摘要:

Summary.It has been shown that hepatitis C virus (HCV) populations in infected individuals are composed of quasispecies with diverse mutations. The analysis of these variants may reveal mechanisms of the persistence of HCV infection, carcinogenesis and resistance to antiviral therapy. Recently, genetic features of interferon‐resistant HCV have been elucidated through the analysis of interferon‐resistant quasispecies, making it possible to predict interferon efficacy by detecting interferon‐resistant st

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00040.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary.An asialoglycoprotein‐based DNA delivery system containing an antisense oligo DNA against the polyadenylation region and adjacent upstream sequences of woodchuck hepatitis virus (WHV) was prepared. Experimental woodchucks were inoculated neonatally with the woodchuck virus 23 weeks before initiating the study, and all animals subsequently developed hepatitis as evidenced by the presence of measurable levels of circulating viral DNA. Animals were injected intravenously (i.v.) with asialoorosomucoid (AsOR)‐poly‐l‐lysine complexes containing 0.1 mg kg‐1antisense DNA for five consecutive days. Levels of surface antigen did not differ substantially between treated and control animals. However, intravenous administration of complexed antisense DNA significantly decreased viraemia, as shown by a five‐to 10‐fold decrease in circulating viral DNA 25 days post treatment. The decline lasted for at least 2 weeks, after which there was a gradual increase in DNA levels. Antisense DNA alone or a complex containing a random oligo DNA of the same size and linkage failed to have any significant effect on viral DNA levels. We conclude that antisense oligo DNA can be targeted to the liver in vivo, resulting in a substantial and prolonged decrease in viral DNA levels in WHV‐infe

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00041.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary.To assess the effects of prednisone and interferon on the distribution of hepatitis B virus (HBV) precore mutants, nine hepatitis B e antibody (HBeAb)‐positive patients with HBV chronic infection were studied. Patients were treated with prednisone (30 mg day‐1for 4 weeks, followed by 20 mg day‐1for 2 weeks and by 10 mg day‐1for 1 week), followed by recombinant interferon‐α (15 MU thrice per week) for 6 months, without a clearance period. The HBV precore region was amplified by polymerase chain reaction (PCR) and distribution of the precore mutants was determined by hybridization of PCR products. Moreover, the glucocorticoid‐responsive element (GRE) was sequenced to determine whether changes in the sequence were produced at the end of prednisone treatment. During prednisone treatment, changes in alanine transaminase (ALT) were observed in only two patients, in whom ALT decreased to nearly normal values. In three patients ALT normalized at the end of interferon treatment. At baseline, wild‐type HBV alone was detected in one patient, while seven patients were infected by a mixture of wild‐type and precore mutants, predominantly wild type. At the end of prednisone treatment, two patients were infected by only wild‐type HBV. The proportion of precore mutants decreased in three cases, while no changes were observed in three. At the end of interferon treatment, the precore mutant proportion decreased in the three responders, while tending to increase or remain unchanged in the rest. No significant changes in GRE sequence were found as a result of prednisone treatment. Our results would appear to confirm the role of the immune system in the selection

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00042.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary.Hepatitis C virus (HCV) is an RNA virus with the NS5B gene encoding an RNA‐dependent RNA polymerase. Interferon‐α (IFN‐α) is effective against HCV and its effect is believed to be related to its antiviral activity. To determine whether sequence variations of the HCV NS5B region correlate with response to IFN therapy, pretreatment serum samples from 40 patients with chronic HCV infection who were subsequently treated with IFN (≥3 MU thrice weekly for 24 weeks) and had well‐characterized biochemical responses were studied. Reverse transcription‐polymerase chain reaction (RT‐PCR) was performed to generate an approximately 365‐bp fragment from which nucleotide sequence and genotypes were determined. By comparing the nucleotide sequences and the encoded amino acid sequences of samples from each group, no response group‐specific nucleotide or encoded amino acid substitution was identified. Most of the substitutions identified were synonymous (usually by changes at the third position of the codon). These data suggest that these substitutions were selective rather than spontaneous events. Of the few non‐synonymous substitutions identified, none was correlated with subsequent response to IFN, either withi

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00043.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary.The genotypes of hepatitis C virus (HCV) were investigated in 28 Saudi patients (21 males, seven females; age range 23–68 years; mean 45.0 years) with histologically proven chronic hepatitis (13 chronic active hepatitis and 15 liver cirrhosis) and in 32 Saudi patients with chronic renal failure maintained on haemodialysis (22 males, 10 females; age range 18–60 years; mean 40.0 years) who also had liver disease due to HCV. Among the 28 patients with chronic liver disease genotype 4 was the predominant one (60.7%), followed by types 1b (21.4%), 1a (14.3%) and 2a (3.6%). The distribution of genotypes was similar in patients with chronic active hepatitis to those with liver cirrhosis. Among the 32 patients with chronic renal failure and maintained on haemodialysis, genotype 4 was also the dominant type (55.0%), followed by 1a (25.0%), 1b (21.9%) and 2a (3.1%). In all categories studied the prevalence of genotypes between males and females was the same. As our patients were selected from various regions of Saudi Arabia, we believe that genotype 4 is the predominant one throughout the whole king

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00044.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary.The distribution of hepatitis C virus (HCV) genotypes was investigated in 89 HCV‐infected Turkish patients. Blood samples were collected from haemodialysis patients (n= 45), chronic liver disease (CLD) patients (n= 38), acute non‐A, non‐B (NANB) hepatitis patients (n= 2) and blood donors (n= 4). HCV RNA sequences were amplified in the 5″ non‐coding region and were typed by restriction fragment length polymorphism analysis. The predominant genotype was 1b (75.3%), followed by 1a (19.1%), 2 (3.4%) and 4 (2.2%). While there was no significant difference in the distribution of HCV genotypes with respect to age, sex, transfusion history, alanine aminotransferase levels or liver histology (in the CLD group), type 1a‐infected patients were younger than type 1b‐infected patients (P<0.05) in the haemodialysis group. Serological reactivity to recombinant HCV proteins was assessed in 58 samples using the Chiron RIBA‐2 assay. The reactivity of samples from patients infected with type 1b with 5–1–1 and c100 antigens was significantly lower (P<0.05) than the reactivity of samples from those infected with type 1a. These results, together with the results of two previous studies, indicate that HCV genotypes 1, 2, 3 and 4 are prevalent in different frequencies in the Turkish population. Determination of the genotype distribution of HCV in a geographical area may provide important clues for studying the epidemiology, transmission and pathogenesis of HCV‐related diseases and may also aid in improving serological assays to

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00045.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary.The clinical and serological course of a haemophilic baby who was transfused with 160 ml of blood containing the hepatitis C virus (HCV) (0.70 Meq. ml‐1) on the sixth post‐natal day is described. He is the infant of an HCV‐negative mother. One month after the transfusion, there was a marked increase in HCV RNA and a small amount of HCV antibody was detected. This case provides evidence that a newborn is capable of producing HCV antib

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00046.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY