摘要:

Summary.Hepatitis B virus (HBV), the causative agent of type B hepatitis in humans, is the prototypic member of the hepadnaviridae, a family of small enveloped DNA‐containing viruses with pronounced host and tissue specificity. This property has greatly hampered progress in understanding the initial events of infection, i.e. attachment, penetration and uncoating. After the discovery, originally made with the duck hepatitis B virus (DHBV), that hepadnaviruses replicate by reverse transcription, DNA transfection of cloned wild‐type and mutant HBV genomes into cell lines supporting virion formation has revealed the molecular mechanisms of the late steps of the infectious cycle in some detail. During the last few years, such studies have emphasized the differences between hepadnaviral and retroviral replication. Very recent research, however, indicates that the border separating the two viral families may not be as strict as previously thought. In this article, we will briefly summarize the pertinent differences, and will then focus on the new data, with particular emphasis on the initiation of reverse transcript

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00047.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.We have previously increased the efficiency of hepatitis B virus (HBV) infection of human hepatocytes in vitro by using polyethylene glycol. After further documenting by neutralization experiments, thisin vitroinfection, we used this model to define new culture conditions that would maintain stable episomal replication for several weeks. We found that in the presence of 10% porcine serum and 2% dimethyl sulphoxide (DMSO), high‐density cultures survived more than 3 months, while addition of hydrocortisone instead of DMSO resulted in survival of less than 1 month. HBV episomal replication was maintained without any evidence of viral integration into the host genome. The maintenance of HBV replication was demonstrated by: first, stability of the covalently‐closed‐circular DNA in the nucleus and relaxed circular and single‐stranded replicative intermediates in the cytoplasm; second, detection of two major transcripts of 3.5 and 2.1–2.4 kb corresponding to the pregenomic and surface genes respectively; and third, continuous secretion of mature viral particles in the supernatant of infected cells. We showed that under these culture conditions, hepatocytes were blocked in the G1 phase of the cell cycle and did not spontaneously proliferate. Upon hepatocyte growth factor (HGF) stimulation, however, the ability of hepatocytes to divide was demonstrated and was compared in infected and non‐infected cells. No change in proliferative capacity and no variation in c‐mycand c‐junlevels could be found. Hepatocyte survival was not modified in infected cells, confirming that HBV is not cytopathic for normal human hepatocytes. These new culture conditions represent substantial progress in the study of HBV‐host

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00048.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.Quantification of hepatitis C virus RNA in liver tissue is likely to be useful in the study of the natural history, pathogenesis, progression and treatment of hepatitis C virus‐associated liver disease. Quantitative measurements of hepatitis C virus RNA in liver biopsy samples using the branched DNA (bDNA) signal amplification assay were carried out. The aims of this study were threefold: first, to assess the level of hepatitis C virus RNA in biopsy samples from the right and left lobes of the liver; second, to evaluate the correlation between hepatitis C virus RNA levels in serum and liver; and third, to investigate the relationship between serum and liver hepatitis C virus RNA levels and the severity of hepatic histology in non‐cirrhotic patients with chronic hepatitis C. There was a strong correlation (r= 0.92,P<0.01) between hepatitis C virus RNA levels in the right and left lobes of the liver as well as a strong correlation between hepatitis C virus RNA levels in liver and serum (r= 0.82,P<0.01). However, there was no significant correlation between the severity of hepatic histology and levels of hepatitis C virus RNA in serum and liver among patients with chronic active hepatitis classified according to Knodell's hepatic activity index (KI). Our results indicate that hepatitis C virus RNA quantification from a single liver biopsy is representative of both lobes in patients with chronic hepatitis, and suggest that serum hepatitis C virus RNA levels are a meaningful reflection of hepatitis C virus RNA levels in the li

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00049.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.Therapy with ribavirin for 6–12 months is associated with decreases in serum aminotransferases in some patients with chronic hepatitis C. We have assessed the practicality and safety of prolonged therapy with ribavirin. Six patients with chronic hepatitis C were given 1000–1200mg of ribavirin daily for 24 months. Serum aminotranferases and hepatitis C virus (HCV) RNA levels were monitored during and after therapy. Liver biopsies were carried out before and at the end of treatment. With therapy, mean serum alanine aminotransferase (ALT) levels fell from 161 U/L to 45 U/L at 12 months and to 39 U/L at 24 months. HCV RNA levels did not change. Liver histology improved in five and was unchanged in one patient. When therapy was stopped, aminotransferases rose to pretreatment levels. Side effects included mild fatigue and headaches. Two patients developed gallstones during therapy, perhaps caused by the chronic haemolysis that occurred in all patients. In conclusion, prolonged therapy with ribavirin can result in sustained improvements in serum aminotransferases and hepatic histology in a proportion of patients with chronic hepatitis C. Ribavirin therapy does not cause decreases in viraemia and, therefore, probably must be continued indefinitely to provide lasting benefit. The advantages of such therapy must be weighed against possible long‐term side‐

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00050.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.Chronic hepatitis B viral infection is common in human immunodeficiency virus (HIV) carriers, but the effectiveness of interferon therapy is still unknown. We report the results of a long‐term pilot study of five patients, who were infected with HIV and chronic hepatitis B, treated by interferon. Five males co‐infected with HIV and hepatitis B virus (HBV) (mean age 2 7 years) were given a 6‐month course of interferon (IFN)‐α2b 5 million units (MU) three times weekly. On initiating the treatment, their CD4 lymphocyte count was 340–553 mm‐3, their CDC stage was IIa‐III; all had histologically proven chronic hepatitis, with Knodell's score ranging from 6–10, and active HBV replication (HBV DNA and hepatitis B e antigen (HBeAg) were detectable). There was no associated hepatitis δ virus (HδV) or hepatitis C virus (HCV) infection. Follow‐up was for 53 months on average (24–74 months). After the treatment, hepatitis B e antibody (HBeAb) and hepatitis B s antibody (HBsAb) sero‐conversion was observed in one patient, HBeAb seroconversion alone in two patients, HBV DNA was absent from serum in three patients, and HBV DNA significantly decreased in one patient. The serum alanine aminotransferase (ALT) activity was normal in four patients. Histological improvement was obtained in four patients. The HIV stage remained unchanged in all patients during the whole follow‐up. These preliminary results suggest that interferon can be successfully used in immunocompetent HIV carriers with chronic hepatitis B as well a

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00051.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.Hepatitis C virus (HCV) genotype 4 is the principal HCV genotype found in Egypt and the Middle East. Little is known concerning its propensity to cause disease and the frequency with which infected individuals respond to interferon‐α (IFN‐α). We have investigated the response to treatment in a cohort of 100 chronic hepatitis C patients infected with genotype 4. All patients had biopsy‐proven chronic active liver disease. Each was treated with 3 million units (MU) IFN‐α, thrice weekly. Response was monitored, in 92 patients who completed treatment, by alanine aminotransferase (ALT) measurements and by polymerase chain reaction (PCR) for HCV. ALT levels remained abnormal in 64 patients during treatment (69.6%). Of the 28 patients who showed a biochemical response during treatment (30.4%), 18 maintained this over the 6‐month post‐treatment period. Amongst the sustained biochemical responders, HCV RNA was cleared from serum in only four of the 18 (22.2%) in this period. Histological improvement was observed in 26/51 (50.9%) of the patients who had a second biopsy.Hence, patients infected with HCV genotype 4 show a poor response to IFN‐α therapy compared with genotypes 2 and 3, but a similar response to IFN‐α compared with those infected with type 1b HCV. These findings have major implications for treatment strategies in the Middle East, including Egypt, where HCV genotype 4 i

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00052.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.The predictive value of IgM antibodies to hepatitis C virus core antigen (HCcAb) is controversial. We studied 79 patients undergoing interferon‐α (IFN‐α) treatment and we found that detectable levels of IgM HCcAb could predict breakthrough on trea

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00053.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Summary.A ligase chain reaction (LCR®)‐based approach to detect hepatitis B virus (HBV) DNA in peripheral blood mononuclear cells (PBMC) is described. Using this new amplification technique, we determined semi‐quantitatively the amount of a short HBV S‐gene fragment in PBMC lysates of 25 patients with different forms of chronic hepatitis (group A (n= 8), hepatitis B s antigen (HBsAg)+/hepatitis B e antigen (HBeAg)+; group B (n= 9), HBsAg+/HBeAg‐; group C (n= 8), HBsAg‐/HBeAg‐). The LCR results were compared with the findings obtained with polymerase chain reaction (PCR) amplification of three distinct HBV gene regions (preS1/2, S and C) and related to the serological profiles of the patients. Depending on the primer pair used for PCR amplification, sensitivity of HBV LCR in PBMC was equivalent or slightly superior to PCR. The highest positivity rate for HBV DNA was observed in the HBeAg+ and HBV DNA seropositive group (8/8) and was lower in the other patient groups B (4/9) and C (1/8). Interestingly, HBV gene sequences could also be detected in the lymphocytes of an HBsAg negative patient and in two patients from group B who were both negative for serum viral particles by PCR. The rapid LCR® procedure represents a reliable alternative to PCR for the sensitive detection of HBV DNA in PBMC samples. In combination with the automated IMx™‐system the new amplification technique may be routinely used for screening for HBV in whole blood samples and thus may help to better evaluate the risk of HBV reinfection in liver tran

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00054.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00055.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY