Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathogenesis and perpetuation of hepatocellular injury in hepatitis C viral infection remains unclear. It has been proposed that a direct viropathic effect, the host immune response, or both mediate cell damage. To address this issue, the immunophenotype of the inflammatory infiltrate in the liver of 18 patients with abnormal liver function tests and serologically detectable hepatitis C virus antibodies was compared with seven control patients (three cases with hepatitis B virus infection, two with alcoholic hepatitis, and one patient each with primary biliary cirrhosis and autoimmune hepatitis). The immunohistochemical markers included UCHL1, L26, Ham-56, Mac-387, CD68, Leu-M1, and cathepsin B. We found that T cells represent the predominant cell type in both histopathologic patterns of hepatitis C, ie, chronic active hepatitis and chronic persistent hepatitis, but the intensity of the T-cell infiltrate displayed marked differences. B-cell infiltrates were only seen in the germinal centers of lymphoid follicles in portal tracts. Furthermore, significant numbers of CD68-positive macrophages/monocytes were seen in the more aggressive form of hepatitis C viral infection. These data suggest that the T-lymphocyte-mediated host immune response is similar in chronic active and chronic persistent hepatitis patterns of hepatitis C viral infection, but varies in its intensity. In addition, macrophages/monocytes may play a role in hepatocyte and bile duct injury in chronic hepatitis C.
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PMID:Chronic hepatitis C. Analysis of host immune response by immunohistochemistry. 753 56

In situ hybridization with oligonucleotide probes has been used to localise hepatitis A virus RNA genomic sequences in formalin-fixed and routinely processed human liver biopsies from three patients. Using radiolabelled Sulphur-35 antisense probes, viral genomic sequences were found in all three cases, but signal intensity was greatest in cases 1 and 2 with fulminant hepatitis, and was minimal in the third case of resolving hepatitis biopsied 2 months after acute illness. Localisation showed the viral RNA to be present in hepatocytes, sinusoidal cells and inflammatory cells in and around the portal tracts. Both cases showed signal in similar cell types, but the distribution of staining was predominantly periportal in case 1, whereas lobular staining was more apparent in case 2. Hybridization with sense polarity probes failed to detect any evidence of replicative intermediates of antigenomic viral RNA. The presence of hepatitis A RNA in phagocytic cells was confirmed using immunohistochemistry for a macrophage marker, CD68, combined with in situ hybridization. In all cases the signal was predominantly cytoplasmic, and this was confirmed with the use of tritiated probes.
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PMID:In situ hybridization studies of hepatitis A viral RNA in patients with acute hepatitis A. 801 50

The pathogenesis of biliary atresia (BA) is still unknown. Progression to cirrhosis despite restoration of bile flow by successful portoenterostomy suggests that it is a progressive disease of the liver and biliary tree. Whether immunologic factors play any role in the development of this disease remains uncertain. Aberrant expression of major histocompatibility complex (MHC) Class II antigens of HLA-DR on hepatocytes and biliary epithelium is regarded as important in the progression of hepatocellular and biliary damage mediated by cytotoxic T cells. This study was undertaken to evaluate expression of MHC Class II antigen and macrophage-associated antigens (CD68) in liver of patients with biliary atresia to determine their prognostic usefulness and possible role in the pathogenesis of the disease. Liver biopsy specimens from infants with BA (n = 15), neonatal hepatitis (n = 3), and normal livers (n = 6) were studied using an indirect immunoperoxidase staining using antibodies against MHC Class II antigen and macrophage-associated antigens (CD68) as well as routine H&E and Masson's trichome stain. In patients with biliary atresia, the liver biopsy specimen was obtained at the time of Kasai portoenterostomy. Expression of HLA-DR antigens and CD68 antigens was either absent or minimal in normal liver biopsy specimens. There were a few HLA-DR antigens and a few CD68-positive cells around portal tracts in all patients with neonatal hepatitis and five of the seven biliary atresia patients with successful Kasai portoenterostomy. In contrast, there was strong expression of HLA-DR antigen in bile ductules, inflammatory cells, and adjacent damaged hepatocytes and marked CD68-positive macrophage infiltrate in the portal tracts as well as hepatic lobules in two patients with good prognosis and in all eight patients with bad prognosis. Hepatic expression of MHC Class II antigen and CD68 antigens correlated well with the severity of clinical course in patients with BA and may act as a prognostic factor in these patients.
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PMID:Hepatic overexpression of MHC class II antigens and macrophage-associated antigens (CD68) in patients with biliary atresia of poor prognosis. 912 61

To study the early stages of cell death in various types of chronic liver injury, liver biopsies from a total of 26 patients, including 7 with chronic hepatitis C(CHC), 4 with chronic hepatitis B(CHB), 7 with alcoholic liver disease (ALD), 4 with autoimmune or drug hepatitis (AI/DH), and 4 with primary biliary cirrhosis(PBC), were examined by an in situ nucleotidyl transferase assay (ISNTA), which detects DNA fragmentation. Positive nuclei in hepatocytes and sinusoidal lining cells were counted in all parenchymal areas, excluding triads and areas of fibrosis, using a computer with Sigmascan software. The number of positive hepatocytes/mm2 was similar in the biopsies of patients with CHC, CHB, ALD and AI/DH, but significantly lower in PBC. The number of positive sinusoidal lining cells/mm2 was significantly greater in biopsies with CHC compared to CHB, ALD, AI/DH and PBC. Double staining revealed that the ISNTA-positive sinusoidal lining cells were also CD68 positive, indicating that they were Kupffer cells. The frequency of ISNTA positivity did not correlate with serum AST or ALT levels, steatosis, cell swelling or cirrhosis. ISNTA-positive hepatocytes were more frequent than acidophilic bodies in every disease category. We conclude that apoptosis may be a common pathway of cell death in different liver diseases, that the high frequency of DNA fragmentation in Kupffer cells in CHC suggests that during chronic hepatitis C infection activated Kupffer cells may be subject to regulatory control by apoptosis and that ISNTA is more sensitive than acidophilic bodies in assessing the degree of cell injury in the liver.
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PMID:Frequency and distribution of DNA fragmentation as a marker of cell death in chronic liver diseases. 933 40

Liver macrophages, which are involved in the different types of hepatitis, may indirectly induce hepatic fibrogenesis, since they have the possibility to activate hepatic stellate cells and fibroblasts by secretion of TGF-beta, TNF-alpha and IL-1. To evaluate variations of the number of liver macrophages and their subpopulations, a quantification was carried out in normal human liver tissue, fatty liver, fatty liver hepatitis and hepatitis B. Identification was performed by the mab PG-M1 (anti-CD68) and, comparatively, four lectins, Griffonia simplicifolia agglutinin I (GSA-I), Erythrina cristagalli agglutinin (ECA), peanut agglutinin (PNA) and soybean agglutinin (SBA). A slight decrease in the frequency of macrophages in pericentral fields was observable in fatty liver and fatty liver hepatitis as compared to normal liver tissue. On the other hand, the number of CD68+ cells was significantly enhanced in hepatitis B with moderate and severe inflammatory activity. The highest incidence of macrophages was found in portal tracts of liver with fatty liver hepatitis and, particularly, hepatitis B. The fraction of cells stained by ECA, PNA or SBA did not increase significantly under pathological conditions. In contrast, the percentage of GSA-I binding macrophages was higher in liver parenchyma of hepatitis B and in portal tract macrophages in fatty liver hepatitis and also hepatitis B. In conclusion, our results indicate that GSA-I may aid in the detection of the subpopulation of activated macrophages which are assumed to play a pivotal role in liver pathology.
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PMID:Comparative quantitative analysis of macrophage populations defined by CD68 and carbohydrate antigens in normal and pathologically altered human liver tissue. 969 43

