摘要:

SUMMARY.Hepatitis delta virus (HDV) is a unique viroid‐like human pathogen that is always associated with hepatitis B infection. Replication of HDV involves the transcription of genomic RNA, probably by the host RNA polymerase II, by a rolling circle mechanism followed by self‐cleavage and self‐ligation. Editing of antigenomic RNA, possibly involving the enzyme adenosine deaminase, generates two functionally distinct forms of delta antigen. The molecular basis for HDV pathogenicity remains unce

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00090.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY.We have studied the proliferation and CD40 antigen expression of lymphocytes, and the cytotoxicity to monocytes, of antisense phosphorothioate oligodeoxynucleotides complementary to the SP II promoter of HBV mRNA (sequence I) and the X gene (sequence II) in patients with chronic hepatitis B. The oligo sequence I stimulated proliferation of both T and, to a lesser extent, B cells. The percentage of cells expressing CD40 in T and B cell co‐cultures increased from 4.2% to 13.8% after oligo stimulation in patients, while it increased from 4.7% to 48.6% in healthy controls. The sense sequence (sequence III) of the X gene also enhanced the expression of CD40 antigen in patients with hepatitis B. The proportion of CD40 cells (26%) in a resting B‐cell preparation from hepatitis B patients decreased to zero after a 5‐day culture with sequence I, but IgG levels in the culture supernatant increased. The cytotoxic properties of monocytes were not influenced by the oligos. These findings indicate that antisense oligos against hepatitis B virus (HBV) have mitogenic effects on the proliferation of human lymphocytes in a non‐specific manner and may activate T cells to express CD40

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00091.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY.The precore stop‐codon variant of hepatitis B virus (HBV) has been associated with fulminant hepatitis but is also found in patients with persistent infection and chronic hepatitis. We have examined the possibility that the severe outcome of infection in patients with fulminant disease may be a result of additional genomic variation. We sequenced the entire HBV genome from three patients of Greek and one patient of Chinese origin with fulminant hepatitis, and from two patients with hepatitis B e antigen (HBeAg) positive chronic infection from the same regions, using direct sequencing of amplified viral DNA. Three of the fulminant cases were infected with the precore stop‐codon variant (HBeAg negative) and the fourth with the wild‐type (HBeAg positive) virus. We compared sequences from our four fulminant isolates, and an additional fulminant isolate reported by others, with HBeAg positive carriers from the same regions and 12 published HBV genomes. There was a higher number of nucleotide and amino‐acid substitutions throughout the HBV genome in the precore variant fulminant sequences than in the wild type. A cluster of mutations previously identified in the X region (126–132) in sequences reported in Japanese patients and encompassing the Enhancer II‐Core Promoter region (1751–1768), were not found in our patients. We conclude that although there are no changes common to all sequences of HBV isolates from fulminant cases, some of these changes are in recognizedcis‐acting regulatory elements, whilst others are in the immediate vicinity of such elements. The effect of these mutations on viral genome transcription must no

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00092.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY.Chronic infection with the hepatitis C virus (HCV) may lead to a variety of hepatic lesions from benign inflammation to liver cancer, but the relationships between infection and development of liver disease are poorly understood. To assess whether virus type and load are of pathogenetic importance, 197 Italian carriers with various hepatic lesions were investigated consecutively. Of these, 187 (95%) patients had serum HCV RNA, by reverse transcription‐polymerase chain reaction (RT‐PCR) with a median level of 1003 × 103genomic equivalents ml‐1according to the branched‐DNA assay (b‐DNA). One hundred and seven patients (54%) had serotype 1, 22 (11%) had serotype 2, 9 (5%) had serotype 3, 17 (9%) had mixed serotypes and 42 (21%) had no specified serotype. One hundred and thirty four patients were also tested for genotype. The genotype distribution was as follows: 17 (13%) had genotype 1a; 67 (50%) 1b; 29 (22%) 2a; 12 (9%) 3a; 3 (2%) had genotype 1 not classified (NC); 3 (2%) had genotype 2 NC; 2 (1.4%) had genotype 4 and 1 (1%) had mixed genotype la + 3a. No virus type was associated with any particular histological diagnosis and all were equally distributed between progressive and non‐progressive liver disease groups. Serum HCV‐RNA levels were similar in the liver diseases groups. By analogy to hepatitis B, there was no direct correlation between type and level of viraemia and the severity of the underlyin

