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)

Hepatocyte proliferative activity is elevated in cirrhotic patients who develop hepatocellular carcinoma (HCC) and decreased in alcohol-induced hepatitis patients with poor outcome. Hepatocyte proliferative activity has not been evaluated in an unselected population of cirrhotic patients regarding the severity of the disease. Forty-six cirrhotic patients (21 alcoholic, 20 viral, and 5 other) were prospectively analyzed by proliferating cell nuclear antigen (PCNA) immunostaining on methanol-fixed, paraffin-embedded liver biopsy specimens. In these conditions, the PCNA-labeling index (PCNA-LI) measures the number of cells in the S-phase and assesses tissue proliferation. The median value of the PCNA-LI for all samples was 4.3% (range, 0%-20.2%). It declined with worsening Child-Pugh score: 9.15% (range, 3.3%-20.2%), 5.3% (range, 1.2%-18%), and 2.4% (range, 0%-4.4%) in Child classes A, B, and C, respectively (P < .05). Using the best cutoff PCNA-LI value to divide cirrhosis into slowly and rapidly proliferating tissue subsets, the PCNA index was independently associated with serum albumin. The probability of survival in patients with a high PCNA-LI ( > 4.4%) was significantly higher than in those with a lower PCNA-LI (0.93 vs. 0.53, at a median follow-up of 153 days; P = .01). In all 6 patients undergoing placement of a transjugular intrahepatic portosystemic shunt (TIPS), the PCNA-LI decreased after the procedure. This early impairment of hepatocyte proliferative activity after TIPS placement might reflect the functional alterations induced by this treatment. In conclusion, hepatocyte proliferative activity assessed by PCNA-LI is increased in cirrhotic patients and decreases with worsening of the disease.
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PMID:Relationship between hepatocyte proliferative activity and liver functional reserve in human cirrhosis. 862 Nov 25

A conjugate of adenine arabinoside monophosphate (ara-AMP) with the liver-targeting molecule lactosaminated human serum albumin (L-HSA) was administered by intravenous infusion for 28 days to eight patients with chronic type B hepatitis. The daily dose varied among the patients, ranging from 34 mg/kg to 53 mg/kg (equal to 1.5 and 2.3 mg/kg ara-AMP, respectively). Pharmacokinetic analysis indicated that, at every dose tested, the conjugate was disposed of without accumulation. Viral DNA serum levels fell markedly during treatment; values rose again when treatment was ceased. The L-HSA-ara-AMP conjugate did not cause either the neurotoxic side effects of free ara-AMP or other adverse clinical reactions. It produced a significant increase both in serum alkaline phosphatase activity and platelet number, and a small but significant decrease in erythrocyte number. These laboratory parameters returned to normal levels within 2 months after treatment. The conjugate induced the production of small amounts of antibodies (approximately 20 pmol of conjugate bound by 1 mL of serum) in one patient only. In conclusion, the present results indicate that the L-HSA-ara-AMP conjugate can exert the antiviral activity of ara-AMP in chronic type B hepatitis patients without producing the neurotoxic side effects which hamper a 4-week period of treatment with the free drug.
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PMID:Adenine arabinoside monophosphate coupled to lactosaminated human albumin administered for 4 weeks in patients with chronic type B hepatitis decreased viremia without producing significant side effects. 866 14

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

Chronic non-A, non-B hepatitis (NANBH) is a common and often progressive liver disease. Based on current serological tests, hepatitis C virus (HCV) infection is responsible for most cases. Interferon-alpha (IFN) treatment at a dose of 3 x 10(6) units given three times per week for 24 weeks has been shown to be effective in normalizing serum alanine aminotransferase (ALT) levels and reducing hepatic inflammation in approximately 40% of these patients. The purpose of this study was to identify pretreatment characteristics in patients with chronic hepatitis C(CH-C) which would best predict a favourable response to IFN treatment (normalization of serum ALT). One hundred and sixty-three adult patients who had participated in a large multicentre treatment trial were included in the study group; 84 had been treated with 3 x 10(6) units of recombinant IFN-alpha-2b (rIFN) subcutaneously three times per week for 24 weeks and 79 patients had been treated with 1 x 10(6) units rIFN in the same dosage schedule. Forty-one pretreatment historical, clinical, laboratory and histological variables were evaluated. In addition, early biochemical improvement during treatment was evaluated as a predictor of ultimate response. Univariate analysis identified six variables (dose, dose m-2, weight, body surface area, ongoing ethanol use, white blood cell count and the presence of symptoms) as potential predictors of response (two-tailed, P < 0.15). By multivariate analysis, however, only the 3 x 10(6) dose of rIFN was independently predictive of response (P < 0.01). When the analysis of response was confined to those patients who received treatment with 3 x 10(6) units of rIFN, seven variables [body weight, surface area, dose m-2, current ethanol use, serum albumin and the presence of chronic persistent hepatitis (CPH) on entry liver biopsy] were more frequent in patients who responded to therapy. In a multivariate model, only CPH and body weight predicted an increased likelihood of response (P < 0.01). However, the model was not a sensitive predictor of response as only 18% of the study group had CPH on liver biopsy. A decrease in serum ALT levels within the first 12-16 weeks of rIFN treatment was found to be the strongest indicator of an ultimate response to treatment. Thus, assessment of early response to IFN treatment is the only practical means of predicting complete response and avoiding prolonged and unnecessary therapy in those with little chance of response.
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PMID:Clinical predictors of response to recombinant interferon-alpha treatment in patients with chronic non-A, non-B hepatitis (hepatitis C). The Hepatitis Interventional Therapy Group. 879 May 60

The biotransformation of the aerosol propellant 1,1,1,2,3,3,3-heptafluoropropane (HFA-227) was investigated in rats in vivo and in rat and human liver microsomes. In the urine of rats exposed to 5000 ppm HFA-227 for 6 hr, very small amounts of hexafluoroacetone trihydrate were identified as an HFA-227 metabolite by 19F-NMR. Fluoride concentrations in the urine samples (0-48 hr after the end of the exposure) from exposed animals were not significantly different from those found in samples from nonexposed rats. In rat and human liver microsomes, fluoride and hexafluoroacetone trihydrate formation from HFA-227 was detected in very low levels only in liver microsomes from pyridine-treated rats and in two of eight human liver microsome samples, which exhibited the highest cytochrome P4502E1 activities. Because some aldehydes may covalently bind to proteins and the formation of fluorinated protein adducts has been implicated in immune-mediated hepatitis induced by halothane, the binding of hexafluoroacetone trihydrate to proteins was also investigated. Hexafluoroacetone trihydrate also gave only a very small resonance in fluorine NMR experiments when binding to human serum albumin was studied in comparison with the acylating agent S-ethyltrifluoroacetate. Moreover, no fluorine-containing products were formed by the reaction of hexafluoroacetone trihydrate with N alpha-acetyl-L-lysine, and hexafluoroacetone trihydrate was not metabolized to fluorine-containing metabolites or inorganic fluoride in rats. Comparative studies in human liver microsomes demonstrated that a halothane metabolite may covalently bind to proteins; in contrast, metabolism and covalent binding of HFA-227 could not be demonstrated. In summary, these data indicate that HFA-227 is biotransformed at very low rates to hexafluoroacetone trihydrate but irreversible binding of hexafluoroacetone trihydrate cannot be demonstrated, even with the application of very sensitive methods, and is considered unlikely, based on the combination of the results obtained.
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PMID:Biotransformation of the aerosol propellant 1,1,1,2,3,3,3-heptafluoropropane (HFA-227): lack of protein binding of the metabolite hexafluoroacetone. 886 27

The anesthetic, halothane, is bioactivated by the liver cytochrome P450 system to trifluoroacetyl-chloride, which can readily acylate liver protein. Covalent binding of the trifluoroacetyl moiety may result in hapten formation leading to the induction of an immune response and ultimately halothane hepatitis. In this study the presence of trifluoroacetylated-protein adducts in Kupffer cells was investigated to learn how the immune system might come in contact with the proteins. Guinea pigs were exposed to 1.0% halothane, 40% oxygen for 4 h. Kupffer cells were isolated on days 1 through 9 post-exposure, by liver perfusion and purification by elutriation. Using gel electrophoresis and Western blotting techniques, it has been demonstrated that Kupffer cells obtained from halothane-treated guinea pigs, do carry trifluoroacetyl-protein adducts as recognized by an anti-trifluoroacetyl-rabbit serum albumin antibody. Apparent molecular weights of polypeptides bound by trifluoroacetyl were of a wide range, 25-152 kDa. Bands were most prominent in the larger Kupffer cells with more appearing at lower molecular weights. Trifluoroacetyl-protein adducts were not detected in lung, spleen, lymph node or peripheral blood macrophages. This work suggests a role for Kupffer cells in the presentation of altered proteins in the liver to cells of the immune system.
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PMID:Kupffer cells from halothane-exposed guinea pigs carry trifluoroacetylated protein adducts. 918 99

An acetaldehyde (AcH) adduct was prepared using rabbit low-density lipoprotein as carrier proteins. An antibody against this adduct was raised in Watanabe heritable hyperlipidemic rabbits and cross-reacted with human low-density lipoprotein and bovine serum albumin adducts. Using this antibody, serum anti-AcH-adduct antibody levels were measured by a direct ELISA method in 56 Japanese adults (healthy adults and patients with nonalcoholic gastrointestinal diseases, alcoholic liver injury, or alcoholic pancreatitis). The antibody level (mean +/- SD) was 22 +/- 10 microg/ml in healthy adults, 22 +/- 11 microg/ml in nonalcoholic gastrointestinal diseases, and 16 +/- 13 microg/ml in alcoholic pancreatitis. These antibody levels tended to increase with the progression of alcoholic liver injury, starting from fatty liver via hepatitis to cirrhosis, 29 +/- 24 microg/ml in fatty liver, 35 +/- 29 microg/ml in alcoholic hepatitis, and 46 +/- 54 microg/ml in alcoholic cirrhosis. The antibody level in patients taking 100 g or more of ethanol per day tended to be higher, compared with those in people taking less ethanol. A follow-up observation revealed that alcohol abstinence after hospitalization raised serum anti-AcH-adduct antibody level in some patients and kept it constantly low in other patients. The immunohistochemical study using the anti-AcH-adduct antibody revealed the presence of adduct-like substance in hepatocytes of liver biopsy specimens obtained from patients with alcoholic liver disease. The results indicate that the anti-AcH-adduct antibody may be associated with the progress of alcoholic liver diseases.
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PMID:An enzyme immune assay for serum anti-acetaldehyde adduct antibody using low-density lipoprotein adduct and its significance in alcoholic liver injury. 962 94

The development of policies to prevent nosocomial transmission of hepatitis C virus (HCV) infection in hemodialysis units is critically dependent on the understanding of the relationship between tests for anti-HCV, HCV RNA, and HCV genotype and the patients' clinical characteristics. We tested sera from all patients on the renal transplant waiting list at the New England Organ Bank between November 1986 and June 1990 for anti-HCV by a third-generation enzyme-linked immunosorbent assay (ELISA3) and a third-generation recombinant immunoblot assay (RIBA3). All ELISA3-positive sera were tested for HCV RNA by reverse transcriptase "nested" polymerase chain reaction, and the genotype was characterized by restriction fragment length polymorphism. Sera were available in 1,544 of 3,243 (48%) patients on the waiting list, of whom 287 (19%) tested positive for anti-HCV by ELISA3. Two hundred eighty-six randomly selected, anti-HCV-negative patients served as controls. Compared with anti-HCV-negative controls, anti-HCV-positive patients had a longer duration since initiation of renal replacement therapy, higher number of previous kidney transplants and blood transfusions, higher proportion of patients with anti-HBc, history of liver disease, history of non-A, non-B hepatitis, and elevated serum alanine aminotransferase, and lower serum albumin concentrations. Of the 287 anti-HCV-positive sera, 261 (91%) were reactive by RIBA3, 21 (7%) were indeterminate, and five (2%) were nonreactive. HCV RNA was detected in 224 of 275 (81%) ELISA3-positive patients, in whom additional sera were available. There were no significant differences in clinical or laboratory characteristics between ELISA3-positive patients with and without HCV RNA. Genotypes 1a, 1b, 2a, 2b, 3a, and 4 were present in 53%, 23%, 8%, 10%, 4%, and 2% of patients, respectively. Infection with one, two, or three different HCV genotypes was present in 92%, 7%, and 1%, respectively. There was no significant association between the type or number of HCV genotypes and RIBA3 reactivity. There were no major differences in clinical or laboratory characteristics between genotypes or between single and mixed infection. In summary, this study provides detailed information regarding the relationship between tests for anti-HCV, HCV RNA, and HCV genotypes and the clinical and laboratory characteristics of a large, well-characterized cohort of patients referred for renal transplant.
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PMID:Serologic and virologic profiles of hepatitis C infection in renal transplant candidates. New England Organ Bank Hepatitis C Study Group. 963 34

