Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Commercially available lots of plasma derivatives prepared between 1957 and 1975 were tested for hepatitis B surface antigen (HBsAg) by radioimmunoassay. In all, 69 per cent of lots of plasma protein fraction, 40 per cent of factor IX concentrate, 20 per cent of normal serum albumin, 13 per cent of antihemophilic factor, 3 per cent of fibrinogen, and 0.7 per cent of immune serum globulin lots tested were HBsAg-positive. There was great variation in the prevalence of HBsAg-positive lots of each product among the different manufacturers, reflecting not only differences in methods of processing plasma, but also differences in donor populations. Those manufacturers relying upon volunteer donor plasma or placental source material demonstrated lower rates of HBsAg-positive lots of final products than those relying upon commercial donor plasma. There was a marked decrease in the prevalence of positive lots during the period 1971 to 1973, coincident with the onset of routine plasma donor screening for HBsAg. However, current requirements for plasma screening have not resulted in totally HBsAg-free plasma products. Use of more sensitive and more reliable tests for HBsAg will probably reduce contamination of plasma pools with HBsAg to undetectable levels. Despite HBsAg-status, however, the "high-risk" plasma products (fibrinogen, antihemophilic factor, factor IX concentrate) must still be considered capable of transmitting hepatitis and used only with the strictest indications.
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PMID:The prevalence of hepatitis B surface antigen in commercially prepared plasma products. 93 29

A high frequency of viral hepatitis has been reported after treatment with the human factor IX concentrate 'Konyne'. Clinical trials with 'Konyne' and a similar factor IX concentrate, called 'Preconativ', was started in Sweden 1969. During the first 2 years, 26 patients were treated with either one or both preparations. Nine patients developed viral hepatitis within 6 months after treatment. 'Preconativ' alone was introduced on the Swedish market in 1971. During the period 1971-1974, another 26 hemophiliacs were treated but only two cases of hepatitis have occurred. Selection of donors and screening for hepatitis B surface antigen in donor blood used for the manufacturing of 'Preconativ', might be contributing factors to this low hepatitis incidence.
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PMID:Incidence of viral hepatitis after administration of factor IX concentrates. 95 72

Among sera from 160 patients with hemophilia B from 9 centers in Europe and North and South America, 2.5% were positive for hepatitis B surface antigen (HBsAg), 60for antibody to HBsAg, and 31% for antibody to the hepatitis B core antigen. Evidence of exposure to the hepatitis B virus appeared to be related to severity of disease and age rather than the source and method of manufacturer of factor IX concentrate.
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PMID:Serologic evidence of hepatitis B virus infection in patients with hemophilia B. a multicenter study. 115 15

We have used gene transfer vectors derived from a replication-defective mutant of herpes simplex virus type 1 (HSV-1) expressing the hepatitis B virus surface antigen (HBsAg), Escherichia coli beta-galactosidase (beta-gal), or canine factor IX (cFIX) from the immediate early promoter of human cytomegalovirus (hCMV) to infect mouse liver by direct injection or through the portal vein. By either route, high levels of transgene expression were demonstrated by the detection of immunoreactive HBsAg or cFIX in the circulation and by histochemical detection of beta-gal activity in situ. The results were striking in that the serum level of cFIX reached 10% of the normal murine levels. Although the level of transgene expression from the hCMV promoter was transient, a significant number of persistent vectors could be rescued from the livers of recipient mice up to 2 months after inoculation. Replacement of the hCMV promoter with the HSV-1 latency-associated transcript (LAT) promoter resulted in reduced but prolonged expression of both HBsAg and cFIX. The very high level of factor IX expression suggests that clinically useful gene transfer may eventually be feasible through direct vector delivery to the liver.
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PMID:Direct gene transfer to the liver with herpes simplex virus type 1 vectors: transient production of physiologically relevant levels of circulating factor IX. 131 45

