1/836. alpha-Interferon therapy for HBV-related glomerulonephritis. We report a case of a patient with hepatitis b virus (HBV)-related membranous glomerulonephritis (MGN) who showed improvement after interferon-alpha (IFN-alpha) therapy. A 35-year-old man with nephrotic syndrome and HBV antigens received a 24-week course of IFN-alpha. At the end of therapy there was an elevation in the level of plasma aminotransferase and an increase in proteinuria, which were followed by antigen/antibody seroconversion. This "flare-up" before seroconversion suggests an increase in disease activity in the liver and kidney, demonstrating in vivo HBV involvement in MGN. ( info) |
2/836. Leukocytoclastic vasculitis, hepatitis B, and the risk of endoscopy. Leukocytoclastic vasculitis, presenting with palpable purpura, is a relatively common problem encountered by both primary care practitioners and dermatologists. A variety of potential etiologies exists and includes autoimmune, neoplastic, and infectious causes. We report a case of leukocytoclastic vasculitis that led to the diagnosis of acute hepatitis B, perhaps acquired through colonoscopy. ( info) |
| A 63-year-old male with lactic acidosis secondary to fialuridine-induced liver failure underwent seven plasma exchanges while awaiting orthotopic liver transplantation. Following plasma exchange, total serum calcium concentrations measured by conventional clinical chemistry methods were significantly lower than the elemental calciums determined by atomic absorption spectroscopy (P = 0.004). The difference in calcium measured by atomic absorption and by conventional methods correlated with serum citrate concentration (R = 0.77) Following the first exchange, the serum lactic acid concentration decreased from 10.2 to 4.4 mmol/L. These results suggest that plasma exchange may aid in the removal of metabolic products such as lactic acid in patients with liver failure. However, the accumulation of unmetabolized citrate may also result in falsely low total calcium measurements in some patients who undergo plasma exchange. ( info) |
4/836. Evaluation of assay methods for hepatitis B surface (HBsAg) antigen and its antibody (anti-HBs) in viral hepatitis B (VHB)-HBsAg-positive. The sensitivity of methods for the detection of HBsAg and its anti-HBs was compared in serial 1200 sera samples from 30 patients with VHB-HBsAg-positive. HBsAg was tested by gel-diffusion (GD), counter-immunoelectrophoresis (CIE), reversed haemogglutination (rHA), redioimmunoassay (RIA), and enzyme immunoassay (EIA). RIA and EIA methods are statistically significantly more sensitive compared with the other methods (P less than 0.0005). By these methods the minimal concentrations of HBsAg in sera can be proved. Although there is no statistically significant difference in the sensitivity between RIA and EIA, the latter is more sensitive if the subtype ay-HBsAg is considered (12 sera samples). In 24 patients the subtype was ay, in two ad, and in four it could not be differentiated. In 70% of patients anti-HBs was proved by RIA and in 10% by CIE, i.e., in 73% and 9% of sera samples, respectively. In 117 sera samples of these patients the sensitivity of RIA and EIA was compared for determination of anti-HBs. No statistically significant difference between the methods for determination of anti-HBs was found (50.42%: 40.17%). No immune response to HBsAg has been observed in 9 cases, but 6 of them have remained permanent carriers of this antigen. ( info) |
5/836. hepatitis b virus variants with lamivudine-related mutations in the dna polymerase and the 'a' epitope of the surface antigen are sensitive to ganciclovir. lamivudine is a new antiviral agent effective against hepatitis B viral (HBV) infections but can result in virus-drug resistance associated with mutations in the conserved 'YM552DD' motif of the HBV dna polymerase. Due to their overlapping coding regions in the HBV genome, mutations in the dna polymerase may result in substitutions in the hepatitis B surface antigen (HBsAg), albeit outside the antigenic 'a' epitope. Here we report the identification of a novel type of lamivudine-related mutations located in both the polymerase (YM552DD-->Y1552DD) and the 'a' epitope of HBsAg (Gly130-->Asp130). The same virus carried a HBsAg Gly145-->Arg145 mutation prior to therapy. Both the wild type HBV and lamivudine-related mutants with the Gly145-->Arg145 HBsAg mutation were suppressed following ganciclovir treatment, indicating a beneficial additive effect of both drugs against different forms of HBV mutants. ( info) |
6/836. Three cases of severe subfulminant hepatitis in heart-transplanted patients after nosocomial transmission of a mutant hepatitis b virus. Fulminant and severe viral hepatitis are frequently associated with mutant hepatitis b virus (HBV) strains. In this study, the genetic background of a viral strain causing severe subfulminant outcome in heart-transplanted patients was studied and compared with viral hepatitis B strains that were not linked to severe liver disease in the same setting. A total of 46 patients infected nosocomially with HBV genotype A were studied. Five different viral strains were detected, infecting 3, 9, 5, 24, and 5 patients, respectively. Only one viral strain was found to be associated with the subfulminant outcome and 3 patient deaths as a consequence of severe liver disease. The remaining 43 patients with posttransplantation HBV infection did not show this fatal outcome. Instead, symptoms of hepatitis were generally mild or clinically undiagnosed. Comparison of this virus genome with the four other strains showed an accumulation of mutations in the basic core promoter, a region that influences viral replication, but also in hepatitis B X protein (HBX) (7 mutant motifs), core (10 mutant motifs), the preS1 region (5 mutant motifs), and the HBpolymerase open reading frame (17 motifs). Some of these variations, such as those in the core region, were located on the tip of the protruding spike of the viral capsid (codons 60 to 90), also known in part as an important HLA class II-restricted epitope region. These mutations might therefore influence the immune-mediated response. The viral strain causing subfulminant hepatitis was, in addition, the only strain with a preCore stop codon mutation and, thus, hepatitis B e antigen (HBeAg) expression was never observed. The combination of these specific viral factors is thought to be responsible for the fatal outcome in these immune-suppressed heart-transplant recipients. ( info) |
7/836. kidney transplantation in a child with posterior urethral valve from a hepatitis B virus-carrier mother. Report of a case with special reference to urinary tract reconstruction for dysfunctionalized uropathies and seroimmunological preparation against viral transmission. The case of a 7-year-old boy with posterior urethral valve (PUV) who underwent successful kidney transplantation for progressive renal failure is reported. He required complex reconstructive surgery for PUV-related disorders, and also specific serological preparation for hepatitis B (HB) as his living donor mother was a proven carrier. By carefully executing the principles of reconstructive surgery and with well-planned seroimmunological preparation, we have demonstrated that successful kidney transplantation can be done from an HB Ag-positive mother to an HB Ag- and HB Ab-negative son, even when his urinary tract is severely dysfunctional due to PUV. ( info) |
8/836. Fulminant hepatitis is significantly increased in hepatitis B carriers after allogeneic bone marrow transplantation. BACKGROUND: bone marrow transplantation (BMT) is effective treatment for many hematologic disease, but performed in a population with a high endemic hepatitis B virus carrier rate, the incidence of liver function impairment and fulminant hepatitis (FH) is expected to be raised. methods: Forty-three hepatitis b virus carriers received high-dose chemotherapy and BMT, 32 patients received an allogeneic graft, and 11 patients autologous marrow. Acute graft-versus-host disease prophylaxis consisted of methotrexate on day 1, 3, 6, and 11 and cyclosporine for 6 months. RESULTS: After a median follow-up period of 68 months (range: 1-11.5 years), 26 (81.3%) allogeneic BMT patients developed impaired liver function (LF), 5 progressed to FH on day 93, 169, 170, 180, and 468, respectively, and died after an average of 13.8 days (range: 1-45 days). Whereas only 4 (36.4%) autologous BMT patients developed impaired LF, and none FH. Impaired LF (P=0.026, chi-square), and FH (odds ratio=12.86, P=0.009 for coefficient) were significantly related to an allogeneic marrow graft, and the timing of liver function impairment coincided with cyclosporine withdrawal. Hepatitis B surface antigen (HbsAg) disappeared from the serum in 4/14 (28.6%) patients receiving a marrow graft from an HbsAg donor. HbsAg was not detected in the serum after BMT in 2/11 (18.2%) autologous BMT patients. CONCLUSIONS: hepatitis b virus carriers receiving a marrow graft from an HbsAg donor have a significantly increased risk of FH. ( info) |
9/836. Prevention of hepatitis B flare-up during chemotherapy using lamivudine: case report and review of the literature. Reactivation of chronic hepatitis B in patients receiving cytotoxic treatment for non-Hodgkin's lymphoma is well documented. We report a case of a patient with chronic hepatitis B who was treated by chemotherapy because of non-Hodgkin's lymphoma. After the second cycle of chemotherapy she developed a severe flare-up of hepatitis B. Liver biopsy revealed highly active hepatitis and confluent necroses. Within 3 weeks, the patient recovered spontaneously. Prophylactic treatment with lamivudine (Epivir,Glaxo-Wellcome, 150 mg b.i.d.) led to a decrease of HBV-dna below the detection limit. Further chemotherapy was administered and autologous stem cell transplantation was successfully performed without another reactivation of hepatitis B. Antiviral treatment was stopped 16 weeks after stem cell retransfusion. So far, no further flare-up of hepatitis B has occurred and the patient's lymphoma has not relapsed. Thus, the case described here indicates a possible role of lamivudine in preventing hepatitis B flare-up during antineoplastic chemotherapy. We suggest that lamivudine be considered for prophylaxis against fulminant hepatitis in patients with chronic HBV infection undergoing high-dose antineoplastic therapy. ( info) |
10/836. Selection of hepatitis B surface "escape" mutants during passive immune prophylaxis following liver transplantation: potential impact of genetic changes on polymerase protein function. CASE REPORT: A patient is described who developed hepatitis b virus (HBV) reinfection five months following liver transplantation. Failure of hepatitis B immunoglobulin prophylaxis was associated with the emergence of mutations. HBV gene sequencing identified nucleotide substitutions associated with amino acid changes, one within the major hydrophilic region (MHR) of the HBV surface antigen at amino acid position 144 and one outside the MHR. Because of the overlapping reading frames of surface and polymerase genes, the latter surface antigen change was associated with an amino acid change in the polymerase protein. The patient developed significant allograft hepatitis and was treated with lamivudine (3TC) 100 mg daily. Rapid decline of serum HBV dna was observed with loss of HBV e antigen and HBV surface antigen from serum. There was normalisation of liver biochemistry, and liver immunohistochemistry showed a reduction in HBV core and disappearance of HBs antigen staining. CONCLUSION: Surface antigen encoding gene mutations associated with HBIg escape may be associated with alteration of the polymerase protein. The polymerase changes may affect sensitivity to antiviral treatment. Selection pressure on one HBV reading frame (for example, HBIg pressure on HBsAg, or nucleoside analogue pressure on polymerase protein) may alter the gene product of the overlapping frame. Such interactions are relevant to strategies employing passive immune prophylaxis and antiviral treatment. ( info) |