Patients with chronic hepatitis C (n Γ
103) were treated cases of acute hepatitis C occur on an annual basis, and an estimated 8,000 to 10,000 deaths occur each year of compli-for 24 weeks with interferon alfa 2b and followed up for 24 weeks after cessation of therapy (week 48). When hepatitis cations of chronic hepatitis C virus (HCV) infection. 3 Also, end-stage liver disease caused by chronic hepatitis C infec-C virus (HCV) RNA at week 48 was used to assess interferon response, 15 (14.6%) were virological complete responders, tion is currently the leading cause for liver transplantation in the United States. 4 Before the discovery of this virus, inves-and all have remained HCV RNA negative for a mean of 3 years. At week 48, 3 of 15 virological complete responders tigators had already begun to treat patients with chronic non-A, non-B hepatitis, and the first report on the use of inter-had elevated alanine transaminase (ALT) values. When serum ALT level was used at week 48 to determine response to feron alfa 2b for this disease appeared in 1986. 5 Subsequently, numerous studies have used a dosing schedule of 3 million interferon, 20 (19.4%) were biochemical complete responders. However, 8 of the 20 patients with normal ALT levels units of interferon alfa 2b three times a week for 24 weeks. [6][7][8] In these last reports, normalization of serum alanine transam-were HCV RNA positive at week 48, and 7 of these individuals have had a recurrence of elevated ALT levels within 3 years inase (ALT) levels was achieved in more than 40% of patients with chronic non-A, non-B hepatitis (hepatitis C). However, after cessation of treatment. These findings indicate that measurement of HCV RNA was more accurate than ALT in de-during the ensuing 24 weeks after cessation of therapy, more than 50% of these biochemical responder patients ''relapsed,'' termining true responses to interferon therapy. Identification of nonresponders early during the course of interferon treat-and serum ALT values again rose to pretreatment levels.
Subsequent studies have used measurement of HCV RNA ment showed that an elevated ALT level at week 12 was 92% predictive (odds ratio 3.7) but misidentified 33% (5 of 15) of in conjunction with serum ALT levels to monitor interferon treatment, and the sustained virological complete response the patients who were virological complete responders at week 48. In contrast, a positive HCV RNA at week 12 of rates to 24 weeks of interferon treatment with permanent loss of HCV RNA have ranged from 10% to 20%. 9 In an treatment was 98% predictive (odds ratio 35.5) and misidentified only 6.7% (1 of 15) of the virological complete respond-effort to determine whether patients could be preselected for treatment, several studies have attempted to identify clinical ers. Thus, positive HCV RNA at week 12 of therapy was more accurate in identifying eventual virological nonresponders or virological features that may distinguish chronic hepatitis C patients who may or may not respond to interferon ther-than measurement of ALT at this time. Termination of interferon therapy in patients who were HCV RNA positive at apy. 10,11 These studies showed that pretreatment prognostic features that were statistically associated with a favorable week 12 would result in a 27% reduction in the direct medical costs and keep patients from undergoing unnecessary treat-response included younger age, female gender, shorter duration of disease, and absence of cirrhosis. Low levels of pre-ment. Therefore, testing for HCV RNA at week 12 to identify nonresponders and then discontinuing their treatment is prac-treatment serum HCV RNA and the presence of viral genotype other than 1 were also reported to be associated with a tical, cost-efficient and beneficial both to patients and to thirdparty payers. (HEPATOLOGY 1997;26:1640-1645.) favorable response to interferon therapy. 12,13 However, there were patients who had responded to interferon therapy but did not meet the specified pretreatment characteristics. Thus Hepatitis C infection is an important cause of chronic liver it is difficult to use prognostic indicators to deny therapy, disease and primary hepatocellular carcinoma in many parts and withholding a potentially useful treatment for a progresof the world. 1,2 In the United States, there are an estimated sive viral disease may not be acceptable to patients who have 3.9 million carriers of hepatitis C, approximately 30,000 new chronic hepatitis C.
In 1991, we began to use the recommended dosing schedule of 3 million units of interferon alfa 2b three times a week Abbreviations: ALT, alanine transaminase; CBC, complete blood count; HCV, hepafor 24 weeks in treatment of hepatitis C patients at two titis C virus; IVDA, intravenous drug abuse; RT-PCR, reverse transcription-polymerase institutions in Southern California. To determine which endchain reaction.