In contrast to the type of bleeding encountered in congenital hemophilia with inhibitors, the diathesis toward bleeding exhibited by patients with spontaneously acquired factor VIII (FVIII) inhibitors often is severe and life threatening. Large hematomas and retropharyngeal or central nervous system hemorrhage may appear suddenly. Thus, a high premium is placed on rapid therapeutic intervention. Several treatment options are at the physician's disposal. The role of factor IX (FIX) complex concentrates, both standard and purposely activated, is discussed. The FIX products are also known as prothrombin complex concentrates (PCCs). Prudent choice of any treatment modality requires weighing its benefits and shortcomings. Advantages of PCCs--particularly the activated products--include availability, ease of reconstitution and administration, and at least partial efficacy; control of bleeding episodes can be achieved with PCCs in many (but not all) instances. One salient disadvantage of therapy with FIX complex concentrates is that they are not subjected to such rigorous viral-attenuation processes as are most of the currently marketed FVIII products. Therefore, a small but definite risk of infection with hepatitis B or C (HBV, HCV) remains. An assay that detects antibodies against HCV has been licensed and is being used to screen blood donors. Nevertheless, up to the present time the U.S. Food and Drug Administration (FDA) has ruled that HCV screening of plasmapheresis donors should not be performed for plasma collections destined to be pooled for fractionation and that units of HCV-positive source plasma (e.g., that provided by American Red Cross donors) found to be HCV positive be sent for fractionation. The starting plasma from which FIX complex concentrates and human FVIII concentrates are made thus contains some HCV and may also contain some HBV. Because nonhemophiliacs with acquired antibodies against FVIII are unlikely to have had prior exposure to blood products and are unlikely to have been vaccinated against HBV, they are at risk of viral hepatitis and its sequelae when treated with FIX complex concentrates. Furthermore, therapy with FIX complex concentrates is not always effective in controlling bleeding in persons with FVIII inhibitors, its mechanism of action in bypassing the need for FVIII remains unclear, very large doses are required, and it has an attendant risk of several adverse effects when used in large, repeated doses. These include disseminated intravascular coagulation, thromboembolism, and acute myocardial infarction. Thus, FIX complex concentrates may play a useful role in the treatment of bleeding in nonhemophiliacs with acquired inhibitors against FVIII, but one must carefully consider their disadvantages profile.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Perspectives on the use of factor IX complex concentrates in the treatment of bleeding in persons with acquired factor VIII inhibition. 174 94

Twenty-seven patients suffering from congenital coagulation defects of the prothrombin complex factors were investigated: six had haemophilia B; 14, factor VII defect; four, factor X defect; and three, factor II defect. Nineteen patients (70.3%) had previously received plasma and/or clotting factors concentrates. Among these, markers of hepatitis B infection (HBV) were present in five cases (26.3%) and hepatitis C (HCV) antibodies were found in seven cases (36.8%). The HIV1 prevalence was similarly high. In fact, five patients (26.3%), previously infused with factor IX or prothrombin complex factors concentrates, developed HIV1 infection. No patient with factor VII deficiency became HIV1 positive, despite the administration of unheated factor VII concentrates and the consequent HBV and HCV contamination. In the HIV1 positive group, three patients showed a false positivity for HIV2 antibodies. Five years after seroconversion, three patients developed AIDS (stage IV) and died, one had persistent generalized lymphadenopathy (stage III), and one with post-hepatitis liver cirrhosis was asymptomatic (stage II) for HIV infection. The significant decrease in total white cells, T4 lymphocytes and platelet counts and increase of beta 2-microglobulin and neopterin levels confirmed the prognostic value of these markers for the progression of HIV1 disease. Only one HIV1 negative transfused patient developed anti-HTLV-I p19 antibodies.
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PMID:Prevalence of HIV infection in a cohort of patients with congenital coagulation defects of the prothrombin complex factors. 178 37

Earlier commercial clotting factor concentrates transmitted hepatitis viruses to 100% and acquired immunodeficiency syndrome viruses to 60% to 80% of patients with hemophilia. Transmission of the human immunodeficiency virus was nearly eliminated by heating concentrates in the lyophilized state, which has been done since 1983. However, human immunodeficiency virus infections were still transmitted by some products "dry heated" under conditions less extreme than 68 degrees C for 72 hours. Newer virus-inactivating procedures include "dry heating" at 80 degrees C for 72 hours, modified heating in n-heptane or water vapor, heating in solution, treatment with solvent-detergent mixtures, monoclonal affinity purification plus inactivation, and alkylation with beta-propiolactone (only for factor IX complex). These procedures have eliminated significant loads of human immunodeficiency virus, hepatitis B virus, and non-A, non-B hepatitis virus in laboratory studies. However, clinical studies have shown transmission of hepatitis non-A, non-B for products "dry heated" except at 80 degrees C and for products heated in n-heptane. Elimination of hepatitis B has been difficult to demonstrate, suggesting a continued need for immunization.
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PMID:Current safety of clotting factor concentrates. 212 21

