Cases reported "Hepatitis B, Chronic"

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1/51. Primary hepatic angiosarcoma: report of a case involving environmental arsenic exposure.

    Hepatic angiosarcoma is a rare malignant tumor with a rapidly fatal course. It has become a subject of interest because of its intimate relationship with environmental carcinogens, such as thorium dioxide (Thorotrast), vinyl chloride monomer, and arsenic. We describe a case of a chronic hepatitis B surface antigen carrier, with a 20-year history of environmental exposure to arsenical-containing agricultural herbicides and bactericides, who developed a hepatic angiosarcoma. He died due to rupture of the hepatic angiosarcoma with acute hemoperitoneum 9 weeks after initial diagnosis. This is a rare case of primary hepatic sarcoma, especially in taiwan where hepatocellular carcinoma is endemic. This case not only serves to give more evidence of the relationship between hepatic angiosarcoma and arsenical exposure, but also demonstrates the key point in the differential diagnosis of liver tumors. Increased familiarity with this disease will facilitate correct diagnosis and help to improve management of the condition in the future.
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2/51. Combined hepatocellular-cholangiocarcinoma. Diagnostic challenge in hepatic fine needle aspiration biopsy.

    OBJECTIVE: To study the cytohistologic features of combined hepatocellular-cholangiocarcinoma (CHCC-CC) in fine needle aspiration biopsy (FNAB) material. STUDY DESIGN: Six hepatic FNAB cases with cell blocks (five) and hepatic resections (two) were analyzed cytohistologically and immunohistochemically. RESULTS: The six cases were diagnosed as CHCC-CC based on clinicopathologic correlation. Unequivocal hepatocellular carcinoma (HCC) cells corresponding to Edmondson and Steiner's grade 3 lesions were identified in the FNAB in three instances. adenocarcinoma, represented by cohesive columnar cells with ovoid, basal nuclei displaying nuclear palisading, acini and/or papillary structures with variable intracytoplasmic intraacinar or brush border mucin production, was identified in all cases. Intermediate cells with hybrid/polymorphic cytologic features straddling malignant hepatocytes and glandular cells were identified in five instances. Tissue alpha-fetoprotein was negative. There was brush border and/or diffuse cytoplasmic p-carcinoembryonic antigen immunoreactivity in the glandular elements. CONCLUSION: FNAB diagnosis of CHCC-CC is possible if the clinical, cytohistologic and immunohistochemical findings support the presence of HCC and adenocarcinoma. Intermediate cells pose a great challenge to recognize and define: they tend to lose the classic cytologic features of malignant hepatocytes and acquire glandular characteristics. At the very least, there should be a high index of suspicion. These cases underscore the necessity for clinicopathologic correlation in enhancing the precision of FNAB diagnoses.
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3/51. Prominent effect of immunoadsorption plasmapheresis therapy in a patient with chronic inflammatory demyelinating polyneuropathy associated with hepatitis B infection.

    We encountered a patient with chronic inflammatory demyelinating polyneuropathy associated with hepatitis B infection. Immunohistochemical study revealed the deposition of immune complex composed of hepatitis B surface antigen (HBsAg) both around the endoneural capillary and in the endoneurium. Neurological signs were significantly improved by immunoadsorption plasmapheresis (IAPP) treatment without incorporating corticosteroid hormone therapy; weekly long-term IAPP has successfully maintained the patient's condition.
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4/51. A novel deletion mutant of hepatitis b virus surface antigen.

    HBsAg is the most important serological marker for acute or chronic hepatitis B. Nevertheless, there are reports of HBsAg-negative virus carriers, either with anti-HBc as the only marker for hepatitis b virus (HBV) infection or even positive for anti-HBs and anti-HBc. We report isolates from a patient, in which a deletion in the HBs-gene was associated with persisting viremia in the presence of anti-HBs. The 62-year-old female, infected most likely by her husband, had detectable markers of chronic active hepatitis B, such as HBsAg, HBeAg, and anti-HBc-IgM, for 2 years. The patient then seroconverted to anti-HBs, although HBeAg and anti-HBc-IgM remained detectable. At this time, semiquantitative polymerase chain reaction showed about 10(4) viral genomes per milliliter of serum. Direct sequencing of the amplified products revealed a major population of dna molecules with a deletion of nucleotide 31 of the HBs-gene, which up to now has not been described. This deletion led to a frame-shift and introduced a stop-codon after 21 amino acids of the sHBsAg. We suspect that this deletion, and the resulting HBsAg lacking the major epitopes recognized by specific antibodies, could favor ongoing viral replication, despite the presence of anti-HBs. However, because the reading frame of the polymerase was also severely damaged by this deletion, it is assumed that a minor population of intact genomes was present to help in the formation of virus particles.
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5/51. 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.
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6/51. Antigenic characterization of pre- and post-liver transplant hepatitis B surface antigen sequences from patients treated with hepatitis B immune globulin.

    BACKGROUND/AIMS: The success of treatment with hepatitis B hyperimmune globulin in preventing recurrence of hepatitis b virus infection in patients undergoing orthotopic liver transplantation depends on maintaining levels of anti-HBs sufficient to neutralise hepatitis b virus and also on patient compliance. Breakthrough infections may occur, and these have been associated with the emergence of variants in HBsAg. methods: Three patients, two who relapsed and one who had no evidence of hepatitis b virus infection post-orthotopic liver transplantation were studied. polymerase chain reaction and sequencing of pre- and post-orthotopic liver transplantation samples was followed by antigenic analysis of the in vitro expressed cloned sequences. RESULTS: In two patients who were treated with hyperimmune globulin, amino acid variation in the region of the immunodominant B cell epitopes of HBsAg occurred. Sequencing of clones revealed fluctuating variant sequences over time. One had clinical relapse and immune escape was evident on in vitro antigenic analysis. Patient two lost HBsAg reactivity post-orthotopic liver transplantation. There was loss of an antigenically critical cysteine molecule; sequencing of clones revealed that this was the dominant species. The third patient relapsed when protective levels of anti-HBs were not maintained; HBsAg showed no variation compared to a standard subtype sequence. CONCLUSION: These data provide strong experimental evidence of immune escape. It appears that hyperimmune globulin provides the selection pressure. In these patients, HBsAg negativity does not exclude infection of the transplanted liver.
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7/51. Case report: lamivudine therapy for submassive hepatic necrosis due to reactivation of hepatitis B following chemotherapy.

