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)

Chronic infection of woodchucks with woodchuck hepatitis virus (WHV) invariably leads, within 2-4 years, to the appearance of hepatocellular carcinoma (HCC). HCC is preceded by an extended period of chronic liver damage, probably resulting from the immune response to viral antigens. It may be that infection itself also induces changes in the hepatocyte population. To begin to identify some of the changes in the liver prior to the appearance of HCC, monoclonal antibodies (MAbs) were generated from mice immunized with hepatocytes from a woodchuck chronically infected with WHV or with a tumor lysate. Immunofluorescence microscopy was used to select MAbs that reacted with host markers whose patterns of expression would distinguish chronically infected from uninfected liver or from liver tumors. One of these MAbs (2F2) reacted strongly with a subset of hepatocytes in chronically infected liver; a similar staining pattern was not detected in uninfected or transiently infected liver. Evidence is presented that this strong staining reaction reflects the overexpression or accumulation of the hepatocyte-specific intermediate filament protein, cytokeratin K18, a protein previously implicated in cryptogenic cirrhosis of the liver in humans (Ku, N. O. , Wright, T. L., Terrault, N. A., Gish, R., and Omary, M. B. J. Clin. Invest. 99: 19-23, 1997). Double immunofluorescent staining with antibodies to K18 and M-envelope protein of WHV suggested that strong reactivity to K18 was limited to cells expressing high levels of one or both of the large viral-envelope proteins, M and L; however, high expression of these viral proteins was not always associated with a strong K18 staining reaction.
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PMID:Aberrant expression of a cytokeratin in a subset of hepatocytes during chronic WHV infection. 974 Jul 78

Autoantibodies, markers of autoimmune diseases, can also be detected in chronic allograft rejection. However, the appearance of these autoantibodies in acute rejection after orthotopic liver transplantation has not yet been reported. Liver-kidney-microsome type-1 (LKM-1) antibodies directed against the autoantigen cytochrome CYP2D6 define a group of patients with autoimmune hepatitis type-2 (AIH-2), distinct from autoimmune hepatitis type-1 (AIH-1) in which anti-nuclear antibodies and anti-smooth muscle antibodies (SMA) with actin specificity are present in patient sera. Autoantibodies were studied by the quantitative CYP2D6 radioligand assay (RLA) that uses a radiolabeled CYP2D6 as antigen, immunoblotting using recombinant CYP2D6 protein and human liver microsomal and cytosolic fractions, and indirect immunofluorescence (IIF) using rat kidney-stomach-liver cryostat sections. In addition, the specificity of anti-SMA was detected by IIF on HEp2 cell line harvested with colchicin. This report describes the time course of CYP2D6 antibodies and the appearance of anti-SMA (without anti-actin, cytokeratin and vimentin reactivity) associated with acute rejection during a 2-year follow-up, in a patient who underwent transplantation at end-stage type 2 autoimmune hepatitis. In addition, we report a new reactivity against an unknown 40-kDa protein using a rat cytosolic fraction. The detection of autoantibodies in sequential samples may be important to better predict rejection or relapse, and to establish adequate therapy.
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PMID:Autoantibodies associated with acute rejection after liver transplantation for type-2 autoimmune hepatitis. 1090 2

