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)

Functional hepatic imaging was performed using 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA), a radiolabeled ligand that reacts specifically to the asialoglycoprotein receptor that resides at the plasma membrane of hepatocytes, in 21 patients: five with chronic active hepatitis (CAH), 14 with compensative liver cirrhosis (LC), one with chronic inactive hepatitis and one with acute hepatitis. The former two diseases were mainly investigated. Serial liver images were acquired at the rates of 10 sec/frame for 0-5 min and 2 min/frame for 6-30 min after the injection of 99mTc-GSA, and the images were compared with 99mTc-phytate images in 2 patients with CAH and 11 with LC, and those with portal scintigrams using 123I-iodoamphetamine (IMP) in 3 patients with LC. The images using 99mTc-GSA were in better agreement with hepatic function than those using 99mTc-phytate, and with the findings of portal scintigraphy using 123I-IMP. LHL15 (liver/liver and heart radioactivities at 15 min after the injection of 99mTc-GSA) correlated with the hepaplastin test (r = 0.978 in CAH, and r = 0.544 in LC), indicators of hepatic reserve. These results suggest that liver scintigraphy using 99mTc-GSA might be a useful method for evaluating liver function.
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PMID:[Clinical evaluation of hepatic scintigraphy using 99mTc-GSA]. 164 14

As part of an investigation into the question of whether virus-induced autoreactivity might contribute to liver damage in viral hepatitis, serial studies (from onset through recovery) of circulating liver autoantibodies have been performed in patients with uncomplicated acute virus A (AVH-A), B (AVH-B) and non-A, non-B (AVH-NANB) hepatitis in whom the time of onset of symptoms could be precisely documented. One hundred and forty-four sera from 35 patients were tested by radioimmunoassay for autoantibodies against the liver-derived lipoprotein complex, LSP, and also against one of its constituents--the asialoglycoprotein receptor, known as hepatic lectin (HL). Anti-LSP antibodies were found in all 10 patients with AVH-A, in 17/18 with AVH-B and in 3/7 with AVH-NANB at titres that declined during recovery. Anti-HL antibodies were detected concurrently in 6 of the AVH-A patients and in 5 with AVH-B but on only 1 occasion in 1 patient with AVH-NANB. Transient cellular immunity to LSP, assayed by a T-lymphocyte migration inhibitory factor test, was detected in 4 of the 6 AVH-B patients tested, 2 of whom also showed concurrent reactivity to HL, but these cellular immune responses did not correlate with production of anti-LSP and/or anti-HL. The findings indicate that humoral immune responses to liver cell surface antigens are frequently triggered by hepatitis A and B viruses, possibly via induction of autoreactive, T-cell independent, liver antigen-specific B lymphocytes. These liver-specific autoreactions have the potential to contribute to hepatocellular damage in virus A and B hepatitis but it seems unlikely that autoimmunity plays a significant pathogenetic role in NANB viral infections.
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PMID:Liver autoreactivity in acute virus A, B and non-A, non-B hepatitis. 313 82

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.
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PMID:Serum autoantibodies reacting with the hepatic asialoglycoprotein receptor protein (hepatic lectin) in acute and chronic liver disorders. 379 1

A 7-year-old patient is reported who suffered from fatigue and jaundice due to chronic hepatitis. He had acquired hepatitis A virus infection in his community and communicated the disease to his German family 4 weeks later. While the other family members recovered from acute viral hepatitis A, the patient presented 10 weeks after the onset of hyperbilirubinemia (12 mg/dl) with the histology of chronic hepatitis, absence of markers for viral persistence, presence of autoantibodies against smooth muscle (1:320) and the asialoglycoprotein receptor (1:600), and marked hypergammaglobulinemia (3700 mg/dl), leading to the diagnosis of autoimmune hepatitis. The patient received immunosuppressive therapy, symptoms of liver disease disappeared, and autoantibodies cleared from circulation. The case is discussed in the context of a putative virus-induced autoimmune hepatitis in childhood. Autoimmune hepatitis may be induced by an external trigger. Hepatitis A virus infection is one of probably several triggers that may induce autoimmune hepatitis in predisposed individuals.
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PMID:Autoimmune hepatitis following hepatitis A virus infection. 749 93

Serial serum samples from 16 Italian patients presenting with acute hepatitis C virus (HCV) infections (which progressed to chronic hepatitis in six) were screened for the non-organ-specific autoantibodies most frequently associated with autoimmune hepatitis (AIH), as well as for antibodies against the hepatic asialoglycoprotein receptor (ASGP-R) and against the GOR peptide. One patient had low titres (1:10-1:80) of liver-kidney microsomal (LKM-1) antibodies during the recovery phase and three others had transient low titres of anti-smooth muscle (IgM class, 1:10) or anti-ASGP-R (1:150-1:300). Anti-GOR was detected in 43 (65%) of 66 sera from 13 of these patients. There was no correlation between any of these findings and progression to chronicity. By comparison, 18 patients with AIH studied concurrently before institution of immunosuppressive therapy all had antinuclear and/or smooth muscle antibodies, or LKM-1, at 1:40-1:640 and anti-ASGP-R at 1:300-1:2,100. None of these 18 had evidence of HCV infection and all were seronegative for anti-GOR. The findings indicate that the autoantibodies usually associated with AIH are rare in HCV infections but the virus can very occasionally induce a transient autoimmune response. Anti-GOR appears to be an antibody specifically related to HCV infection and is probably not a marker of induced autoimmunity, and it does not predict progression to chronic hepatitis.
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PMID:Virus-induced autoimmunity in hepatitis C virus infections: a rare event. 750 90

During follow-up of healthy relatives of 13 patients with autoimmune hepatitis, seven cases of infectious mononucleosis due to Epstein-Barr virus (EBV) occurred. In two of these seven, before EBV infection, there was a defect in suppressor-inducer T lymphocytes specifically controlling immune responses to the asialoglycoprotein receptor, an antigen expressed on the hepatocyte surface. In these two, antibodies to this autoantigen persisted and increased after infectious mononucleosis, and autoimmune hepatitis developed within 4 months. In susceptible individuals, EBV is a trigger for autoimmune hepatitis.
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PMID:Epstein-Barr virus as a trigger for autoimmune hepatitis in susceptible individuals. 756 12

To assess whether the hepatocyte asialoglycoprotein receptors are affected in patients with autoimmune hepatitis, the function of the hepatocyte asialoglycoprotein receptor was investigated in patients with autoimmune hepatitis or chronic hepatitis C. A new radionuclide liver imaging technique, Technetium-99m diethylenetriamine-pentaacetic acid-galactosyl human serum albumin, was applied to evaluate the function of the receptor. A Receptor Index (LHL 15) was calculated by dividing the radioactivity of the liver region-of-interest (ROI) by that of the liver plus heart ROI 15 min after radiolabeled ligand injection. Serum albumin, prothrombin time, hepaplastin test and plasma retention rate of indocyanine green at 15 min were not significantly different between patients in the autoimmune hepatitis group and chronic hepatitis C group. In addition, the Receptor Index of patients with autoimmune hepatitis, in whom the asialoglycoprotein receptor is a candidate target antigen for autoimmune response, was similar to that of patients with chronic hepatitis C. These results indicate that the hepatocyte receptor for asialoglycoproteins is not affected in patients with autoimmune hepatitis.
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PMID:Asialoglycoprotein receptor function of hepatocytes in patients with autoimmune hepatitis. 785 28

Susceptibility to autoimmune hepatitis in white patients is associated with the human leukocyte antigen class II antigens DR3 and DR4. To analyze the molecular basis of these associations, we used oligonucleotide probes to determine the DRB, DQA and DQB hypervariable nucleotide sequences in 119 patients with autoimmune hepatitis and 177 matched controls. DRB3*0101, which encodes DR52a, predisposed patients most strongly to the disease. It was present in 58% of patients and 25% of controls (corrected P < 0.000005), whereas DQA1*0101 and 0102 conferred protection in males only. The DR4 subtype, DRB1*0401, was raised in the DRB3*0101-negative patients; 81% possessed either DRB3*0101 or DRB1*0401, compared with 42% of controls (corrected P < 0.0000001). These alleles encode the amino acid sequence Leu-Leu-Glu-Gln-Lys-Arg at positions 67 to 72 of the DR beta polypeptide, which was present in 94% of patients and 64% of controls (corrected P < 0.000001) and in all patients who tested positive for autoantibodies to the hepatic asialoglycoprotein receptor. The patients with DRB1*0401 had less severe disease, relapsed less frequently and were first seen significantly later in life than those patients with DRB3*0101; and whereas a single copy of DRB1*0401 predisposed to autoimmune hepatitis, DRB3*0101-associated susceptibility had a dose-related effect. These data provide evidence that specific residues in the DR beta polypeptides predispose to autoimmune hepatitis in white patients and genes linked to DRB3*0101 and DRB1*0401 may determine two clinically distinct disease patterns.
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PMID:Allelic sequence variation in the HLA class II genes and proteins in patients with autoimmune hepatitis. 811 85

The hepatic asialoglycoprotein receptor (ASGPR) was recently identified as a target antigen for both humoral and cellular immune response in inflammatory liver diseases. Thereby anti-ASGPR autoantibodies directed against human substrate were closely associated with autoimmune chronic active hepatitis. The present study compares the occurrence, titer and immunoglobulin classification of anti-human(h-)-ASGPR antibodies in 23 patients with newly diagnosed autoimmune chronic hepatitis before and after initiation of immunosuppressive therapy to 22 patients with autoimmune hepatitis in remission. Additionally, 1-year follow-up examinations of 42 patients with HBsAg-positive chronic hepatitis and of 32 patients with chronic hepatitis C receiving recombinant interferon-alpha were included. Nineteen of 23 patients with newly diagnosed and 9/22 with autoimmune hepatitis in remission, 5/42 with untreated chronic hepatitis B and 5/32 patients with chronic hepatitis C exhibited anti-h-ASGPR at the beginning of the study. In autoimmune hepatitis anti-h-ASGPR were found in higher titers (median > 1:1000) than in viral hepatitis (maximum 1:400). After initiation of immunosuppressive therapy in autoimmune hepatitis anti-h-ASGPR decreased sharply. Eight of 19 patients eliminated anti-h-ASGPR within 18 months in contrast to 11 patients with persistent anti-h-ASGPR titer over 18 months and longer. Anti-h-ASGPR with maximum titer of 1:600 were detected in 5 patients with chronic hepatitis B (transiently in 4/5 patients) and in 2 patients with chronic hepatitis C during interferon-alpha. Anti-h-ASGPR were from immunoglobulin classes IgG and IgM in cases with untreated autoimmune hepatitis and chronic hepatitis B and C exhibiting mainly IgG2-subclass in autoimmune and IgG4 in viral hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Autoantibodies against the human asialoglycoprotein receptor: effects of therapy in autoimmune and virus-induced chronic active hepatitis. 830 Oct 43

Dideoxycytidine (ddC) is a nucleoside analogue active against human immunodeficiency virus and with in vitro activity against human hepatitis B virus. We investigated the ability of ddC to inhibit one of the Hepadnaviridae, the woodchuck hepatitis virus and compared the results with the effect obtained by a conjugate of lactosaminated human serum albumin 2',-3'-dideoxycytidine monophosphate (L-HSA ddCMP). This compound specifically enters the hepatocyte via the asialoglycoprotein receptor. We treated five chronic woodchuck hepatitis virus carriers with intravenous injections of 0.5 mg/kg body weight of ddC for 5 consecutive days, and under the same protocol five woodchucks with 10.4 mg/ kg L-HSA ddCMP, a dose equivalent to 0.25 mg/kg of free ddC. A reduction of serum woodchuck hepatitis virus DNA (5-125 fold) was observed during therapy in three out of five animals receiving ddC and in two of the five animals treated with L-HSA ddCMP. In responding woodchucks, virus DNA levels rebounded immediately after stopping therapy. No signs of toxicity were observed during or after the course of therapy. These preliminary results of short-term treatment indicate that ddC has anti-viral activity against woodchuck hepatitis virus. When the dose was reduced by 50%, L-HSA ddCMP showed anti-viral activity to an even lesser degree.
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PMID:Treatment of woodchuck hepatitis virus infection in vivo with 2', -3'-dideoxycytidine (ddC) and 2',-3'-dideoxycytidine monophosphate coupled to lactosaminated human serum albumin (L-HSA ddCMP). 874 Aug 40


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