Eiji Kajiwara

Kyushu University, Hukuoka, Fukuoka, Japan

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Publications (26)100.28 Total impact

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    ABSTRACT: Background and AimsThrombocytopenia (TCP) of chronic hepatitis C patients with cirrhosis has a negative impact on the management of interferon-based treatment. The aim of this study is to evaluate the efficacy and safety of telaprevir (TVR)-based triple therapy for patients who have undergone splenectomy (Spx).Methods This prospective, multicenter study consisted of 80 patients, including 32 Spx and 48 non-Spx/TCP (platelet count: 60-99×109/L) patients with advanced fibrosis infected with HCV genotype 1b. All received 12 weeks of TVR in combination with 24 weeks of pegylated interferon (PEG-IFN) α2b and ribavirin.ResultsThe sustained virological response (SVR) rate of the Spx group (75.0%) was significantly higher than that of the non-Spx/TCP group (52.1%) (P<0.05). Under favorable conditions such as treatment-naïve/prior relapse and interleukin-28B (IL28B) TT allele (rs8099917), the SVR rates of the Spx group were significantly higher than those of the non-Spx/moderate TCP (60-79×109/L) groups (91.3% vs. 50.0% and 93.8% vs. 37.5%, respectively; both P<0.05). Adequate PEG-IFNα2b adherence was associated with SVR. However, the percentage of patients who achieved 80% adherence to PEG-IFNα2b in the non-Spx/moderate TCP (42.9%) group was significantly lower than that of the Spx (79.3%) and non-Spx/mild TCP (80-99×109/L) (80.0%) groups. Treatment discontinuation due to adverse effects and the development of bacterial infection did not differ between the Spx and non-Spx/TCP groups.Conclusion The increase of platelet count after splenectomy contributed to treatment success, especially for moderate to severe TCP patients who are treatment-naïve/prior relapse or IL28B TT allele.
    Journal of Gastroenterology and Hepatology 04/2014; · 3.33 Impact Factor
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    ABSTRACT: Elevated serum low-density lipoprotein cholesterol (LDL-C) level has been associated with sustained virological response (SVR) by chronic hepatitis C patients treated with pegylated-interferon (PEG-IFN) α and ribavirin (RBV). The aim of this study was to investigate the relation between the baseline LDL-C level and the treatment outcome from telaprevir (TVR)-based triple therapy. This prospective, multicenter study consisted of 241 treatment-experienced patients infected with HCV genotype 1b. All received 12 weeks of TVR in combination with 24 weeks of PEG-IFNα2b and RBV. The SVR rate was 81.3% (196 of 241) by intention-to-treat analysis. Higher LDL-C level was strongly associated with SVR (P=1.3×10-8). The area under the receiver operating characteristic curve for predicting SVR was 0.78 and the cutoff value for the LDL-C level at baseline was 95 mg/dL. InmultivariablelogisticregressionanalysisofpredictorsofSVR,°LDL-C°⩾°95°mg/dL°(odds°ratio°[OR]°3.60,°P=0.0238),°α-fetoprotein°⩽°5.0°ng/mL°(OR°5.06,°P=0.0060),°prior°relapse°to°PEG-IFNα°and°RBV°(OR°5.71,°P=0.0008),°and°rapid°virological°response°(HCV°RNA°undetectable°at°week°4)°(OR°5.52,°P=0.0010)°were°extracted°as°independent°predictors°of°SVR. For prior partial and null responders, the SVR rates of the groups with LDL-C ⩾ 95 mg/dL were significantly higher than those of the < 95 mg/dL groups with IL28B TG/GG and pretreatment platelet count < 150×109/L (both P<0.05). The baseline LDL-C level exerted a potent influence on the SVR of treatment-experienced patients treated with TVR-based triple therapy, especially for prior partial and null responders to PEG-IFNα and RBV.
    Antiviral research 01/2014; · 3.61 Impact Factor
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    ABSTRACT: Due to advances in interferon (IFN) therapy for chronic hepatitis C, most elderly patients, and even many of those with advanced hepatic fibrosis, now achieve a sustained virological response (SVR). However, carcinogenesis remains problematic in these patients. Hence, we aimed to elucidate risk factors for hepatocarcinogenesis in SVR patients and to present an appropriate follow-up protocol for improving outcomes. We retrospectively studied 562 consecutive SVR patients for a median observation period of 4.8 years. Hepatocellular carcinoma was diagnosed in 31 patients (5.5 %). Respective cumulative incidences were 3.1, 10.1, and 15.9 % at 5, 10, and 15 years after completion of IFN therapy. The proportional hazards model identified moderate or advanced fibrosis stage, advanced age, habitual alcohol consumption, and alpha-fetoprotein elevation as determinants of carcinogenesis, with hazard ratios of 10.7 (p < 0.001), 4.1 (p < 0.01), 3.9 (p < 0.01), and 2.6 (p < 0.05), respectively. Carcinoma was diagnosed in 26 % of patients more than 10 years after completion of IFN therapy. Unexpectedly, F2 fibrosis was detected in 42 % of these patients. The 5-year survival rate was 93 % in the patients who had received periodic cancer screening but only 60 % in those who had not. We recommend that SVR patients be observed at 6-month intervals, at a minimum, to facilitate diagnosis at an early stage, for as long as possible after completion of therapy even if not at an advanced stage of fibrosis.
    Journal of Gastroenterology 12/2013; · 3.79 Impact Factor
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    ABSTRACT: Thrombocytopenia in patients with chronic hepatitis C may represent an obstacle for the initiation of antiviral treatment. The aim of this study was to evaluate factors predictive of successful pegylated interferon (PEG-IFN) α2b and ribavirin (RBV) treatment for patients with thrombocytopenia with no history of splenectomy or partial splenic embolization. One hundred and fifty-one chronic hepatitis C patients (genotype 1: n = 110, genotype 2: n = 41) with TCP (<100 × 10(9) /L) at baseline were enrolled. Pretreatment variables included interleukin 28B (IL28B) genotype (rs8099917) and homoeostasis model assessment of insulin resistance score (HOMA-IR). The kinetics of haemoglobin and platelets according to the inosine triphosphatase (ITPA) genotype (rs1127354) were investigated. Sustained virological response (SVR) was significantly more frequent in hepatitis C virus (HCV) genotype 2 (65.9%) than in genotype 1 (34.5%) patients (P < 0.0001). Multiple logistic regression analysis of HCV genotype 1 extracted IL28B TT genotype [odds ratio (OR) 5.97, P = 0.006] and HOMA-IR <2.5 (OR 7.14, P = 0.0016) as significant independent pretreatment predictors of SVR. The analyses of HCV genotype 2 showed that HOMA-IR was significantly related to SVR, but IL28B genotype was not. Patients with ITPA CC genotype showed a significant haemoglobin reduction and lower degree of platelets decrease than those with ITPA CA/AA genotypes. The most common reason for premature discontinuation of treatment was the development of hepatocellular carcinoma (n = 8, 5.3%). In conclusion, HOMA-IR is a useful predictor of SVR for patients with thrombocytopenia infected with HCV genotype 1 or 2 treated with PEG-IFNα2b and RBV. The inclusion of IL28B, ITPA genotypes and HOMA-IR adds valuable therapeutic information.
