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Hepatitis C virus (HCV) is known to infect and replicate within peripheral blood mononuclear cells (PBMC), thereby enabling the direct evaluation of antiviral mechanisms by analyzing HCV dynamics in PBMC. To address potential molecular differences associated with distinct antiviral regimens, we studied HCV dynamics in both serum and PBMC in 44 patients with HCV genotype 1b and high viral load who were randomly assigned to the following 4 different treatment groups: 1) combination therapy with 6 MU daily of interferon alfa 2b (IFN‐α2b) plus 800 mg of ribavirin; 2) monotherapy with 6 MU daily of IFN‐α2b; 3) monotherapy with twice‐daily intravenous administration with 3MU of IFN‐β; and 4) monotherapy with daily intravenous administration with 6 MU of IFN‐β. HCV‐RNA levels were measured serially using highly sensitive real‐time detection polymerase chain reaction (PCR). HCV dynamics in both the serum and PBMC showed a “biphasic” pattern. The exponential decay slopes of the second phase were significantly higher in the combination or twice‐daily dosing regimen groups compared with groups 2 or 4 (0.10 ± 0.08 vs. 0.02 ± 0.09 or 0.16 ± 0.09 vs. 0.02 ± 0.04 day−1; P < .05 or P < .0005, respectively). Moreover, the viral half‐lives in the second phase were significantly shorter in these groups (73.2 ± 42.5 vs. 240.1 ± 120.7 or 56.0 ± 44.6 vs. 361.6 ± 293.5 hours; P < .05 or P < .05, respectively). Additionally, the slope of HCV decline in PBMC tended to be higher in the combination regimens, as compared with monotherapy. Taken together, our data on HCV dynamics provide molecular insight into utilization of combination or twice‐daily dosing regimens to increase rates of sustained viral eradication of HCV.

BACKGROUND In patients with hepatocellular carcinoma (HCC), recurrences in the distant liver often are observed after curative treatment. Microwave coagulation therapy (MCT) and radiofrequency ablation (RFA) have been developed as less invasive alternatives than surgical resection for small HCCs. In the current study, risk factors for distant recurrence of HCC were analyzed in patients in whom complete coagulation was achieved. METHODS Ninety‐two patients with HCCs < 3 cm in greatest dimension were treated by MCT or RFA percutaneously or laparoscopically. Eighty‐four patients in whom complete coagulation was achieved without recurrence in the same subsegment as the primary nodule were included in this study. Distant recurrences were observed in 22 patients. Fifteen possible risk factors for a distant recurrence were analyzed. RESULTS When comparing the patients with a recurrence of HCC nodules in the remnant liver to those without recurrence, the authors observed a statistically significant difference only in serum α‐fetoprotein. The distant recurrence‐free survival was analyzed by the Kaplan–Meier method. A statistically significant difference was observed in hepatitis C virus (HCV) infection as an etiopathic agent of underlying liver diseases (P < 0.005) and in the number of the primary HCC nodules (P < 0.05, log‐rank test). A multivariate stepwise Cox hazard model revealed that HCV infection and the number of primary HCC nodules were statistically independent risk factors. CONCLUSIONS Patients who had more than two HCC nodules accompanied by HCV infection had a high incidence of recurrence of HCC in the remnant liver, even when coagulation by microwave or ablation by radiofrequency was complete. Cancer 2001;91:949–56. © 2001 American Cancer Society.

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Background/Aims: The efficacy and side effects of interferon (IFN) therapy have not been well clarified in hemodialysis patients with chronic hepatitis C. Methods: In 6 of 9 hemodialysis patients with chronic hepatitis C, 3 million units (MU) or 6 MU of recombinant IFN-α2b or natural IFN-α were administered intramuscularly daily for the first 2 weeks, followed by three times a week for 22 weeks. In the remaining 3 patients, 3 MU of IFN-α2b were given three times a week for 24 weeks. Serum concentrations of IFN-α2b were measured sequentially after the injection of interferon. Responders were defined as the patients with normal serum aminotransferase and negative serum HCV RNA 6 months after the cessation of IFN therapy. Results: Three of the 6 patients who were administered IFN daily in the first 2 weeks were responders, while the other 3 withdrew from the therapy due to serious adverse events such as depression, loss of consciousness and persistence of high-grade fever. Serious adverse events were not observed in the 3 patients without daily administration. Half-lives of IFN-α2b in hemodialysis patients were significantly longer than those in nonuremic patients (10.0 vs. 6.0 h, p < 0.05). Moreover, the areas under the serum concentration curve of the hemodialysis patients were significantly larger than those of nonuremic patients (756 ± 223 vs. 324 ± 223 IU·h/ml, p < 0.05), despite the fact that the dose of IFN-α administered to hemodialysis patients was half that administered to nonuremic patients. Conclusions: In hemodialysis patients with chronic hepatitis C, pharmacokinetic parameters of IFN may be different from those in nonuremic patients, and daily or high-dose administration of IFN may lead to serious adverse events in those patients.