Akiyoshi Saga

Three cases of acute or fulminant hepatitis E caused by ingestion of pork meat and entrails in Hokkaido, Japan: Zoonotic food-borne transmission of hepatitis E virus and public health concerns.

Aim:  In developed countries including Japan, the transmission route of indigenous hepatitis E virus (HEV) infection is obscure. Accordingly, public health implications of indigenous HEV infection have not been well addressed. The aim of this study was to clarify the route of transmission of a small outbreak of acute hepatitis E and assess the public health implications of indigenous zoonotic HEV transmission.

Phase II Study of Combined Treatment with Irinotecan and S-1 (IRIS) in Patients with Inoperable or Recurrent Advanced Colorectal Cancer (HGCSG0302)

Objectives: This phase II study was designed to evaluate the efficacy and safety of oral fluoropyrimidine S-1 plus irinotecan (IRIS regimen) in patients with previously untreated metastatic colorectal cancer. Methods: The response rate was the primary endpoint. Safety, progression-free survival time, and median survival time were secondary endpoints. The subjects were untreated patients with inoperable advanced colorectal cancer. Irinotecan was administered at a dose of 100 mg/m2 (on days 1 and 15). S-1 (40 mg/m2) was administered for 2 weeks (on days 1 to 14) and followed by a 2-week rest. Results: Forty patients were enrolled. Four patients had grade 4 neutropenia, and six patients had grade 3 diarrhea. No other serious hematologic or nonhematologic adverse reactions occurred, and all patients received IRIS safely on an outpatient basis. The response rate was 52.5% (95% confidence interval [CI], 36.1–68.5%). Median progression-free survival was 8.6 months (95% CI, 5.3–11.9), and median survival time was 23.4 months (95% CI, 15.9–30.8). Conclusions: IRIS produced a high response rate and could be given safely. IRIS may become a first-line treatment for inoperable or recurrent advanced colorectal cancer.

Treatment of chronic non-A, non-B hepatitis with interferon

SummaryThe efficacy of interferon therapy (IFN) was investigated in 46 patients with chronic non-A, non-B (NANB) hepatitis, of would 40 (87.0%) were positive for anti-HCV antibody (Ab) (C-100-3). Three kinds of IFN were used; human lymphoblastoid interferon (HLBI), interferon alpha-2b and interferon beta. Total doses of IFN ranged from 1 million units (MU) to 10 MU and treatment duration ranged from 2 weeks to 144 weeks. Of 46 patients 34 (73.9%) responded to IFN. Nine patients have maintained normal ALT levels and 5 patients have maintained near-normal ALT levels for more than 6 months after cessation of IFN treatment. In these cases the titers of anti-HCV Ab had decreased significantly at the end of IFN therapy and 6 months after IFN therapy respectively. The mean age was young and the mean disease duration was short in effective cases. As for doses and treatment duration of IFN, low doses of IFN requires long treatment duration to acquire continuous efficacy and high doses of IFN requires rather short treatment durations. Therefore, early IFN treatment, higher doses and longer periods of IFN treatment may improve the response rate of patients with chronic NANB hepatitis.

Relationship Between Serum 2-5AS Activity and the Reduction of HCV-RNA During Interferon Therapy

The efficacy of using serum 2-5AS activity as the monitoring marker for the anti-viral effect of interferon (IFN) therapy in type C chronic hepatitis was evaluated. Thirty-seven patients were treated with IFN-α or IFN-β. HCV genotypes were determined by polymerase chain reaction according to the method of Okamoto et al. HCV-RNA disappeared in 22 of 37 patients (59.4%) after 28 consecutive days of IFN injection. As for HCV genotype, in types III and IV, eight of nine patients lost HCV-RNA irrespective of serum 2-5AS activity. In contrast, in type II, 13 of 27 patients lost HCV-RNA and the anti-viral effect of IFN (negativity of HCV-RNA) became apparent with a concurrent increase of serum 2-5AS activity. Thus, serum 2-5AS activity was closely related to the anti-viral effect of IFN therapy in type II HCV patients.

Serum 2′-5′oligoadenylate synthetase as a monitoring marker of antiviral effect during interferon therapy for chronic type B hepatitis

SummaryWe evaluated the usefulness of serum 2′–5′oligoadenylate synthetase (2–5AS) activity assay in monitoring the anti-viral activity of chronic type B hepatitis patients during IFN therapy. The serum 2–5AS activity was rapidly increased during the above therapy and was maintained at a medium-to-high level throughout the therapy period, although the capacity for increase reflected differences among individuals. The kinetics of serum 2–5AS activity during the therapy was almost consistent with that of the PBMCs 2–5AS activity. 2–5AS activity had an inverse correlation with DNA-P; i.e. DNA-P often disappeared from serum after interferon treatment in patients with a marked response in serum 2–5AS activity. The enhancement of serum 2–5AS activity during IFN therapy seemed to correlate with an increase in anti-viral activity. The results suggest that the serum 2–5AS activity assay is a useful probe for monitoring the anti-viral activity of chronic type B hepatitis patients during interferon therapy.