To characterize cellular responses during hepatic regeneration, we examined 13 explant livers and 5 liver allografts by immunohistochemistry for cytokeratin 7, HepPar1, CD68, alpha-smooth muscle actin (alpha-SMA) and proliferating cell nuclear antigen as well as reticulin and Masson-trichrome staining. Within a week after liver damage, elongated CD68-positive cells were detected along the border of necrotic area. The number of alpha-SMA-positive cells was slightly increased along the sinusoids. Ductular proliferation or fibrosis was negligible. After one or two weeks, the size and number of CD68-positive cells were markedly increased. alpha-SMA-positive cells increased in number within lobules and portal tracts. Ductular proliferation occurred predominantly at the limiting plate or along the border of necrotic areas. After one month, necrotic parenchyma was replaced by many ductules, CD68-positive cells, alpha-SMA-positive cells. Nodules of regenerating hepatocytes and irregular fibrosis were diffusely present. Other nonparenchymal cells were not significantly changed. These observations indicate that chronological interaction between nonparenchymal and parenchymal cells occur during the course of human hepatic regeneration and suggest extensive porto-periportal fibrosis more than a few months after the onset of fulminant hepatitis is a major indicator of chronic functional impairment necessitating liver transplantation.
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PMID:Parenchymal and nonparenchymal cellular responses in human hepatic regeneration. 1151 89

Juvenile xanthogranulomas (JXG) is a histiocytic disorder, primarily but not exclusively seen throughout the first two decades of life and principally as a solitary cutaneous lesion. This study is a retrospective clinical and pathologic review of 174 cases documenting the cutaneous and extracutaneous manifestations in patients presenting from the neonatal period to 20 years of age (mean 3.3 years; median 1 year). There was a male predominance (99 male:75 female) in all categories of clinical presentation, but especially notable in the group with multiple cutaneous lesions (12 male:1 female). A solitary cutaneous lesion accounted for 67% of all cases, followed by a solitary subcutaneous or deep soft tissue mass (28 cases, 16%), multiple cutaneous lesions (13 cases, 7%), a solitary extracutaneous, nonsoft tissue lesion (9 cases, 5%), and multiple cutaneous and visceral-systemic lesions (8 cases, 5%). The recorded deaths due to disease included two neonates with systemic JXG who developed hepatic failure and thrombocytopenia and at autopsy had giant cell-neonatal hepatitis in addition to JXG in the liver and other visceral sites. A third death in a 3-month-old boy with a retroperitoneal-pelvic JXG occurred after failure to control severe hypercalcemia. The characteristic Touton giant cell in variable numbers was a consistent feature of the cutaneous lesions; however, these cells were either absent or present in reduced numbers in the various extracutaneous lesions when compared with JXG in the skin. Spindle cells intermingled among the mononuclear cells or forming short fascicles were seen in both cutaneous and extracutaneous lesions. Immunohistochemistry was performed on all extracutaneous lesions, and the constituent cells, regardless of their individual morphologic features, were uniformly positive for vimentin, CD68, and factor XIIIa and negative for S-100 protein and CD1a. It is widely held that JXG is a proliferative disorder of dendrocytes, possibly dermal dendrocytes; thus, its clinical and pathologic similarities to Langerhans cell histiocytosis are not entirely unexpected in light of the most recently proposed international classification of histiocytic disorders, which includes JXG and Langerhans cell histiocytosis together as "dendritic cell-related" histiocytoses.
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PMID:Juvenile xanthogranulomas in the first two decades of life: a clinicopathologic study of 174 cases with cutaneous and extracutaneous manifestations. 1271 44

Previous studies have suggested that increased nitric oxide (NO)-mediated products are found in the livers of subjects with primary biliary cirrhosis (PBC), but the mechanisms involved remain enigmatic. We took advantage of immunohistochemistry and several unique monoclonal antibodies to study inflammatory cells responsible for the generation of NO, the enzymes responsible for NO production, the expression of 3-nitrotyrosine, and the presence of CD68(+) and/or myeloperoxidase (MPO)(+) cells. We examined a total of 113 liver specimens, including 64 with PBC, 19 with primary sclerosing cholangitis (PSC), 6 with non-A, non-B hepatitis, 6 with alcoholic liver disease, 4 with cryptogenic cirrhosis, 4 with biliary atresia, and 10 normal subjects. Twenty-two percent of PBC had elevated expression of 3-nitrotyrosine in their bile duct epithelial cells (BECs) (P =.0316). Furthermore, the BECs in PBC also demonstrated apoptotic changes. MPO-positive inflammatory cells were also noted adjacent to the basement membrane. In contrast, the liver of normal subjects showed few apoptotic changes in the bile ducts, with no evidence of MPO staining in the portal area. Furthermore, sections from livers of subjects with stage I or stage II PBC demonstrated significantly increased inflammatory cell infiltration (P =.0064) and elevated 3-nitrotyrosine expression in BECs (P =.0246) compared with stage III and IV. The presence of 3-nitrotyrosine was closely associated with infiltrating CD68- and/or MPO-positive cells. There was also a stage-associated difference in the presence of bile duct infiltrating cells and 3-nitrotyrosine in PBC with an increase dominant in early stage disease. In conclusion, NO and reactive oxygen species, collectively determined as 3-nitrotyrosine, are associated with bile duct destruction in PBC and are particularly prevalent in early stage disease.
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PMID:Myeloperoxidase-positive inflammatory cells participate in bile duct damage in primary biliary cirrhosis through nitric oxide-mediated reactions. 1451 89

A proposed mechanism in the pathogenesis of biliary atresia involves an initial virus-induced, progressive T cell-mediated inflammatory obliteration of bile ducts. The aim of this study was to characterize the inflammatory environment present within the liver of infants with biliary atresia to gain insight into the role of a primary immune-mediated process versus a nonspecific secondary response to biliary obstruction. Frozen liver tissue obtained from patients with biliary atresia, neonatal giant cell hepatitis, total parenteral nutrition (TPN)-related cholestasis, choledochal cysts, and normal control subjects was used for fluorescent immunohistochemistry studies of cellular infiltrates, cytokine mRNA expression, and in situ hybridization for localization of cytokine-producing cells. Immunohistochemistry revealed increases in CD8(+) and CD4(+) T cells and Kupffer cells (CD68(+)) in the portal tracts of biliary atresia. Reverse transcription-PCR analysis of biliary atresia tissue showed a Th1-type cytokine profile with expression of IL-2, interferon-gamma, tumor necrosis factor-alpha, and IL-12. This profile was not seen in normal, neonatal hepatitis or choledochal cyst livers but was present in TPN-related cholestasis. In situ hybridization revealed that the Th1 cytokine-producing cells were located in the portal tracts in biliary atresia and in the parenchyma of TPN-related cholestasis. A distinctive portal tract inflammatory environment is present in biliary atresia, involving CD4(+) Th1 cell-mediated immunity. The absence of similar inflammation in other pediatric cholestatic conditions suggests that the portal tract inflammation in biliary atresia is not a secondary response to cholestasis but rather indicates a specific immune response involved in the pathogenesis of biliary atresia.
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PMID:Biliary atresia is associated with CD4+ Th1 cell-mediated portal tract inflammation. 1512 25

Fulminant hepatitis is characterized by massive or submassive liver necrosis. Massive liver necrosis can be induced by activated macrophages infiltrating into the liver. Osteopontin, an extracellular matrix, is a secretory glycoprotein as well essential for Th1 immune response, contributing to macrophage activation and infiltration. To know the significance of osteopontin in the development of fulminant hepatitis, plasma osteopontin levels were measured in patients with fulminant hepatitis. The levels were significantly greater in patients with fulminant hepatitis than in those with acute or chronic hepatitis as well as healthy adults. Among patients with fulminant hepatitis except one in whom bacterial infection was complicated, plasma osteopontin levels were elevated especially in the patients who developed hepatic encephalopathy of grade II or more within 10 days of the disease onset, a clinical type characteristic of massive liver necrosis. Immunohistochemical examination revealed that osteopontin was stained in macrophages positive for CD68, a marker for macrophages, in necrotic areas of the liver in a patient with fulminant hepatitis. In conclusion, plasma osteopontin levels were elevated in patients with fulminant hepatitis, probably reflecting production of osteopontin in Kupffer cells and hepatic macrophages, which might be involved in the development of massive liver necrosis in fulminant hepatitis.
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PMID:Plasma osteopontin levels in patients with fulminant hepatitis. 1528 11


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