摘要:

SUMMARY.A large number of viruses are capable of inducing acute or chronic hepatitis. The syndrome of chronic hepatitis encompasses not only viral but also autoimmune liver diseases. The hepatitis C virus, and recently also the hepatitis D virus have been found to be associated with an array of autoimmune syndromes, diseases and markers of autoimmunity. The relationship of hepatotropic virus infection and the immune system leading to virus‐associated autoimmunity, and its distinction from genuine autoimmune disease represents a fascinating field of research. Clinically, the differentiation between autoimmune liver diseases, virus infection and virus‐associated autoimmunity is difficult and epidemiological evaluations have not come up with universally applicable and valid classification criteria. However, both autoimmune liver diseases and viral hepatitis can readily be diagnosed and distinguished through precise and molecularly determined immunological testing systems. The overlap of both, virus‐associated autoimmunity, is still at the centre of research activities aimed at establishing diagnostic and risk‐assessment criteria. Studies of molecular autoantigens and autoepitopes have begun to define the differences of the B‐cell response in autoimmune disease and virus‐associated autoimmunity. This provides data that may contribute to the safe application of therapeutic strategies as different as immunosuppression and interferon‐α (IFN‐α). The present review focuses on the clinical, epidemilogical and molecular aspects of these

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00081.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY.Duck hepatitis B virus (DHBV) belongs to the same virus family as the human hepatitis B virus (HBV). Domestic ducks infected with DHBV can be used as an animal model for chronic hepatitis B virus infection in therapeutic trials. In this study the antiviral effect of the guanosine analogue 2′,3′‐dideoxy‐3′‐fluoroguanosine (FLG) was triedin vivoon chronically DHBV‐infected ducks. The ducks were either congenitally infected, or inoculated with DHBV immediately post‐hatch. FLG was given as intraperitoneal injections twice daily, at different dosages. Serum DHBV levels were determined by DNA dot‐blot hybridization. A strong inhibition of serum DHBV DNA was observed with FLG doses down to 1 mg kg‐1day‐1. given for 7 to 10 days. With the corresponding thymidine analogue, 2′,3′‐dideoxy‐3′‐fluorothymidine; however, no inhibition was obtained. This difference may be due to different phosphorylation mechanisms. Independently of FLG dose, serum DHBV DNA returned to pretreatment levels within a few days after cessation of therapy. After a long‐term trial (FLG, 5mg kg‐1day‐1for 33 days), the same relapse of DHBV production was seen. Thus, FLG is an efficient inhibitor of DHBV replication, and is a candidate for treatment of HBV infections. However, the effect is transient, and therefore combination with other types

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00082.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY.A recombinant protein corresponding to part of the amino‐terminal domain of hepatitis B virus (HBV) polymerase was expressed inEscherichia coli.Antisera raised against this protein stained hepatocytes, from human liver biopsies, predominantly in the nucleus but some cytoplasmic staining was also observed. No staining was observed in hepatocytes from uninfected patients. Liver biopsies, taken from patients who were infected with human immunodeficiency virus (HIV) as well as HBV showed more intense staining with these antisera than that seen in patients who were infected with HBV alone. The staining pattern suggests that either the whole HBV polymerase protein, or a portion encoding the amino‐terminal domain, is translocated to the nucleus. This event may be an important early step in replication of the HBV gen

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00083.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY.A recently available assay to quantify serum viral load in hepatitis C virus (HCV) infection has been used to evaluate the effects of anti‐viral therapies. However, variability in HCV RNA levels in untreated patients with HCV infection has not yet been established. We therefore prospectively measured the biological fluctuations of HCV RNA in sera from untreated patients with chronic HCV infection. Sera were collected from seven patients at 8 am and 4 pm on the same day to assess the effect of diurnal variation, daily for 5 days in a further 10 patients, biweekly for 6 weeks in nine patients and monthly for 3 months in 11 patients. All patients had biopsy‐proven chronic liver disease with elevated alanine aminotransferase (ALT) values and had not received anti‐viral treatment. HCV RNA was measured blinded, in duplicate, using the quantitative branched (bDNA) amplification assay (Quantiplex™ HCV RNA. Chiron Co. Erneryville. CA) 36 of the 37 patients studied had measurable HCV RNA throughout the study. There was no significant correlation between HCV RNA levels and ALT values or histological activity. HCV RNA levels did not appear to vary significantly within any of the groups studied and there did not appear to be a change associated with diurnal variation. All individual patients demonstrated less than a threefold fluctuation in HCV RNA throughout the study period. Hence HCV RNA levels remain relatively stable in untreated individuals with chronic HCV infection. Changes of a magnitude of threefold (0.5 log) or greater in HCV RNA levels were not observed in untreated p

