We thank Craxi and colleagues for providing interesting information. We have been following 10 patients with chronic hepatitis C who received interferon- and became long-term responders with detectable HCV RNA for 1.5 to 3 years. No patient had subsequent relapse, even with their detectable HCV RNA. We therefore agree with Craxi and colleagues that late alanine aminotransferase relapse is uncommon.

As we described in our article, liver histologic findings significantly improved in all long-term responders at the end of therapy, regardless of the presence of HCV RNA. However, we saw further improvement only in the long-term responders who showed loss of HCV RNA in 1- to 3-year follow-up examination of liver histologic findings. The ultimate goal of interferon treatment of chronic hepatitis C must be to clear the virus. However, when the chance of this is low, the next goal would be to prevent progression of the disease and the development of hepatocellular carcinoma. Can the long-term responders who did not lose HCV RNA reach this goal?

One of our 10 long-term responders with detectable HCV RNA was a 60-year-old Japanese man whose chronic hepatitis C was treated with interferon for 6 months. He became a long-term responder with detectable HCV RNA for 21 months after therapy ended. Liver histologic findings before treatment showed moderate chronic hepatitis, but those after treatment showed no significant improvement. Dynamic computed tomographic and ultrasound examinations of the liver were done before therapy was initiated and 9 months after therapy was discontinued. Neither showed a space-occupying lesion in the liver. Twenty-one months after the cessation of therapy, a 25-mm space-occupying lesion was detected in the liver by these examinations; abdominal angiography confirmed hepatocellular carcinoma.

Although patients with histologically chronic hepatitis rarely develop hepatocellular carcinoma, this patient had no history of consuming drugs or alcohol. This hepatocellular carcinoma may have already existed in the liver before therapy, or the persistent presence of HCV RNA may have caused the carcinoma. Because the follow-up period in most of our patients has not been long enough to provide definite answers to these questions, long-term responders, especially those with detectable HCV RNA, should have careful follow-up.