Ductular reaction and putative progenitor cells (or 'progenitor cells'), which are presumed to be the human counterpart of the oval cells in rat liver, have been discerned in various human liver diseases, including chronic viral hepatitis. Since in experimental models of chronic hepatitis the activation of oval cells is correlated with the inflammatory infiltrate, this study investigated whether there is a correlation in chronic viral hepatitis between the number of 'progenitor cells' extending into the lobule and the severity of parenchymal inflammation, on the one hand, and the extent of ductular reaction and the severity of interface hepatitis, on the other hand. Liver biopsies of 55 patients with chronic hepatitis B and/or C were used. The severity of parenchymal inflammation and of interface hepatitis was semiquantitatively graded on a haematoxylin and eosin-stained paraffin section, while the number of 'progenitor cells' and the extent of the ductular reaction were assessed on a serial section stained for cytokeratin (CK) 7. In addition, more extensive phenotyping of 'progenitor cells' was performed on sections from frozen material from five patients, using antibodies against CK7, CK8, CK18, CK19, chromogranin-A, and the rat oval cell marker OV-6. The number of more centrally located 'progenitor cells' correlated significantly with the severity of the parenchymal inflammation, while the extent of the ductular reaction correlated significantly with the severity of interface hepatitis. These findings suggest that in chronic viral hepatitis, inflammation plays a role in 'progenitor cell' activation and its topography. In cases with moderate and severe lobular inflammation, 'progenitor cells' were strikingly scattered throughout the parenchyma and surrounded by intermediate hepatocyte-like cells, suggesting their migration into the parenchyma and their differentiation towards the hepatocytic lineage.
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PMID:Deep intralobular extension of human hepatic 'progenitor cells' correlates with parenchymal inflammation in chronic viral hepatitis: can 'progenitor cells' migrate? 1105 21

Most of the alpha-fetoprotein-producing gastric cancer is advanced at the time of presentation, and alpha-fetoprotein-producing early gastric cancer is extremely rare. Alpha-fetoprotein-producing early gastric cancer was confirmed by immunohistochemistry and serum analysis of alpha-fetoprotein concentration. Alpha-fetoprotein carbohydrate chain microheterogeneity was further evaluated by lectin binding specificity. A 71-year-old-male patient underwent total gastrectomy due to a depressed type of gastric cancer in the upper third of the stomach. There was no evidence of synchronous liver metastasis and hepatitis. Histological examination revealed that the tumor invasion was limited to the submucosal layer, and that the tumor consisted of both well-differentiated, papillo-tubular growth areas and trabecular and medullary growth areas resembling hepatoid carcinoma. Immunohistochemically, alpha-fetoprotein and cytokeratin localization were confirmed in the cancer cells, whereas simultaneous localization of carcinoembryonic antigen, carbohydrate antigen 19-9, and human chorionic gonadotropin could not be observed. The elevated preoperative serum alpha-fetoprotein concentration (113 ng/mL) promptly decreased to and remained within normal levels postoperatively (3.6 ng/mL). The predominance of a strong-bound fraction with lectin, which was demonstrated by lens culinalis agglutinin affinity chromatography, suggests that the alpha-fetoprotein carbohydrate chain species in the present case was a hepatic type. The patient received adjuvant intravenous chemotherapy consisting of 5-fluorouracil and cisplatin, and has been further supported by oral 5-fluorouracil administration. The patient has been disease free for 15 months following surgery. We report here a rare case of alpha-fetoprotein producing early gastric cancer. The alpha-fetoprotein carbohydrate phenotype analysis helps to consider the primary differentiation of alpha-fetoprotein-producing gastric cancer.
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PMID:A rare case of alpha-fetoprotein-producing early gastric cancer. 1146 4

Antibodies to cytokeratin (CK) are found in some patients with autoimmune hepatitis (AIH). We hypothesized that serum antibodies to CK8, CK18 and CK19 may be formed in patients with AIH. We established an enzyme-linked immunosorbent assay (ELISA) to quantify anti-CK8, anti-CK18 and anti-CK19 antibodies in sera of patients with AIH. In addition, we quantified circulating CK8:anti-CK8 antibody as well as CK18:anti-CK18 antibody immune complexes in patients' sera, by an enzyme-linked immunosorbent assay (ELISA). Furthermore, to evaluate the expression of CK8, CK18 and CK19 in liver tissue, immunohistochemical stainings were performed. Significantly high levels of anti-CK8, anti-CK18 and anti-CK19 antibodies were demonstrated in patients with AIH compared with normal volunteers and patients with chronic active hepatitis C (CH-C). In addition, these antibodies were significantly decreased after steroid treatment. Levels of CK8:anti-CK8 and CK18:anti-CK18 immune complexes in sera of patients with AIH were significantly high compared with those of patients with CH-C and normal volunteers. Immunohistochemically, CK8 or CK18 were absent from some hepatocytes of AIH. CK19 was aberrantly expressed in periportal hepatocytes in patients with AIH, but not CH-C. This is the first study to quantify anti-CK8, anti-CK18, anti-CK19 antibodies and immune complexes in patients with AIH. The clinical significance of anti-CK antibodies and their immune complexes of AIH is also discussed.
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PMID:Anti-cytokeratin antibodies in sera of the patients with autoimmune hepatitis. 1152 22

Piecemeal necrosis, currently called interface hepatitis, is a feature of viral hepatitis as well as autoimmune hepatitis and steatohepatitis. The mechanism of liver cell loss and piecemeal necrosis needs to be determined. We hypothesize that piecemeal necrosis in hepatitis is due to a piecemeal removal of hepatocyte cytoplasm by lymphocytic ingestion. To test this hypothesis, 61 consecutive liver biopsies were examined by light microscopy, by immunohistochemistry and by electron microscopy, and the lymphocytic-hepatocytic interaction was morphologically assessed. In cases of hepatitis C, hepatitis B, autoimmune hepatitis, primary biliary cirrhosis, and steatohepatitis, piecemeal necrosis was found. Using cytokeratin stains, it was apparent that the lymphocyte-hepatocyte interaction and piecemeal necrosis leads first to binding of the lymphocyte to hepatocyte plasma membrane and then blebbing or indentation of the hepatocyte by the lymphocyte, followed by endocytosis of liver cell cellular components and digestion in the lymphocyte lysosomes. This process is repeated while the cytoplasm and the nucleus of the hepatocyte disappear bite by bite, and only nubbins of residual hepatocytic cytoplasm remain, either attached to intact hepatocytes or surrounded and sequestered within scar tissue and lymphocytes. We conclude that piecemeal necrosis is a gradual disappearance of hepatocytes as a result of lymphocyte-hepatocyte binding and ligand internalization of liver surface molecules by the lymphocyte. This gradual process leads to a slow reduction of hepatocyte size and eventual disappearance at the interface between the lobule and portal tracts. To term this new kind of necrosis, we propose the name troxis necrosis, after the Greek noun meaning "nibbling."
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PMID:"Piecemeal" necrosis: renamed troxis necrosis. 1159 20

It has recently been shown that epithelial cells derived from stem cells originating outside the liver are integrated into liver allografts. Whether epithelial intragraft chimerism protects transplants from rejection or chronic transplant dysfunction, and whether it interferes with recurrence of primary liver disease, is not known. Twenty-seven sequential biopsies derived from 9 liver-transplant recipients were studied for chimerism of hepatocytes and cholangiocytes. The target cells were isolated by laser microdissection after cytokeratin immunolabeling and genotyped using DNA analysis of a highly polymorphic short tandem repeat. Irrespective of whether early (up to 4 weeks) or late (more than 12 months) posttransplantation biopsies were studied, cholangiocyte chimerism was almost constantly found in 91% of the samples. No significant differences occurred between samples derived from patients with chronic organ dysfunction (n = 3), recurrent hepatitis (n = 3), or mild, unspecific changes (n = 3). By contrast, hepatocyte chimerism tended to occur later (55% vs. 22%) and appeared to be associated with recurrent hepatitis (67% vs. 27%). In this respect, chronic organ dysfunction did not differ from mild, unspecific changes. While cholangiocyte chimerism represents a constant and early phenomenon in liver transplantations, an enhanced chimeric integration of recipient-derived hepatocytes can be observed in recurrent hepatitis, supporting the concept of an increased recruitment of extrahepatic progenitor cells to the liver in chronic hepatitis.
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PMID:High frequency of epithelial chimerism in liver transplants demonstrated by microdissection and STR-analysis. 1178 66

