These findings suggest that HCV infection was eradicated in most of the long-term responders to interferon-alpha therapy because HCV RNA could no longer be detected in their serum and liver samples and because a significant improvement gradually occurred in their liver histologic results. The persistent presence of hepatic HCV RNA at the end of therapy was the most important predictor of relapse.

In Japanese patients, peg-IFNalpha-2a plus ribavirin provided significant improvement in SVR rates compared with peg-IFNalpha-2a alone in treatment-naïve patients, and was effective as re-treatment for non-responders or relapsers to previous treatment with interferon monotherapy.

We investigated anti-hepatitis C virus (HCV) titers, HCV RNA levels in liver and serum, genetic variability in the hypervariable region of the genome, the form of the virus in the circulation, and liver histology in 21 anti-HCV-positive subjects with sustained normal liver biochemical values. Titer of anti-HCV was determined by second generation anti-HCV-passive hemagglutination assay, and HCV RNA levels were semiquantitated by reverse transcriptase polymerase chain reaction (PCR). In 19 (90%) of the 21 subjects who had a higher titer of anti-HCV (> or = 2(14)), HCV RNA was detected in both serum and liver, and histological examination showed minimal or mild chronic hepatitis in all. In the remaining 2 patients who had a lower titer of anti-HCV, HCV RNA was not detected in serum and liver, and liver histology was normal. Anti-HCV titers and HCV RNA levels in serum and liver in the 19 HCV RNA-positive subjects were compared with those levels in the 41 patients with biopsy-proven chronic hepatitis C and elevated serum aminotransferase levels as a control group. There were no significant differences in viral levels in serum and liver between the two groups. To further investigate virological differences between the two groups with regard to degree of genetic variability and the form in the circulation, we performed the PCR-single strand conformation polymorphism (PCR-SSCP) of the hypervariable region 1 and the immunoprecipitation analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

We measured 2',5'-oligoadenylate synthetase activities in serum and peripheral blood mononuclear cells from 10 patients with chronic hepatitis B who were being treated with interferon so as to determine whether 2',5'-oligoadenylate synthetase activity in serum reflected 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells, and whether it could be used to monitor interferon treatment. Pretreatment values of 2',5'-oligoadenylate synthetase activity in patients' serum and peripheral blood mononuclear cells were not statistically different from values from control subjects. When interferon was administered, serum levels of 2',5'-oligoadenylate synthetase began to rise within 3 hr, reached peak values at 12 hr and then declined. The levels of 2',5'-oligoadenylate synthetase activity both in serum and peripheral blood mononuclear cells increased substantially during interferon treatment, ranging 2- to 50-fold greater than initial levels. The levels of 2',5'-oligoadenylate synthetase in serum correlated closely with levels in peripheral blood mononuclear cells. In addition, when the levels of 2',5'-oligoadenylate synthetase rose during interferon administration, serum hepatitis B virus DNA polymerase values fell, and, in some cases, DNA polymerase rose again when 2',5'-oligoadenylate synthetase fell after discontinuation of interferon. These findings suggest that 2',5'-oligoadenylate synthetase activity in serum accurately reflects the antiviral effect of interferon and could be used to monitor interferon treatment.

A proportion of chronic hepatitis C patients who were treated with interferon have a sustained normalization of transaminase levels after interferon therapy without hepatitis C virus (HCV)-RNA clearance. We determined their clinical characteristics and long-term outcome in relation to progression to liver cirrhosis (LC) and the development of hepatocellular carcinoma (HCC). A total of 250 patients with chronic hepatitis C who were treated with interferon were studied for 8 to 11 years' posttherapy. Sixty-seven patients (27%) were complete responders with clearance of HCV RNA. Twenty-six (10%) were biochemical responders who had sustained normal alanine transaminase (ALT) levels without viral clearance. The remaining patients were short-term responders (n ‫؍‬ 70) and nonresponders (n ‫؍‬ 87). Biochemical responders were older, had higher levels of pretreatment HCV RNA in serum than complete responders, and had less advanced liver histology than nonresponders. Histologic grading scores decreased significantly at the end of therapy, while the staging scores did not change significantly. The annual incidence of cirrhosis was 0% in biochemical and complete responders, which was significantly lower than nonresponders and the controls (P ‫؍‬ .0001). The annual incidence of HCC was 0.37% in complete responders and 0.50% in biochemical responders, which was significantly lower than nonresponders (P ‫؍‬ .0001 for both). Our findings suggest that biochemical responders had high pretreatment viral levels with less advanced liver histology, and their long-term outcome appeared to be good irrespective of the persistence of the virus. (HEPATOLOGY 2001;33:1299-1302.)Chronic hepatitis C is a major cause of liver cirrhosis (LC) and hepatocellular carcinoma (HCC) worldwide. [1][2][3][4][5] Interferon alfa (IFN) has been used for over 10 years in the treatment of this condition. Approximately 30% of patients with chronic hepatitis C who have been treated with IFN clear the virus and have sustained normal alanine transaminase (ALT) levels, but in the remaining patients, viremia persists. [6][7][8][9][10][11][12][13] Among the latter group, some patients have developed a sustained normal ALT activity despite a lack of virologic response. 14-17 Most of these patients make an initial biochemical and virologic response, but while the viral levels may return to pretreatment levels, the ALT levels remain in the normal range during long-term follow-up, suggesting that IFN has suppressed the liver disease activity without eradicating the virus. Little is known of the clinical significance and longterm outcome of patients with persistent viremia and normal ALT activity after cessation of IFN therapy. It is not known whether this condition is caused by viral factors such as mutations in the viral genome or by host factors such as immune response to the infection, or whether this situation should be regarded as a predictor of reactivation of liver damage and progression of disease. To clarify these issues, we studied a group of patients with l...