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D Shouval

Publications and source records attributed to D Shouval.

At least 37 records · Page 2Linked to original sources
PubMed2000

Transient transmission of hepatitis C virus from mothers to newborns.

A study was performed in Israel to determine the rate of mother-to-infant HCV transmission in newborns at risk. A group of 22 HCV-infected mothers and their 23 newborns were followed up from early after birth by testing their serum for the presence of HCV antibodies and HCV-RNA. Antibody against HCV was detected in the blood of all newborns immediately after birth, but dropped to low or undetectable levels by 7 months of age. HCV-RNA was detected 2 days after birth in the blood of five infants (22%) but fell to undetectable levels by 6 months. HCV-HVR1 sequence analysis performed in one mother-infant pair on the second day after birth revealed two nucleotide changes. Two months later the same sequence was detected again in the HVR1, suggesting a very low replication rate. Thus, the study showed that vertically transmitted HCV was eliminated in all newborn infants by 6 months after delivery, with concomitant disappearance of HCV antibodies. The mechanism of HCV elimination in newborns at risk remains to be elucidated.

Adult↗
PubMed2000

Flow cytometric analysis of autonomous growth of erythroid precursors in liquid culture detects occult polycythemia vera in the Budd-Chiari syndrome.

BACKGROUND/AIMS: Hepatic vein thrombosis (Budd-Chiari syndrome) is associated with various hypercoagulable states, such as polycythemia vera (PV), presence of the lupus anticoagulant, paroxysmal nocturnal hemoglobinuria (PNH) and deficiencies of antithrombin III, protein C and protein S. In recent years, it has become evident that patients with the Budd-Chiari syndrome may have more than one risk factor that may cause a state of hypercoagulability. The aim of the current study was to assess the prevalence of occult PV in patients with Budd-Chiari syndrome using a novel method for the detection of spontaneous erythroid growth. METHODS: Twenty-two patients with Budd-Chiari syndrome were evaluated. As controls, we studied normal donors and four patients with liver cirrhosis and five patients with right-side heart failure, two conditions that in part mimic Budd-Chiari syndrome. The presence of PV was determined by flow cytometric analysis of autonomous growth of erythroid precursors. Patients were considered as having occult PV if they had spontaneous erythroid cell growth in the absence of erythropoietin and with no features of overt PV. RESULTS: Cells from ten patients with Budd-Chiari syndrome demonstrated spontaneous erythroid cell growth; eight patients (32%) were found to have occult PV and two patients had overt PV. None of the controls had spontaneous erythroid growth. Of the eight Budd-Chiari patients with occult PV, six had one or more additional recognized hypercoagulable states. Seven patients (32%) had protein C deficiency, six patients (27%) had activated protein C resistance, five (23%) had anti-cardiolipin antibodies, five (23%) had antithrombin III deficiency, and four patients (18%) had protein S deficiency. Three patients (14%) were homozygous to methyltetra hydrofolate reductase and ten (45.5%) were heterozygous. One patient had PNH. Overall, in 12 patients there were two or more combined risk factors. CONCLUSIONS: Using a flow cytometric analysis of autonomous growth of erythroid precursors we found a clear correlation between Budd-Chiari syndrome and occult PV.

Adult↗
PubMed2000

Maintenance of immune memory to the hepatitis B envelope protein following adoptive transfer of immunity in bone marrow transplant recipients.

Adoptive transfer of immunity against hepatitis B surface antigen (HBsAg) has been documented in mice and humans. In the present study, we report long-term follow-up of antibodies to HBsAg in humans who received allogeneic bone marrow transplantation (BMT) from donors immunized with HBsAg. BM donors were immunized with recombinant HBsAg. BM or PB cells were transplanted to HLA matched recipients. Recipients were followed for anti-HBs seroconversion. Control groups included non-immunized or rHBsAg immunized healthy adults as well as individuals that had had hepatitis B and recovered spontaneously. PBLs were stimulated in vitro with rHBsAg and stimulation was expressed as stimulation index. Adoptive transfer of immunity to HBsAg was initially documented in 12 recipients of BM from anti-HBc+/anti-HBs+ donors. An almost 4 year follow-up showed detectable protective anti-HBs levels (>10 mIU/ml) in 50% of patients. Immunity to HBV was also documented in 22/35 BMT recipients (62%), who received their bone marrow from actively immunized donors. In 7/9 of these BMT recipients, anti-HBs antibodies levels were documented 25 months following BMT. In 6/8 (75%) of patients who received only PBLs from HBV immune donors, adoptive transfer of immunity to HBV, and seroconversion to HBsAg+, were documented within 2 months of i.v. injection. Evidence for specific cellular immune response with increased SIs was documented for healthy vaccinees, and BMT recipients, and in none of the healthy non-vaccinated controls. These results suggest that adoptive transfer of immunity to HBV is a useful method for providing long-lasting protection for BM recipients.

