Hideo Hirofuji

Changes in serum hepatitis C virus RNA titer and response to interferon therapy in patients with chronic hepatitis C

Response to interferon (IFN) therapy for chronic hepatitis C has been determined by the alteration of serum alanine aminotransferase (ALT) values. However, eradication of hepatitis C virus (HCV) could be another aim of the therapy. Thus, we serially measured serum HCV RNA levels during therapy and for at least 12 months after cessation of therapy in 65 patients with chronic hepatitis C who received IFN-α (49 cases) or -β (16 cases). The presence of HCV and its amount were measured by the combination of nested and competitive PCR. Twenty-seven patients, who were categorized as complete responders, showed sustained normalization of ALT values for more than six months posttreatment. The viral RNA titers at pretreatment were significantly lower in complete responders (logarithmic copy numbers/ml: 5.4±1.3,P<0.001) than in partial and nonresponders. Complete response rate was significantly higher in patients with HCV genotype III (68.4%,P<0.01) than those with type II (23.6%). Among 27 complete responders, HCV RNA became undetectable in only 13 patients six months after completion of therapy, and 11 still had low levels of viremia; however, none experienced relapse of the disease during follow-up of 12–24 months. Three complete responders showed lasting high-titered viremia, and their ALT values rose again during follow-up. Our data suggest that IFN treatment of chronic hepatitis C is often ineffective in eradicating HCV infection even in responders, and long-term follow-up study is necessary to determine the sustained beneficial effect of IFN.

Randomized controlled trial of twice-a-day administration of natural interferon β for chronic hepatitis C

Abstract We conducted a randomized controlled trial to assess the efficacy of twice-a-day administration of natural interferon β (IFNβ) as an induction of IFN therapy for chronic hepatitis C. Seventy-one patients with chronic hepatitis C were enrolled into the trial and randomly assigned into three treatment groups. Six million units (MU) of IFNβ were administered once-a-day for the first 4 weeks, and then thrice weekly for 12 weeks in 20 patients (once-a-day group). Three milion units of IFNβ were administered twice-a-day for the first 2 weeks, 6 MU once-a-day for the next 2 weeks, and then thrice weekly for 12 weeks in 23 patients (twice-a-day+β group), or 6 MU of lymphoblastoid IFNα were administered thrice weekly for the last 12 weeks instead of IFNβ in 28 patients (twice-a-day+α group). Four patients in once-a-day group (20%), 9 in twice-a-day+β group (39%), and 12 in twice-a-day+α group (43%) obtained sustained response. Sustained response rate in twice-a-day groups was higher than in once-a-day group, although there was no statistical significance. The present study suggested the possible superiority of twice-a-day administration of IFNβ as an induction therapy to once-a-day administration, but further studies are needed to confirm this regimen.

Randomized controlled trial of lymphoblastoid interferon α for chronic hepatitis C (comparison of 9-MU and 6-MU doses)

Abstract Objective: We conducted a randomized controlled trial to compare the efficacy of two different dosages of lymphoblastoid interferon α (IFN) for the treatment of chronic hepatitis C. Methods: Eighty-four patients with chronic hepatitis C were enrolled and randomly assigned into the two groups; group A was treated with 6 million units (MU) and group B with 9 MU daily for the first 2 wk, and then thrice weekly for an additional 14 or 22 wk. Results: Eighty patients were evaluated (39 patients in group A and 41 in group B); 14 patients in group A (35.9%) and 15 in group B (36.6%) obtained sustained response. The percentages of patients who became negative for HCV RNA at the end of the second wk differed slightly between the groups, without statistical significance (56.4% and 68.3%). When assessed in detail, patients with genotype 1 and

Proliferation and immunoglobulin synthesis of peripheral blood mononuclear cells from patients with chronic liver disease stimulated by staphylococcus aureus cowan 1 and interleukin 2

SummaryProliferation and IgG synthesis of peripheral blood mononuclear cells (PBMC) in response to stimulation with recombinant interleuldn 2 (IL-2) and Staphylococcus aureus Cowan 1 (SAC) were evaluated in 32 patients with chronic persistent hepatitis (CPH), chronic active hepatitis (CAH) and liver cirrhosis (LC). Eleven patients had serum HBe antigen, 10 presented with HBe antibody and 11 had non-A, non-B hepatitis. IgG synthesis of PBMC induced with the two stimuli was significantly decreased in patients with CAH and LC when compared with that of controls. However, the generated amounts of IgG were not associated with the HB virus carrier state. B cells and T4+ cells were responsible for the diminished IgG synthesis in patients with CAH and LC when assessed by coculture experiments. On the other hand, proliferative response of PBMC to IL-2 and SAC were similar in controls and patient groups. These findings indicate that IgG production level of PBMC stimulated with IL-2 and SAC can reflect the severity of the underlying disease in chronic hepatitis patients.