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Tatsuo Kanda,
Keizo Kato,
Akihito Tsubota, Nobuo Takada,
Takayoshi Nishino,
Shigeru Mikami,
Tatsuo Miyamura,
Daisuke Maruoka,
Shuang Wu,
Shingo Nakamoto,
Makoto Arai,
Keiichi Fujiwara,
Fumio Imazeki,
Osamu Yokosuka
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ABSTRACT: To examine the epidemiological data, hematological safety and treatment responses of peginterferon-alpha 2a plus ribavirin therapy for hepatitis C.
Between March 2008 and February 2011, 196 hepatitis C virus (HCV) genotype 1 infected Japanese (127 treatment-naive and 69 treatment-experienced patients) patients treated with peginterferon-alpha 2a plus ribavirin were enrolled. We examined the epidemiological data and treatment responses were retrospectively analyzed in terms of hematological safety. HCV RNA was measured by the COBAS TaqMan HCV test.
Overall sustained virological response (SVR) rates of treatment-naive and treatment-experienced patients were 56% and 39%, respectively. Multivariate logistic regression analysis showed that SVR was attained independently of early virological response in both treatment-naive and treatment-experienced patients. SVR rates did not differ between the pretreatment hemoglobin < 13 g/dL and ≥ 13 g/dL groups. However, in treatment-naive patients, the SVR rate of the pretreatment platelet count < 130000/µL group was significantly lower than that of the pretreatment platelet count ≥ 130000/µL group.
Attention should be paid to potential thrombocytopenia in the treatment of chronic hepatitis C patients.
World journal of hepatology. 04/2013; 5(4):182-8.
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Tatsuo Kanda,
Shingo Nakamoto,
Takayoshi Nishino, Nobuo Takada,
Akihito Tsubota,
Keizo Kato,
Tatsuo Miyamura,
Daisuke Maruoka,
Shuang Wu,
Takeshi Tanaka,
Makoto Arai,
Shigeru Mikami,
Keiichi Fujiwara,
Fumio Imazeki,
Osamu Yokosuka
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ABSTRACT: Some patients infected with hepatitis C virus (HCV) genotype 2 could be cured with treatment shorter than 24 weeks using peginterferon plus ribavirin, but there are still treatment-refractory patients. Direct-acting antivirals (DAAs) are not currently available for HCV genotype 2 patients, different from genotype 1 patients, in clinical practice. We investigated 29 HCV genotype 2-infected Japanese patients who had been previously treated and failed to clear HCV. We retreated them with peginterferon alfa-2a plus ribavirin and measured HCV RNA level to assess the efficacy and safety of this treatment in patients who had failed previous therapy. We found that retreatment of HCV genotype 2-infected Japanese patients with peginterferon alfa-2a plus ribavirin for 24-48 weeks led to 60 to 66.6% sustained virological response (SVR) in patients previously treated with (peg-)interferon monotherapy and to 69.9% SVR in relapsers previously treated with peginterferon plus ribavirin. Attention should be paid to certain patients with unique features. Selection of patients according to their previous treatment could lead to optimal therapy in HCV genotype 2 treatment-experienced patients.
International journal of medical sciences 01/2013; 10(1):43-9. · 2.24 Impact Factor
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ABSTRACT: The efficacy of infliximab (IFX) has validated the role of TNF-α in the immunopathogenesis of Crohn's disease (CD). However, antibodies to IFX emerge, which impair its efficacy. This study investigated factor(s) associated with the loss of response (LOR) to IFX and how IFX non-responders may be treated.
Seventy-four patients, 36 IFX responders (GI) and 38 with LOR (GII) were included. Trough IFX level, CD activity index (CDAI) and immunological markers during IFX maintenance therapy were measured. Adsorptive granulocyte/monocyte apheresis (GMA) was applied to patients with LOR.
The durations of CD, 9.3 ± 5.5 yr and IFX therapy, 3.4 ± 2.0 yr in GII were longer vs GI (P=0.02, P=0.01). Similarly, C-reactive protein (P<0.0001) and CDAI (P<0.0001) in GII were higher. The median trough IFX was 4.7 μg/mL in GI and 8.4 μg/mL in GII, while the dose frequency was 8 weeks in GI and 4 weeks in GII. Soluble interleukin-2 receptor (sIL-2R) was higher in GII vs GI (P<0.001). Seropositive rates of anti-nuclear antibodies (ANA) and circulating immune complexes (CIC) in GII were 50.0% and 68.4%, significantly higher vs GI (P<0.05, P<0.01). Patients with LOR duration <1.5 yr showed higher CDAI and sIL-2R (P<0.05) vs patients with LOR duration <1.5 yr. Fifteen GII patients received GMA plus IFX combination and 46.7% responded. IL-10 increased in GMA-responders (P<0.05), while CIC and ANA decreased (P=0.0237, P=0.0463).
Patients with LOR to IFX had dysregulated immune response despite uncompromised trough IFX level. Further, inadequate T-cell differentiation by IFX was suggested. GMA appeared to benefit LOR patients by immunoregulation.
