Hepatitis, viral

Viral hepatitis refers to the clinically important hepatotropic viruses responsible for hepatitis A (HAV), hepatitis B (HBV), delta hepatitis, hepatitis C (HCV), and hepatitis E. 

HAV infection primarily occurs through transmission by the fecal-oral route, person-to-person, or by ingestion of contaminated food or water. The incidence of HAV correlates directly with low socioeconomic status, poor sanitary conditions, and overcrowding. Rates of HAV infection have increased among international travelers, injection drug users, and men who have sex with men. 

HAV infection usually produces a self-limited disease and acute viral infection with a low case-fatality rate, and confers lifelong immunity. 

The disease exhibits three phases incubation (averaging 28 days, with a range of 15 to 50 days), acute hepatitis (generally lasting 2 months), and convalescence. Most patients have full clinical and hiochemical recovery within 12 weeks. Nearly all individuals will have chnical resolution within 6 months of the infection. HAV does not lead to chronic infections. 

The diagnosis of acute HAV infection is based on clinical criteria of acute onset of fatigue, abdominal pain, loss of appetite, intermittent nausea and vomiting, jaundice or elevated serum aminotransferase levels, and serologic testing for immunoglobulin (Ig) G anti-HAV. 

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Obviously the best treatment for cirrhosis is removal of the injurious event. In the case of viral hepatitis, viral load can at least be temporarily reduced with anti-viral agents such as lamivudine, ribavirin and/or IFNa [76]. Unfortunately, complete removal of the injurious event is frequently not possible. Moreover, by the time cirrhosis is diagnosed the fibrotic process has usually progressed beyond the point of no return and removal of the injurious event will have little effect. Successful pharmacological treatment to reverse the fibrotic... 

There is evidence supporting a role for hepatic damage by intravascular proteases in the pathogenesis of neonatal hepatic disease, as reviewed in the previous edition of this textbook,The AAT deposits in the hepatic endoplasmic reticulum do not bind normally to calnexin, one of the chaperones for protein synthesis and release it is known that proteolytic enzymes reduce the activity of intracellular, membrane-bound proteins involved in metabolic processes. An additional component in congenital and neonatal hepatic disease may be exposure to maternal estrogens, which increase susceptibility to damage from hepatitis viral infections and some toxins. 

AndriuUi A, Festa V, Leandro G, Rizzetto M. Usefulness of a liver biopsy in the evaluation of patients with elevated ALT values and serological markers of hepatitis viral infection An AIGO study. Dig Dis Sci 2001 46 1409-15. 

Paya CV. Prevention of fungal and hepatitis viral infections in liver transplantation. Clin Infect Dis 2001 33(suppl l) S47-52. 

McDonald JA, Harris S, Waters JA, et al. Effect of human immunodeficiency virus (HIV) infection on chronic hepatitis B hepatic viral display. / Hepatol. 1987 4 337-342. 

Inactivation and Removal of Viruses. In developing methods of plasma fractionation, the possibiHty of transmitting infection from human vimses present in the starting plasma pool has been recognized (4,5). Consequentiy, studies of product stabiHty encompass investigation of heat treatment of products in both solution (100) and dried (101) states to estabHsh vimcidal procedures that could be appHed to the final product. Salts of fatty acid anions, such as sodium caprylate [1984-06-17, and the acetyl derivative of the amino acid tryptophan, sodium acetyl-tryptophanate [87-32-17, are capable of stabilizing albumin solutions to 60°C for 10 hours (100) this procedure prevents the transmission of viral hepatitis (102,103). The degree of protein stabilization obtained (104) and the safety of the product in clinical practice have been confirmed (105,106). The procedure has also been shown to inactivate the human immunodeficiency vims (HIV) (107). 

The early immunoglobulin products prepared by cold-ethanol fractionation were found to be free from transmitting hepatitis infection (106,108) this was not the case with products prepared by alternative methods (109). Subsequentiy, some batches of intravenous immunoglobulin transmitted hepatitis infection (110), emphasizing the importance of estabHshing vaHdated procedures for dealing with potential viral contaminants (111). 

FIAC also strongly inhibits HCMV and Epstein-Barr vims (EBV) in vitro the two vimses known not to induce a specific viral thymidine kinase for their repHcation. However, HCMV may stimulate cellular kinases that can anabolize FIAC to its 5 -triphosphate, which specifically inhibits the HCMV-encoded DNA polymerase. This selective activity suggests that FIAC should be evaluated against HCMV infections. FIAC-ttiphosphate incorporated into DNA has shown strong in vitro activity against the DNA polymerases of human hepatitis B vims (HBV) and of woodchuck hepatitis vims (WHV) (37). 

Ara-A-5 -monophosphate [29984-33-6] (ara-AMP), C2QH24N OyP, is more water-soluble than ara-A, and therefore can be used in higher dosage during the first hours of treatment of viral infections. Ara-AMP has been shown to decrease virion-associated DNA polymerase concentrations in ground squirrels carrying ground squirrel hepatitis vims. The hypoxanthine derivative, ara-HxMP [54656-49-4] (24) is more water-soluble, appears to have a similar antiviral spectmm to ara-A, and is considerably less toxic (48). 

Yellow phosphorus was the first identified liver toxin. It causes accumulation of lipids in the liver. Several liver toxins such as chloroform, carbon tetrachloride, and bromobenzene have since been identified. I he forms of acute liver toxicity are accumulation of lipids in the liver, hepartxiellular necrosis, iii-trahepatic cholestasis, and a disease state that resembles viral hepatitis. The types of chrome hepatotoxicity are cirrhosis and liver cancer. 

TABLE 5.13 Examples of Drugs that Induce Intrahepatic Cholestasis or Liver Damage Resembling That Induced by Viral Hepatitis... 

Ribavirin, an antiviral agent used against hepatitis C and viral pneumonia, contains a 1,2,4-triazole ring. Why is the ring aromatic ... 

Hepatitis B virus (HBV) Hepatocellular carcinoma Progenomic RNA Inhibition of viral gene expression... 

Viruses are small infectious agents composed of a nucleic acid genome (DNA or RNA) encased by structural proteins and in some cases a lipid envelope. They are the causative agents of a number of human infectious diseases, the most important for public health today being acquired immunodeficiency syndrome (AIDS), hepatitis, influenza, measles, and vituses causing diarrhoea (e.g., rotavirus). In addition, certain viruses contribute to the development of cancer. Antiviral drugs inhibit viral replication by specifically targeting viral enzymes or functions and are used to treat specific virus-associated diseases. 

Cytokines and biological response modifiers represent a broad class of therapeutic agents that modify the hosts response to cancer or cancer therapies. The enormous body information about their clinical uses and their side effects is beyond the scope of this essay that can only give illustrative examples. For an up-to-date information the reader can resort to reference [5]. As many as 33 different interleukins are known and the list continues to grow IL-2 used in the treatment of kidney cancer is one example. Interferon alpha is used for chronic myelogenous leukeia, hairy cell leukaemia and Kaposi s sarcoma. Interferons are also used in the treatment of chronic infections such as viral hepatitis. Tumor necrosis factor (alpha), G/GM/M-CSF, and several other cellular factors are used in treatment of various cancers. Many of these cytokines produce serious side effects that limit their use. 

Hepatitis is acute or chronic inflammation of the liver, which is frequently caused by infection with hepato-tropic viruses. Several forms of viral hepatitis (A, B, C, D, E) are known, which result from infection with viruses belonging to separate virus families, differing in their genomic organization, replication strategies, morphology and modes of transmission. 

HBV infection remains a major worldwide public health problem. The World Health Organization estimates that there are still 350 million chronic carriers of the vims, who are at risk of developing chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The success of IFN-a treatment - mainly performed as combined treatment with adenine-arabinoside - has been measured by the normalization of liver enzymes, loss of HBe antigen and of detectable viral DNA in the serum of patients. It has been estimated from several clinical trials that as many as 40% of treated HBV patients would respond to therapy with IFN-a or combined treatment with nucleoside analogues and IFN-a. 

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