1/10. 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 = 1keywords = hybridization (Clic here for more details about this article) |
2/10. Postmortem diagnosis of "occult" klinefelter syndrome in a patient with chronic renal disease and liver cirrhosis.This report describes a patient not suspected of having klinefelter syndrome during life but diagnosed with it following postmortem examination using fluorescent in situ hybridization (FISH) for sex chromosomes and hormone serum analysis. A 49-year-old Japanese man had a history of nephrosis, heavy alcohol consumption, diabetes mellitus, and liver cirrhosis and had been undergoing dialysis for 10 years. He died of ruptured esophageal varices. autopsy revealed hypogonadism, suggesting klinefelter syndrome. This was confirmed by FISH, which showed a mosaic 46XY, 47XXY karyotype, and by serum analysis, which revealed high luteinizing hormone and follicle-stimulating hormone and low testosterone levels. autopsy also revealed a nodular, bilateral, testicular Leydig cell hyperplasia. This report illustrates the value of postmortem laboratory investigations, particularly FISH for sex chromosomes and serum hormone analysis, for the demonstration of clinically uncertain or "occult" klinefelter syndrome.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/10. Genetic evaluation of the dysplasia-carcinoma sequence in chronic viral liver disease: a detailed analysis of two cases and a review of the literature.Hepatocellular carcinoma (HCC) is one of the most frequent human malignancies, especially in Asia and africa, but also in the western world its incidence is increasing. HCC is a complication of chronic liver disease with cirrhosis as the most important risk factor. Viral co-pathogenesis due to hepatitis b virus (HBV) and hepatitis c virus (HCV) infection seems to be an important factor in the development of HCC. Curative therapy is often not possible due to the late detection of HCC. Thus, it is attractive to find parameters which predict malignant transformation in HBV- and HCV-infected livers. In the past decade, preneoplastic lesions, i.e. dysplastic foci or nodules, have gained interest as possible markers for imminent malignancy. Noteworthy, dysplastic liver lesions are increasingly detected by imaging techniques. We describe here two cases of chronic viral liver disease, one HBV-and one HCV-related, in which dysplastic lesions were present adjacent to HCC. In the HBV case, a (smaller) satellite of HCC was present as well. The neoplastic specimens were investigated by comparative genomic hybridization (CGH) and in situ hybridization (ISH). Both methods revealed multiple genetic alterations in the HCCs. The genetic patterns of the HBV-related HCC and the satellite tumor showed many shared alterations suggesting a clonal relationship. A subset of genetic changes were already present in dysplasias illustrating their preneoplastic nature. Surrounding liver cirrhosis samples did not display chromosomal aberrations. A literature survey illustrates the relative paucity of information concerning genetic alterations in preneoplastic liver lesions. However, all the data strongly suggests a role for liver cell dysplasia as a precursor condition of liver cell cancer.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
4/10. lamivudine induced stable reversal in HBV liver cirrhosis child C: a case report.A 40-year-old viremic woman with HBV related liver cirrhosis (child-Plugh - C) received 100 mg lamivudine daily for 24 months. Initially the patient was with hepato-splenomegaly, marked ascites and mild jaundice. There were no signs of portal encephalopaty and gastrointestinal haemorrhage. The baseline ALT was about 6 times above the upper limit of normal. hypoalbuminemia of 29 g/l as well as hyperbilirubinemia of 40 mmol/L and decreased protrombin index of 47% was found. Serological tests showed positive serum HBsAg and anti-HBe antibodies. The patient was HBeAg negative, but with detectable serum HBV dna (500 pg/mL) by dot-blot hybridization HDV, HCV and hiv co-infections were excluded. A marked improvement in liver function had been found at the end of the third month of therapy, with normalization of bilirubin and ALT activity. serum albumin and protrombine index increased from 29 g/l to 36 g/l and from 47% to 92%, respectively. The patient was without ascites and child-Plough score decreased from 10 to 5 points. Serum HBV dna rapidly decreased at the end of first treatment month and was undetectable three months after the initiation of lamivudine therapy. We found two viremic episodes during the lamivudine treatment. However, child-Pugh score did not increased and the patient remained with compensated liver disease and with lower ALT than baseline value. The main question is haw long such patients have to receive the lamivudine treatment.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/10. Successful treatment with tenofovir in a child C cirrhotic patient with lamivudine-resistant hepatitis b virus awaiting liver transplantation. Post-transplant results.Antiviral treatment can be complex in decompensated hepatitis b virus (HBV) cirrhosis because of potential emergence of lamivudine-resistant mutants and worsening liver function, and to multifactorial nephrotoxicity. Negative HBV-dna status by hybridization before liver transplantation is a favorable prognostic factor. We present the case of a 54-year-old HBV liver transplantation candidate who, after testing negative for HBV-dna, developed YMDD lamivudine-resistant mutants resulting in a deteriorated clinical condition. After 8 months of adefovir plus lamivudine double therapy, only partial response was achieved. Tenofovir was added to this regimen, and an early decline of HBV-dna was seen at 4 weeks without adverse events. The patient underwent transplantation. At 21-month postoperative follow-up, the patient's outcome was excellent. Post-transplantation HBV prophylaxis, taking into account the prior development of mutants, consists of hepatitis B immunoglobulin plus lamivudine and adefovir. Tenofovir was well tolerated and produced a fast antiviral response, suggesting its potential value in combined antiviral treatment for liver transplantation candidates.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/10. Study of preneoplastic changes of liver cells by immunohistochemical and molecular hybridization techniques.The status of hepatitis b virus dna was investigated by in situ hybridization in multifocal areas of a noncancerous hepatitis b virus-associated cirrhosis. This liver exhibited a marked degree of dysplasia and adenomatous hyperplasia. The results of these studies were correlated with the histopathology and immunohistochemical stains for hepatitis B core and surface antigens. There was clear evidence of a marked reduction to absence of hepatitis B viral dna by in situ hybridization and absence of HBc and HBsAg in the foci of liver cell dysplasia and adenomatous hyperplasia. These results support the hypothesis that liver cell dysplasia and adenomatous hyperplasia are preneoplastic in nature.- - - - - - - - - - ranking = 6keywords = hybridization (Clic here for more details about this article) |
