ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1994.tb00056.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARY.Chronic type C hepatitis is a potentially serious disease that can lead to cirrhosis and hepatocelluler carcinoma. This complex disease is caused by the hepatitis C virus (HCV), a positive sense, single‐stranded RNA virus. HCV has been assigned to a separate genus within the Flaviviridae, and shares a close relationship to the pestiviruses. Nucleotide sequence variation has been observed in genomes amplified from serum of patients with HCV infection, and cloning of RNA amplified from patients infected with HCV has confirmed the heterogeneity of the agent responsible for post‐transfusion and sporadic hepatitis C. The variability of HCV is structured in a way that immediately suggests a two tiered classification: this nomenclature comprises ‘types’ corresponding to the major branches in a phylogenetic tree of sequences from genomic or subgenomic regions of the genome, and ‘subtypes’, corresponding to the more closely related sequences within some of the major groups. This genotyping designation has provided an epidemiological tool for studying geographical differences in hepatitis C infection. Clearly discernible patterns of genotype distribution have been found in those countries that have been studied so far. In many European countries genotype distributions vary with the age of patients, reflecting rapid changes in genotype distribution with time within a single geographical area. Unfortunately we know very little about modes of transmission within different communities. There is considerable interest in the clinical significance of different HCV genotypes, and the intriguing question of whether these differences may affect the spectrum of the disease associated with hepatitis C. These data also have implications for diagnosis and treatment of acute and chronic hepatitis C. A uniform typing scheme and nomenclature will facilitate our understanding of the disease caused by this viru

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1994.tb00057.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARY.Some of the multiple factors involved in the molecular pathogenesis of hepatocellular carcinoma have been elucidated in recent years but no clear picture of how and in what sequence these factors interact at the molecular level has emerged yet. Transformation of hepatocytes to the malignant phenotype may occur irrespective of the aetiological agent through a pathway of chronic liver injury, regeneration and cirrhosis. The activation of cellular oncogenes, the inactivation of tumour suppressor genes and overexpression of certain growth factors contribute to the development of HCC. There is increasing evidence that the hepatitis B virus may play a direct role in the molecular pathogenesis of HCC. Aflatoxins have been shown to induce specific mutations of the p53 tumour suppressor gene thus providing a clue to how an environmental factor may contribute to tumour development at the molecular level.

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1994.tb00058.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARY.Recently we identified human liver endonexin II (EII) as a specific hepatitis B surface antigen (HBsAg) binding protein. To investigate whether EII is also able to interact with the HBsAg envelope of the hepatitis δ virus (HδV). immunoprecipitation experiments were performed. HδV particles could be co‐precipitated by polyclonal rabbit anti‐EII, but not by rabbit anti‐glutathiontransferase (GSTφ) antibodies from an HδV‐enriched fraction containing EII or GSTφ. These findings suggest that HδV particles were co‐precipitated by anti‐EII as a consequence of the binding between HBsAg present in the HδV envelope and EII. Furthermore, binding of HδV particles to human hepatocytes could be inhibited by incubation of the liver cells with rabbit anti‐EII IgG or the HδV particles with anti‐idiotypic (anti‐HBsAg) antibodies, developed spontaneously in rabbits immunized with EII. These findings support the assumption that small HBsAg present in the HδV envelope is important for the attachment to the hepatocytes and that EII plays an im

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1994.tb00059.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARY.The presence of hepatitis B surface protein (HBs) and hepatitis B core protein (HBc) was investigated, by flow cytometry, on the surface of peripheral mononuclear cells (PBMC) from cells of the following phenotype: CD3 (T lymphocytes), CD4 (T helper/inducer), CD8 (T cytotoxic/suppressor). CD19 (B lymphocytes) and CD56 [natural killer (NK) cells] among eight patients suffering from chronic hepatitis B and five healthy HBV‐negative subjects. This study demonstrated the presence of HBsAg and HBcAg on the lymphocyte surface for most of the patients. The mean percentage of labelled cells was 17% for HBsAg and 15% for HBcAg. Among the different lymphocyte subsets only B lymphocytes and the NK cells expressed HBsAg for 57% and 26% of cells, respectively. Similarly HBcAg was also detected among CD19 and CD56 cells only. Polymerase chain reaction (PCR) was used to search for the presence of hepatitis B virus (HBV) DNA and RNA in PBMC, using primers located in the S gene. HBV DNA was detected with variable intensity in the CD3, CD4, CD19 and CD56 subsets following their separation with a cell sorter. For HBV RNA the signal obtained after PCR and Southern blotting was higher for CD56 and CD19 cells than for CD3 cells and undetectable for CD4 cells. This study demonstrates that replication and transcription of the HBV can occur in CD19‐ and CD56‐positive cells. Positive signals in CD3 cells may be due to contamination of this subpopulation by NK

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1994.tb00060.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARY.Alterations in the expression of the RB tumour suppressor gene were found by Western immunoblot in three of seven hepatocellular carcinoma and hepatoblastoma cell lines. Abnormalities were detected by single‐strand conformation polymorphism (SSCP) within exons 17–21 in RB cDNA from two of these three cell lines and within exons 20–21 in the third cell line. In these three cell lines with abnormal RB expression, abnormal expression of the p53 tumour suppressor gene was also found, apparently the product of a mutant gene. Thus, mutations within the RB gene (or splice‐site mutations with exon‐skipping) and apparent mutations of the p53 gene together may have contributed to the development of three of these tumours or to the establishment of these c

