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1、Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Academic Press,2000.,Chapter 7:Pathogenesis,Slide,*,/47,Pathogenesis,90%of cases).,Fulminant hepatitis,developing quickly&lasting a short time,causing liver failure&a mortality rate of

2、 approximately 90%(1%of cases).,Chronic infection,leading to the establishment of a carrier state with virus persistence(about 10%of cases).,Academic Press,2000.,HBV&Hepatocellular Carcinoma(HCC),There are approximately 350 million chronic HBV carriers worldwide.,The total population of the world is

3、 approximately 6 billion,therefore about 5%of the world population is persistently infected with HBV.,All of these chronic carriers of the virus are at 100-200 times the risk of non-carriers of developing HCC.,HCC is a rare tumour in the West,where it represents 2%of fatal cancers.,Most cases which

4、do occur in the West are alcohol-related&this is an important clue to the pathogenesis of the tumour.However,in South-East Asia&in China,HCC is the most common fatal cancer,causing about half a million deaths every year.,The virus might cause the formation of the tumour by three different pathways:d

5、irect activation of a cellular oncogene(s),trans-activation of a cellular oncogene(s),or indirectly via tissue regeneration.,Academic Press,2000.,HBV&Hepatocellular Carcinoma(HCC),Academic Press,2000.,HBV&Hepatocellular Carcinoma(HCC),As with EBV&Burkitts lymphoma,the relationship between HBV&HCC is

6、 not clear cut:,Cirrhosis(a hardening of the liver which may be the result of infections or various toxins,e.g.alcohol)appears to be a prerequisite for the development of HCC.,It would appear that chronic liver damage induces tissue regeneration&that faulty DNA repair mechanisms result eventually in

7、 malignant cell transformation.,Unrelated viruses which cause chronic active hepatitis,such as the flavivirus hepatitis C virus(HCV),are also associated with HCC after a long latent period.,A number of co-factors,such as aflatoxins&nitrosamines,can induce HCC-like tumours in experimental animals wit

8、hout virus infection.Such substances could also be involved in human HCC.,There is no consistent evidence for the integration of the HBV genome or even the persistence of particular HBV genes(e.g.the X gene,which encodes a trans-activator protein functionally analogous to the HTLV tax protein)in tum

9、our cells.,Academic Press,2000.,New&Emergent Viruses,There are numerous examples of such viruses which appear to have mysteriously altered their behaviour with time,with significant effects on their pathogenesis.,One example of this phenomenon is poliovirus.,It is known that poliovirus&poliomyelitis

10、 have existed in human populations for at least 4,000 years.,For most of this time,the pattern of disease was endemic rather than epidemic,i.e.a low,continuous level of infection in particular geographical areas.,During the first half the twentieth century,the pattern of occurrence of poliomyelitis

11、in Europe,North America&Australia changed to an epidemic one,with vast annual outbreaks of infantile paralysis.,Although we do not have samples of polioviruses from earlier centuries,the clinical symptoms of the disease give no reason to believe that the virus changed substantially.,Why then did the

12、 pattern of disease change so dramatically?,Academic Press,2000.,Poliomyelitis,In rural communities with primitive sanitation facilities,poliovirus circulated freely.,Serological surveys in similar contemporary situations reveal that more than 90%of children of 3 years of age have antibodies to at l

13、east one of the three serotypes of poliovirus.,Even the most virulent strains of poliovirus cause 100-200 subclinical infections for each case of paralytic poliomyelitis seen.In such communities,infants experience subclinical immunizing infections while still protected by maternal antibodies-a form

14、of natural vaccination.,The relatively few cases of paralysis&death which do occur are likely to be overlooked,especially in view of high infant mortality rates.,Academic Press,2000.,Poliomyelitis,During the nineteenth century,industrialization&urbanization changed the pattern of poliovirus transmis

15、sion.,Dense urban populations&increased travelling afforded opportunities for rapid transmission of the virus.,In addition,improved sanitation broke the natural pattern of virus transmission.,Children were likely to encounter the virus for the first time at a later age&without the protection of mate

16、rnal antibodies.,These children were at far greater risk when they did eventually become infected&it is believed that these social changes account for the altered pattern of disease.,Fortunately,the widespread use of poliovirus vaccines has since brought the situation under control in industrialized countries,&global eradication of poliovirus is anticipated by 2005.,Academic Press,2000.,New&Emergent Viruses,There are many examples of the epidemic spread of viruses caused by movement of human pop