Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mother-to-child transmission is an important route for hepatitis B virus (HBV) dissemination. It has been established that HBV traces persist for years after complete clinical recovery from hepatitis B. Similarly, resolution of hepatitis caused by HBV-related woodchuck hepatitis virus (WHV) is followed by occult lifelong carriage of pathogenic virus. In this study, we documented that WHV persisting after termination of acute hepatitis is transmittable to newborns as an asymptomatic long-term infection. All 11 offspring from 4 dams studied carried transcriptionally active WHV genomes for 3.5 years after birth without immunovirological markers of infection. WHV genomes and mRNA were detected both in the liver and lymphoid tissue in the majority of offspring; WHV covalently closed circular DNA was detected in some samples. In 4 offspring, however, the virus was restricted to the lymphatic system. In the circulation, WHV DNA-reactive particles were DNase resistant and of comparable size and density to complete virions. Importantly, the virus in offspring with or without hepatic WHV DNA expression was infectious to WHV-naive woodchucks. Finally, offspring challenged with WHV were not protected against reinfection. These findings show that mothers with occult hepadnaviral carriage transmit pathogenic virus to their offspring, inducing a persistent infection invariably within the lymphatic system but not always in the liver.
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PMID:Persistence of infectious hepadnavirus in the offspring of woodchuck mothers recovered from viral hepatitis. 1041 50

Woodchuck hepatitis virus (WHV), similar to human hepatitis B virus, causes acute liver inflammation that can progress to chronic hepatitis and hepatocellular carcinoma. WHV also invades cells of the host lymphatic system, where it persists for life. We report here that acute and chronic hepadnavirus hepatitis is characterized by a profound difference in the expression of class I major histocompatibility complex (MHC) molecules on the surface of infected hepatocytes and, notably, lymphoid cells. While acute WHV infection is accompanied by the enhanced hepatocyte surface presentation of class I MHC antigen and upregulated transcription of the relevant hepatic genes, inhibition of class I antigen display on liver cells is a uniform hallmark of chronic WHV infection. This inhibition in chronic hepatitis occurs despite augmented (as in acute infection) expression of hepatic genes for class I MHC heavy chain, beta(2)-microglobulin, and transporters associated with antigen processing (TAP1 and TAP2). Further, the class I antigen inhibition is not related to the histological severity of hepatocellular injury, the extent of lymphocytic infiltrations, the level of intrahepatic gamma interferon induction, or the hepatic WHV load. Importantly, the antigen expression is also inhibited on organ lymphoid cells of chronically infected hosts. The results obtained in this study demonstrate that the defective presentation of class I MHC molecules on cells supporting persistent WHV replication is due to viral posttranscriptional interference. This event may diminish the susceptibility of infected hepatocytes to virus-specific T-cell-mediated elimination, hinder virus clearance, and deregulate the class I MHC-dependent functions of the host immune system. This multifarious effect could be critical for perpetuation of liver damage and evasion of the antiviral immunological surveillance in chronic infection and therefore could be supportive of hepadnavirus persistence.
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PMID:Posttranscriptional inhibition of class I major histocompatibility complex presentation on hepatocytes and lymphoid cells in chronic woodchuck hepatitis virus infection. 1077 84

