It appears that treatment that lowers the titer of HBV DNA can considerably decrease the risk of the dire long term effects of HBV infection, chronic liver disease, liver failure, and cancer of the liver. It may not be necessary to completely eliminate the virus. That implies that a moderately effective antiviral or a very effective one in low dose that decreases the probability of detrimental side effects, would be satisfactory for long term treatment. This dosage level could be adjusted to achieve significant reduction of disease risk and minimize drug side effects. An essential characteristic of a good antiviral; would be a low incidence of resistance to therapy along with effective antiviral action. Combination therapy is effective and the future invention of drugs that act on different features of pathogenesis could further improve outcome (26
). The Hepatitis B Foundation maintains a current list of available medications for chronic HBV infection (28
The treatment by delay approach is an unusual form of cancer therapy. Most forms of cancer treatment are based on the elimination of cancer cells by the use of surgery, radiation, and/or chemotherapy. This is often accomplished with the concomitant loss of normal cells to the great discomfort of the patient. Antiviral treatment is directed to decreasing viral replication and other approaches to diminish the viral pathogenic effects. The destruction of the patient's non-infected cells could be minimal with subsequent benefit to the patient.
In many medical communities current practice is to treat only carriers with symptoms, biopsy evidence of chronic disease and other indicators of established disease. However, in some communities (e.g., Taiwan, Germany) criterion for starting treatment are less stringent including treatment of patients with sustained elevations of ALT above normal, and/or HBV DNA titers greater than 104
copies/mL. There could be a re-evaluation of the upper limits of normal if the ALT elevation criterion is used. Recently, in a study of adolescent boys in a correctional institution, a significantly lower upper limit of normal ALT was recommended (29
). The decision to extend the number of carriers treated will depend on the accumulation of more data and ongoing analysis of the evidence-based criterion.
If treatment of more carriers is instituted there will be several important consequences. Screening of high risk and other populations will need to be increased to identify those who should be treated. It would also help to identify those who come in contact with carriers and require vaccination. Treatment of potentially infectious but asymptomatic carriers will enhance the vaccination program as it will decrease the pool of carriers who could infect others. This would speed the eventual control of HBV.
An unfortunate outcome of the identification of carriers of HBV is that, in some situations, it has led to their stigmatization (30
). Carriers without any evidence of disease and who in normal social interactions were not infectious have been forced to leave their jobs, been excluded from professional school and have had difficulties with relationships. It remains a serious issue particularly in places where there is inadequate knowledge of HBV. Appropriate treatment of carriers would decrease their infectivity and thereby greatly decrease the risk of transmission. This would be advantageous to the carrier and to those he or she contacts, and may also relieve the public anxiety and stigmatization of carriers. The resolution of this problem would be a major benefit of the treatment of carriers including those who are asymptomatic.
Early in the HBV and cancer research we encouraged the search for other vaccine preventable cancers (32
). We noted (33
The associations of HBV and WHV with this carcinoma suggest that there may be other, similar virus-cancer relations that could be dealt with by primary-prevention strategies. We believe that searching for such viruses and cancers in animals and human beings is an important … direction for cancer research.
In 2007, the second cancer prevention vaccine was introduced (18
). A vaccine against certain strains of papilloma virus is effective in preventing infection with these viruses and cancer of the cervix. It may also be protective against other cancers. It has taken nearly forty years since the invention of the HBV vaccine and about 25 years since its widespread use, for the introduction of the second vaccine, but there is every reason to hope that additional cancer prevention vaccines will be developed soon.
There are a number of candidates - EBV and Burkitt's lymphoma and nasopharyngeal cancer; HHV-8 and Kaposi's sarcoma; HCV and hepatocellular carcinoma; HTLV–1 and Adult T cell leukemia/lymphoma; HTLV – 2 and hairy cell leukemia (34
). Other possibilities include Adenoma virus and mesothelioma. An interesting association, not yet fully explored, is between HBV and cancer of the pancreas. A population based cohort study found that the presence of HBsAg along with HBeAg was an independent risk factor for cancer of the pancreas with a seven-fold increased risk (35
). A recent study has confirmed the association (36
). If confirmed, this implies that HBV may have an etiological role in the pathogenesis of pancreatic cancer, and/or that there is a similar virus that is part of its etiological process.