Adult↗
PubMed2000

Preclinical evaluation of two human anti-hepatitis B virus (HBV) monoclonal antibodies in the HBV-trimera mouse model and in HBV chronic carrier chimpanzees.

Two human monoclonal antibodies (mAbs) against hepatitis B surface antigen (HBsAg) generated in the Trimera mouse system are described. Both mAbs 17.1.41 and 19.79.5 are of the IgG1 isotype and have high affinity constants for HBsAg binding in the range of 10(-10) mol/L. Monoclonal antibody 17.1.41 recognizes a conformational epitope on the a determinant of HBsAg whereas mAb 19.79.5 recognizes a linear one. The 2 mAbs bind to a panel of hepatitis B virus (HBV) subtypes with distinct patterns. The neutralizing activity of these antibodies was tested in 2 different animal model systems. Administration of each mAb to HBV-Trimera mice, a system that provides a mouse model for human hepatitis B infection, reduced the viral load and the percentage of HBV-DNA-positive mice in a dose-dependent manner. These 2 mAbs were more effective than a polyclonal antibody preparation (Hepatect; Biotest Pharma, Dreieich, Germany) in both inhibition of HBV liver infection and reduction of viral load. A single administration of a mixture of these mAbs into HBV chronic carrier chimpanzees resulted in immediate reduction in HBsAg levels followed by recurrence to initial levels within few days. Thus, these mAbs may be potential candidates for preventive therapy or in combination with other antiviral agents against HBV. Further studies in humans are needed to assess these mAbs in various clinical indications.

Animals↗
PubMed2000

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Journal Article↗
PubMed2000

Posttransplantation: future therapies.

Recent advances in prophylaxis and treatment of hepatitis B virus (HBV) infection after liver transplantation have improved the outcome of liver transplantation for hepatitis B. Currently, the long-term use of hepatitis B immune globulin (HBIG) and/or nucleoside analogues are the only effective therapies to prevent or ameliorate HBV recurrence in liver transplant patients. However, they are very expensive, and breakthrough infections due to resistant HBV mutants are not infrequent. New strategies are being sought to decrease the risks of breakthrough infection and to increase the cost-effectiveness of liver transplantation for hepatitis B. Vaccination to prevent de novo infection is strongly recommended before transplantation, despite a decreased response in this immunosuppressed population. Adoptive transfer of immunity with such therapies as bone marrow or cytotoxic T lymphocyte transplants or xenotransplantation of an organ from a donor, which is not susceptible to infection by HBV may be effective in preventing or treating recurrent HBV posttransplantation. In addition, gene therapies and use of nucleoside and nucleotide analogues to disrupt various stages of the HBV life cycle may prevent or slow viral replication or assembly of the virus. Ultimately, the most effective therapy for the prevention of recurrent hepatitis B after liver transplantation will involve a combination of HBIG with one or more of the new antiviral agents.

Antiviral Agents↗
PubMed1999

Comparison of immunogenicity of two hepatitis A vaccines--VAQTA and HAVRIX--in young adults.

Two new hepatitis A vaccines have been developed, and their immunogenicity tested using different immunoassays. The present study was designed to compare the immunogenicity of these two hepatitis A virus (HAV) vaccines--VAQTA and HAVRIX--as determined by seroconversion rates and anti-HAV titers, and using the same immunoassay. Healthy volunteers (15-30 y), seronegative for anti-HAV, were randomized in an open single center study to four groups of 20-21 vaccinees each, to receive either a 25 U or a 50 U dose of VAQTA, or HAVRIX at 720 EU or 1440 EU/dose, administered at 0, 1 and 6 m or at 0 and 6 m, respectively. Four weeks after primary immunization, seroconversion rates were 100% for VAQTA and 95% for HAVRIX, following injection of 50 U or 1440 EU, respectively (p = NS) and anti-HAV GMTs were 40 and 37 mIU/ml for VAQTA and HAVRIX, respectively. At 6 months, prior to the booster dose, seroconversion rates were 100% for both vaccines, with anti-HAV GMTs of 111 and 70 mIU/ml for VAQTA and HAVRIX, respectively (P < 0.05). At month 7, four weeks after the only booster injection, using the two dose regimen, anti-HAV titers were 2212 and 1511 mIU/ml for VAQTA and HAVRIX, respectively (P < NS). Using three doses of 25 U/dose of VAQTA or 720 EU/dose of HAVRIX at 0, 1 and 6 m did not produce any clinically evaluable advantage over the two dose regimen for either vaccine. No significant adverse events were observed using either vaccine. In summary, both vaccines have similar immunogenicity demonstrated using identical immunoassays for evaluation. These results also confirm the outstanding immunogenicity of a single dose of either of the HAV vaccines and support their use in pre- and possibly postexposure prophylaxis against hepatitis A virus infection.

Adolescent↗
PubMed1999

The hepatitis B virus-trimera mouse: a model for human HBV infection and evaluation of anti-HBV therapeutic agents.