    Journal of Viral Hepatitis 12/2013; 20(12):838-46. · 3.08 Impact Factor
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    ABSTRACT: Antiviral treatment is recommended for chronic hepatitis C patients with advanced fibrosis to reduce and prevent cirrhosis-related complications. To evaluate the efficacy and safety of telaprevir (TVR)-based triple therapy for patients with advanced fibrosis in a clinical practice setting. This prospective, multicentre study consisted of 102 patients with advanced fibrosis (METAVIR score F3-4) who were infected with HCV genotype 1b. All received 12 weeks of TVR in combination with 24 weeks of pegylated interferon (PEG-IFN) α2b and ribavirin (RBV). The sustained virological response (SVR) rate was 69.6% (71 of 102). Notably, for treatment-naïve and prior relapse patients the SVR rate was over 80%. Previous treatment response, interleukin 28B polymorphism (rs8099917) and rapid virological response (undetectable HCV RNA at week 4) were independently associated with SVR. To achieve SVR, an adequate dosage of PEG-IFNα2b (≥1.2 μg/kg/week) and RBV (≥7.5 mg/kg/day) is preferable; however, the mean weight-adjusted TVR dosage had little impact on treatment outcome. Although severe blood cytopaenia and a dermatological disorder were frequently found, the rate of discontinuation due to adverse effects was 12.7%. The inosine triphosphatase CC allele (rs1127354) was independently associated with the development of severe anaemia, and lower serum albumin level (<35 g/L) was associated with the occurrence of infection. The great gain in the SVR rate by telaprevir-based triple therapy offsets the problems with adverse effects; thus, it should be considered as a potent treatment protocol for patients with advanced fibrosis, especially for those with treatment-naïve and prior relapse.
    Alimentary Pharmacology & Therapeutics 11/2013; 38(9):1076-1085. · 4.55 Impact Factor
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    ABSTRACT: BACKGROUND & AIMS: Anemia is a common adverse effect of telaprevir (TVR) in combination with pegylated interferon (PEG-IFN) α and ribavirin (RBV) therapy. It occurs at a higher incidence with the TVR relative to PEG-IFNα and RBV alone. We herein evaluate the baseline and on-treatment predictors of the development of severe anemia by chronic hepatitis C virus (HCV) patients receiving TVR-based triple therapy. METHODS: This prospective, multicenter study consisted of 292 patients (median age: 62 years) infected with HCV genotype 1. All received 12 weeks of TVR in combination with 24 weeks of PEG-IFNα2b and RBV. The definition of severe anemia during antiviral treatment is hemoglobin (Hb) <85 g/L. RESULTS: 101 (34.6%) patients developed severe anemia during the treatment period. Multivariable logistic regression analysis of possible pretreatment predictors of the development of severe anemia extracted baseline Hb<135 g/L (Hazard ratio [HR], 2.53; P=0.0013), estimated glomerular filtration rate <80 mL/min/1.73m(2) (HR, 1.83; P=0.0265), and inosine triphosphatase (ITPA) CC genotype (rs1127354) (HR, 2.91; P=0.0024). For patients with ITPA CC (n=227), multivariable logistic regression analysis of possible pretreatment and on-treatment predictors of the development of severe anemia extracted Hb level at week 2 (HR, 0.96; P=0.0085) and the initial four weeks of weight-adjusted TVR (HR, 1.05; P=0.0281). CONCLUSIONS: Anemia remains a risk for all patients treated with TVR-based triple therapy. However, ITPA polymorphism (rs1127354) is useful for predicting the development of severe anemia and will be helpful in the management of treatment.
    Journal of Hepatology 05/2013; · 9.86 Impact Factor
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    ABSTRACT: BACKGROUND AND AIMS: This study was done to evaluate the efficacy of a triple therapy by older Japanese patients; Telaprevir (TVR) added to pegylated interferon-α2b and ribavirin. METHODS: This prospective study enrolled 120 genotype 1b patients with chronic hepatitis C who received 12 weeks of triple therapy followed by a 12-week dual therapy that included pegylated interferon-α2b and ribavirin. Patients were categorized according to age: group A, 64 patients aged>60 and group B, 56 patients aged⩽60. Serum HCV RNA levels were monitored by COBAS TaqMan HCV test. RESULTS: The rates of undetectable HCV RNA at week 4 (rapid virological response, RVR) were 73.4% in group A and 73.2% in group B. No significant difference in sustained virological response (SVR) was found between groups A (76.6%) and B (83.9%) (P=0.314). The SVR rates for patients with interleukin 28B (IL28B) (rs8099917) TT allele (89.4% and 91.9% for groups A and B) were significantly higher than for those with the IL28B TG/GG allele (41.2% and 68.4%, respectively) (both P<0.05). Multivariate analysis extracted IL28B TT and RVR as independent factors associated with SVR. Adverse effects resulted in treatment discontinuation by 12.5% in each group. Hemoglobin decrease significantly differed between groups A and B: the decrease to ⩾100g/L, to 85 - <100g/L, and to <85g/L, 9.4%, 40.6%, and 50% of group A patients, respectively, and 41.1%, 25%, and 33.9% of group B patients, respectively (P=0.0006). CONCLUSIONS: TVR-based triple therapy can be used successfully to treat older patients with genotype 1b chronic hepatitis C.
    Journal of Hepatology 03/2013; · 9.86 Impact Factor
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    ABSTRACT: We report a case of repeat hepatectomies for hepatic malignant lymphoma and hepatocellular carcinoma (HCC). A 75-year-old man with chronic hepatitis C underwent partial hepatectomy for a 25 mm hepatic tumor in S5. The histological diagnosis was diffuse large B-cell malignant lymphoma and as postoperative (18)F-fluorodeoxyglucose-positron emission tomography showed no hot spots, the mass was presumed to be primary hepatic lymphoma. Thus, adjuvant systemic chemotherapy was given following the hepatectomy. Abdominal ultrasonography, done 12 months after the hepatectomy, showed a hepatic tumor in S6 and repeat partial hepatectomy was performed. This tumor was histologically diagnosed as HCC.
    Surgery Today 02/2013; · 0.96 Impact Factor
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    ABSTRACT: BACKGROUND AND AIMS: The effects of pegylated interferon (PEG-IFN) α and ribavirin (RBV) treatment for chronic hepatitis C on the incidence of hepatocellular carcinoma (HCC) have not been well established. This study investigated the impact of treatment outcome on the development of HCC by chronic hepatitis C patients treated with PEG-IFNα2b and RBV. METHODS: This large-scale, prospective, multicenter study consisted of 1,013 Japanese chronic hepatitis C patients with no history of HCC (non-cirrhosis, n=863 and cirrhosis, n=150). All patients were treated with PEG-IFNα2b and RBV and the follow-up period started at the end of antiviral treatment (median observation period of 3.6 years). The cumulative incidence rate of HCC was estimated by the Kaplan-Meier method according to treatment outcome. RESULTS: Forty-seven patients (4.6%) developed HCC during the observation period. In the non-cirrhosis group, the 5-year cumulative incidence rates of HCC for the sustained virological response (SVR) (1.7%) and transient virological response (3.2%) (TVR: defined as relapse or breakthrough) groups were significantly lower than that of the non-virological response (NVR) group (7.6%) (P=0.003 and P=0.03, respectively). A significantly low rate of incidence of HCC by TVR patients in comparison with NVR patients was found for patients with aged 60 and over, but not for those aged under 60. In the cirrhosis group, the 5-year cumulative incidence rates of HCC for the SVR (18.9%) and TVR groups (20.8%) were also significantly lower than that of the NVR group (39.4%) (P=0.03 and P=0.04, respectively). CONCLUSIONS: SVR and complete viral suppression during treatment with relapse (TVR) were associated with a lower risk of the development of HCC when compared with NVR.
    Journal of Hepatology 10/2012; · 9.86 Impact Factor
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    ABSTRACT: AIM: A sustained virological response (SVR) to interferon (IFN) therapy for chronic hepatitis C decreases but does not eliminate the risk of hepatocellular carcinoma (HCC). The significance of hepatectomy for HCC in patients with SVR has not been clarified. The short- and long-term outcomes of hepatectomy for HCC in patients with SVR were studied. METHODS: From 2006-2011, 69 patients with chronic hepatitis C underwent hepatic resection for primary HCC in our hospital. Of these, 12 patients (17.4%) had SVR to IFN therapy at the time of hepatectomy. The clinicopathological factors and long-term outcomes of these patients were retrospectively reviewed and were compared with those of patients without SVR. RESULTS: The mean time from achievement of SVR to diagnosis of HCC was 62 months (range, 7-174). The histological inflammation of liver parenchyma had improved after IFN therapy in SVR cases. The preoperative serum alanine transaminase, albumin and prothrombin time were significantly preserved in patients with SVR. Intraoperative blood loss and blood transfusion rate were lower, and recurrence-free survival rate was significantly higher, in patients with SVR. CONCLUSION: In patients undergoing hepatectomy for HCC, those with SVR had better perioperative safety and a more favorable long-term prognosis than those without SVR.
    Hepatology Research 10/2012; · 2.07 Impact Factor
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    ABSTRACT: BACKGROUND & AIMS: Early menopause in women with chronic hepatitis C virus (HCV) infection is associated with a low likelihood of a sustained virological response (SVR) in conjunction with their antiviral treatment. This is potentially related to their reduced estrogen secretion. The study was done to determine whether selective estrogen receptor modulator administration might improve the efficacy of the current standard of care (SOC) treatment, pegylated interferon (PegIFN) α2a plus ribavirin (RBV), for postmenopausal women. METHODS: One hundred and twenty-three postmenopausal women with genotype 1b chronic hepatitis C were randomly assigned to one of two treatment groups: raloxifene hydrochloride (RLX) (60mg/day) plus SOC (PegIFNα2a 180μg/week and RBV 600-1000mg/day) (n=62) or SOC only (n=61). Genotyping was performed of the polymorphism in the interleukin-28B (IL28B) gene region (rs8099917) of DNA collected from each patient. RESULTS: One RLX-treated patient discontinued RLX because of a systemic rash following 2weeks of treatment. Twenty-four weeks after treatment, the SVR rate was significantly higher for RLX plus SOC patients (61.3%) than for SOC only patients (34.4%) (p=0.0051). Further, the SVR rate was significantly higher for RLX plus SOC patients with IL28B TT (72.5%) than for SOC only patients with IL28B TT (39.2%) (p=0.0014), but no such relationship was observed in patients carrying the minor IL28B allele. CONCLUSIONS: RLX improved the efficacy of SOC in the treatment of postmenopausal women with chronic hepatitis C. RLX shows promise as an adjuvant to the standard antiviral treatment of such patients.
    Journal of Hepatology 08/2012; · 9.86 Impact Factor
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    ABSTRACT: BACKGROUND: We investigated whether the administration of maintenance doses of interferon prevented hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. METHODS: Study 1: A multicenter, retrospective, cooperative study was carried out to determine whether long-term administration of low-dose peginterferon alpha-2a (PegIFNα-2a) prevented HCC development in patients with chronic hepatitis C. In total, 594 chronic hepatitis C patients without a history of HCC were enrolled and treated with 90 μg PegIFNα-2a administered weekly or bi-weekly for at least 1 year. Study 2: HCC developed in 16 of 99 additional patients without PegIFNα-2a treatment during 3.8 years of observation. A propensity-matched control study was then carried out to compare the incidence of HCC between the 59 patients who received low-dose PegIFNα-2a (PegIFNα-2a group) and 59 patients who did not receive PegIFNα-2a treatment (control group), matched for sex, age, platelet count, and total bilirubin levels. RESULTS: Study 1: HCC developed in 49 patients. The risk of HCC was lower in patients with undetectable hepatitis C virus RNA, ≤40 IU/L alanine aminotransferase (ALT), or ≤10 ng/L alpha-fetoprotein (AFP) 24 weeks after the start of therapy. Study 2: The incidence of HCC was significantly lower in the PegIFNα-2a group than in the control group. CONCLUSIONS: Low-dose and long-term maintenance administration of PegIFNα-2a decreased the incidence of HCC in patients with normalized ALT and AFP levels at 24 weeks compared with patients without normal ALT and AFP levels.
