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)

Cytotoxic T lymphocytes (CTL) are closely related to the mechanism of liver injury in chronic viral hepatitis. Recently, it has been suggested that antigen-specific T cell activation requires both presentation of antigen by major histocompatibility complex (MHC) molecules and the delivery of costimulatory signals. Such signals are provided by B7/BB-1, one of the most important accessory molecules, sufficient for causing antigen-specific MHC-restricted T cell activation. To evaluate the role of B7/BB-1 in chronic hepatitis C, we immunohistochemically studied its expression in liver tissues obtained from 61 patients with hepatitis C virus (HCV) infection and compared them based on hepatitis activity. In HCV-infected liver, B7/BB-1 was strongly expressed in the cytoplasm of hepatocytes. B7/BB-1-positive cells accompanied liver-infiltrating lymphocytes and were mainly detected in the periportal region. B7/BB-1 expression was closely correlated with the activity of viral hepatitis as evaluated from scores of periportal or intralobular inflammation and necrosis, or serum alanine transferase (ALT) levels. Further study by immunostaining with anti-HCV core and anti-human leukocyte antigen (HLA) class I antibody showed B7/BB-1 positive cells near HCV core antigen- and HLA class I-positive cells, with B7/BB-1-positive cells mostly included among HLA class I-positive cells. These findings suggested that B7/BB-1 expression by hepatocytes may be induced by HCV infection and may trigger generation and activation of CTL, which may cause damage to HCV-infected HLA class I-expressing hepatocytes.
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PMID:B7/BB-1 expression and hepatitis activity in liver tissues of patients with chronic hepatitis C. 904 24

Despite careful selection of cirrhotic patients with hepatocellular carcinoma (HCC), liver resection remains associated with a greater risk than in patients without underlying liver disease. In this study we assessed by multivariate analysis parameters associated with in-hospital mortality and morbidity in a selected group of 108 Child-Pugh A cirrhotic patients undergoing liver resection of HCC. The overall incidences of in-hospital deaths and postoperative complications were 8.3% and 48.1%, respectively. By univariate analysis, the preoperative serum alanine transferase (ALT) level (p = 0.001) and intraoperative transfusions (p = 0.01) were significantly associated with in-hospital death; however, only the serum ALT concentration was an independent risk factor. In-hospital mortality rates in patients whose serum ALT was below 2N (twofold the upper limit of the normal value), between 2N and 4N, and more than 4N were 3.9%, 13.0%, and 37.5%, respectively. An ALT level greater than 2N was predominantly observed in patients with a hepatitis C virus infection and significantly associated with histologic features of superimposed active hepatitis. Patients with an ALT level greater than 2N experienced an increased incidence of postoperative ascites (58% versus 32%, p = 0.01), kidney failure (16% versus 0%, p = 0.0003), and upper gastrointestinal bleeding (6.4% versus 0%, p = 0.02). These results indicate that the preoperative ALT level is a reliable predictor of in-hospital mortality and morbidity following liver resection in Child-Pugh A cirrhotic patients. Cirrhotic patients with ALT > 2N should undergo only a limited resection; if a larger resection is required, those patients should be considered for nonsurgical therapy or liver transplantation.
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PMID:High preoperative serum alanine transferase levels: effect on the risk of liver resection in Child grade A cirrhotic patients. 914 70

Serum hepatitis B virus (HBV) DNA from 4 infants with fulminant hepatitis B, 3 infants with acute self-limited hepatitis B, and 15 infants with chronic HBV infection were amplified by polymerase chain reaction followed by direct sequencing of the region of HBV genome encoding the major antigenic epitopes of hepatitis B surface antigen (HBsAg). All infants were born to carrier mothers and administered immunoprophylaxis from birth. Serum HBV DNA from 13 carrier children born to carrier mothers who did not receive immunoprophylaxis and had comparable length of infection were studied as controls. An S mutant (residue 126, Thr to Ala) initially found in an infant with fulminant hepatitis was replaced by another S mutant (residue 145, Gly to Arg) 4 days later. In a girl with chronic hepatitis B, Ala-126 variant and Arg-145 variant were found at 17 and 25 months of age, respectively. The Arg-145 variant persisted for 8 years in an asymptomatic male carrier and for 1 year in an infant with chronic hepatitis B. The Ala-126 variant persisted for 11 years in one child who had an early loss of hepatitis B e antigen. In the majority of the infants' mothers, corresponding mutations in HBsAg were not detected in serum by direct sequencing. The S mutants detected in three carrier infants were not found in their mothers' serum after cloning and sequencing of 10 DNA clones from each maternal sample. None of the 13 control patients had detectable S mutants. These results suggest that S variants emerge or are selected under the immune pressure generated by the host or by administration of hepatitis B immune globulin and hepatitis B vaccination. An S mutant (residue 129, Gln to Arg) found in one mother-infant pair suggested a direct maternal-infant transmission, resulting in immunoprophylaxis failure. None of the family members of children infected with Arg-145 variant had the same variant infection, implying this variant's low transmissability.
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PMID:Surface gene mutants of hepatitis B virus in infants who develop acute or chronic infections despite immunoprophylaxis. 930 14

Envelopment of the hepatitis B virus (HBV) nucleocapsid depends on the large envelope protein L, which is expressed as a transmembrane polypeptide at the endoplasmic reticulum membrane. Previous studies demonstrated that the cytosolic exposure of the N-terminal pre-S domain (174 amino acids) of L was required for virion formation. N-terminal truncations of L up to Arg 103 were tolerated. To map sites in the remaining C-terminal part of pre-S important for virion morphogenesis, a series of 11 L mutants with linker substitutions between Asn 98 and Pro 171 was generated. The mutants formed stable proteins and were secreted in transfected cell cultures, probably as components of subviral hepatitis B surface antigen particles. All four constructs with mutations between Asn 98 and Thr 125 were unable to complement in trans the block in virion formation of an L-negative HBV genome in cotransfected HuH7 cells. These mutants had a transdominant negative effect on virus yield in cotransfections with the wild-type HBV genome. In contrast, all seven mutants with substitutions downstream of Ser 124 were able to envelop the nucleocapsid and to secrete HBV. The sequence between Arg 103 and Ser 124 is highly conserved among different HBV isolates and also between HBV and the woodchuck hepatitis virus. Point mutations in this region introducing alanine residues at conserved positions blocked virion formation, in contrast to mutations at nonconserved residues. These results demonstrate that the pre-S sequence between Arg 103 and Ser 124 has an important function in HBV morphogenesis.
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PMID:A short linear sequence in the pre-S domain of the large hepatitis B virus envelope protein required for virion formation. 937 94

It has been shown in experiments on Wistar rats that the antitumor agent platidiam given in MTD causes increased activity of alanine and aspartate aminotransferases (up to the 15th day after administration), persisting changes in the beta- and pre-beta-lipoprotein level, and intensified LPO in the blood (up to 3-months). Acute toxic hepatitis induced in rats by injection of CCl4 1, 3, and 6 months after a single platidiam administration is characterized by hepatic disorders which are more pronounced than those than those in intact animals with CCl4 hepatitis.
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PMID:[The early and late sequelae of the toxic action on the liver of a platinum antitumor preparation]. 937 61

Four agents are in clinical development for the treatment of chronic hepatitis B infection. These nucleoside analogs are incorporated into the growing DNA chain and terminate replication. Lamivudine, a cytadine analog that inhibits the synthesis of negative strand DNA from pre-genomic RNA, predictably inhibits replication and improves liver enzymes and histology in infected individuals. Following cessation of treatment, relapse is common, and genetic causes of viral resistance have been described. Other drugs for HBV infection include famciclovir, a guanosine analog that has also shown to suppress replication in immunocompetent as well as in immunocompromised patients; lobucavir, a guanosine analog; and adevfovir, an adenine nucleotide analog. The future of drug therapy against HBV likely includes combination agents with one or more nucleoside/nucleotide analogs and immune stimulants, such as interferon, or therapeutic vaccines. Recent advances in the treatment of HCV have been less impressive. An effective vaccine is greatly needed yet development in the near future is unlikely. Recommendations for therapy of chronic HCV have been proposed following the National Institutes of Health Consensus Conference. Interferon alpha is advised in patients with elevated serum alanine aminotransferases and liver histology demonstrating active hepatitis, regardless of level of pretreatment viremia or infecting genotype. Therapy should be continued for three months, at which time response should be assessed. If a biochemical and/or virological response has been achieved, treatment should be continued for a year. Trials are underway to evaluate interferon in combination with ribavirin. Recent identification of the crystalline structure of the HCV NS3 protease promises development of effective inhibitors of this critical viral enzyme.
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PMID:Hepatitis B and C viruses: molecular identification and targeted antiviral therapies. 954 65

The pre-S envelope protein of duck hepatitis B virus (DHBV) contains a region, Asp-Asp-Pro-Leu-Leu (DDPLL), that is specifically required for virus assembly and secretion (Lenhoff and Summers, J Virol 1994;68:4565-4571). We found that amino acids 201 to 205 of the pre-S envelope protein of woodchuck hepatitis virus (WHV) form a conserved amino acid cluster, Gly-Asp-Pro-Ala-Leu (GDPAL), which resembles the DDPLL sequence of DHBV. To determine whether the GDPAL region was functionally equivalent to the DDPLL region, we deleted this region from the pre-S protein of WHV or mutated individual amino acids within the region. The mutant DNA was transfected into human hepatoma cell line Huh7, and the medium was assayed for virion production by immunoprecipitation and Southern blot analysis. We found that an in-frame deletion of this small region inhibited virion formation, suggesting that the GDPAL region of the pre-S envelope protein was required for virus assembly and/or secretion of WHV. Individual replacement of alanine 204, leucine 205, or serine 206 with other amino acid residues did not affect virus production. However, substitution of either aspartic acid 202 with valine or proline 203 with leucine dramatically inhibited WHV production. Furthermore, the GDPAL mutants were individually tested for their abilities to complement a pre-S1 defective genome. The results showed that the GDPAL region functioned as part of the pre-S1 protein but was not required to function as part of the pre-S2 protein.
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PMID:The GDPAL region of the pre-S1 envelope protein is important for morphogenesis of woodchuck hepatitis virus. 958 99

Expression studies have shown that the coronavirus small envelope protein E and the much more abundant membrane glycoprotein M are both necessary and sufficient for the assembly of virus-like particles in cells. As a step toward understanding the function of the mouse hepatitis virus (MHV) E protein, we carried out clustered charged-to-alanine mutagenesis on the E gene and incorporated the resulting mutations into the MHV genome by targeted recombination. Of the four possible clustered charged-to-alanine E gene mutants, one was apparently lethal and one had a wild-type phenotype. The two other mutants were partially temperature sensitive, forming small plaques at the nonpermissive temperature. Revertant analyses of these two mutants demonstrated that the created mutations were responsible for the temperature-sensitive phenotype of each and provided support for possible interactions among E protein monomers. Both temperature-sensitive mutants were also found to be markedly thermolabile when grown at the permissive temperature, suggesting that there was a flaw in their assembly. Most significantly, when virions of one of the mutants were examined by electron microscopy, they were found to have strikingly aberrant morphology in comparison to the wild type: most mutant virions had pinched and elongated shapes that were rarely seen among wild-type virions. These results demonstrate an important, probably essential, role for the E protein in coronavirus morphogenesis.
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PMID:Analysis of constructed E gene mutants of mouse hepatitis virus confirms a pivotal role for E protein in coronavirus assembly. 973 25

Although the risk of transfusion-transmitted hepatitis has been recently reduced, transfusion-dependent beta-thalassemia patients may still develop liver disease due to viral infection or iron overload. We assessed the frequency and causes of liver dysfunction in a cohort of anti-hepatitis C virus (HCV) negative thalassemics. Of 1,481 thalassemics enrolled in 31 centers, 219 (14.8%) tested anti-HCV- by second-generation assays; 181 completed a 3-year follow-up program consisting of alanine-aminotransferase (ALT) measurement at each transfusion and anti-HCV determination by third-generation enzyme-immunoassay (EIA-3) at the end of study. Serum ferritin levels were determined at baseline and at the end of follow-up. Ten patients were anti-HCV+ by EIA-3 at the end of follow-up. Of them, seven were already positive in 1992 to 1993 when the initial sera were retested by EIA-3, one tested indeterminate by confirmatory assay, and two had true seroconversion (incidence, 4. 27/1,000 person years; risk of infection, 1/7,100 blood units, 95% confidence interval [CI], 1 in 2,000-1 in 71,000 units). At baseline, 67 of 174 thalassemics had abnormal ALT. Of those with normal ALT, seven subsequently developed at least one episode of moderate ALT increase (incidence, 24.6/1,000 person-years). All of the 20 patients with ferritin values >/=3,000 ng/mL had clinically relevant ALT abnormalities, as compared with 53 of 151 with <3,000 ng/mL (P < .005). Hepatic dysfunction is still frequent in thalassemics. Although it is mainly attributable to siderosis and primary HCV infection, the role of undiscovered transmissible agents cannot be excluded.
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PMID:A multicenter prospective study on the risk of acquiring liver disease in anti-hepatitis C virus negative patients affected from homozygous beta-thalassemia. 978 88

The efficacy and safety of lomefloxacin in the treatment of patients with hepatitis due to the use of routine antituberculosis agents were estimated. The trial group included 20 patients (10 with increased activity of enzymes such as alanine and asparagine transaminases, alkaline phosphatase and gamma-glutamate dehydrogenase) who were treated for various forms of tuberculosis with antitubeculosis drugs. The treatment course with lomefloxacin was 4 weeks (400 mg twice a day at 12-hour intervals). The criteria of the enrolment to the trial group were a more than 2-3 times higher activity of the enzymes and the absence of the markers of the virus hepatitis A, B and C. The therapy efficacy before and after the use of lomefloxacin was estimated clinically and by the findings of the laboratory and instrumental investigations. As a result of the treatment with lomefloxacin normalization of the enzyme activity and a favourable time course of the main disease were observed in the patients with drug hepatitis due to the use of antituberculosis agents requiring continuation of the antituberculosis therapy. An important result of the complex treatment with lomefloxacin and antituberculosis agents was discontinuation of the tubercle bacilli isolation in 70 per cent of the patients. Lomefloxacin proved to be a safe and efficient up-to-date agent for the treatment of tuberculosis in patients with hepatitis due to the use of antituberculosis drugs.
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PMID:[Lomefloxacin in phthisiatric practice]. 982 4


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