No abstract

The development of inhibitory antibodies to factor VIII is a serious complication of hemophilia. FEIBA (factor VIII inhibitorbypassing activity), an activated prothrombin complex concentrate (aPCC), and NovoSeven, recombinant factor VIIa (rFVIIa), are used as hemostatic bypassing agents in treating patients with inhibitors. The FENOC study was designed to test equivalence of the products in the treatment of ankle, knee, and elbow joint bleeding. A prospective, open-label, randomized, crossover, equivalency design was used. The parameters of interest were the percentage of patients who reported efficacy in response to FEIBA and the percentage that reported efficacy in response to NovoSeven. A difference in these percentages of no more than 15% was determined to be a clinically acceptable magnitude for equivalence of the 2 products. The primary outcome was evaluation 6 hours after treatment. Data for 96 bleeding episodes contributed by 48 participants were analyzed. The criterion for declaring the 2 products equivalent at 6 hours was not met; however, the confidence interval of the difference in percentages of efficacy reported for each product only slightly exceeded the 15% boundary (؊11.4%-15.7%), P ‫؍‬ .059. FEIBA and NovoSeven appear to exhibit a similar effect on joint bleeds, although the efficacy between products is rated differently by a substantial proportion of patients. This trial was registered at www.clinicaltrials.gov as #NCT00166309. (Blood. 2007;109:546-551)

Previous studies have suggested that hepatitis B virus (HBV) variants may account for the presence of HBV DNA in hepatitis B surface antigen (HBsAg)-negative patients (occult HBV infection). However, it is not known how widespread these variants are and how they influence the course of liver disease. To determine the prevalence of variants within the major hydrophilic region (MHR) of HBsAg, we investigated 2,565 subjects, including subjects with chronic hepatitis, cryptogenic cirrhosis, hemodialysis patients, and blood donors. Chronic hepatitis B virus (HBV) infection is a global public health problem that affects over 300 million individuals, or 5% of the world's population.

A previous study

cleoside analogues, [8][9][10] the only established treatment option Hepatitis B virus (HBV) replicates via an intermediate to prevent reinfection is the administration of polyclonal hep-RNA step. High frequency of polymerase errors with adatitis B surface antigen antibody (anti-HBs) (hepatitis B imditional selection pressure leads to mutations in the mune globulin [HBIG]). HBIG reduces the rate of reinfection HBV genome. We investigated the number, type, and anfrom about 90% to less than 30% and improves the long-term tigenic effects of mutations in the coding region of the outcome of patients who underwent OLT for HBV-related HBV surface antigen in eight patients who underwent disease. 2-4orthotopic liver transplantation (OLT) for HBV-related A number of explanations for graft infection have been end-stage liver disease and were experiencing infection proposed. First, virions from the explanted liver are circulatof the graft and who received hepatitis B surface antigen ing in the blood during or soon after transplantation. Second, antibody (anti-HBs) prophylaxis (hepatitis B immune virions are replicating at extrahepatic sites. HBIG interferes globulin [HBIG]) after OLT. Controls were chronic HBV with this process and probably prevents virions from entering patients who underwent kidney transplantation and rehepatocytes. 11 The mechanisms that lead to reinfection in ceived the same immunosuppressive regime but no 30% of patients receiving HBIG after OLT are not under-HBIG. The S-gene was amplified from serum before and stood. after transplantation, sequenced, and changes in the ge-HBV employs reverse transcriptase for its replication; this nome were analyzed. In the five patients who experilacks proofreading capability, and thus leads to a higher enced reinfection while receiving anti-HBs, clear mutanumber of mutations in the HBV genome. 12 Some of these tions occurred in the S-gene. In the patient who did not variants may have a replication advantage and become domireceive HBIG and those who experienced reinfection nant. From the pool of variants with similar replication poonly after termination of HBIG, no mutations were tential, some will be positively selected by forces such as found in the S-gene. In the kidney recipients, mutations the humoral or cellular immune response 13; these are termed in the S-gene occurred in only one of eight patients. Beescape mutants. Evolution of viruses under antibody prescause the a determinant contains neutralizing epitopes, sure, either monoclonal or polyclonal, has been well studied this region was chosen for antibody binding to quantify both in vitro and in vivo. The addition of neutralizing antibodantigenic effects of the mutations. The two patients who ies to virus cultures regularly results in isolates that are not selected mutations in the a determinant and became reneutralized by the added antibodies. This is particularly true infected while receiving HBIG had reduced antibody with monoclonal reagents, because the change in viral antibinding after OLT. Our results...

Antibody to the common "a" determinant of hepatitis B surface antigen (HBsAg) protects against infection with hepatitis B virus. A number of variant surface antigens with amino acid substitutions within the "a" determinant have been described in patients around the world. Both wild type and variant HBsAgs were expressed in the yeast Pichia pastoris and the antigens were semi-purified and quantitated. The effect on antigenicity of these changes was investigated in a quantitative fashion using four monoclonal antibodies known to bind to different epitopes within the common "a" determinant. The results suggest that amino acid substitution of T131I, K141E and G145R and insertion of 3 amino acids between residues 123 and 124 markedly affect the antigenic structure of HBsAg. These substitutions and insertions in the viral envelope may lead to evasion of the virus neutralizing antibody response and also to reduce efficiency of detection by immunoassays used for diagnosis and blood-bank screening.

In a chimpanzee model of acute type B hepatitis, at the time of onset of hepatitis B virus replication and before the development of immunity to hepatitis B virus, interferon is present in the plasma. This is followed by an increase in the display of HLA class I, but not class II proteins, on the hepatocyte membrane. In chronic hepatitis B virus infection, there is a low density of HLA class I protein display on the infected hepatocyte. Administration of alpha-interferon enhances HLA display and in many cases is followed by a transaminase elevation, seroconversion of HBe antigen to antibody and disappearance of hepatitis B virus DNA from serum, changes implying clearance of infected hepatocytes. Successful response to interferon therapy may be predicted by a rapidly rising serum beta 2-microglobulin, a component of the HLA class I molecule, during the first 2 weeks of therapy, before the rise in transaminases.

The prevalence of a G1862T variant of hepatitis B virus (HBV) has been investigated in patients with fulminant hepatitis and chronic liver disease, using primer mismatch amplification, followed by restriction fragment length polymorphism analysis. This variant was five times more common in patients with fulminant hepatitis (13n7 %, 7 of 52) than in chronic carriers (2n5 %, 2 of 81). The G T substitution at position 1862 leads to an amino acid change in codon 17 of the precore protein of the virus, which is part of a signal peptidase recognition motif. Variants with this mutation were only seen in patients infected with genotype B. In vitro translation experiments showed that this variant has greatly reduced capacity to produce hepatitis B e antigen (HBeAg) from its precore protein precursor. Furthermore, 88n5 % of patients with fulminant hepatitis had mutations that are known to be associated with abrogated or reduced production of HBeAg. This suggests that, following HBV infection, the absence or reduced amounts of HBeAg may be a contributing factor in fulminant disease.