    This report describes the case of a 53-year-old woman who developed severe hepatitis following chemotherapy for breast carcinoma. The patient was hepatitis B surface antigen positive, e antigen negative and e antibody positive and had high levels of hepatitis b virus-dna. Liver biopsy revealed submassive hepatic necrosis, consistent with reactivation of hepatitis B. Treatment with lamivudine resulted in rapid loss of hepatitis b virus-dna, resolution of hepatitis and clinical recovery.
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8/51. Case report: dramatic response to lamivudine therapy following corticosteroid priming in chronic hepatitis B.

    A 21 year-old male patient with chronic hepatitis B was treated with lamivudine 150 mg daily after withdrawal of a short course of oral prednisolone (30 mg daily for 3 weeks, 15 mg daily for 1 week). serum hepatitis b virus (HBV)-dna increased during prednisolone pretherapy and serum alanine aminotransferase (ALT) was increasing after withdrawal of prednisolone. Clearance of HBV-dna with hepatitis B e antigen seroconversion and ALT normalization occurred within 2 months after starting lamivudine therapy. If this dramatic response to lamivudine therapy after corticosteroid priming is confirmed by further studies, the regimens used in this particular case might become a powerful therapeutic tool for chronic HBV infection.
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9/51. hepatitis b virus core promoter mutations in children with multiple anti-HBe/HBeAg reactivations result in enhanced promoter activity.

    Sera of two children were examined to determine whether specific hepatitis b virus (HBV) mutants may contribute to anti-hepatitis B e/hepatitis B e antigen (anti-HBe/HBeAg) reactivations during the course of chronic hepatitis B. The full-length HBV genome isolated from sera of patient 1 and the basic core promoter (BCP) from patient 2 were amplified and sequenced before and after several reactivations. The functional significance of the mutant BCP from patient 1 was studied using the luciferase assay. In both patients, rare mutations were found in the BCP at nucleotides 1764(G-->T)/1766(C-->G) and 1766(C-->T)/1768(T-->A) in case 1 and 2, respectively. In the BCP from patient 1, a putative new binding site for the transcription factor hepatocyte nuclear factor 3 (HNF3) was generated. The functional analyses of the mutant showed a 2.8-fold increase of core promoter activity, whereas the BCP variant of patient 2 was also identified to result in enhanced promoter activity. The alignment of full-length genomes from child 1 to the reference sequence showed 61 nucleotide substitutions. Furthermore, the time of reactivations from child 1 was always accompanied by selection of a precore mutation at nucleotide position 1899. In liver tissue of patient 1 before development of hepatocellular carcinoma only free viral sequences were found, whereas a single site integration of HBV was detected in hepatocytes after activation of carcinogenesis. Specific mutations in the HBV BCP of the two patients that are rarely present in chronic carriers were identified to increase the core promoter activity possibly by altering transcription factor binding, suggesting that these variants may be involved in the pathogenesis of frequent HBV reactivations.
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10/51. Clinicopathological characteristics of surgically resected minute hepatocellular carcinomas.

    BACKGROUND/AIMS: The multistep development of overt hepatocellular carcinoma from very well-differentiated early hepatocellular carcinoma, and of early hepatocellular carcinoma from adenomatous hyperplasia has been strongly suggested. The clinicopathologic and immunohistochemical characteristics of solitary minute hepatocellular carcinomas smaller than 1 cm in size have yet to be clarified. METHODOLOGY: Fourteen minute hepatocellular carcinomas were divided into 2 groups consisting of: 1) hepatocellular carcinoma of hepatitis B surface antigen positive patients (B-HCC) (n = 5), and 2) hepatocellular carcinoma of hepatitis c virus antibody positive patients (C-HCC) (n = 9), then they were all analyzed histopathologically and clinicopathologically. Immunohistochemical studies were also performed using the antibodies against p53 protein. RESULTS: Six of the 14 minute hepatocellular carcinoma were demonstrated to be moderately or poorly differentiated tumors. Among the 8 well-differentiated minute hepatocellular carcinomas, 2 tumors already contained less differentiated components. B-HCC tended to be less differentiated than C-HCC (P < 0.05). Adenomatous hyperplasia was detected in only 2 cases of C-HCC. Small cell liver dysplasia was detected significantly more frequently in C-HCC than in B-HCC (P < 0.05). The prognosis of the 14 minute hepatocellular carcinomas varied considerably. Immunohistochemically, some tumor cells were positive for p53 in 3 cases. CONCLUSIONS: Our study suggests that 1) the multistep carcinogenesis through adenomatous hyperplasia may not be so frequent, 2) De novo carcinogenesis from not only well-differentiated hepatocellular carcinoma, but also from less differentiated hepatocellular carcinoma, especially B-HCC, may be present, 3) the carcinogenesis in the B-HCC cases may behave differently from that in C-HCC cases, and 4) minute hepatocellular carcinomas demonstrate varying prognoses after hepatectomy.
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