Hepatitis C cure rates top 40%, but CDC balks at calling for PEP policy

Infected worker: Let mine be the last horror story’

Citing dramatic advances in cure rates with combination drug therapy for hepatitis C virus infections, some clinicians attending the recent Frontline Healthcare Workers Safety Conference in Washington, DC, called on public health officials to recommend post-exposure prophylaxis (PEP) for needlesticks involving HCV-positive blood.

Once considered virtually untreatable, HCV now is the subject of a new sense of urgency to "use current therapies as primary prophylaxis to [protect] the 500 to 700 health care workers a year in this country who otherwise would be doomed to occupationally acquired hep C," said Robert Ball, MD, an infectious disease physician at the University of South Carolina in Columbia and an epidemiologist at the state department of health. The Centers for Disease Control and Prevention is in the process of revising its post-exposure guidelines for bloodborne pathogens, but it is not expected to officially recommend a PEP protocol for HCV due to data limitations and concerns about side effects with the available drugs, Hospital Infection Control learned at the Aug. 6-8 conference.

"At this point, I don’t think we are going to add post-exposure prophylaxis for hepatitis C yet," said Denise Cardo, MD, chief of the HIV infections branch in the CDC’s hospital infections program, "because we don’t have enough information. With the drugs available, the risk of getting a huge side effect is much higher than getting the infection. Early treatment [after seroconversion] is a good option, but we still need to learn a little bit more. If you look at the [HCV] guidelines right now, it doesn’t say don’t do [early treatment]. It says consider.’ That is what many institutions are doing. We encourage them to do PCR [testing] four to six weeks after the exposure, and if they detect infection, then treat."

Nevertheless, the CDC’s hesitancy to endorse PEP with HCV drugs immediately after an exposure does not sit well with Ball. "If institutional memory serves me correctly, we had no data in the late ’80s when we as health care professionals were putting workers on AZT monotherapy early on — indeed same-day stat — post-exposure prophylaxis," he told meeting attendees. "The [CDC] hospital infections program collected that data for a number of years until we actually had proof that what we were doing intuitively worked. I suggest that the same approach now will save lives from this point on."

In an interview at the conference, Ball cited data indicating a 41% cure rate — two of five patients — for HCV using a combination of interferon and ribavirin.¹ "We no longer have the luxury of waiting until hepatitis C declares itself as chronic liver disease or cirrhosis, because by then, the return on investment — the cure rates — are much lower," he said. "We must intervene early, and as early as possible for the exposed health care worker means same-day response. This is exactly what we were doing with AZT for HIV in the late ’80s. Why aren’t we doing the same thing for hepatitis C? I think there ought to be a more aggressive recommendation from the CDC."

A silent epidemic finds its voice

Of the roughly 400,000 health care worker needlestick exposures annually in this country, 20,000 to 30,000 are to HCV, Ball said. Of those exposed health care workers, 500 to 700 will acquire the disease, though symptoms may not appear for years. When they do, the effect can be devastating, as evidenced by the case of Diane Mawyer, RN, who received a standing ovation after describing her grim odyssey from HCV blood exposures in the 1980s to liver and kidney transplants in the 1990s. (See story, p. 116.) "If I had access to the safety devices and treatments available today, perhaps my transplants could have been avoided, and I wouldn’t be here telling this horrible story," she told conference attendees. "No matter what your role in the health care system — caregiver, administrator, researcher, government regulator, or manufacturer of medical devices — I beg you, do not underestimate the risk to health care workers. Do everything in your power to develop, provide, and utilize the best safety devices. And provide the best possible post-exposure treatment. . . . Please, let mine be the last horror story you hear."

HCV deaths, cirrhosis expected to increase

Unfortunately, there are "most certainly" other health care workers like Mawyer who will begin experiencing symptoms related to an HCV exposure in the past, said John Wong, MD, a physician at Tufts University Medical Center in Medford, MA, who spoke on HCV at the conference. Those who have concerns (e.g., a history of documented needlesticks) may want to be tested and seek the benefits of early treatment, he told HIC.

"[Approximately] 85% who are acutely infected go on to develop progressive, chronic liver disease," Wong said. "But for the most part, the disease is asymptomatic — up to 20 years and even longer. There are 5% of patients who are rapid progressors, 90% average progressors, and another 5% who are slow progressors. Health care workers might have acquired infection during the ’80s who were asymptomatic when they got it acutely and have remained pretty much asymptomatic over the next 10 or 20 years. And unless they have had blood tests to look at liver enzymes, which is not necessarily routinely done, or [they] identified a needlestick injury, they won’t be aware."

