Third International Conference on Therapies for Viral Hepatitis
Monday, December 13, 1999, Maui, Hawaii

David S. MacDougall

David S. MacDougall is a medical writer in New Jersey. E-mail: dsmac@earthlink.net.

Multiple Injections Pose High Risk for Viral Hepatitis

Unsafe injection practices in hospital and outpatient settings account for a significant proportion of cases of viral hepatitis worldwide, said Harold Margolis, MD, Centers for Disease Control and Prevention, Atlanta, Georgia.

Speaking here at the Third International Conference on Therapies for Viral Hepatitis, Margolis said that about 12 billion intramuscular injections are administered worldwide each year, and that about 90% of these are given for therapeutic indications. The risk of transmission from needlestick injury is about 30% for hepatitis B virus (HBV) and about 3% for hepatitis C virus (HCV), he said. "The incidence of viral hepatitis in a given population is a good indicator of the effectiveness of hospital infection control and injection safety practices in that setting," Margolis said. "A significant proportion of cases of viral hepatitis is iatrogenic."

Epidemiologic studies have shown that the risk of HBV in adults is significantly associated with a history of injections received in hospitals, dental offices, and clinics and other outpatient settings. In some parts of the world, Margolis said, 50% of cases of HBV infection in adults are directly related to a history of receiving intramuscular injections while only about 15% of cases are attributed to sexual transmission. In children in developing countries, a history of injection is a predominant risk factor for both HBV and HCV infection.

Margolis said that greater efforts are needed to coordinate anti-HBV therapy and HBV immunization practices, and that the goals of anti-HBV treatment should not compete with those for HBV immunization. "We need to link hepatitis B immunization with antiviral therapy, so that every time you put somebody on antiviral therapy for hepatitis B you also vaccinate their household and other contacts to prevent disease transmission," he said.

Evidence for new emerging hepatitis viruses was presented by Harvey Alter, MD, National Institutes of Health, Bethesda, Maryland. According to Alter, the existence of still unidentified causes of infectious hepatitis is supported by the observations that the cause of about 30% of cases of chronic hepatitis is never identified, and that 10-20% of cases of acute hepatitis test negative for all known infectious hepatitis agents. In addition, Alter said, most cases of fulminant hepatitis and hepatitis-associated aplastic anemia are unexplained and suggest a novel viral etiology.

Advances in molecular technology recently led to the discovery of hepatitis G virus (HGV). Alter said that HGV is found in about 2% of blood donors, parenterally transmitted, and may result in persistent infection. No specific associations between HGV and viral hepatitis or concurrent hepatitis C virus (HCV) infection have been identified, Alter said, and there is still no confirmed evidence of intrahepatic HGV replication.

The discovery of HGV was followed by the identification of TT virus (TTV), a non-enveloped member of the circovirus family. The prevalence of TTV in blood donors is about 12%, Alter said, and about 26% of patients develop new TTV infection following blood transfusion. TTV is found in about 40% of patients with HCV hepatitis and may cause disease in rare cases or may mutate into pathogenic variants.

Does interferon-alpha (INF-a) function as an antiviral or immunomodulator in patients with HCV infection? A mathematical modeling approach that has been used successfully to increase understanding of HIV dynamics may provide an answer to this question, said Alan Perelson, PhD, Los Alamos National Laboratory, New Mexico.

According to Perelson, plasma HCV RNA levels decrease rapidly following the initiation of high-dose daily INF-a therapy, and this decline is followed by a slower second phase of viral inhibition. These observations were combined with clinical trial data to create a mathematical model that predicts the biphasic fall of serum HCV RNA levels during high-dose INF-a therapy.

Application of the model revealed that the efficacy of INF-a in blocking HCV at a daily dose of 10 MU is 95% and 99.7% in persons with HCV genotype 1 and genotype 2 infection, respectively, and that the mean half-life of HCV in serum is about 2.7 hours for genotype 1 and 2.0 hours for genotype 2. Perelson said that the model suggests that INF-a functions primarily as an antiviral in patients with HCV infection by preventing the release of virus particles by HCV-infected hepatocytes,

David MacDougall's comprehensive report on this conference will be featured in the March Journal of the International Association of Physicians AIDS Care.