Microcystin-LR (MCLR) is a potent hepatotoxin produced by the cyanobacterium Microcystis aeruginosa. The histology of acute lethal toxicity has been well characterized, but histology is limited regarding sublethal exposure. Balb/C mice were given a single sublethal dose of MCLR (45 microg/kg) and euthanized at 2, 4, 12, and 24 hours after exposure. Centrilobular to midzonal hepatocellular hypertrophy with loss of cytosolic vacuolation consistent with glycogen depletion occurred at 2 hours. At 4 hours, central lobular hepatocytes exhibited eccentric areas of eosinophilic cytoplasmic condensation that were partially aggregated around the outer nuclear membrane. The areas were weakly positive for cytokeratin and somewhat resembled the Mallory bodies of alcoholic human hepatitis. Small numbers of apoptotic hepatocytes were seen at 24 hours. The toxin was detectable by immunohistochemistry (IHC) as early as 2 hours and was colocalized with the areas of hepatocellular hypertrophy. Intense nuclear staining occurred at 4 hours; this was no longer evident after 12 hours. Strong staining of apoptotic bodies occurred at 24 hours. Mice that received two daily doses had a marked increase in apoptotic hepatocytes in the centrilobular areas. Lesions at four and seven doses consisted of marked hepatocytomegaly and karyomegaly with parenchymal disarray and cytosolic vacuolation. IHC revealed diffuse staining throughout the liver parenchyma consistent with toxin accumulation. An anti-MCLR monoclonal antibody detected bands at the 40-kDa mark in nuclear extracts that were identified as protein phosphatases 1 and 2A by western blotting, consistent with a covalent interaction between MCLR and nuclear protein phosphatases.
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PMID:Characterization of sublethal microcystin-LR exposure in mice. 1210 14

Preoperative diagnosis of hepatic angiomyolipoma is difficult, and the treatment for it remains controversial. The aim of this study is to review our experience in the treatment of hepatic angiomyolipoma and to propose a treatment strategy for this disease. We retrospectively collected the clinical, imaging, and pathological features of patients with hepatic angiomyolipoma. Immunohistochemical studies with antibodies for HMB-45, actin, S-100, cytokeratin, vimentin, and c-kit were performed. Treatment experience and long-term follow-up results are summarized. During a period of 9 years, 10 patients with hepatic angiomyolipoma were treated at our hospital. There was marked female predominance (nine patients). Nine patients received surgical resection without complications. One patient received nonoperative management with biopsy and follow-up. One patient died 11 months after surgery because of recurrent disease. We propose all symptomatic patients should receive surgical resection for hepatic angiomyolipoma. Conservative management with close follow-up is suggested in patients with asymptomatic tumors and meet the following criteria: (1) tumor size smaller than 5 cm, (2) angiomyolipoma proved through fine needle aspiration biopsy, (3) patients with good compliance, and (4) not a hepatitis virus carrier.
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PMID:Management of hepatic angiomyolipoma. 1743 29

Primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis are the three major immune-mediated liver diseases. The etiologies of primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis are largely unknown, but seem to be influenced by genetic and environmental factors. Autoantibodies can be found in nearly all patients with primary sclerosing cholangitis and autoimmune hepatitis, and in the vast majority of patients with primary sclerosing cholangitis. In addition, autoimmune hepatitis is associated with high concentrations of serum globulins. Enhanced liver cell death by apoptosis has been described in all of these liver diseases, although the precise mechanisms remain unclear. In general, apoptosis can be initiated via an extrinsic pathway that is triggered by engagement of death receptors on the cell surface, or via an intrinsic pathway that is induced by mitochondrial injury and is influenced by members of the Bcl-2 family. In both pathways, effector caspases are finally activated that cleave and degrade cell structures, resulting in the release of apoptotic products into the circulation. New diagnostic tests can detect these apoptotic markers and programmed cell death ligands such as Fas and Fas-ligands, nucleosomes, caspases, cytokeratin fragments, macrophage migration inhibitory factor, soluble intracellular adhesion molecule, natural killer cells group 2D and programmed death ligands. Several of these markers have been found to be altered in tissue and/or blood of immune-mediated liver diseases, some also in nonimmune-mediated liver diseases. Beyond their potential usefulness as additional diagnostic markers, they may be valuable for the estimation of disease severity and therapy monitoring. This review summarizes current knowledge on apoptotic mechanisms, death receptor ligands and circulating apoptotic markers in immune-mediated liver diseases.
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PMID:Immune-mediated liver diseases: programmed cell death ligands and circulating apoptotic markers. 1929 38


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