The objective of this project is to determine the relationship of cigarette smoking to viral replication and liver damage in men who are chronically infected with the hepatitis B virus (chronic carriers). Evidence from our clinic suggests that carriers who smoke are less likely to replicate virus than carriers who do not smoke. As viral replication is closely related to liver damage, those same carriers may be less likely to have liver damage and suffer the long-term consequences of hepatitis B virus (HBV) infection than non-smokers. If an inverse relationship between smoking and viral replication can be convincingly demonstrated, a non-toxic anti-viral agent could be developed for a group of people who currently lack an effective therapy: hepatitis B carriers. Though the long-term effect of smoking can not be determined in this project, a pilot study would assess the importance of undertaking a more extensive investigation. The hypotheses to be tested are: 1) There is an inverse relationship between cigarette smoking and HBV replication, as assessed by: (a) the presence of HBV DNA, and (b) the level of HBV DNA polymerase activity, in the sera of HBV carriers. 2) Cigarette smoking does not increase liver damage, as measured by alanine aminotransferase levels, in the sera of hepatitis B virus carriers. The study will be cross-sectional in design and will include a total of 400 men. Study participants will be chronic carriers of the hepatitis B virus who attend the Liver Cancer Prevention Center of the Fox Chase Cancer Center. Viral replication will be assessed by measurement of serum HBV DNA and HBV DNA polymerase activity. Liver damage will be determined by the level of serum alanine aminotransferase. Smoking histories will be obtained via a telephone interview and will be confirmed by measuring the participants' sera for cotinine, a metabolite of nicotine. If, as this finding suggests, smoking appreciably affects viral replication, it would argue for searching in cigarette distillates for a specific inhibitory factor. At present, once a person has become a chronic carrier, these is no accepted therapy that will alter the risk of liver cancer. Therefore, the potential identification of an anti-viral agent is of great importance.
