurrence time of 308 (224), 82 (52), 61 (64), and 125 (70) days, respectively. The number of deaths (their median survival times) were: group I = 4 (374 days), group II = 4 (794 days), group III = 1 (1,143 days), and group IV = 5 (448 days). The earliest histological findings of lobular injury was the presence of acidophil bodies and Kupffer cell hyperplasia, the latter being more prominent in recurrent HC cases. Recurrent HB presented in 2 forms: early (before 150 days) with poor survival and with either severe necroinflammatory histology or with features of fibrosing cholestatic hepatitis, and delayed (after 150 days), with mild necro-inflammatory activity and prolonged survival. HC with or without anti-HB antibodies had early recurrence, but the course was slowly progressive. Patients with HB&C had recurrence of both viruses; however, the course was dictated by HB virus.