Real-time PCR assays for hepatitis C virus RNA (genotype 1) is useful for evaluating virological response to the treatment with peginterferon-alpha2b and ribavirin.

BACKGROUND: The real-time PCR, such as Abbott RealTime assay, have replaced end-point PCR, such as Amplicor assays, for the measurement of HCV RNA. However, 'response-guided therapy' to use on-treatment response for tailoring the duration of treatment with peginterferon-alpha and ribavirin has not been fully evaluated for real-time PCR. METHODS: 43 patients with HCV genotype 1 (24 who had complete early virological responses (cEVR) on Amplicor assay and received 48-week therapy, and 19 who had late virological responses (LVR) and received 72-week therapy) were recruited. Using a RealTime assay, we retrospectively measured HCV RNA in stored sera. RESULTS: In 10 samples obtained during therapy, HCV RNA was undetectable on the Amplicor assay, but detectable on the RealTime assay. Among patients with cEVR on the Amplicor assay, those with detectable HCV RNA on the RealTime assay at week 12 were less likely to have a sustained virological response (SVR) than those without (2/4 vs 17/20, p = 0.116). Among patients with LVR on the Amplicor assay, those with HCV RNA detectable on the RealTime assay at week 24 were significantly less likely to have SVR than those without (1/4 vs 12/15, p = 0.041). CONCLUSIONS: The RealTime assay may be useful for tailoring duration of treatment for the patient with HCV genotype 1.

Changes in sequences of core region, interferon sensitivity-determining region and interferon and ribavirin resistance-determining region of hepatitis C virus genotype 1 during interferon-alpha and ribavirin therapy, and efficacy of retreatment.

AIM: Some regions associated with sensitivity to interferon-α and ribavirin have been identified in the hepatitis C virus (HCV) genome, including amino acid 70 in the core region (core a.a. 70), a.a. 2209-2248 (interferon sensitivity-determining region, ISDR) and a.a. 2334-2379 (interferon and ribavirin resistance-determining region, IRRDR). METHODS: We examined changes in the sequences of these regions in 25 patients with chronic HCV genotype 1 infection who had not had sustained virological response (SVR) to interferon-α and ribavirin for 24-48 weeks and subsequently received retreatment for 48-72 weeks. RESULTS: At baseline, the core a.a. 70 was mutant (resistant) type in seven patients. At the start of retreatment, the core a.a. 70 had changed from sensitive to resistant type in 2 patients, and SVR was not achieved by retreatment. The ISDR variations were resistant type (0-1 mutations) in 17 patients at baseline. After 2 weeks of treatment, amino acid change was found in two patients; in one, the substitutions returned to baseline status after treatment, and in the other, the substitution persisted. At the start of retreatment, ISDR sequences had changed from resistant to sensitive type in two patients and SVR was achieved and from sensitive to resistant type in three patients and SVR was not achieved. The IRRDR variations were resistant type (<6 mutations) in 19 patients at baseline and at the start of retreatment. CONCLUSION: Sequences of the core region and ISDR sometimes change during anti-HCV therapy, potentially affecting the outcomes of retreatment.

Usefulness of noninvasive transient elastography for assessment of liver fibrosis stage in chronic hepatitis C.

AIM: To evaluate the method of noninvasive transient elastography for assessment of histological stage of liver fibrosis in patients with chronic hepatitis C (CHC). METHODS: Two hundred and thirty-seven patients with CHC were included in this study. Liver biopsy was performed under ultrasonography on 217 of the patients, excluding twenty with clear clinical evidence of liver cirrhosis. Fifty subjects without liver disease were enrolled as a control group (stage 0). Twenty-five patients with sustained virological response (SVR) to interferon (IFN) therapy were also enrolled. These patients underwent liver biopsy before IFN therapy. Examination of liver stiffness (LS) was performed by elastography. RESULTS: Medians (50% levels) of LS were 4.1 (3.5-4.9), 6.3 (4.8-8.5), 8.8 (6.8-12.0), 14.6 (10.5-18.6), and 22.2 (15.4-28.0), respectively, in the fibrosis stages 0-4 (P < 0.001). LS was significantly correlated with four serum fibrosis markers. LS values in patients with SVR were 3.8 (3.5-5.6), 5.2 (4.4-6.8), 6.8 (6.1-7.6), and 6.1 (3.6-7.9), respectively, in the fibrosis stages 1-4. In all stages, LS for patients with SVR was significantly lower than that for patients who did not undergo IFN therapy. LS was significantly correlated with serum concentrations of hyaluronic acid, type IV collagen, type IV collagen 7S, and type III procollagen N peptide. CONCLUSION: LS correlated well with the histological stage of fibrosis. Changes in liver fibrosis stage may thus be estimated noninvasively using transient elastography.