bromochloroacetic-acid and Hepatitis--Autoimmune

Giant cell hepatitis is rare in adult patients. This form of hepatitis shows fast progression to cirrhosis. A 65-year-old woman was admitted to our hospital with jaundice. She was negative for hepatitis virus markers and positive for antinuclear antibodies. We diagnosed her as autoimmune hepatitis. Liver biopsy findings revealed typical features of interface hepatitis and giant cell hepatitis. Giant cells were positive for keratin 8/18, but not for keratin 19, keratin 7 or Ki-67. These results suggest that giant cell formation is associated with the fusion of matured hepatocytes rather than the active proliferation of immature cells.

Topics: Aged; Autoantibodies; Female; Giant Cells; Hepatitis, Autoimmune; Humans; Keratins; Ki-67 Antigen; Liver

Graft dysfunction mimicking autoimmune hepatitis rarely develops after liver transplantation for nonautoimmune disease. The mechanism(s) and causes of de novo autoimmune hepatitis are unknown. We examined autoantibodies serially in a patient with de novo autoimmune hepatitis and in patients without de novo autoimmune hepatitis after liver transplantation. Anticytokeratin 8/18 antibodies were detected in the first patient's sera after the onset of de novo autoimmune hepatitis, whereas other patients without de novo autoimmune hepatitis were seronegative throughout the follow-up period even with acute cellular rejection or other cause of liver dysfunction. In conclusion, the changes in cytokeratin 8/18 in hepatocytes might be one of the sources of pathogenesis of de novo autoimmune hepatitis after liver transplantation.

Topics: Adolescent; Adult; Autoantibodies; Child; Child, Preschool; Female; Follow-Up Studies; Hepatitis, Autoimmune; Hepatocytes; Humans; Keratins; Liver Failure; Liver Transplantation; Living Donors; Male; Postoperative Complications

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Chronic Disease; Cytosine; Guanine; Hepatitis, Autoimmune; Hepatitis, Viral, Human; Histidine; Humans; Keratin-8; Keratins; Liver Cirrhosis; Liver Diseases; Middle Aged; Mutation, Missense; Tyrosine

Progenitor cell activation with subsequent maturation to hepatocytes and cells of the biliary lineage has been demonstrated in a variety of chronic liver diseases but the kinetics and magnitude of the progenitor cell response has not been adequately studied in detail in chronic hepatitis. We undertook this study to evaluate factors responsible for the progenitor cell/ductular response and further dissect the role of disease grade and stage as determinants of hepatocellular differentiation of bipotential progenitor cells in chronic hepatitis.. Cytokeratin 7 (and 19) stained biopsies from patients with chronic hepatitis C (n = 47), hepatitis B (n = 20), and autoimmune hepatitis (n = 20) were studied. Ploidy analysis and proliferation indices were evaluated in a subset of cases.. Ductular reactions were present in the majority of cases (97%), appeared early in disease, and correlated with disease activity, while progenitor cell derived hepatocyes appeared later in disease and their extent correlated with disease stage. Proliferation indices of all cell types correlated with disease activity.. Progenitor cell derived hepatocytes accrue in chronic hepatitis, possibly related to native hepatocellular dysfunction. However, the fate of these hepatocytes is unclear.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bile Ducts; Cell Division; Child; Child, Preschool; DNA; Female; Hepatitis B, Chronic; Hepatitis C, Chronic; Hepatitis, Autoimmune; Hepatocytes; Humans; Immunohistochemistry; Infant; Keratin-7; Keratins; Liver; Liver Regeneration; Male; Middle Aged; S Phase; Stem Cells

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.

Topics: Adolescent; Adult; Aged; Antigen-Antibody Complex; Autoantibodies; Enzyme-Linked Immunosorbent Assay; Female; Hepatitis, Autoimmune; Humans; Immunohistochemistry; Keratins; Liver; Male; Middle Aged

We studied nondiagnostic liver biopsy specimens from 20 patients with definite primary biliary cirrhosis (PBC) and 18 with definite autoimmune hepatitis (AIH) to identify distinguishing features. All patients had early-stage disease; biopsy specimens were devoid of granulomas or diagnostic features of PBC or AIH. Diagnoses were based on serologic and clinical variables. Sixteen specimens from each group were immunostained with cytokeratin 7. The density of portal tract eosinophils and number with cytokeratin 7-reactive periportal hepatocytes were quantified. Sixteen of 18 patients with AIH and 13 of 20 with PBC had no or minimal bile duct injury. Histologic activity index scores were 5.8 in AIH and 5.7 in PBC. The mean portal eosinophil score was greater in PBC than in AIH. Cytokeratin 7 identified many central bile ducts that were obscured by portal inflammation. The mean periportal cytokeratin 7-reactive hepatocyte score was greater in PBC than in AIH. Portal eosinophils and cytokeratin 7 reactivity in periportal hepatocytes are supportive of PBC rather than AIH. No morphologic features were supportive of AIH. Cytokeratin 7 reactivity in periportal hepatocytes may be an early response to PBC-induced biliary obstruction in other regions of the liver.

Topics: Adult; Bile Ducts, Intrahepatic; Biomarkers; Diagnosis, Differential; Eosinophils; Fluorescent Antibody Technique, Direct; Hepatitis, Autoimmune; Hepatocytes; Humans; Immunoenzyme Techniques; Keratin-7; Keratins; Liver Cirrhosis, Biliary; Middle Aged; Portal System

"Soluble liver antigen" (SLA) has been reported to be an infrequent but in certain cases a unique marker of autoimmune hepatitis, with cytokeratins 8 and 18 as major antigenic components. Using precharacterized sera, we could confirm trypsin sensitivity and a molecular weight of approximately 50 kD of the reactive protein. However, the reaction differed from that of cytokeratins 8 and 18 by molecular weight and a pI of 7.5. A significant reactivity to cytokeratin 8 and 18 preparations was seen in only 1/12 patients. Immunoscreening of a human liver expression gene bank yielded no clones with sequence homology to cytokeratins. We conclude that reactivity in SLA positive sera is not mainly directed against cytokeratins 8/18 and recommend native antigen preparations for diagnostic use until the exact molecular nature of the 52 kD SLA antigen has been elucidated.

Topics: Autoantibodies; Autoantigens; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Female; Hepatitis, Autoimmune; Humans; Keratins; Liver; Middle Aged; Molecular Weight; Restriction Mapping; Sensitivity and Specificity