Antipyrine metabolism is widely used as an index of the drug-metabolizing reserve of the liver. It is well known that metabolism of this drug is impaired in subjects with acute hepatitis or cirrhosis, but conflicting data have been reported regarding patients with chronic postinfectious hepatitis or liver cancer. We studied conventional liver-function parameters and antipyrine metabolism (antipyrine per o.s. 18 mg/kg) in 518 subjects. One hundred and one patients had liver metastases (various primaries). Based on the number and size of lesions, the hepatic involvement was considered minimal in 47 and massive in 54 (groups B1 and B2, respectively). One hundred and two had chronic active hepatitis (CAH); 51 patients with histological evidence of fibrosis/early cirrhosis and 51 patients were without histological evidence of fibrosis/early cirrhosis. Ninety-two had histologically confirmed cirrhosis (group D), and the remaining 120 had cirrhosis and hepatocellular carcinoma (group E). The control group was composed of 103 subjects with healthy livers (group A). Antipyrine clearance (AP Cl) in CAH patients with fibrosis (0.246 +/- 0.98 mL/min per kg) was similar to that observed in patients with cirrhosis (0.223 +/- 0.148 mL/min per kg), and both values were significantly lower than that found in CAH patients without fibrosis (0.406 +/- 0.159 mL/min per kg, P < 0.01). Antipyrine clearance in patients with liver metastases (0.426 +/- 0.174 mL/min per kg) was similar to that of the healthy group (0.489 +/- 0.210 mL/min per kg). Cirrhotics and cirrhotics with hepatocellular carcinoma (HCC) presented similar degrees of impairment. Antipyrine clearance was positively correlated with serum albumin (r2 = 0.10, P = 0.01) and prothrombin time (r2 = 0.129, P < 0.01) in all groups, except those with liver metastases. In patients with CAH, the presence of fibrosis/cirrhosis is associated with impaired antipyrine metabolism. The lack of impairment in groups with liver metastases suggests that the functional hepatic reserve is maintained even in the presence of massive neoplastic invasion.
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PMID:Antipyrine clearance in chronic and neoplastic liver diseases: a study of 518 patients. 964 40

The clinical impact of GB virus-C (GBV-C)/hepatitis G virus (HGV) infection on various causes of acute hepatitis and fulminant hepatitis is controversial. In this study, serum samples from 164 patients with acute hepatitis of various causes, 34 asymptomatic hepatitis B virus (HBV) carriers, and 34 healthy adults were tested for GBV-C/HGV RNA by reverse transcription-nested polymerase chain reaction using primers based on the 5'-untranslated region. Nucleotide sequences of GBV-C/HGV RNA from various groups were compared. The prevalence of GBV-C/HGV RNA was significantly higher in patients with acute hepatitis D virus (HDV) superinfection than in HBV carriers or healthy controls (10/37 vs. 2/34, P < 0.02; 10/37 vs. 1/34, P < 0.005). GBV-C/HGV RNA was detected in 11.1% of acute hepatitis A patients, 9.5% of acute hepatitis B patients, 15.8% of acute hepatitis C patients, 12.5% of acute hepatitis E patients, 11.8% of chronic hepatitis B patients with acute exacerbation, and 11.1% in patients with non-A to -E hepatitis; each was not significantly higher than that in HBV carriers or healthy adults. There were no significant differences in gender, age, serum albumin, bilirubin, and alanine aminotransferase levels nor in the occurrence of fulminant hepatitis (6/28 vs. 36/136) between patients with or without GBV-C/HGV RNA. All six patients with fulminant hepatitis who had GBV-C/HGV RNA were complicated by infection with hepatitis B, C, or D. The GBV-C/HGV clones from 21 patients with or without fulminant hepatitis belonged to group 3. No particular strain of GBV-C/HGV was associated with fulminant hepatitis.
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PMID:Prevalence, implication, and viral nucleotide sequence analysis of GB virus-C/hepatitis G virus infection in acute fulminant and nonfulminant hepatitis. 974 66


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