Blood coagulation factor IX (Christmas factor) is a plasma protein which is required for normal haemostasis. A functional deficiency of factor IX results in haemophilia B, a bleeding disorder which is generally treated by infusions of factor IX concentrates prepared from pooled human plasma. The use of human blood products is connected with the risk of transmitting viral agents responsible for diseases such as hepatitis B and AIDS. Recombinant DNA techniques may provide the means to produce the required proteins without exposing the patients to these risks and at lower costs. One of the problems which has to be overcome before recombinant factor IX can be used for therapeutical purposes is related to the vitamin K-dependent carboxylation of its 12 NH2-terminal glutamate residues. In cell cultures this carboxylation, which is required to render the protein its procoagulant activity, is far from complete, especially at high expression levels. In this paper we describe the in vitro carboxylation of non and/or partly carboxylated recombinant factor IX produced by transformed Chinese hamster ovary cells. The identity of the newly formed Gla residues was verified and it could be demonstrated that all carboxyl groups had been incorporated into the recombinant factor IX.
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PMID:In vitro carboxylation of a blood coagulation factor IX precursor produced by recombinant-DNA technology. 274 97

Blood product sterilization with 0.3% tri(n-butyl)phosphate (TNBP)/0.2% sodium cholate (CA), a combination known to permit high recovery of factor VIII and factor IX, was evaluated for its effect on hepatitis B (HBV), non-A, non-B (NANB), and human T-lymphotropic type III (HTLV-III) viruses. 2 chimpanzees received factor VIII preparations contaminated with 100,000 chimpanzee infectious doses of HBV and treated with TNBP/CA. Neither had evidence of HBV during the 9 month follow-up, but hepatitis B surface antigen (HBsAG) developed 5 and 6 weeks, respectively, after challenge with untreated inoculum. 2 chimpanzees were similarly exposed to NAMB inoculum treated with TNBP/CA. Neither became infected during 26 weeks of follow-up, but both had characteristic NANB-associated ultrastructural changes 3-5 weeks after exposure to untreated inoculum. 2 chimpanzees inoculated with TNBP/CA-treated factor VIII derived from a pool of 13 lots obtained from 5 US manufacturers remained free of any evidence of NANB infection during 32 weeks of follow-up. Subsequently, NANB infection developed in both animals 3-4 weeks after exposure to untreated inoculum. Exposure of HTLV-III diluted into a factor VIII preparation to TNBP/CA inactivated tissue culture infected doses within 20 minutes. These results demonstrate that exposure of labile blood derivatives to TNBP/CA effectively inactivates HBV, NANB, and HTLV-III viruses, although additional experiments with more potent inocula are needed to establish limits of inactivation efficacy against these agents. To provide absolute safety, a process efficacy of = or 5-6 log 10 is preferable.
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PMID:Sterilisation of hepatitis and HTLV-III viruses by exposure to tri(n-butyl)phosphate and sodium cholate. 287 Feb 24

32 patients with coagulation factor deficiencies and likely to be susceptible to non-A, non-B hepatitis (NANBH) virus infection were treated with a total of 20 batches of a factor VIII concentrate and 10 batches of a factor IX concentrate, both heated at 80 degrees C for 72 h in the freeze-dried state. Serial measurements of serum aminotransferase levels for 4 months revealed no patterns of rises attributable to NANBH. Severe dry heating appears to have reduced the risk of NANBH transmission from about 90% in untreated concentrates to a statistically determined rate of 0-9%. No evidence was found in recipients of infection with hepatitis B or human immunodeficiency virus.
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PMID:Effect of dry-heating of coagulation factor concentrates at 80 degrees C for 72 hours on transmission of non-A, non-B hepatitis. Study Group of the UK Haemophilia Centre Directors on Surveillance of Virus Transmission by Concentrates. 290 65


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