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00093.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY.This open label study was initiated to assess the safety and efficacy of lymphoblastoid interferon‐α (IFN‐α) and thymosin α1(Tα1) in the treatment of 11 patients with chronic hepatitis B, who had failed to respond to standard IFN‐α2b therapy, and in four interferon naive patients. These fifteen hepatitis B surface antigen (HBsAg) positive and serum hepatitis B virus (HBV) DNA positive patients were given Tα1(1 mg) subcutaneously (sc) on 4 consecutive days. Low‐dose lymphoblastoid IFN‐α (3 MU) was administered intramuscularly (IM) on the fourth day. Beginning with the second and for the subsequent 25 weeks, patients self‐administered Tα1twice weekly in the morning followed, 12 h later, by 3 million units (MU) lymphoblastoid IFN‐α. Patients were followed‐up for 12 months. Nine (60%) of the 15 patients, including six (55%) of the 11 patients previously treated with IFN‐α2b, responded by losing serum HBV DNA and normalizing alanine aminotransferase (ALT) values. Six of the nine responders seroconverted to HBsAg negativity. Significant improvements in the Knodell histological activity index were observed in the responders and no significant adverse effects were observed. Combination low‐dose lymphoblastoid IFN‐α and Tα1treatment may provide a safe and potentially effective therapeutic approach in chronic hepatitis B. These results require confirmation in fut

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00094.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY.Developed western countries are considered to be relatively free from endemic foci of hepatitis E virus (HEV) infections. The aim of this study was to assess the seroepidemiology of HEV in north‐east Italy. Of the 2361 individuals studied 1889 were representative of the general population and 472 were from groups at high risk for viral infections: 279 drug users and 193 patients on chronic haemodialysis. All sera were tested for hepatitis C virus antibody (HCVAb), human immunodeficiency virus antibody (HIVAb) and for hepatitis B virus (HBV) serology. Two solid‐phase enzyme‐linked immunosorbent assays (ELISA) were used to study the seroepidemiology of HEV IgG, the first (using recombinant antigens) for screening, the second (using synthetic peptides) for confirmation of initially reactive samples. The prevalence of circulating hepatitis E virus antibody (HEVAb) was 2.6% in the open population, 5.4% among drug users and 9.3% among patients on chronic haemodialysis. In the open population a positive relationship between age and prevalence of HEVAb was observed. A relationship between presence of HEVAb and serological evidence of previous HBV or HCV infections was also observed in this study. It was concluded that HEV infections are present in north‐east Italy and are more frequent among subjects at risk for blood‐borne viral infections. The positive correlation, observed in the open population, between age and prevalence of HEVAb suggests the presence of a coho

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00095.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY.The seroprevalence of antibodies against hepatitis E virus (HEV) and hepatitis C virus (HCV) was investigated in Saudi children with sickle cell anaemia (SCA) (50 patients: 28 boys, 22 girls; age range 2–14 years) and P‐thalassemia major (28 patients: 12 boys. 16 girls; age range 2–12 years). The SCA patients were from the Gizan area (South) while the thalassemics were from the Riyadh area (Central province). The prevalence of hepatitis E virus antibody (HEVAb) in patients with SCA (18.0%) and in those with β‐thalassemia major (10.7%) was higher than in the control groups (5.5% and 2.8%) but this did not reach the level of statistical significance. In contrast to the situation with HEV, hepatitis C virus antibody (HCVAb) positivity was significantly higher in patients with SCA (16.0%) and in thalassemics (57.1%) than in the respective control groups. Although the difference in HEV seropositivity between P‐thalassemia major, SCA patients and their respective controls is not statistically significant, the possibility of blood‐borne HEV in the Saudi population cannot be excluded. Further investigations using HEV‐specific polymerase chain reaction techniques are required to confirm whether transmission of HEV through blood preparations or transfusi

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00096.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY.Recovery of hepatitis C virus (HCV) RNA, after variable time intervals from collection, was assessed using a closed‐tube system for collection, separation and transport (SST(tm)tubes). Blood from four hepatitis C‐infected patients was collected in 12 SST(tm)tubes and centrifuged within 1 to 3 h of collection. Tubes were then left 0, 8, 12, 24. 48 and 72 h at room temperature and at 4°C before removing serum. Hepatitis C virus RNA levels were measured by quantitative polymerase chain reaction (PCR) using the AMPLICOR HCV MONITOR(tm)assay. Hepatitis C virus RNA levels in these samples were stable for at least three days at both temperatures. Polymerase chain reaction signals never decreased by more than 0.5 log. The reproducibility of the assays showed that the quantitative PCR method can be used with the storage conditions tested here. Our data suggests that processing blood in SST(tm)tubes may be very useful in following hepatitis C virus RNA titres in infected patients, especially those receiving treat

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00097.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY.This is the first double‐blind controlled study of famciclovir, an oral antiviral agent, as potential therapy for chronic hepatitis B virus (HBV) carriers. A fall of more than 90% in HBV DNA levels was noted in six of 11 evaluable patients treated with a 10 day course of oral famciclovir. Further studies with more prolonged therapy are ongoin

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00098.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY