Chronic Active Liver Disease Research Articles

Serum autoantibodies reacting with the hepatic asialoglycoprotein receptor protein (hepatic lectin) in acute and chronic liver disorders

Circulating autoantibodies reacting with affinity-purified, hepatic asialoglycoprotein receptor protein, hepatic lectin (HL), were detected by radioimmunoassay in 15 (83%) of 18 patients with autoimmune chronic active hepatitis (AI-CAH) who had active disease, at titres that showed a positive correlation (P less than 0.05) with severity of periportal inflammation assessed histologically. In contrast, 10 AI-CAH patients whose disease was in remission were all anti-HL seronegative. Anti-HL was also detected in 16 (73%) of 22 patients with hepatitis B virus-related CAH-a similar frequency to that in active AI-CAH but at significantly lower (P less than 0.005) titres. Only 1 of 8 patients with chronic active liver disease due to presumed non-A, non-B (NANB) viral infection and 5 (22%) of 23 with primary biliary cirrhosis were anti-HL seropositive (P less than 0.001 vs active AI-CAH and HBV-CAH) and there was no correlation with severity of periportal inflammation. Anti-HL antibodies were also found in sera from 7 (35%) of 20 patients with acute virus B hepatitis (AVH-B) but were not detected in 10 patients with AVH-A nor in 12 with AVH due to presumed NANB infection. Anti-HL was not found in sera of 12 patients with autoimmune thyroid disease. Hepatic lectin, a highly purifiable, liver-specific cell surface component, by analogy with the acetylcholine and thyrotropin receptors which are, respectively, targets of the pathogenetically-related autoimmune reactions in myasthenia gravis and autoimmune thyroid disease, may be an important target of autoreactions in liver disease.

Naturally occurring serum antiidiotypic antibody against antiliver-specific membrane lipoprotein in patients with hepatitis.

Studies were undertaken to evaluate whether antiidiotypic antibody against antiliver-specific membrane lipoprotein is related to the disease activity of patients with hepatitis. Sera from normal individuals, patients with viral hepatitis and medical staffs were depleted of antiliver-specific membrane lipoprotein antibody by absorbing with liver-specific membrane lipoprotein-bearing cell line SK-Hep-1. Anti-antiliver-specific membrane lipoprotein was detected by binding activity to antihuman liver-specific membrane lipoprotein monoclonal antibody using solid-phase radioimmunoassay and by inhibitory activity for binding of antiliver-specific membrane lipoprotein monoclonal antibody to SK-Hep-1 using competitive radioimmunoassay. The results obtained by the two assays were equivalent for detecting anti-antiliver-specific membrane lipoprotein. Sera from patients with acute viral hepatitis during recovery phase (n = 6) and chronic persistent hepatitis (n = 12), respectively, showed significantly increased anti-antiliver-specific membrane lipoprotein activity (p less than 0.01) when compared to those from normal individuals (n = 10), whereas sera from patients with chronic active liver disease (n = 12) did not reveal significantly different values from controls. Sera from the medical staff (n = 11) who had contact with hepatitis patients also demonstrated increased anti-antiliver-specific membrane lipoprotein activity (p less than 0.05). Inhibitory activity of anti-antiliver-specific membrane lipoprotein in the serum appeared localized within the F(ab')2 fragments of immunoglobulin G fraction by competitive radioimmunoassay. The specificity of the inhibitory activity of the serum was confirmed by its inability to block unrelated antigen-antibody reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Liver-specific autoantibodies in chronic hepatitis B virus infection.

Anti-liver-specific protein (LSP) antibody and liver membrane autoantibody (LMA) have been evaluated in 88 patients with hepatitis B virus (HBV)-induced chronic liver disease by means of radioimmunoprecipitation and immunofluorescence. Among our patients, 38 presented circulating HBe antigen while 43 had HBe antibody and seven were negative for both. Anti-LSP was mainly found in HBeAg positive chronic active hepatitis (CAH), anti-HBe in positive CAH and in anti-HBe positive chronic persistent hepatitis (CPH). Similar prevalences of LMA (range 13-33%) were detected in the various groups studied. Taking into account the histological diagnosis of disease activity (periportal inflammation and piecemeal necrosis) no significant differences were found between active and inactive patients. Taking into account the HBeAg/anti-HBe status, no significant differences were found between the patients positive for 'e' antigen or 'e' antibody. Humoral autoimmune reactions may also play a role in HBV-induced chronic (active) liver disease irrespective of HBeAg/anti-HBe status and hence of the viral replication activity of the patients.

Thymostimulin effectiveness in HB SAg + chronic active liver disease

Thymostimulin effectiveness in HB SAg + chronic active liver disease

K cell activity is independent of both thymus and spleen.

K cells, mediating antibody-dependent cellular cytotoxicity of nucleated dividing target cells, are highly efficient effectors in the presence of minute amounts of antibody in vitro (MacLennan,1972). Their distinct Fc receptor may now be identified by a monoclonal antibody, B73.1 (Perussia et al.,1983a). The role they may play in vivo, in normal and/or pathological situations remains unknown. K cells may be involved in the lysis of virus-infected cells (Kohl and Moore,1983), and of established tumour cell-lines as Chang cells — Also, sera from patients with chronic active liver disease (Kawanishi and McDermott,1979) rheumatoid arthritis (MacLennan,1969) may mediate ADCC of relevant target cells. Recently, a role of K cells in the regulation of immune responses has been considered. Anti-idiotypes have been shown to be able to mediate ADCC against mouse hybridoma cells (Caraux and Weigle,1983) or plasmocytoma cells (Chassoux and Stanislawski, in preparation). The origin and conditions of maturation of K cells are not known. K/NK cells do not appear to be B cells (Chassoux et al.,1983a). Their relationships with other lymphoid cell lineages has received attention with the development of monoclonal antibodies. Some authors have described common antigens on T and K/NK cells and therefore consider that they are part of the same lineage (Fast, Hansen and Newman, 1981):other reagents, however, may separate T from K/NK cells (Beverley and Callard,1981).KeywordsNatural Killing Cell CytotoxicityHuman Natural Killer CellLymphoid Cell LineageNormal LittermateEfficient EffectorThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Basement membrane production by hepatocytes in chronic liver disease.

The immunohistologic distribution of fibronectin, laminin, type IV collagen and whole basement membrane was evaluated in liver biopsies from patients with chronic active liver disease. Fibronectin was consistently increased in the areas of piecemeal necrosis, portal tracts and fibrous septa. Laminin was not detected in normal liver parenchyma. In contrast, laminin positive linear basement membrane structures were prevalent in portal tracts, fibrous septa and the peripheral sinusoids of cirrhotic nodules. In areas of piecemeal necrosis, the hepatocytes, single or assembled in "rosettes", were frequently underlined by linear deposits of laminin and type IV collagen. This immunoreactivity was often polarized, being confined to the stromal side of liver cells, while the parenchymal side was negative for both proteins. Electron microscopy revealed a typical basement membrane in corresponding areas. Hepatocytes normally do not produce a basement membrane, but do so following chronic injury. We suggest that the polarized basement membrane accumulation by hepatocytes is a hallmark of hepatocyte regeneration following damage.

HLA-DR antigens in HBsAg-positive chronic active liver disease with and without associated delta infection.

The A, B, C and DR locus specificities of the human leukocyte antigens system (HLA) were determined in 45 delta-positive and 44 delta-negative Italian patients, all with HBsAg-positive chronic active liver disease; controls were 526 healthy Italian blood donors matched for age, sex and geographical origin. HLA-A, B, C gene frequencies were not significantly changed. In delta-positive patients, the frequencies of the DR locus specificities were: DR2, 37.8%; DR3, 20%; DR4, 11.1%. In the delta-negative patients, the frequencies were: DR2, 13.6%; DR3, 36.4%; DR4, 0%. Control frequencies were: DR2, 19.4%; DR3, 17.1%; DR4, 18.5%. The corrected p values of the differences between controls and delta-positive patients were: DR2, pc = 0.046; DR3, pc = NS (not significant); DR4, pc = NS. The corrected p values of the differences between controls and delta-negative patients were: DR2, pc = NS; DR3, pc = 0.03; DR4, pc = 0.002. These findings show that: (a) DR3, a genetic marker of autoimmunity, might assist the establishment of chronic HBsAg liver disease in the absence of delta superinfection; (b) DR2 is linked with failure to clear the delta agent, and (c) DR4 may protect from virus B persistence. Identification of adventitious factors such as delta may help uncover a subgroup of HBsAg carriers who are genetically predisposed to develop chronic liver disease.

Delta agent infection in acute hepatitis and chronic HBsAg carriers with and without liver disease.

Hepatitis B virus (HBV) is a major cause of chronic liver disease in southern Italy. In the same area superinfection with the delta agent is endemic. To assess the prevalence of delta infection in a large population of patients with acute and chronic HBV related liver disease and to look for differential features among delta infected and uninfected subjects sera from 592 consecutive HBsAg positive patients were tested for the delta/anti-delta system by RIA. In no case was delta Ag found in serum. The prevalence of anti-delta was low in acute hepatitis (6.6%) and in asymptomatic carriers (6.4%) but raised in chronic active hepatitis with or without cirrhosis (52.3%). A decrease in frequency of anti-delta was seen in inactive cirrhosis (38.8%) and in hepatocellular carcinoma (11.9%). A younger mean age of delta-infected subjects was observed in each type of chronic liver disease. Our data confirm that delta agent superinfection is definitely associated with severe chronic active liver disease. The difference in age between anti-delta positive and negative patients suggests that delta infection accelerates the natural history of HBV related liver disease.

An enzyme-linked immunosorbent assay (ELISA) for detecting antimitochondrial antibody.

We have developed an enzyme linked immunosorbent assay (ELISA) for antimitochondrial antibody. Polyvinyl microtiter plate wells are coated with partially purified rat kidney mitochondria, and excess protein binding sites are blocked with bovine serum albumin. Human serum, diluted 1:1,000, is incubated for 1 hr. Then beta-galactosidase-goat-anti-human IgG (H + L) is added followed by the substrate, p-nitrophenyl-beta-D-galactopyranoside. The plates are then read at 404 nM in a microelisa autoreader. A positive result was defined as optical density greater than or equal to 0.100, more than 5 standard deviations above the mean of 36 normal individuals. With this technique, 56 of 60 patients with primary biliary cirrhosis were positive for antimitochondrial antibody (93%), mean O.D., 0.456 +/- 0.031 S.E. Seventeen of 17 patients with extrahepatic bile duct obstruction and 14 or 14 patients with alcoholic cirrhosis were negative. Only 1 of 29 patients with chronic active liver disease was positive (4%). Antinuclear antibody and antimicrosomal antibody do not bind in this assay, and activity is absorbed from sera by preincubation with suspensions of rat kidney mitochondria. The ELISA is approximately 20 times more sensitive than a quantitative microtiter complement fixation technique and more convenient than radioimmunoassay. It is rapid, quantitative and uses stable reagents. In contrast to immunofluorescence techniques, it is not affected by observer interpretation.

Measurement of secretory IgA in serum by radioimmunoassay in patients with chronic nonalcoholic liver disease or carcinoma.

The authors describe the development of a double antibody radioimmunoassay specific for human secretory IgA (sIgA), and they report the results of measurements of serum sIgA concentrations in patients with chronic, nonalcoholic liver disease or carcinoma. Above-normal sIgA concentrations (greater than 25 micrograms/mL) were found in 22 of 38 sera from patients with chronic active liver disease and in 37 of 40 sera from patients with primary biliary cirrhosis. Markedly increased concentrations (greater than 118 micrograms/mL) were specific for primary biliary cirrhosis. Above-normal sIgA concentrations were found frequently in patients with colorectal (29/86, 34%), pancreatic (38/70, 54%), gastric (11/30, 37%), or mammary (6/46, 13%) carcinoma. An above-normal concentration of sIgA was more specific for hepatic metastases than an above-normal alkaline phosphatase activity in each type of carcinoma. The authors conclude that measurement of sIgA in serum is a useful diagnostic test in patients with chronic liver disease suspected of having primary biliary cirrhosis or in patients with carcinoma suspected of having hepatic metastases.

Patterns of chronic liver disease in Kuwait with special reference to localisation of hepatitis B surface antigen.

Two hundred and fifty six consecutive liver biopsy specimens (without secondary malignancy) collected over five years were reviewed to characterise the pattern of liver diseases encountered in the Kuwait region. A relatively high proportion of chronic active hepatitis (19%) and cirrhosis (40%) was found. Localisation of HBsAg was carried out by the histochemical orcein method and the immunohistological peroxidase-antiperoxidase (PAP) procedure. The PAP technique was superior to orcein both in quality and quantity in addition to its specificity. Three immunohistological staining patterns were observed: diffuse pancytoplasmic , partial perinuclear, and peripheral cytoplasmic. The positivity rate of HBsAg in chronic hepatitis was 29% and 27%, in all cases of cirrhosis. The results of immunohistology and serology of HBsAg were compared in 52 patients in whom both tests were carried out; almost one third of chronic active liver diseases were positive by both methods. Our data clearly show the sensitivity of immunohistology and its value in detecting HBsAg, especially in retrospective studies where serology is not always available. Additionally, the data show that hepatitis B infection is often associated with the development of chronic liver disease in Kuwait.

Liver membrane antibodies detected by immunoradiometric assay in acute and chronic virus-induced and autoimmune liver disease.

In this study, we describe a radioimmunoassay to detect liver membrane binding antibodies. The assay was designed to exclude binding of aggregated IgG or immune complexes to Fc gamma receptors of hepatocytes. When this assay was applied to sera from 142 patients, antibodies were found in highest titer in patients with autoimmune chronic active hepatitis, rarely in patients with hepatitis B virus-induced chronic active liver disease, and in 32% of patients with primary biliary cirrhosis. IgM antibodies were found in 100% of patients with acute Type A but not B or non-A, non-B hepatitis. IgA class antibodies were found in the sera of 57% of patients with alcohol-induced hepatitis. All patient groups showing significant titers of liver membrane antibodies display the lesion of piecemeal necrosis except those with alcohol-induced hepatitis. Further studies are needed to determine whether this antibody is the cause of the lesion.

Platelet-associated IgG in hepatitis and cirrhosis.

Increasing evidence is accumulating which indicates that immunological abnormalities contribute to the development of liver disease and its signs and symptoms. Platelet-associated IgG (PAIgG) levels were quantified in 42 patients with biopsy-proven liver disease of various etiologies to determine the relationship of thrombocytopenia to immunologic abnormalities in these disorders. Five of six nonthrombocytopenic patients with acute viral hepatitis B had elevated PAIgG. Six of ten patients with chronic active hepatitis had elevated PAIgG and thrombocytopenia. In contrast, only one of six patients with chronic persistent hepatitis had elevated PAIgG. Nine of ten patients with alcoholic hepatitis had elevated PAIgG; seven of the nine were thrombocytopenic. Seven of ten alcoholic patients with cirrhosis had elevated PAIgG; six of seven were thrombocytopenic. Thus the increase in PAIgG may be present without thrombocytopenia in acute liver injury, while patients with chronic persistent hepatitis do not usually exhibit this abnormality. Severe chronic active liver disease is accompanied by thrombocytopenia and an increase in PAIgG levels.

Albumin receptors on HBsAG particles and subsequent sero-conversion designate HBeAG-positive patients among chronic active liver disease patients.

An enzyme-linked immunosorbent assay (ELISA) for the purpose of detecting the albumin receptor on hepatitis B virus surface antigen (HBsAg) particles was developed. Patient sera with moderate to high receptor values demonstrated significant correlations with serum DNA-polymerase activity (p less than 0.005), but not with HBeAg titer. Within one year of the study of 47 HBeAg-positive patients, only in the group of 12 patients with the moderately high values and 9 with low values, did 2 (16.7%) and 6 cases (66.7%) sero-convert, respectively. These results suggest that the albumin receptor might be a useful marker of HBsAg-positive patients.

Neuraminidase activity in human peripheral lymphocytes: its increase in chronic active liver disease.

The activity of neuraminidase (sialidase) in peripheral white blood cells was measured by a fluorometric method using 4-MU NANA as a substrate. The activity in mononuclear cells, which was predominantly lymphocytes, was 2.5 times higher than that in polymorphonuclear cells (neutrophils). The former's activity was directly proportional to the number of the cells, but that of the latter was found to be suppressed by an increasing number of cells. Thus, the increased number of PMN contaminated in MNC fraction somewhat obscured neuraminidase activity affecting suppressively . The enzyme activity in MNC of 25 control subjects (15 males and 10 females) was 254 +/- 73 pmoles per hour per 10(6) cells and there was no difference between the values in males and females (233 +/- 59 vs. 284 +/- 81). The activity in 20 patients with chronic active liver disease was significantly higher than that in controls (551 +/- 135, p less than 0.01). The amount of sialic acid in MNC, which was 1.4 times more than that in PMN, revealed a tendency for a positive correlation between neuraminidase activity. A new finding of the increase of lymphocyte neuraminidase activity was introduced and its pathological significance particularly in liver disease was discussed.

Organ-specificity and clinical significance of antibody to insoluble liver cell mebrane antigen (anti-LM) in sera from patients with chronic active liver diseases

The specificity of insoluble liver cell membarne antigen (LMAg) different from liver specific lipoprotein (LSP), was investigated by immunodiffusion using 2% polyethylene glycol (PEG-ID), immunofluorescence technique and enzyme-linked immunosorbent assay (ELISA). Serum anti-LM against acetone-fixed rat liver was detected in 9 of 13 patients with anti-HBs-positive chronic liver diseases (CLD) and 10 of 25 healthy persons with positive anti-HBs by immunofluorescence technique. Results of ELISA indicated that sera of 21 patients with lupoid hepatitis from Intractable Liver Diseases Committee, the Ministry of Health & Welfare, Japan and 25 patients with HBsAg-negative CLD had high levels of anti-LM. In immunohistological demonstrations of LMAg and LSP, the anti-LM prepared from an anti-HBs-positive patient with chronic active hepatitis bound to each of the human and rat acetone-fixed liver cell membranes, but not bind to any of human and rat kidney tissues. The absorbed rabbit anti-rat LM also bound to liver cell membranes, but the absorbed anti-rat LSP lacked organ-specificity to acetone-fixed liver tissues. Results of PEG-ID indicated that the absorbed rabbit antirat LM had precipitated to two organ-specific components of rat liver homogenate, and one of the two was identified as the one of the absorbed anti-LSP.In conclusion, it is indicated that the appearance of serum anti-LM is associated with a host immune response against the surface antigen components on hepatitis B virus (HBV).

Chronic Active Liver Disease

Chronic Active Liver Disease

Chronic Active Liver Disease, Vol. 2, Contemporary Issues in Gastroenterology

Chronic Active Liver Disease, Vol. 2, Contemporary Issues in Gastroenterology

BOOK REVIEWS

Book Reviews in this article.COMPREHENSIVE MANUALS IN RADIOLOGY: ARTHROGRAPHY By Murray K. DalinkaSURGICAL REVIEW 3 Edited by J. S. P. Lumley, MS, FRCS and J. L. Craven BSC, MD, FRCS.RECONSTRUCTIVE PROCEDURES IN SURGERY Edited by P. Gilroy Bevan, ChM, FRCS.HANDBOOK OF CRITICAL CARE Edited by James L. Berk, MD and James E. SamplinerCONTEMPORARY ISSUES IN GASTROENTEROLOGY VOLUME 2 CHRONIC ACTIVE LIVER DISEASE Edited by Sidney Cohen, MD and Roger D. SolwayBASIC AND CLINICAL IMMUNOLOGY By Daniel P. Stites.MD, John D. Stobo, MD,H. Hugh Fudenberg, MD and J. Vivian WellsESOPHAGEAL MANOMETRY: METHODS AND CLINICAL PRACTICE By Thomas R. WeihrauchCONTEMPORARY ISSUES IN GASTROENTEROLOGY VOLUME 1 DISEASES OF THE ESOPHAGUS Edited by Sidney Cohen, MD and Roger D. SolowayMODERN NEUROSURGERY 1 Edited by M. Brock

The spectrum of chronic active liver disease.

Much progress has been made in the classification of chronic hepatitis syndromes, based on correlation of specific histologic features with progressive liver destruction. Four etiologic subtypes have been defined--drug-induced, hepatitis B, non-A, non-B hepatitis, and autoimmune hepatitis. The last paradoxically is least understood etiologically and pathophysiologically but the most amenable to specific therapy.