Cytokine 05/2012; 59(2):410-6. · 3.02 Impact Factor
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Journal of the American Geriatrics Society 01/2012; 60(1):185-7. · 3.74 Impact Factor
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Journal of the American Geriatrics Society 12/2011; 59(12):2373-5. · 3.74 Impact Factor
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Tatsuo Kanda,
Fumio Imazeki,
Shigeru Mikami,
Keizo Kato,
Noritomo Shimada,
Yutaka Yonemitsu,
Tomoo Miyauchi,
Makoto Arai,
Keiichi Fujiwara,
Akihito Tsubota, Nobuo Takada,
Takayoshi Nishino,
Motohide Takashi,
Nobuyuki Sugiura,
Michio Kimura,
Kenichi Fukai,
Osamu Yokosuka
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ABSTRACT: Advanced chronic hepatitis C patients with sustained virolological response by antivirals remain at risk for hepatocellular carcinoma (HCC). We investigated the incidence of HCC during and immediately after peginterferon-alfa-2a and ribavirin (RBV) treatment in patients with chronic hepatitis C in Japan. HCC was detected in 8 of 238 patients during and after these treatments (mean follow-up period: 572 ± 252 days). In conclusion, occurrence of HCC is not a rare event during and immediately after peginterferon-alfa-2a plus RBV treatment. In cases with cirrhosis, higher α-fetoprotein levels, old age, or a previous history of HCC treatment, clinicians should be especially alert for the possible development of HCC during and immediately after peginterferon-alfa-2a and RBV treatment. Clinicians should regularly check for the possible development of HCC even in chronic hepatitis C patients under treatment.
Oncology 08/2011; 80(5-6):366-72. · 2.27 Impact Factor
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ABSTRACT: Infliximab (IFX) is an antitumor necrosis factor (TNF)-α antibody used to treat Crohn's disease (CD). However, antibodies to IFX (ATI) emerge, which can impair its efficacy. A fluid-phase enzyme immunoassay (FP-EIA) was established for measuring serum functional IFX (f-IFX) in CD patients receiving maintenance IFX.
In 31 patients, 16 had maintained response (GI) and 15 had lost response to IFX despite good initial response (GII) were selected. Serum f-IFX was measured just before and immediately after IFX infusion and the values together with CD activity index (CDAI) and C-reactive protein (CRP) were compared.
IFX therapy in GI and GII were 1.8 ± 1.2 years and 2.7 ± 1.5 years, respectively, while the median dose frequency was 56 days in GI and 29 days in GII. Our FP-EIA for f-IFX showed TNF-α binding increasing with the IFX dose, which was suppressed by antibodies to IFX. On the infusion day, CRP and CDAI in GII were significantly higher than in GI, while median trough f-IFX for GI and GII were 4.7 μg/mL and 6.3 μg/mL, respectively. The median f-IFX immediately after IFX infusion for GI and GII were 149.5 μg/mL and 126.3 μg/mL, respectively (P = 0.0488), and binary logistic regression showed conditional maximum likelihood estimate to be -0.0258 (P = 0.0395), supporting association of low postinfusion f-IFX to the loss of response.
FP-EIA could accurately measure f-IFX. High serum ATI strongly impacted f-IFX levels immediately after an infusion. The postinfusion f-IFX level was associated with clinical response. f-IFX level should be valuable in decision-making to optimize treatment efficacy.
Inflammatory Bowel Diseases 03/2010; 16(11):1898-904. · 4.86 Impact Factor
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ABSTRACT: Intestinal microflora has been implicated in the etiology of ulcerative colitis (UC). Over the past few years, the use of probiotics in UC has gained attention. The aim of this study was to evaluate the efficacy of probiotics therapy for mild to moderate distal UC refractory to conventional therapies.
Twenty patients with mild to moderate distal UC took 9 BIO-THREE tablets per day for 4 weeks. Clinical symptoms and endoscopic findings were evaluated as ulcerative colitis disease activity index (UCDAI) scores before and after administration of BIO-THREE. Fecal samples were collected from all patients before and after probiotics administration, and fecal microflora was analyzed by the terminal restriction fragment length polymorphism (T-RFLP) method.
Remission (UCDAI score < or =2) was observed in 45% (9/20) of the patients; response (decrease in UCDAI > or = 3, but final score > or = 3) in 10% (2/20); no response in 40% (8/20); and worsening (UCDAI > 3) in 5% (1/20). T-RFLP analysis indicated that the principal alteration in microflora was an increase in bifidobacteria.
This study showed that administration of BIO-THREE improved the clinical symptoms and endoscopic findings in patients with UC, indicating that administration of BIO-THREE is safe and efficacious for the treatment of UC.
Scandinavian Journal of Gastroenterology 12/2007; 42(11):1306-11. · 2.02 Impact Factor
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ABSTRACT: Adacolumn selective granulocyte and monocyte apheresis (GMA) depletes activated leukocytes in patients with ulcerative colitis (UC). However, this per se cannot fully explain the efficacy of GMA. We have investigated the effects of GMA on the expression of toll-like receptors (TLRs) and plasma interleukin-8 (IL-8). Twenty-two patients with clinical activity index (CAI) of 5-17, 15 with total colitis and 7 with left-sided colitis, were included. Each patient could receive up to 10 GMA sessions, at 1 or 2 sessions per week. GMA was added to the patients' ongoing medication following a relapse or worsening UC, but no additional medication was given. Further, at entry and pre-GMA, blood samples were taken for full blood cell count, expression of TLRs on leukocytes, and plasma IL-8. Seventy-five percent of patients achieved remission after the 10th session (CAI, < or =4; P < 0.005) and there was a marked fall in C-reactive protein (P < 0.01), plasma IL-8 (P < 0.001), and granulocytes (P < 0.05) but an increase in lymphocytes (P < 0.05). The expression of TLR2 on granulocytes was down-modulated (P < 0.05) together with suppression of inflammatory cytokines produced by peripheral blood leukocytes. In conclusion, GMA appears to be an effective adjunct therapy to induce remission in the majority of patients, who are then spared from excess drug therapy. The procedure is associated with sustained immunomodulation. Control studies should strengthen these findings.
Digestive Diseases and Sciences 06/2007; 52(6):1427-33. · 2.12 Impact Factor