7/10. Seroconversion from HBs-Ag to anti-HBs in a case of liver cirrhosis associated with hepatocellular carcinoma.This paper reports a case of liver cirrhosis associated with hepatocellular carcinoma (HCC) of a woman who was converted from hepatitis B surface antigen (HBs-Ag) positive to antibody against HBs-Ag (anti-HBs) positive in the serum through an immunoregulatory steroid rebound phenomenon. The histology of the biopsy specimen taken before the seroconversion showed an early stage of liver cirrhosis with moderate infiltration of mononuclear cells. At autopsy about 3 years after the seroconversion, the liver tissue free of the tumor was in an early stage of liver cirrhosis. fibrosis did not advance as compared with the biopsy specimen. In addition, mononuclear cell infiltration decreased remarkably and piecemeal necrosis disappeared after the seroconversion. The immunohistologic examination of hepatocytes demonstrated that positive stainings for HBs-Ag and for hepatitis B core antigen (HBc-Ag) in the biopsy specimen turned to be negative in the autopsy specimen. These facts indicate that the steroid rebound phenomenon eliminated free hepatitis b virus (HBV) in the hepatocytes in the absence of massive necrosis of hepatocytes. HBV-dna integration was proved in the genome of HCC by molecular hybridization method.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
8/10. Discordance of hepatitis B e antigen/antibody and hepatitis b virus deoxyribonucleic acid in serum. Analysis of 1063 specimens.hepatitis b virus dna was determined in 1063 serum samples from 252 patients with hepatitis B surface antigen by the spot hybridization technique. The results were correlated with hepatitis B e antigen and antibody. hepatitis b virus dna was detected in 87% of hepatitis B e antigen-positive patients, in 18% of hepatitis B e antibody-positive patients, and in 18% of those negative for both. Discordance of antigen/antibody and hepatitis b virus dna, i.e., the presence of the dna in antibody-positive sera or the absence of the dna in antigen-positive sera, was observed in 209 of 997 (21%) samples. Of 121 patients with histologic diagnosis, this discordance was observed in none of 20 patients with nonspecific changes, in 13% of 39 with chronic persistent hepatitis, in 21% of 38 with chronic active hepatitis, and in 38% of 24 with cirrhosis. Thus, hepatitis B e antigen/antibody testing alone failed to predict the presence or absence of circulating hepatitis B virion in a significant proportion of patients with advanced chronic liver disease.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
9/10. Rapid development of lymphoma following liver transplantation in a recipient with hepatitis B and primary hemochromatosis.We report a case of a posttransplant lymphoproliferative disorder (PTLD) which presented in a liver allograft shortly after transplantation. The patient, who had been transplanted because of cirrhosis due to primary hemochromatosis and chronic hepatitis B infection (HBV), developed early recurrent HBV in the graft, and 2 months after transplantation, liver biopsies showed a malignant large-cell lymphoma. The neoplastic cells demonstrated Epstein-Barr virus dna by in situ hybridization. The patient died 3.5 months posttransplant due to liver failure. At autopsy, the liver showed nodules of malignant lymphoma, massive hepatic necrosis, and iron overload, but no evidence of rejection. This report suggests that the grafted liver can be the site of PTLD in recurrent HBV and hemochromatosis.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
10/10. Beneficial effect of lamivudine in recurrent hepatitis B after liver transplantation.Orthotopic liver transplantation (OLT) in patients infected with hepatitis b virus (HBV) is known to be associated with a high recurrence rate and poor prognosis. Interferon treatment in these patients offers little benefit and may lead to further complications. lamivudine, the (-)enantiomer of 3'-thiacytidine, a 2'3'-dideoxynucleoside, is known to be a potent inhibitor of HBV replication in patients with chronic HBV infection. Three HBV-positive OLT patients were administrated lamivudine, 100 mg x 1 orally, for a period of at least 20 weeks, in an open, compassionate-use basis. All three patients were HBV dna-negative before OLT. HBV reinfection occurred at a median time of 7 months (range, 6-9 months) after OLT, in spite of adequate immunoprophylaxis. All three patients had high serum transaminase levels (alanine aminotransferase [ALT], 103-324 U/L) and histologic evidence of recurrent HBV infection of the grafted liver, and HBV dna was evident in the sera of all of them. Six weeks after lamivudine treatment, HBV dna disappeared from the serum of all patients (detected by hybridization); by the 10th week, HBV dna was also negative by polymerase chain reaction in two out of three patients. Interestingly, the one patient who was HBV dna positive by polymerase chain reaction still has mildly elevated ALT levels, whereas the other two patients have normal ALT levels. We also noted that on the 5th week there was a transient elevation of serum ALT levels in two patients. No adverse effects or rejection episodes were noted. In conclusion, lamivudine is a beneficial and well-tolerated therapy in OLT patients with recurrent HBV infection. We are studying the effect of lamivudine in other patients and for a longer period of time.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
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