Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Up to now Interferon (IFN) has been the only licensed treatment for chronic type B and D viral hepatitis. However, IFN monotherapy is efficacious only in HBeAg positive chronic hepatitis B and is aggravated by important side effects in many patients. To overcome the limits of IFN monotherapy, combination therapies of this cytokine together with other synergistic drugs have been proposed and many antivirals that directly act on Hepatitis B Virus (HBV) synthesis have been developed. Combination therapies with acyclovir, levamisole, and cortisone have not been more advantageous than IFN alone. Of the antivirals, Adenine Arabinoside monophosphate, though active against HBV, causes severe neurotoxicity and Famciclovir has not shown significant efficacy in a large multicenter study of chronic HBeAg positive hepatitis. Lamivudine appears the most promising in terms of clinical benefit, safety and tolerance. It is active on wild type HBV as well as on HBeAg-minus variants of the virus. However, although HBV is consistently repressed while on therapy, only a part of the patients are cured or remain in remission after Lamivudine withdrawal. Maintenance therapy is in order, but the long-term use of Lamivudine is complicated by the emergence of polymerase gene-mutants which may recapitulate disease. Combination with other antivirals active also against Lamivudine escape mutants opens promising new prospects. There is as yet no valid therapy for chronic HDV hepatitis; IFN is of no benefit in most cases.
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PMID:Therapy for chronic hepatitis B. Present status. 1649 43

Famciclovir is converted rapidly and efficiently after oral administration to the selective antiviral compound, penciclovir. In cell culture, penciclovir is a potent inhibitor of herpes simplex virus (HSV) types 1 and 2, varicella-zoster virus (VZV), Epstein-Barr virus (EBV) and hepatitis B virus (HBV). Phosphorylation of penciclovir and aciclovir in uninfected cells is limited, and penciclovir, like aciclovir, has minimal effect on replicating cells in culture as expected for a selective antiviral agent. Mode of action studies with VZV and HSV have shown that the phosphorylation of penciclovir in infected cells is far more efficient than for aciclovir. This compensates for differences observed between penciclovir triphosphate and aciclovir triphosphate in the inhibition of HSV and VZV DNA polymerases. Because HBV is not known to encode a thymidine kinase, a different rationale for the selective inhibition of this virus by penciclovir is required. Recent data indicate that the DNA polymerase of HBV is far more sensitive to inhibition by penciclovir triphosphate than cellular DNA polymerases, suggesting that for this virus, selectivity operates at the DNA polymerase. Penciclovir triphosphate is more stable within infected cells than aciclovir triphosphate, and consequently penciclovir has more prolonged antiviral activity than aciclovir. Similarly, famciclovir is more effective than aciclovir or valaciclovir in suppressing HSV replication when given at a lower dosing frequency in certain animal models. These preclinical properties have helped to provide the foundation for the famciclovir clinical programme.
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PMID:Famciclovir, from the bench to the patient--a comprehensive review of preclinical data. 1861 46


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