Hepatitis C: the silent epidemic
Though frequently asymptomatic in its initial stages, hepatitis C infection can have serious consequences, including cirrhosis, liver failure, cancer, and death. Early detection of the virus is beneficial, as it enables women to take advantage of increasingly effective treatments and alerts them to the need for preconception counseling.
Acute infection with the hepatitis C virus (HCV) progresses to chronic disease in 50% to 84% of cases. Once HCV infection is chronic, combination therapy with interferon alfa-2b and ribavirin elicits a sustained virologic response in only 41% of cases. Even the latest therapy for chronic HCV—a combination of pegylated interferon alfa-2a or 2b and ribavirin—eradicates the virus in only 54% of patients.1 For these reasons, a team of researchers in Germany explored the effectiveness of treating HCV during the acute phase of infection using high-dose interferon alfa-2b to prevent progression.2
‘Peginterferons’ elicit a greater sustained virologic response.
Because the viral load of patients with HCV infection starts to rise within 24 hours after a single dose of inter-feron alfa-2b, investigators used a daily dosing regimen—rather than the standard thrice-weekly therapy—for the first 4 weeks of treatment. They then followed the standard schedule for another 20 weeks, measuring serum HCV RNA levels before, during, and 24 weeks after the termination of therapy.
All 44 patients in the study were given 5 million units of subcutaneous interferon alfa-2b daily for 4 weeks, after which time they received the same dosage 3 times a week. Twenty-four weeks after the end of therapy, 43 patients (98%) had normal serum alanine aminotransferase (ALT) and undetectable levels of serum HCV RNA. Side effects caused 1 patient to stop treatment after 12 weeks.
Although the investigators concluded that the treatment of acute HCV infection with interferon alfa-2b prevents progression to chronic disease, a number of issues remain unresolved. The primary one is whether all patients with acute disease should undergo treatment with a costly therapy that can be hard to tolerate, when many of these patients would recover without it. Further, since pegylated interferon has proven more effective than standard interferon in treating chronic HCV, it also may be more effective in treating acute disease. (“Peginterferons,” as they are called, can be administered weekly and elicit a greater sustained virologic response.) Finally, since acute infection is no longer common in the United States—dropping from 250,000 to 500,000 cases annually in the 1980s to less than 40,000 today—and since not all infections are clinically acute, this approach has limited applicability.3
These and other issues require further exploration. —Katherine Chen, MD, MPH
REFERENCES
1. Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b in combination with ribavirin compared with interferon alfa-2b plus rib-avirin for initial treatment of chronic hepatitis C: results of a randomized trial. Lancet. 2001;358:958-965.
2. Jaeckel E, Cornberg M, Wedemeyer H, et al. for the German Acute Hepatitis C Therapy Group. Treatment of acute hepatitis C with interferon alfa-2b. N Engl J Med. 2001;345(20):1452-1457.
3. Hoofnagle JH. Therapy for acute hepatitis C [editorial]. N Engl J Med. 2001;345(20):1495-1497.
Conclusion
Chronic HCV infection can lead to serious medical consequences, such as cirrhosis, liver failure, hepatocellular cancer, and death. Unfortunately, 75% of individuals infected with HCV are asymptomatic. By the time symptoms do occur, the disease often is in its advanced stages. Thus, both the CDC and ACOG recommend that Ob/Gyns screen women in high-risk groups. The early identification of chronic HCV infection is important, as it enables women to take advantage of increasingly effective treatments and alerts them to the need for preconception counseling.
Both the CDC and ACOG recommend that Ob/Gyns screen women in high-risk groups.
Although perinatal HCV transmission is a known risk, we lack strategies to prevent it. In addition, the effects of pregnancy on the progression of chronic HCV infection, and the effects of chronic HCV infection on pregnancy outcome, are unknown. However, the identification of HCV-positive pregnant women will lead to screening of their infants and earlier identification of infected children.
