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Hepatitis B and Other Viral Diseases
Pages 34-41

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From page 34...
... Others are not so easily managed: these viruses often mutate at a high rate in response to the defense mechanisms of the host immune system and cause persistent or chronic disease; viruses can hide in cells in the body or in parts of cells that may not be readily accessible to drugs aimed at killing these organisms; and viruses develop resistance to drugs by changing or mutating with time. Intense research in the last decade has yielded encouraging results in the war against these viruses' but although some persistent viral infections Allah ~~ uTV earl 1^ ~_~ ~ ~ ~ do /T Tom TN ~ 1_ ~ 1 · .
From page 35...
... . Fewer than 5 percent of adults will develop chronic liver disease, often with only minor complaints of fatigue, joint pains, poor appetite and abdominal pain Children who acquire HBV infection from their mothers are often asymptomatic and develop pro Hems only alter prolonged infection.
From page 36...
... An important feature noted in studies of the natural history of chronic HBV infection is that of the spontaneous loss of viral replication (indicated by the disappearance from the blood of HBV envelope antigen, a viral protein highly correlated with active infection, and the loss of HBV DNA in serum)
From page 37...
... Herpes simplex virus is controlled effectively with the oral nucleoside analog acyclovir, and CMV infection is treated effectively with the intravenously administered nucleoside analogs ganciclovir and phosphonoformate (foscarnet)
From page 38...
... THE FLARE PHENOMENON Immunological activation with T-cell destruction of infected hepatocytes has been the postulated explanation for the rise in ALT and/or AST levels; the so-called flare phenomenon, seen in association with spontaneous and therapeutically induced clearance of virus. In either circumstance, this rise in enzyme levels is frequently accompanied by conversion from a replicative state (HBV DNA positive)
From page 39...
... Moreover, the information regarding the flare associated with nucleoside analogs is derived from very few cases. Since these drugs have no known immunomodulatory properties, the explanation for the phenomenon occurring in these circumstances is that the drug lowers HBV DNA levels to a point where host immune mechanisms can effectively clear the remaining virus, with associated necrosis of infected hepatocytes.
From page 40...
... , and rash. All of the agents approved by the FDA for use against the human immunodeficiency virus are nucleoside analogs, most of which were originally developed as drugs to potentially treat cancer.
From page 41...
... Elevations in ALT or AST in patients being treated for HBV infection are thus open to conflicting interpretations - indicating either successful therapy or a toxic effect of the liver. Finally, we have briefly reviewed what was known about toxic effects produced by nucleoside analogs other than FlAC and FlAU, in part because some have suggested these effects should have provided ample warning that FlAU would produce dangerous effects and in part because many of the subjects in the trials we review here took these drugs before, during or after their FlAU treatment, confounding interpretation of adverse events.


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