Noting that HCV already is responsible for 8,000 to 10,000 deaths per year, Wong said some computer projection models suggest that HCV deaths and cases of cirrhosis will continue to increase until 2010 to 2020. "We have an opportunity now to potentially treat some of those cases earlier, when they are more likely to respond to therapy," he said. "If you progress to the point where you have very advanced liver disease, there is no treatment except liver transplant, and there is a tremendous shortage of liver donor organs."

Indeed, hepatitis C has taken an insidious toll as the leading cause of chronic liver disease and liver transplants in the United States. A highly mutable virus for which there is no vaccine, HCV infection far exceeds the estimated 1 million U.S. infections with HIV. Some 4 million Americans have HCV antibodies, and 2.7 million of those people are chronically infected with the virus.²

"There is no doubt that there was a silent epidemic of hepatitis C infections during the 1980s, and it was transmitted rapidly to a huge [group]," Robert Haley, MD, a former medical epidemiologist at the Centers for Disease Control and Prevention and now a professor of medicine at the University of Texas Southwestern Medical Center in Dallas, recently told HIC. "At least 1.5% of the population of the United States [was infected]. That is the biggest viral epidemic in our history, probably second only to fatal flu in 1918-1919. It is a huge proportion."

Weighing your odds

While injection drug use and a history of transfusions have been among the most frequently cited risk factors, 1.4% of HCV cases reported in a recent CDC study were health care workers. Although that percentage does not place health care workers as a group at higher risk for acquiring HCV than the general population, one needlestick with HCV-positive blood changes the odds considerably. Indeed, given its greater prevalence — and a much higher likelihood of infection after a needlestick than HIV (.3% range vs. 1.8%) — some have argued that HCV is now the greatest occupational threat to health care workers. (See HIC, October 1998, pp. 150-151.)

While the primary goal in revising the CDC post-exposure guidelines was to update the HIV recommendations (see related story, p. 115), the increasing discussions about HCV are not going unheard at the CDC, another agency official told HIC at the conference.

"As things have come out — some of the studies that you are mentioning, and there has been more work on early [HCV] treatment — those issues are certainly being discussed," said Elise Beltrami, MD, medical epidemiologist in the CDC hospital infections program, who added that the new PEP guidelines will be issued by year’s end. "We don’t want to be too far behind the times in addressing them, but when you are putting together a consensus document for the Public Health Service, there are a lot of people involved. Not just CDC, but FDA and other federal agencies."

Indeed the post-exposure question is complex, and one can view it differently depending on whether the perspective is public health policy or the best advice to an individual patient, Wong said. First, with the latest estimates showing a 1.8% risk of transmission per needlestick, roughly 98% of workers exposed to HCV-positive blood will not seroconvert for the virus. Of those 2% who are infected, some 15% will resolve the illness, but 85% will develop chronic hepatitis. Of those, about one-fourth will progress to cirrhosis and/or death.

"Part of the issue is dealing with the uncertainty," he said. "Clearly, not everyone develops complications. Clearly, not everyone responds to treatment. How do you weigh that? How do doctors and patients weigh that? In my mind, you have to look at the advantages of treating early vs. potentially delaying treatment until the disease has progressed."

Likewise, the aforementioned HCV combination therapy involves several injections a week, and side effects commonly include fatigue and malaise, and, rarely, depression and even suicide.¹ On the other hand, there is the strong possibility, as Ball argues, that PEP for HCV likely would prevent seroconversions.

"I showed some data that suggests treatment of acute seroconversion leads to a higher viral eradication rate," Wong told HIC after his conference presentation. "Logical inference would make me think that the same treatment given post-exposure sooner might lead to even higher [HCV eradication]. We just don’t have data to confirm that. On a policy level, I don’t think yet there are sufficient data to make a clear recommendation. On the other hand, as a practicing physician, on a patient-to-physician basis, I would most likely encourage seroconversion [early] treatment. I would also weigh with the [exposed] health care worker the pros and cons of post-exposure prophylaxis."

References

1. Liang JT, Rhermann, Seeff, et al. NIH conference: Pathogenesis, natural history, treatment, and prevention of hepatitis C. Ann Intern Med 2000; 132:296-305.

2. Alter MJ, Kruszon-Moran D, Nainan OV, et al. The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Eng J Med 1999; 341:556-562.