Hepatitis G discovery raises new worries
'We are working in a sea of viruses'
Researchers have identified and named hepatitis G virus (HGV), a bloodborne infectious agent that is transmissible by needlestick and "distantly related" to hepatitis C.1
As with HCV, the virus has apparently caused hepatitis infections for years while remaining undetectable as a causative agent.
"It is not an emerging virus, it is a virus that we can now detect," says Harvey Alter, MD, co-author of the article and chief of the infectious diseases section, department of transfusion medicine at the National Institutes of Health in Bethesda, MD. "It's clearly bloodborne. That is probably the main route and may be the only route of transmission."
An RNA virus, HGV was molecularly cloned from the plasma of a patient with chronic hepatitis. HGV is transmissible by transfusion, has a global distribution, and is present within approximately 1% to 2% of the volunteer blood donor population in the United States, the authors reported.
To examine whether HGV is associated with acute disease, serum specimens from patients with community-acquired hepatitis of unknown etiology were tested for HGV RNA. Of 38 patients identified from 1985 to 1993, five (13%) were HGV RNA-positive at the time of their acute illness. None developed chronic hepatitis, but four remained HGV RNA-positive over a follow-up period of 2 to 9 years.
Of 107 patients with HCV identified over the same period, 19 (18%) were also HGV RNA-positive. The clinical characteristics of acute hepatitis in patients with HGV infection alone did not differ from those of patients co-infected with HCV. In addition, risk factors for infection did not differ between the two groups, and included transfusion, injection drug use, and multiple sexual partners, the researchers reported. They designated the virus HGV because a 1994 report of a possible enteric agent used the term hepatitis F virus.
While adding another letter to a veritable alphabet soup of hepatitis viruses, the discovery comes with a host of unanswered questions for the clinical setting -- including progression to and severity of resulting disease.
"No doubt the virus is there, it circulates in the blood and causes a persistent infection, but what disease it causes is open for a lot of questions," says Harold Margolis, MD, co-author of the research study and chief of the hepatitis branch at the Centers for Disease Control and Prevention in Atlanta. "Direct needlestick exposure is going to raise a whole set of issues with this virus, but again, the question is, 'Is it causing disease?' This may be one of those viruses looking for a disease. It clearly causes some degree of hepatitis, but whether it is going to become clinically significant or a health issue is something that has to be sorted out."
The question of severity of the infection is complicated because CDC data suggest chronic liver disease appears to be occurring in those co-infected with and HGV and HCV, Margolis tells Hospital Infection Control.
"[There are] people with chronic liver disease who are HGV positive, but there is no data there that says there is a true association with chronic liver disease," he says. "In fact, our patients who had HGV alone didn't go on to have elevated liver enzymes. While people may show HGV [infection] in patients with chronic liver disease, most of them have hepatitis C. The question of whether HGV causes chronic liver disease alone has to be answered."
Finding underscores infection control
Still, the unanswered questions regarding HGV are concerning to clinicians -- particularly the possibility of an asymptomatic carrier state, says Donald Fry, MD, chairman of the department of surgery at the University of New Mexico Hospital in Albuquerque.
"That's alarming because we are talking about a potential carrier state that may actually not be causing disease in the patient who is the carrier," he says. "There is some evidence that there may be synergisms now of hepatitis G with other hepatitis particles and that this may in part explain why we have seen inconsistency in which patients with hepatitis C get cirrhosis. It may be that the patients who have two or more [hepatitis] particles are at greater risk for developing cirrhosis than patients who have only a single particle."
A frequent medical lecturer on the growing importance of hepatitis as an occupational threat to health care workers, Fry estimates the disease now affects millions of people in America who now have hepatitis B, C, G, or some combination of the bloodborne viruses.
"It seems to me that the message to health care workers is clear -- we are indeed working in a sea of viruses, and contact with patient blood is not acceptable," he says. "Each health worker has got to be the guardian of his or her own health. Not that they should be afraid or refuse to care for patients with proven or suspected hepatitis disease, but I think that we have to be cognizant that any patient, regardless of their socioeconomic status, represents a potential source of a virus that could be contracted. Blood is a toxic substance. We have to renew our commitment to precautions that minimize the risk of blood exposure."
No test available
Indeed, with no test available for HGV, it will be impossible to conduct follow-up of workers following needlesticks and other blood exposures. That makes infection control measures against the entire array of bloodborne viruses all the more important, notes Angela Goetz, MNEd, infection control practitioner at the VA Medical Center in Pittsburgh, a facility that does a high volume of liver transplants associated with HCV.
"Maybe it is not a bad idea that OSHA requires keeping records for 30 years for employee injury, if they are going to find all of these other viruses," she notes. "It just emphasizes the importance of universal precautions and safety in the workplace. We should monitor our health care workers after exposure and keep that documentation -- because who knows what else they are going to find."
Indeed, the discovery further narrows the spectrum of the long-suspected "non-ABC" hepatitis agents -- though it appears there may be at least one other undetected virus currently causing infections. Prior to the discovery of HGV, about 90% of hepatitis infections have been ascribed to the known causative agents -- with the remainder generally referred to as non-ABC, Alter notes.
"Somewhere between 15% and 25% of the cases that were previously classified as non-ABC will turn out to be HGV," he estimates.
Likewise, Margolis estimates HGV appears to account for 10% to 15% of cases of the non-ABC hepatitis in sentinel surveillance, opening the possibility of another infectious agent.
"The remainder -- at least in terms of risk factors -- looks like they could be parenterally or bloodborne transmitted," Margolis says. "So there is always the possibility that there is something else out there."
Though HGV is a bloodborne virus, Alter emphasizes the identification of the agent does not really change the safety of the blood supply -- because it has always been there. Since 1992, when second-generation tests became available for HCV, hepatitis has been reduced to almost background incidence in the blood supply.
"It's not zero, but it is approaching zero risk in the blood supply," he says. "The development of a test for HGV may add a small margin of safety but may not be necessary, given the already documented low risk of post-transfusion hepatitis."
Reference
1. Linnen J, Wages Jr. J, Zhang-Keck Z, et al. Molecular cloning and disease association of hepatitis G virus: A transfusion-transmissible agent. Science 1996; 271:505-508. *
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