1/441. 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.- - - - - - - - - - ranking = 1keywords = infection (Clic here for more details about this article) |
2/441. 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.- - - - - - - - - - ranking = 1keywords = infection (Clic here for more details about this article) |
3/441. 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.- - - - - - - - - - ranking = 1keywords = infection (Clic here for more details about this article) |
4/441. 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.- - - - - - - - - - ranking = 1keywords = infection (Clic here for more details about this article) |
5/441. HBsAg carrier with simultaneous amebic liver abscess and acute hepatitis E.hepatitis e virus (HEV) infection and amebiasis are waterborne diseases that are endemic in india. However, their co-occurrence has never been described. We report a patient who presented with fever, jaundice and tender hepatomegaly and on investigation was found to have coexisting acute hepatitis E and amebic liver abscess. Incidentally, he was also an HBsAg carrier.- - - - - - - - - - ranking = 1keywords = infection (Clic here for more details about this article) |
6/441. Weils' syndrome and concomitant hepatitis B infection.leptospirosis is a ubiquitous, spirochetal zoonosis which presents with a broad clinical spectrum. Weil's syndrome, characterised by jaundice, renal failure and bleeding manifestations is the most severe form. A high index of suspicion for the diagnosis is required to institute therapy promptly. We describe a case of serologically confirmed Weil's syndrome with concomitant hepatitis B infection.- - - - - - - - - - ranking = 5keywords = infection (Clic here for more details about this article) |
7/441. Quantitative dna analysis of low-level hepatitis B viremia in two patients with serologically negative chronic hepatitis B.Low-level viremia due to hepatitis b virus (HBV) was demonstrated in the sera of two patients diagnosed previously as having non-B, non-C chronic hepatitis. Both patients had a "silent" HBV infection, because they were negative for both hepatitis B surface antigen (HBsAg) and anti-hepatitis B core antibody. The TaqMan chemistry polymerase chain reaction (PCR) amplified the HBV dna, enabling quantitation of the virus in their sera. Their serum HBV dna concentrations were low: the amount of each HBV S or X gene amplified showed there were approximately 10(3) copies/ml and HBV dna was detected occasionally during clinical follow-up. Positive HBsAg staining in liver tissues was demonstrated by an immunoperoxidase technique. Vertical transmission of silent HBV from one patient to her daughter was confirmed. Direct nucleotide sequencing of the amplified HBV X region revealed several mutations, suggesting reduced viral replication. One patient had a T-to-C mutation at the extreme 5'-terminus of the direct repeat 2 region and the other exhibited a coexisting X region with a 155-nucleotide deletion. These findings suggest that HBV replication is suppressed considerably in patients with silent hepatitis B.- - - - - - - - - - ranking = 1keywords = infection (Clic here for more details about this article) |
8/441. association of lamivudine resistance in recurrent hepatitis B after liver transplantation with advanced hepatic fibrosis.BACKGROUND: Orthotopic liver transplantation (OLT) in patients with hepatitis b virus (HBV) infection is known to be associated with a high recurrence rate and poor prognosis. lamivudine, a nucleoside analogue, is a potent inhibitor of HBV replication, but it is associated with a 14-39% rate of resistance. methods: We report on four patients who underwent OLT for HBV infection. In all cases, the HBV infection recurred in the grafted liver and was treated with lamivudine (100 mg daily) on a compassionate-use basis. The patients were monitored closely for serum liver enzymes, hepatitis B surface antigen and HBV dna (by hybridization). Liver biopsy was performed before and after lamivudine therapy. HBV dna was amplified from serum for each patient and sequenced through a conserved polymerase domain, the tyrosine-methionine-aspartate-aspartate (YMDD) locus. RESULTS: All four patients exhibited lamivudine resistance 9-20 months after initiation of the drug. In all patients with a clinically mild disease, liver histology findings (12-24 months after lamivudine therapy) showed progressive fibrosis as compared to biopsies performed before lamivudine therapy, with a significant increase (> or =2 points) in the Knodell score in three patients. Moreover, two patients exhibited worsening of the necroinflammatory process. A mutation at the YMDD motif of the HBV polymerase gene was detected in all cases. CONCLUSIONS: lamivudine resistance frequently occurs in patients with recurrent HBV infection after OLT and is associated with advanced hepatic fibrosis and necroinflammatory process. A combination of antiviral therapies may be necessary.- - - - - - - - - - ranking = 4keywords = infection (Clic here for more details about this article) |
9/441. hematopoietic stem cell transplantation from non-replicative hepatitis b virus carriers is safe.BACKGROUND/AIMS: hepatitis b virus can cause serious problems in individuals undergoing organ transplantation. The aim of this study was to evaluate the hepatic events among HBs-Ag positive recipients and HBs-Ag negative recipients who received products from hepatitis b virus carriers. methods: A total of 151 patients received an allogeneic hematopoietic stem cell transplantation at the Department of hematology-Oncology, University of Ankara, between June 1989 and June 1998. Among these, eight HBs-Ag positive and four HBs-Ag negative recipients received a product from a hepatitis b virus positive donor. The median follow-up period for these 12 patients was 13.2 months. RESULTS: Three of the eight HBs-Ag positive recipients died (one from hepatic failure); of the remainder, two are HBs-Ag negative, two HBs-Ag positive with normal liver injury tests and one HBs-Ag positive with elevated ALT levels. Of the four HBs-Ag negative recipients who received stem cells from a hepatitis B positive donor, two died; none of the patients in this group became HBs-Ag positive after transplantation. CONCLUSION: hepatitis b virus infection is a common problem in patients being considered for allogeneic hematopoetic stem cell transplantation, especially in areas where hepatitis b virus infection is endemic. We believe that the presence of HBs-Ag positivity is not an absolute contraindication for allogeneic hematopoetic stem cell transplantation unless the hepatitis b virus is in a replication phase.- - - - - - - - - - ranking = 2keywords = infection (Clic here for more details about this article) |
10/441. Clearance of HCV rna in a chronic hepatitis c virus-infected patient during acute hepatitis b virus superinfection.The routes of hepatitis b virus and hepatitis c virus transmission are quite similar and coexistence of both viruses in one patient is not a rare phenomenon. Until now, the natural course of liver diseases induced by coinfections has not been well documented and the mechanisms of interaction between the two viruses and the human host have not been fully clarified. We report the case of a patient suffering from chronic hepatitis due to hepatitis c virus who developed an acute hepatitis b virus superinfection. serum hepatitis c virus ribonucleic acid became undetectable by reverse transcriptase/polymerase chain reaction at diagnosis of acute hepatitis b virus infection. At the same time, there was a striking increase in the serum concentrations of the antibodies against C22 and C33c hepatitis c virus antigens. Four months after clinical resolution of the acute hepatitis, hepatitis B surface antigen was undetectable in serum and three months later antibodies against hepatitis B surface antigen appeared. Two years after acute hepatitis b virus infection, the patient has had no relapse of markers for viral replication of hepatitis b virus. transaminases are within the reference range and hepatitis c virus ribonucleic acid is undetectable in both serum and liver tissue. We hypothesize that acute hepatitis b virus infection stimulated a specific humoral response against hepatitis c virus as well as triggering non-specific defense mechanisms which finally eliminated both viruses.- - - - - - - - - - ranking = 9keywords = infection (Clic here for more details about this article) |
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