We report a patient, a 23-year-old man, who was a hepatitis B virus(HBV) carrier complicated with nephrotic syndrome. He was admitted to our hospital because of generalized edema and massive ascites. Laboratory data on admission were as follows: proteinuria 9,850 mg/day, Cr 2.7 mg/dl, BUN 73 mg/dl, albumin 1.9 g/dl, cholesterol 501 mg/dl, GOT 23 IU/l, GPT 19 IU/l, HBsAg(+), and HBeAg(222.7). Since his nephrotic symptoms were seriously complicated with renal failure, we selected steroid therapy for nephrosis preference. His renal function was improved and the urinary protein decreased immediately, but his liver function deteriorated. The renal biopsy revealed focal mesangial proliferative glomerulonephritis. Immunofluorescent examination revealed slight deposits of IgG, IgM, and C3 along the glomerular basement membrane and mesangial matrix. He was not compliant and often stopped taking the steroid therapy, thereby causing nephrosis to recur each time. After all, nephrotic symptoms have been well-controlled with cyclosporin and steroid. In spite of the seroconversion of HB virus by formation of HBe antibody, mutant HBV infection continued. The fact that liver biopsy revealed severe lymphoid infiltration at the portal area suggested chronic active hepatitis. His clinicopathologic course suggests that HBV-associated nephropathy does not always remit as there are some cases in whom hepatitis remains in an active state even after seroconversion, due to its mutant status. In these cases, the long-term prognosis of HBV nephropathy has not been defined. Further study is necessary to establish the optimal treatment for HB nephropathy in adults.
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PMID:[A case of hepatitis B virus carrier complicated with nephrotic syndrome]. 1099 20

Woodchuck hepatitis virus (WHV) and human hepatitis B virus are closely related, highly hepatotropic mammalian DNA viruses that also replicate in the lymphatic system. The infectivity and pathogenicity of hepadnaviruses propagating in lymphoid cells are under debate. In this study, hepato- and lymphotropism of WHV produced by naturally infected lymphoid cells was examined in specifically established woodchuck hepatocyte and lymphoid cell cultures and coculture systems, and virus pathogenicity was tested in susceptible animals. Applying PCR-based assays discriminating between the total pool of WHV genomes and covalently closed circular DNA (cccDNA), combined with enzymatic elimination of extracellular viral sequences potentially associated with the cell surface, our study documents that virus replicating in woodchuck lymphoid cells is infectious to homologous hepatocytes and lymphoid cells in vitro. The productive replication of WHV from lymphoid cells in cultured hepatocytes was evidenced by the appearance of virus-specific DNA, cccDNA, and antigens, transmissibility of the virus through multiple passages in hepatocyte cultures, and the ability of the passaged virus to infect virus-naive animals. The data also revealed that WHV from lymphoid cells can initiate classical acute viral hepatitis in susceptible animals, albeit small quantities (approximately 10(3) virions) caused immunovirologically undetectable (occult) WHV infection that engaged the lymphatic system but not the liver. Our results provide direct in vitro and in vivo evidence that lymphoid cells in the infected host support propagation of infectious hepadnavirus that has the potential to induce hepatitis. They also emphasize a principal role of the lymphatic system in the maintenance and dissemination of hepadnavirus infection, particularly when infection is induced by low virus doses.
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PMID:In vitro and in vivo infectivity and pathogenicity of the lymphoid cell-derived woodchuck hepatitis virus. 1116 Jun 75

Pleural effusion presentation of posttransplant lymphoproliferative disorder (PTLD) is relatively uncommon. Most examples of effusion-based PTLD have been secondary to widespread solid organ involvement, and are associated with an aggressive clinical course. We report on a case of primary effusion PTLD in a 70-yr-old male liver transplant recipient with a history of hepatitis B infection. Cytomorphologically, the pleural fluid specimen showed a monomorphous population of intermediate to large-sized transformed lymphoid cells, with irregular multilobated nuclear contours and readily identifiable mitotic figures. Flow cytometric immunophenotypic studies revealed a CD5-negative, CD10-negative, lambda immunoglobulin light chain-positive, monoclonal B-lymphocyte (CD19-positive/CD20-positive) population. The immunocytochemical stain for CD30 antigen was negative. In situ hybridization study for Epstein-Barr virus (EBV) early RNA (EBER) and Southern blot analysis for EBV terminal repeat sequences were both positive. Southern blot analysis for human herpes virus-8 (HHV-8) was negative. No solid-organ PTLD was identified, and the cytologic results supported the diagnosis of primary effusion PTLD. Immunosuppression was decreased, and 8 mo following the diagnosis of pleural fluid PTLD, the patient was stable and his pleural effusion had markedly diminished. Recognition of primary effusion PTLD and its distinction from PTLD secondarily involving the body fluids and from other lymphomas is important, since the behavior and prognosis appear different.
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PMID:Primary pleural effusion posttransplant lymphoproliferative disorder: Distinction from secondary involvement and effusion lymphoma. 1146 13