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00084.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY.Hepatitis C virus (HCV) RNA was tested for, and HCV genotypes determined, in 96 patients with haemophilia A in Japan. Of 88 patients aged ≥ 10 years, 74 (84%) were positive for HCV RNA at a frequency higher than that in patients aged less than 10 years (one of eight, 13%P<0.001). Genotype I/1a was detected in 30 (40%), II/1b in 12 (16%), III/2a in eight (11%), IV/2b in five (7%) and V/3a in 12 (16%); mixed infection with HCVof twodifferent genotypes was identified in the remaining nine (12%). This distribution was markedly different from that in 767 Japanese HCV carriers without haemophilia, in whom II/1b accounted for the majority (68.7%), I/1a was rare (0.5%), V/3a was absent, and mixed infection was observed rarely (1.3%). Mixed infection was transient in all of the seven haemophilic patients who were followed for 1 to 7 years. One of them was infected with genotype II/ 1b and an unclassifiable genotype, which showed nucleotide sequence similarity to genotype 4c from Zaire (82% homology in the El gene) and to 4a from Egypt (91% homology in a part of the NS5b region). In this patient, HCV of genotype II/1b disappeared while that of group 4 survived during a 4‐year observation period. These results indicate different epidemiology of HCV genotypes in Japanese haemophiliacs, attributable to HCV contaminating factor VIII imported in the past, and an increased opportunity in haemophiliacs for mixed infection with HCV of different genoty

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00085.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY.Virus and host factors have both been linked to the response to interferon treatment among patients with chronic hepatitis C but their relative importance and potential interactions are unclear. Hepatitis C virus genotype and level of viraemia were determined in pretreatment sera from 65 Australian patients treated with interferon‐α2b (IFN‐α2b). 3 MU tiw for 6 months. Hepatitis C viraemia was quantitated by a competitive reverse transcription‐polymerase chain reaction (RT‐PCR) method and genotype was determined by a line probe assay. By univariate analysis, there were positive associations between initial (short‐term) responses to IFN treatment and younger age (P= 0.004). absence of cirrhosis (P= 0.01). and injecting drug use as risk factor for infection (P= 0.05) but not gender, duration of infection, or level of viraemia. Genotype appeared to be important (P= 0.06) but failed to reach statistical significance. By multivariate analysis, absence of cirrhosis was the only significant independent predictor of treatment response (P= 0.01). Among initial responders, the factors associated with long‐term response were the pretreatment HCV RNA titre and the duration of infection. There was a close association between viral genotype, but not viral load, and the severity of liver disease. An interplay of factors determines the outcome of a 6‐month course of interferon treatment for hepatitis C. Severity of liver disease, but not the viral load, is the most crucial determinant of initial response to interferon, and histological severity appeared to be influenced by the viral genotype. The level of hepatitis C virus (HCV) viraemia and the duration of infection are independent determinants of long‐term response by affecting the relapse rate after int

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00086.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY.To evaluate the intrafamilial transmission of heptitis C virus and related risk factors among the Saudi population, two groups were investigated: 120 index patients with chronic liver disease and their 127 family contacts, and 220 blood donors who were anti‐HCV‐positive but with no chronic liver disease and their 91 family contacts. After a questionnaire on the risk factors for parenteral exposure, blood samples were obtained and tested for liver biochemistry and antibody to HCV (anti‐HCV) by a third‐generation enzyme immunoassay (UBI HCV HA4.0). Only two spouses of 20 index patients were anti‐HCV‐positive while the remaining 125 family contacts were anti‐HCV‐negative. None of the 91 family contacts of the 20 anti‐HCV‐positive blood donors was anti‐HCV‐positive. The two spouses were wives of index patients but had a history of blood transfusion on at least two different occasions. Our results clearly indicate the intrafamilial transmission of HCV is not the route of transmission of HCV among Saudis and our results argue against sexual transmission of hepatitis C virus despite a relatively lo

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00087.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

SUMMARY.A modification of a commercial assay for anti‐HEV to allow detection of specific IgM has been validated. Its use has shown that acute cases of HEV do occur in the UK. To date these have all been patients returning from highly endemic area

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1996.tb00088.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.tb00089.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY