Critical overview and outlook: pathogenesis, prevention, and treatment of hepatitis and hepatocarcinoma caused by hepatitis B virus.
Viral hepatitis B is an enigmatic disease in which the host's own immune response to persistent viral infection may bring about host destruction through antiviral inflammatory responses which might otherwise present as a benign or inapparent disease. The simple solution to the hepatitis B problem is by immunoprophylaxis using the vaccine licensed in 1981, which prevents both infection and the late sequelae of liver cirrhosis and hepatocarcinoma. Immunotherapeutic vaccines against persistent hepatitis B infection have not been successful and new explorations are being directed to therapies which include antisense, ribozymes, gene silencing by RNA interference (RNAi) and aptamer approaches. Limited benefits from nucleoside therapy and limitations in opportunity for liver transplantation have left a large void of curative treatments. Findings with respect to e antigen tolerance provide a basis for exploration to determine whether passively administered e antigen might suppress cell-mediated immunity, creating a commensal state in which virus persists but without pathologic damage to the host. Therapy of hepatocarcinoma by conventional chemotherapy, radiation, or surgical resection and ablation gives little hope for restoration of health unless the tumor is detected very early. The large engagement of the world medical science community to develop therapeutic vaccines against cancer is now in major clinical trials to determine the hope and credibility for the immunization approach. Vaccines based on tumor peptides which are linked to heat shock proteins and directed to host dendritic cells give reason for excitement and may be the "best show in town". A new era of tumor therapy will need to be based on new discoveries in immune function which are required to pursue immunotherapy on a more rational basis. The many facets of current hepatitis B virology, pathogenesis, immunoprophylaxis, immunotherapeusis, chemotherapy, and tumor pathogenesis and therapy are discussed here, in depth, but in keeping with needed brevity.
Merck Institute for Vaccinology, 770 Sumneytown Pike, West Point, PA 19486, USA. maurice_hilleman@merck.com
Maurice R
MR
Hilleman
D000970:Antineoplastic Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use; D019496:Cancer Vaccines; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000628:therapy* / Q000821:virology; D017325:Hepatitis B Vaccines / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology / Q000472:pathogenicity*; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D006801:Humans; D008113:Liver Neoplasms / Q000628:therapy* / Q000821:virology
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D019496:Cancer Vaccines; D017325:Hepatitis B Vaccines