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1994.tb00061.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARY.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‐α (IFN) treatment at a dose of 3 × 106units 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 multi‐centre treatment trial were included in the study group: 84 had been treated with 3 × 106units of recombinant IFN‐α‐2b (rIFN) subcutaneously three times per week for 24 weeks and 79 patients had been treated with 1 × 106units 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 × 106dose 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 × 106units 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 thos

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1994.tb00062.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARY.Patients on maintenance haemodialysis in four dialysis centres were tested for markers of hepatitis C virus (HCV) infection. Antibody to HCV (anti‐HCV) was detected by the second‐generation enzyme immunoassay in 142 (26%) of the 543 patients and HCV RNA in 117 (22%) of whom four were without detectable anti‐HCV in serum. Seventy‐seven (66%) were infected with HCV of genotype II/1b, 31 (27%) with genotype III/2a and eight (7%) with genotype IV/2b. in a distribution similar to that in blood donors who carried HCV asymptomatically. Haemodialysis patients had high HCV RNA titres comparable to those of patients with chronic hepatitis C. HCV RNA was detected in 96 (26%) of the 365 patients with a history of transfusion more frequently than in 21 (12%) of the 178 without previous transfusion (P<0.001). In transfused patients, frequencies of anti‐HCV and HCV RNA increased in parallel with the duration of haemodialysis. The frequency of anti‐HCV in non‐transfused patients, however, did not change appreciably with the duration of haemodialysis up to 22 years. The patients with anti‐HCV had a higher frequency of HCV RNA in serum than symptom‐free blood donors with anti‐HCV (113/142 or 80%vs109/166 or 66%P<0.01) and the patients with HCV RNA had a lower frequency of elevated aminotransferase levels than blood donors with HCV RNA (5/113 or 4%vs27/109 or 25%,P<0.00l). These results indicate that transfusion is a significant cause of HCV infection in patients on maintenance haemodialysis, and that these patients are prone to establish the HCV carrier st

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1994.tb00063.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARY.The aim of this study was to determine if using hepatitis C antibody (anti‐HCV) enzyme immunoassay version 2.0 (EIA2) in addition to version 1.0 (EIA1) increased the safety of the blood supply. Blood non‐reactive by anti‐HCV EIA1 was transfused in 1990‐92. Stored samples from 40098 units, donated prior to 13 March 1992 were later tested by EIA2. For donor units reactive for anti‐HCV by EIA2. a recombinant immunoblot assay (RIBA2) was also carried out. In 63 cases, recipients of transfusions which were EIAZ negative or EIA2 reactive were tested for anti‐HCV and elevated alanine aminotransferase (ALT) levels 9‐1 2 months after transfusion: pretransfusion anti‐HCV status of recipients was unknown. Among these multitransfused patients receiving units that were negative by both EIA1 and EIA2, 1/26 (4%) had anti‐HCV. Among transfusion recipients of units negative by EIA1, but who received at least one unit reactive by EIA2,4/37 recipients (11%) were anti‐HCV reactive (P = 0.59). For the recipients of EIA2 reactive blood, when the donor unit was RIBA2 non‐reactive. 0/23 recipients were reactive by anti‐HCV. Among the recipients of a RIBA2 indeterminate unit, 1/10 recipients had anti‐HCV, but for patients who received at least one RIBA2 reactive unit, 3/4 recipients had anti‐HCV (P = 0.0 3). Hence. second‐generation anti‐HCV testing detected additional units capable of transmitting hepatitis C that were not detected by first‐generation testing. However, RIBA2 is a more specific method than EM2 for determining

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1994.tb00064.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

SUMMARY.The product of the pre‐S plus S gene of hepatitis B virus appears to be more immunogenic in mice than the S‐gene product (HBsAg) alone. Therefore, we tested the immunogenicity in healthy adults of a hepatitis B vaccine containing the ‘middle protein’ gene product of pre‐S2 plus S (pre‐S vaccine). We compared the immunogenicity of three doses of the pre‐S vaccine with that of a commercially available recombinant hepatitis B vaccine (Recombivax‐HB®): 87 seronegative adults were randomized to receive 12 μg (group 1), 24 μg (group 2), or 48 μg (group 3) of the pre‐S vaccine or 10μg of Recombivax‐HB (group 4) by deltoid injection at 0, 1 and 6 months. Antibody to HBsAg (anti‐HBs) appeared after booster vaccination in 94% of vaccinees. Immunogenicity was best in recipients of 48 μg of the pre‐S vaccine and Recombivax‐HB, and geometric mean titres (GMT) for the pre‐S vaccine were higher than those for Recombivax‐HB only at the pre‐S vaccine dose of 48 μg (group 3). Antibody to pre‐S2 developed in 75% of the pre‐S2 vaccine recipients (not in Recombivax‐HB recipients) within 7 months. These findings indicate that the pre‐S vaccine is immunogenic in healthy adults but that a dose of 48 μg of the current formulation is required to equal or exceed the immunogenicity of currently available, recombinant S‐only vaccine. Studies in non‐responders to S‐only vaccines will be necessary to define an immunological advantage of the pre‐S vaccines, and additional assessments will be necessary to det

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1994.tb00065.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY