Early HCV treatment may prevent chronic disease
Stunning study boosts early testing, follow-up
Hospital employee health professionals (EHPs) are reconsidering their follow-up of employees exposed to hepatitis C in light of new research that shows that early treatment can prevent chronic infection. In an article in the New England Journal of Medicine, German researchers reported that 42 of 43 patients who completed a 24-week series of interferon therapy had undetectable levels of HCV RNA and normal liver enzyme levels.1 Although the report does not apply to post-exposure prophylaxis (PEP), it could affect the treatment of employees who seroconvert.
Currently, the Centers for Disease Control and Prevention (CDC) in Atlanta recommends HCV antibody testing at four to six months, but suggests that HCV RNA testing may occur at four to six weeks, if desired.
In counseling patients after exposure, clinicians now may tell employees that "there is considerable evidence that interferon therapy might be beneficial" in treating acute infection, says Ronald H. Goldschmidt, MD, director of the family practice inpatient service at San Francisco General Hospital and co-director of the PEPline post-exposure hotline. Those employees may choose to have RNA testing and more frequent monitoring, he says. Goldschmidt also says clinicians should be aware of the need for close follow-up.
"Clinicians managing occupational exposures need to be as aware of the risk of hepatitis C as they are of HIV," he says. "This is critically true now that there appears to be effective treatment for acute hepatitis C. We recognize that the study doesn’t answer all the important questions [about HCV treatment], but health care workers need to know that treatment of acute hepatitis C is an important option. They need to talk to their clinicians about it."
Many employee health professionals had taken a stance toward treating early HCV infection. "I had decided to be very aggressive and monitor people and treat as soon as there’s evidence of disease," says Geoff Kelafant, MD, MSPH, FACOEM, medical director of the occupational health department at the Sarah Bush Lincoln Health Center in Mattoon, IL. Kelafant, who is chairman of the medical center occupational health section of the American College of Occupational and Environmental Medicine in Arlington Heights, IL, conducts his first tests at about four weeks after exposure. Although he has had no seroconversions, his protocol calls for treatment at serologic evidence of infection. "If I had a patient of mine that converted, I would very strongly recommend [that person] get [interferon] therapy," Kelafant says.
The article caused a ripple of excitement because of its strong findings in favor of early treatment. In fact, the Massachusetts Medical Society released the article on Oct. 1, six weeks before its publication in the Nov. 15 issue, citing "potential clinical implications."
While typically 70% to 85% of those with acute HCV infection progress to chronic infection,2 98% of those receiving the full treatment regimen in the study resolved their infection. "It is likely that about 30% of our patients would have had self-limited disease, regardless of whether they received interferon alfa-2b," acknowledge the authors, who conducted the study at the Hanover Medical School in Germany. "So far, there are no means to identify such patients at presentation. Since the current treatment for chronic HCV infection eliminates the virus in only about half of cases, we suggest that all patients with acute hepatitis C should be treated," the researchers concluded.
However, inherent limitations of the study raised a number of other questions.
David K. Henderson, MD, deputy director for clinical care at the Warren G. Magnuson Clinical Center of the National Institutes of Health in Bethesda, MD, notes that 14 of the 44 study subjects were occupationally exposed health care workers. "They’re not separated out in the paper. I would love to know exactly how they were managed." He also noted that the researchers reported that the average time from exposure to "signs and symptoms" of infection was 54 days, and the average time to start of therapy was 89 days. That actually is a longer period than would usually occur in the monitoring of exposed health care workers, who could receive testing as early as 28 days after exposure.
As far as those showing "signs and symptoms," which could include jaundice, fever, and weight loss, Henderson notes that their cellular immune response might predispose them to respond to early interferon treatment. "I know of no other paper on the treatment of hepatitis C infection that shows this kind of [positive] result. The best numbers are a 40% or 50% cure rate. This is a substantial difference and incredibly encouraging. [But] we don’t know exactly what it means, and we should not leap to the conclusion that preemptive therapy works."
The CDC already had been scheduled to reconsider its recommendations through a National Institutes of Health Consensus Development Conference on Management of Hepatitis C in June 2002. But the findings of this study do not conflict with the current guidelines, notes Miriam J. Alter, PhD, chief of the epidemiology section in the division of viral hepatitis at the CDC.
The updated recommendations, published in the June Morbidity and Mortality Weekly Report (MMWR), noted that "intervention with antivirals when HCV RNA first becomes detectable might prevent the development of chronic infection." However, it’s not clear how effective the treatment is in patients who haven’t showed any signs of infection and who have normal serum alanine aminotransferase (ALT) levels, Alter says. All the patients in the German study had elevated ALT levels. "When you identify health care workers early in acute infection after exposure, they’re still asymptomatic. They may not even have ALT elevations," she says.
Although only one person in the German study halted treatment, Alter noted that interferon can have significant side effects.
"We don’t know whether treating early in the course of chronic infection or disease might be just as effective as treating during acute hepatitis C. Should we be using this regimen or another regimen that could be just as useful? What about the side effects? These are all unknown. The unknowns are the same now as they were when we wrote the MMWR," she says.
References
1. Jaeckel E, Cornberg M, Wedemeyer H, et al. Treatment of acute hepatitis C with interferon alfa-2b. N Engl J Med 2001; on-line publication: www.nejm.org.
2. Centers for Disease Control and Prevention. Updated U.S. Public Health Service Guidelines for the Management of Occupational Exposures to HBV, HCV, and HIV and Recommendations for Postexposure Prophylaxis. MMWR June 29, 2001; 50(RR11):1-42.
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