Previous studies have demonstrated the feasibility of implantation of human blood cells or tissues in lethally irradiated mice or rats, radioprotected with SCID mouse bone marrow cells: The Trimera system. In the present study, we describe the development of a mouse Trimera model for human hepatitis B virus (HBV) infection. In this model, viremia is induced by transplantation of ex vivo HBV-infected human liver fragments. Engraftment of the human liver fragments, evaluated by hematoxylin-eosin staining and human serum albumin mRNA expression, was observed in 85% of the transplanted animals 1 month postimplantation. Viremia levels were determined in these mice by measuring serum HBV DNA using polymerase chain reaction (PCR), followed by dot-blot hybridization. HBV DNA is first detected 8 days after liver transplantation. Viremia attains a peak between days 18 and 25 when HBV infection is observed in 85% of the transplanted animals. The HBV-Trimera model was used to evaluate the therapeutic effects of human polyclonal anti-HBs antibodies (Hepatect) and of two reverse-transcriptase inhibitors, lamivudine (3TC) and beta-L-5-fluoro-2',3'-dideoxycytidine (beta-L-5FddC). Treatment of HBV-Trimera mice with these drugs effectively reduced both the percentage of infected animals and the viral load in their sera. Treatment cessation resulted in rebound of viral load, indicating HBV replication upon drug withdrawal. These results show that the HBV-Trimera model represents a novel experimental tool for simulating human HBV infection and evaluating potential anti-HBV therapeutic agents.

Animals↗
PubMed1999

Comparison of immune reactivity and pharmacokinetics of two hepatitis B immune globulins in patients after liver transplantation.

Hepatitis B virus (HBV) immune globulin (HBIg) administration will prevent HBV graft reinfection in HBV patients after orthotopic liver transplantation (OLT). However, the expenditure for such prophylaxis is extremely high ranging between $2,000 to $10,000 per month in various countries for an undefined period and presumably for life. As a consequence, there is a need for introduction of additional and less expensive modes of treatment. In a preliminary clinical trial a new HBIg preparation has been shown to induce longer lasting levels of circulating antibodies to hepatitis B surface antigen (anti-HBs) in patients after OLT compared with previous experience with conventional HBIg preparations. In the present study the pharmacokinetics of this new HBIg, OMRI-Hep-B, were studied and compared with a conventional, licensed preparation, Hepatect. Fifteen post-OLT patients (2-8 years post-OLT, 18-62 years of age, 6 men, 9 women) were treated intravenously with 49 doses of OMRI-Hep-B or Hepatect given at least once, alternately, at 10,000 to 14,000 units per injection ( approximately 130 IU/kg body weight). The new HBIg was well tolerated and no adverse effects were observed. Administration of OMRI-Hep-B was shown to induce high and long-lasting levels of circulating anti-HBs antibodies and greater areas under the curve (AUC) compared with the conventional preparation. Thus, anti-HBs half-life was 22 +/- 1.3 days for OMRI-Hep-B recipients and 13 +/- 1.3 days for Hepatect recipients (P <.001). Time to reach trough anti-HBs levels of 150 mIU/mL was significantly longer after administration of OMRI-Hep-B than after Hepatect (79 +/- 4.5 and 52 +/- 3.8 days, respectively; P <.001). In summary, the pharmacokinetic profile of the new HBIg, and in particular its prolonged elimination half-life, may reduce the cost of administration by approximately 30% and improve the quality of life of patients by extending the interval between repeated immune globulin injections.

Adolescent↗
PubMed1999

"Silent" presentation of veno-occlusive disease after liver transplantation as part of the process of cellular rejection with endothelial predilection.

Hemorrhagic centrilobular necrosis and fibrous stenosis of hepatic venules, suggesting veno-occlusive disease (VOD) have rarely been observed after orthotopic liver transplantation (OLT). The aim of this study was to determine the prevalence of this syndrome after OLT in relation to the course with particular reference to acute rejection and to azathioprine administration. VOD was identified in 19 of 1,023 patients transplanted over a 9-year period. VOD occurred at a median of 30 days posttransplantation, without clear cut clinical evidence for hepatic vein outlet obstruction. Seventeen of the 19 patients had an episode of acute rejection before or at the time of VOD. These episodes were compared with that of patients without VOD. In patients with VOD, portal inflammation and endothelialitis were enhanced (P =.014 and P =.048) and endothelialitis was also higher than bile duct damage (P =.03). The incidence of a centrilobular endothelialitis for both groups was not different although an increased trend was observed in the study group (64% vs. 46%; P =.18). The incidence of persistent rejection was similar between both groups (47% vs. 41%). The incidence of chronic rejection was higher in the study group (29% vs. 10%; P =. 04). All patients with VOD received azathioprine as part of immunosuppressive regimen. Despite azathioprine withdrawal, zone 3 changes persisted in 57% of patients. In conclusion, the incidence of VOD was 1.9% after OLT. The association of prominent endothelial involvement and VOD with acute rejection in most cases suggests an immunological phenomenon.

Adult↗