Eight patients were not eligible for IFN treatment because of LC, complication (depression), or advanced age. Seven patients had received IFN therapy in the past. Six patients were non-responders to IFN and 1 discontinued therapy because of Erlotinib HCl side effect (depression). All patients assessed the tolerability as excellent. Table 1 Characteristics of patients During fucoidan treatment, 11 patients received a glycyrrhizin preparation. Fucoidan (provided by Kanehide Bio Co., Okinawa, Japan) was given orally as capsules containing 166 mg of dry extract from C. okamuranus Tokida per capsule in a dose of five capsules daily for 12 mo. Informed consent was obtained from all patients enrolled in the study, after a thorough explanation of the aims, risks, and benefits of this therapy.
Test parameters The outcome parameters included the course of alanine aminotransferase (ALT), aspartate aminotransferase (AST), quantitative HCV RNA levels, subjective symptoms associated with CHC, LC, and HCC (such as fatigue, abdominal discomfort, depression, and dyspepsia), safety, and compliance. Data on all clinical parameters were documented at each visit. HCV RNA levels were determined using the AMPLICOR GT HCV Monitor test (Roche Diagnostics, Basel, Switzerland), which has a lower limit of quantitation of 0.5 kIU/mL at a linear range up to 850 kIU/mL. Statistical analysis Data are expressed as mean �� SD. The results of biochemical tests and HCV RNA levels were compared by the Student��s t test. A P < 0.05 was considered significant.
RESULTS Fucoidan suppresses HCV replication To assess the effects of fucoidan on intracellular replication of the HCV genome, HCV subgenomic replicon cells FLR3-1 were cultured in the presence of various concentrations of fucoidan in the medium. The luciferase activities of the FLR3-1 cells showed a concentration-dependent suppression of replication of HCV replicon by fucoidan. The WST-8 assay showed that fucoidan had negligible effect on cell viability (Figure (Figure1).1). These results suggest that fucoidan inhibits HCV replication but does not have cytotoxic effects. Figure 1 Anti-hepatitis C virus effects of fucoidan in hepatitis C virus replicon cells. Luciferase (LUC) activity (a marker of replication level) and cell viability of FLR3-1 cells, which constitutively express hepatitis C virus replicon, were measured in the …
Effect of fucoidan therapy on HCV RNA and alanine aminotransferase levels Changes in HCV RNA and serum ALT levels in patients treated with fucoidan GSK-3 are shown in Figure Figure2.2. The mean HCV RNA for the 15 patients was 736 �� 118 kIU/mL (range, 100-850 kIU/mL) before fucoidan therapy. As shown in Figure Figure2A,2A, fucoidan tended to reduce the mean HCV RNA level with time relative to the baseline, with significant falls registered at 8-10 mo of treatment. However, HCV RNA increased after 11 and 12 mo.