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Reuters Health Information (2013-07-15): T-cells may show HCV exposure in healthcare workers with negative antibodies


T-cells may show HCV exposure in healthcare workers with negative antibodies

Last Updated: 2013-07-15 13:44:21 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Measuring T-cell responses reveals exposure to hepatitis C in healthcare workers who test negative for antibodies against the virus, a new study has found.

T-cell proliferation assays may be a more sensitive test, the results suggest. But the low-level exposures that the assays can detect are highly unlikely to be a health risk for the patient or for others, according to experts who spoke to Reuters Health.

Rather, the results suggest that T-cell assays should be included in surveillance studies that monitor exposure to hepatitis C, said Dr. Barbara Rehermann, Chief of the Immunology Section of the Liver Diseases branch of the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, in email to Reuters Health.

Dr. Rehermann and her team published their research online June 28 in the Journal of Infectious Diseases.

They performed T-cell assays on samples from 72 healthcare workers who had been in contact with a source of the virus, most of them through an accidental stick by a contaminated needle. During six months of follow-up, none of the workers tested positive for a chronic hepatitis C infection, but nearly half had evidence of an immune response to the virus, denoted by white blood cells, not by antibodies.

"Part of the interest of this study is we're learning more about how our bodies control viruses and how quickly we're able to respond to them," said Dr. Henry Bodenheimer at Beth Israel Medical Center in New York City, who was not involved in the research.

"It seems that very low level infection can be controlled by our immune systems. That's new information. Much of the time people have relied on antibodies. Studying T-cells is a more difficult, but a novel approach," Dr. Bodenheimer told Reuters Health.

The findings may lead to new approaches to vaccine development or treatments that stimulate the immune response to fight hepatitis infection, Dr. Bodenheimer said.

But, he added, this study does not suggest that testing methods should be changed. Antibody tests can detect chronic infection, but there is no evidence that the infection detected by T-cell assays was transmissible or linked to long-term consequences in the healthcare workers, Dr. Bodenheimer pointed out.

Past studies have offered a range of estimates of the risk of transmission of the virus to exposed healthcare workers, from 0 to 10.3%, with an average of 0.5%, according to a 2005 report in Clinical Infectious Diseases (see The reason for that variation is not clear, however.

In this new study, assays of peripheral blood mononuclear cells in proliferation found hepatitis C-specific T-cell responses in 30 out of 63 participants tested, or 48%.

Interferon-gamma enzyme assays found at least two hepatitis-specific responses in 26 out of 62 participants tested, or 42%.

Fifty-three subjects underwent both tests. Thirteen (24%) responded to both, 21 (40%) did not respond to either, and 19 (36%) responded to one but not the other.

Those who were exposed to the virus after high-risk, rather than low-risk, needle sticks had higher proliferative T-cell responses.

"Whether these T-cell responses reflect protective immunity or whether they are downstream events of protective innate immune responses or abortive replication of defective viral genomes requires further studies in suitable models," Dr. Rehermann and her team write.

In the general population, the Centers for Disease Control and Prevention now recommends that all Baby Boomers, those born from 1945 to 1965, be tested for hepatitis C.


J Infect Dis 2013.

From Dr. Rehermann, please see responses to your questions below. Feel free to contact her by email prior to your deadline if you need clarification.

Q.) How many healthcare workers are likely infected without knowing? Any guess?

A.)None of the 72 healthcare workers that we studied after a defined, documented exposure (mostly accidental needlestick with blood from an HCV-infected patient) had chronic HCV infection. However, about 50% had evidence of immune responses against the virus, which is evidence that they had been exposed and mounted an immune response. These immune responses were mediated by white blood cells, not by antibodies.

Q.) And are they likely to seek a diagnosis?

A.)Possibly, because they had a defined exposure (needlestick). However, it is important to remember that even acute HCV infection is typically clinically asymptomatic, i.e. patients do not feel sick.

Q.) Based on your findings, what recommendations do you have for practicing physicians / healthcare workers?

A.) Two recommendations:

1. Regarding monitoring of HCV exposure in large epidemiological studies: Our study shows that HCV-specific T cell reposes are a more sensitive marker of HCV exposure than antibodies. Some of the largest studies on virus exposure in healthcare workers were conducted by the Centers for Disease Control and Prevention Needlestick Surveillance Group as multicenter case-control studies. In those studies, healthcare workers who developed antibodies to either HCV [4] or human immunodeficiency virus (HIV) [5] are typically classified as cases, whereas those who do not seroconvert are classified as controls. Our data suggest that T cell assays should be included in surveillance studies to monitor HCV exposure.

2. Regarding diagnosing HCV infection: The CDC now recommends that all baby boomers should be tested for HCV. See the following we blind:

Henry Bodenheimer, MD at Beth Israel Hospital in New York

Tel: 212.420.4059

Henry C. Bodenheimer, Jr. MD

Chairman, Department of Medicine

Professor of Medicine, Albert Einstein College of Medicine

Beth Israel Medical Center,

First Avenue at 16th Street, New York, NY 10003

(212) 420-4059 - phone

(212) 420-2912 - fax

Please see new of my comments related to the questions that you pose. HCV exposure is common in the healthcare setting and results in more frequent HCV infection than previously recognized. Fortunately, low level infection is able to be effectively eliminated by the human immune defenses.

Since the subject and this study showed effective control of HCV without virus reaching the usual detectable levels, the risk of these subjects transmitting HCV to others during they're very brief infection is extremely remote and has not been observed.

None of these subjects developed chronic transmissible infection so these subjects do not pose a health risk to others. However, high risk exposure in the healthcare setting can lead to hepatitis C infection and oral healthcare workers need to utilize precautions to assure that they protect themselves. High-risk needle stick exposure may transmit hepatitis see infection with a proximal with approximately a 1.8% risk of infection. (CDC data)

At present the use of functional lymphocyte assays to detect hepatitis see exposure is a research pool to help us better understand how our bodies handle hepatitis C infection. Since these subjects did not acquire chronic hepatitis C infection and have not shown to be responsible for infection to others nor to have accrued long-term adverse health consequences, these assays are not being proposed to replace our current testing technology.

As background information Dr. Barbara Rehermann who is the senior author of this study is a highly respected and knowledgeable investigator well experienced in studying the body's immune response to hepatitis C infection.

On the phone:

These subjects had specific exposure incidents - Not just all healthcare providers. You had to have had a needlestick or some event to be in this study. So, if you're going to use controls

Is their immune response na�ve - probably not. They've been working in the hospital a long time. Take

It seems that it must have been an infection because the immune system was responding to parts of the virus that you would only see if the immyne system was responding to a n infection. It seems that very low level infection can be controlled by our ummybne systems. That's new information. Much of the time, people have relied on antibodies. Styduying T0cells is a more difficult, but a novel approach. As Dr. R and her group have demonstrated, it is probably more senseitive

Part of the interest of this study is we're learning mor about how our bodies control viruses and how quickly we're able to respond to them.

More people got infected than we realized, but fortunately our iummyne syustem is more effective than we realized and there weren't health consequences.

Healthcare workers are safer now than they were 30 years ago because of the awareness of people getting infected and appropriate measures to prevent infection.

Everybody should protect themslevs as they are doing now and we can't reduce our vigilance.

Could lead to methods of either vaccines or treatment modalities that stimulate the cellular immyune response to help eliminate Hep infection.

A pretty high-level paper - the tech being used is of high quality and I think it's a good report and a well-done study.


Leona Kim-Schluger MD


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