Background In people who are infected with the hepatitis C virus (HCV), chronic infection often develops and is difficult to eradicate. We sought to determine whether treatment during the acute phase could prevent the development of chronic infection. Methods Between 1998 and 2001, we identified 44 patients throughout Germany who had acute hepatitis C. Patients received 5 million U of interferon alfa2b subcutaneously daily for 4 weeks and then three times per week for another 20 weeks. Serum HCV RNA levels were measured before and during therapy and 24 weeks after the end of therapy. Results The mean age of the 44 patients was 36 years; 25 were women. Nine became infected with HCV through intravenous drug use, 14 through a needle-stick injury, 7 through medical procedures, and 10 through sexual contact; the mode of infection could not be determined in 4. The average time from infection to the first signs or symptoms of hepatitis was 54 days, and the average time from infection until the start of therapy was 89 days. At the end of both therapy and follow-up, 43 patients (98 percent) had undetectable levels of HCV RNA in serum and normal serum alanine aminotransferase levels. Levels of HCV RNA became undetectable after an average of 3.2 weeks of treatment. Therapy was well tolerated in all but one patient, who stopped therapy after 12 weeks because of side effects. Conclusions Treatment of acute hepatitis C with interferon alfa-2b prevents chronic infection. (N Engl J Med 2001;345:1452-7.) Copyright © 2001 Massachusetts Medical Society. CHRONIC infection with hepatitis C virus (HCV) is the leading cause of chronic liver disease in the United States and the most common indication for liver transplantation.Almost 4 million people in the United States and about 170 million people worldwide are estimated to be infected,and cirrhosis will eventually develop in 10 to 30 percent of these people.Since the introduction of programs that screen blood products for HCV, less than 10 percent of new infections are caused by transfusions of contaminated blood. New infections continue to occur through such routes as intravenous drug abuse and sexual transmission. Progression from acute to chronic HCV infection occurs in 50 to 84 percent of cases'; however, current therapies for chronic infection are not very effective. Even the latest approach — combination therapy with peginterferon alfa-2a or 2b and ribavirin — eliminates the virus in only 54 to 56 percent of cases of chronic infection.An alternative approach is to treat the acute infection early with the goal of preventing progression. Two pieces of evidence suggest that early treatment can prevent the progression of chronic infection. First, in patients with acute human immunodeficiency virus (HIV) infection, antiretroviral therapy sufficiently decreased the viral load to allow the patients' immune systems subsequently to control viral replication.Second, early control of viral load in a murine model of lymphocytic choriomeningitis virus infection enabled the host's immune system to clear the virus and thus prevent the development of chronic infection. In contrast, if viral replication is not controlled early, virus-specific CD4 T cells and CDS T cells are deleted from the T-cell repertoire by apoptosis or are rendered anergic. The strong responses of CD4 T cellsand CDS T cells' to acute HCV infection in humans are similar to those in the murine model of lymphocytic choriomeningitis virus infection. These strong immune responses during acute infection are weakened if viral replication is not controlled. In the light of these data, we assessed whether early control of viral replication in patients with acute HCV infection could prevent the development of chronic hepatitis. Since the viral load in such patients again begins to rise 24 hours after the administration of a single dose of interferon alfa-2b, we decided to use a daily dosing regimen for the first four weeks of therapy rather than the standard of three times a week. Treatment was then continued for another 20 weeks according to the standard schedule. Most patients with acute HCV infection are commonly seen first by physicians in private practice. In order to enroll such patients, we conducted a nationwide, prospective study in Germany with the support of the German Association for the Study of the Liver.