Interferon Alfa-2b Treatment of Acute Hepatitis C Leads to Sustained Virologic Response
Interferon Alfa-2b Treatment of Acute Hepatitis C Leads to Sustained Virologic Response
Source: Jaeckel E, et al. N Engl J Med. 2001;345:1452-1457.
In a multi-center study conducted in germany, Jaeckel and colleagues identified 44 patients with acute hepatitis C infection. All patients had elevated alanine aminotransferase levels (885 ± 554 U/L) and hepatitis C virus (HCV) RNA was detectable in blood by PCR. Needlestick injury was the most common source of infection (32%), followed by sexual contact with an infected partner (23%), IV drug abuse (20%), and medical procedures (16%). Sixty-one percent of patients were infected with HCV genotype.1
Patients received 5 million units of interferon alfa-2b subcutaneously on a daily basis for 4 weeks, followed by 5 million units 3 times a week for 20 weeks. The primary end point was sustained virologic response, defined as undetectable serum levels of HCV RNA at 24 weeks after the completion of therapy. Forty-three patients completed 24 weeks of therapy. In all patients, serum HCV RNA became undetectable during therapy, at an average time of 3.2 weeks. At 24 weeks after the end of therapy, 43 (98%) still had undectable HCV RNA in serum. Eighty percent of patients had normal transaminase levels at the end of therapy, and all had normal levels at the end of treatment. One patient stopped therapy at 12 weeks due to alopecia and flu-like symptoms. She experienced a flare of hepatitis with recurrent viremia 8 weeks later, both completely resolved. Another patient had relapse of hepatitis and virema following therapy. She was treated with combination interferon alfa-2b and ribavirin therapy with complete biochemical and virologic response. With the exception of the single patient that withdrew, therapy was well tolerated. All patients experienced a modest decrease in leukocyte and platelet counts that was without apparent clinical significance.
Comment by Robert Muder, MD
Chronic hepatitis C infection is a major cause of liver disease, and the most frequent reason for liver transplantation in the United States. Most acute infections are minimally symptomatic and unrecognized. Although estimates vary, 50-80% of patients will develop chronic infection, and 15-20% will develop clinically significant chronic liver disease.1 Treatment of chronic infection is unsatisfactory. A 24-week course of interferon alfa leads to sustained virologic response in less than 10% of patients. The combination of interferon alfa and ribavirin given for 28 weeks is more effective, but the sustained virologic response rate is only 41%.1 Patients infected with HCV genotype 1 have a poorer response than do patients infected with genotype 2 or 3.
Although the study was uncontrolled, the results of the trial conducted by Jaeckel et al are dramatic, with 98% of patients showing complete virologic and biochemical remission 24 weeks after cessation of interferon alfa therapy. The results were the same regardless of viral genotype. There can be little doubt that this outcome is considerably different than the natural history of acute HCV infection. The difficulty of conducting a randomized controlled trial is highlighted by the fact that the study was conducted at 24 centers in Germany with nationwide recruitment of patients. Acute hepatitis C infection is often unrecognized, and a large proportion occurs in users of illicit drugs, so finding appropriate patients to enroll in trials is difficult.
The study has a practical aspect for hospital epidemiologists and hospital employee health services. Hepatitis C is an occupational hazard for health care workers exposed to blood. Unlike hepatitis B, neither a vaccine nor postexposure prophylaxis is available. However, current CDC recommendations call for serologic monitoring of health care workers exposed to bloodborne pathogens as a result of a needlestick incident.2 In the absence of effective postexposure prophylaxis, the major practical benefit of this follow-up has probably been the ability to document a workman’s compensation claim. Based on the current study, I would recommend that employees who seroconvert to HCV after such exposure should have measurement of HCV RNA and transaminase levels. Those with viremia and evidence of hepatitis should be offered treatment with interferon alfa.* What to do with those who show viremia without evidence of hepatitis remains problematic. A period of observation may be a reasonable alternate strategy, with initiation of treatment in the event of biochemical hepatitis or persistent viremia. (*Editor’s Note: Some institutions are using a qualitative HCV RNA test at 2-6 weeks postexposure in order to detect acute infection as early as possible.)
References
1. Liang TJ, et al. Ann Intern Med. 2000;132:296-305.
2. Centers for Disease Control. MMWR Morb Mortal Wkly Rep. 1998;47(RR19):1-39.
Dr. Muder is Hospital Epidemiologist, Pittsburgh VA Medical Center, Pittsburgh, Penn.
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