Many individuals infected with hepatitis B virus (HBV) and hepatitis C virus (HCV) are unable to clear these viruses following an acute infection and become chronically infected. There are more than 400 million HBV and HCV carriers in the world and a considerable number of these patients would eventually develop more severe complications like liver cirrhosis and hepatocellular carcinoma. It is not clearly known how an individual develops a chronic hepatitis virus carrier state; however, a defective immune response of the host is thought to play a critical role in the underlying pathogenetic mechanism. On the other hand, dendritic cells (DCs), the most potent antigen-presenting cells, are widely distributed in both lymphoid and nonlymphoid tissues. Recognition of the microbes or microbial antigens by DCs is one of critical events for the initiation of an immune response. DCs also play a cardinal role during the progression and termination of an immune response. The aim of this overview is to provide information regarding the role of DCs in the pathogenesis of chronic hepatitis due to HBV and HCV in humans and in animal models of HBV and HCV carrier states. First, we summarize our current understanding of the pathogenesis of hepatitis virus carrier states and also of general properties of DCs. Next, we discuss the data on the phenotypes and functions of DCs in both human and murine HBV and HCV carriers. We also discuss vaccine therapy in murine HBV carriers because activation of DCs due to vaccination-initiated HBsAg-specific immune responses in HBV transgenic mice (HBV-Tg), which in turn resulted in complete clearance of hepatitis B surface antigen and hepatitis B e antigen and decreased levels of HBV DNA in some HBV-Tg. Finally, we discuss the extracted questions and future research directions.
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PMID:Dendritic cells and chronic hepatitis virus carriers. 1150 80

Hepatitis B virus (HBV) reactivation of various degrees of severity, including fulminant hepatitis, may develop in 20-50% of hepatitis B virus surface antigen (HbsAg)-positive patients undergoing immunosuppressive or cytostatic treatment. Lamivudine is a nucleoside analogue that can directly suppress HBV replication. We have performed a pilot study to test the efficacy and tolerability of lamivudine as a primary prophylaxis of HBV reactivation in 20 consecutive patients treated for haematological malignancies, mainly of lymphoid origin. Lamivudine, 100 mg/d, was given orally from the start until 1 month after the end of chemotherapy, which included corticosteroids and/or purine analogues in 85% of cases. It was well tolerated and did not cause any unexpected reduction of cytostatic drugs dosages. The chemotherapy programme was completed in all patients without modifications. A transient threefold increase in serum amylase was observed in one case. HBV-DNA levels decreased in six out of six patients (P = 0.039) and ALT levels in five out of six patients (P = 0.057) whose serum levels were abnormal at the onset of therapy. Two patients developed transient hepatitis. HBV reactivation was documented in only one of these patients who had stopped lamivudine 1 month before. No signs of HBV reactivation were detected both during and after treatment in 18 patients with a median follow-up of 6 months (range 3-12). Thus, primary prophylaxis with lamivudine may be a well tolerated and effective method to reduce the frequency of chemotherapy-induced HBV reactivation in chronic HBsAg carriers.
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PMID:Primary prophylaxis with lamivudine of hepatitis B virus reactivation in chronic HbsAg carriers with lymphoid malignancies treated with chemotherapy. 1172 10

The mechanism(s) by which human immunodeficiency virus (HIV) causes depletion of CD4 lymphocytes remains unknown. Evidence has been reported for a mechanism involving HIV binding to (and signaling) resting CD4 lymphocytes in lymphoid tissues, resulting in up-regulation of lymph node homing receptors and enhanced homing after these cells enter the blood, and induction of apoptosis in many of these cells during the homing process, caused by secondary signaling through homing receptors. Supportive evidence for this as a major pathogenic mechanism requires demonstration that CD4 lymphocytes in HIV(+) individuals do migrate to lymph nodes at enhanced rates. Studies herein show that freshly isolated CD4 lymphocytes labeled with (111)Indium and intravenously reinfused back into HIV(+) human donors do home to peripheral lymph nodes at rates two times faster than normal. They also home at enhanced rates to iliac and vertebral bone marrow. In contrast, two hepatitis B virus-infected subjects displayed less than normal rates of blood CD4 lymphocyte migration to peripheral lymph nodes and bone marrow. Furthermore, the increased CD4 lymphocyte homing rates in HIV(+) subjects returned to normal levels after effective, highly active antiretroviral therapy treatment, showing that the enhanced homing correlated with active HIV replication. This is the first direct demonstration of where and how fast CD4 lymphocytes in the blood traffic to tissues in normal and HIV-infected humans. The results support the theory that the disappearance of CD4 lymphocytes from the blood of HIV(+) patients is a result of their enhanced migration out of the blood (homing) and dying in extravascular tissues.
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PMID:CD4 lymphocytes in the blood of HIV(+) individuals migrate rapidly to lymph nodes and bone marrow: support for homing theory of CD4 cell depletion. 1214 17

Hepatitis B virus (HBV) causes a generally non-cytopathic infection in the liver. Even though HBV is a DNA virus, it replicates via reverse transcription which is coordinated within the viral nucleocapsid by the virus-specific polymerase. The major transcriptional template is the viral mimichromosome from which the viral DNA exists as a covalently closed circular (ccc) molcule. The virus infects hepatocytes but can also be found in non-hepatocyte reservoirs such as bile-duct epithelium, mesangial cells of the kidney, pancreatic islet cells and lymphoid cells. When patients infected with HBV are treated with either interferon alpha or lamivudine, responses are variable and unpredictable. Sophisticated mathematical models analysing the dynamics of viral clearance during antiviral therapy have recently been applied to chronic hepatitis B. Typically complex profiles, rather than the usual biphasic responses seen with other diseases have been observed, indicating that antiviral efficacy requires substantila improvement. This may be achieved with combination chemotherapy. However, chronic hepatitis B is a complex and heterogeneous disease entity, and the challenge for the future is to define measurable end-points of treatment and address key virological issues such as the role of cccDNA and extra-hepatocyte replication in treatment failure. Clearly, new therapies and effective combination therapy protocols are urgently required in order to improve the present poor response rates in patients undergoing treatment.
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PMID:Hepatitis B treatment: rational combination chemotherapy based on viral kinetic and animal model studies. 1220 77

Recent studies have shown that tumor necrosis factor alpha (TNF-alpha) plays critical roles in not only viral clearance but also lymphoid tissue development and stem cell differentiation. In this study, we attempted to induce hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) by immunization of TNF-alpha knockout (TNF-alpha(-/-)) mice with HBsAg-encoding plasmid DNA. An immunization with the HBV plasmid failed to induce CTL responses in TNF-alpha(-/-) mice, although CTLs were readily induced in wild-type mice by the same protocol. Weak CTL responses were produced in TNF-alpha(-/-) mice after two sessions of immunization with the HBV plasmid; however, TNF-alpha was required to maintain the responses of these CTL lines to in vitro stimulation and, even then, the responses were lost after 3 weeks. Interestingly, a limiting dilution of a CTL line showed that HBV-specific CTL clones with high specific cytotoxicity were present in TNF-alpha(-/-) mice, but these clones again failed to proliferate for more than 3 weeks. Furthermore, since exogenously added TNF-alpha enhanced the proliferation of a TNF-alpha(-/-) clone but suppressed that of a TNF-alpha(+/+) clone in vitro, TNF-alpha also has a direct effect on the proliferation of CTLs. In conclusion, TNF-alpha is essential rather than important for the proliferation of HBV-specific CTLs both in vivo and in vitro and this effect is not only due to the activation of dendritic cells but is also induced by the direct effect on CTLs.
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PMID:Lack of tumor necrosis factor alpha induces impaired proliferation of hepatitis B virus-specific cytotoxic T lymphocytes. 1255 85


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