    Journal of Gastroenterology 08/2012; · 3.79 Impact Factor
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    ABSTRACT: The aim of this large-scale analysis was to assess the effect of 48-week pegylated interferon (PEG-IFN) α-2b and ribavirin (RBV) therapy on virological relapse by patients infected with hepatitis C virus (HCV) genotype 1. The relationship between virological relapse and the dose of PEG-IFNα-2b and RBV was investigated in 619 patients who had once cleared HCV RNA during PEG-IFNα-2b and RBV treatment for 48 weeks. The overall virological relapse rate was 34.1% (211 of 619). The relapse rate was 59.5% (22 of 37) for patients who received <6 mg/kg/day of RBV, even if a sufficient dose of PEG-IFNα-2b (≥1.5 μg/kg/day) was received. In contrast, the relapse rate was 28.1% (16 of 57) for patients who received ≥12 mg/kg/day of RBV, irrespective of the PEG-IFNα-2b dose. The relapse rates were significantly increased with the reduction of the RBV dose for both PEG-IFNα-2b doses of ≥1.2 and <1.2 μg/kg/week (P < 0.0001 and P = 0.0006, respectively). Moreover, the relapse rate was 41.2% (35 of 85) for patients with an early virological response (EVR) who received <6 mg/kg/day of RBV. The relapse rates were significantly increased with the reduction of the RBV dose in both those patients with an EVR and those with a late virological response (P = 0.0006 and P = 0.0088, respectively). To summarize, for HCV genotype 1 patients treated with PEG-IFNα-2b and RBV, the virological relapse of HCV was RBV dose-dependent, irrespective of the dose of PEG-IFNα or the effect of early viral kinetics.
    Journal of Infection and Chemotherapy 03/2012; · 1.55 Impact Factor
  • Eiji Kajiwara, Aritune Ooho, Naoki Yamashita
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    ABSTRACT: Aim:  The purpose of this clinical study was to determine the effect of a biweekly low-dosage peginterferon α-2a treatment program on serum alanine aminotransferase (ALT) and α-fetoprotein (AFP) levels. Methods:  Fifty-five patients participated in the study. The inclusion criteria included chronic genotype 1b hepatitis C virus (HCV) infection, liver cirrhosis, or the absence of cirrhosis in subjects 65 years old or above, and interferon therapy naivety or a lack of sustained response to therapy with interferon-plus-ribavirin or peginterferon-plus-ribavirin. Patients were divided into naïve, relapser, and non-responder groups. The median age of the patients was 70 years, and 73% of patients had cirrhosis. All patients were treated with peginterferon α-2a at 90 µg biweekly. Results:  The rates of normalization (≤30 IU/l) of ALT levels at week 24 in the relapser group and the ≥2 log(10) HCV RNA decline group were high (74% and 68%, respectively). However, the ALT and AFP levels decreased significantly in each group, including the non-responder group. The ALT levels decreased significantly even in patients in whom the HCV RNA levels did not decrease. Furthermore, the AFP levels decreased significantly in the patients showing no decline in the ALT and HCV RNA levels. Only three patients discontinued treatment within 48 weeks due to adverse events, and more than 70% of the patients experienced no subjective symptoms during treatment. Conclusion:  A biweekly low-dosage peginterferon α-2a therapy is effective for reducing the serum levels of ALT and AFP and may reduce hepatocarcinogenesis in patients with liver cirrhosis and in the elderly individuals.
    Hepatology Research 12/2011; 42(3):254-63. · 2.07 Impact Factor
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    ABSTRACT: Aim:  To investigate the efficacy and safety of a pegylated interferon (PEG-IFN) α-2b plus ribavirin (RBV) combination treatment for patients with chronic hepatitis C virus (HCV) infection who have persistently normal alanine aminotransferase (NALT). Methods:  This multicenter study included 989 patients with HCV genotype 1 (114 with NALT and 875 with elevated ALT) who received weight-based doses of PEG-IFN α-2b plus RBV for 48 weeks. We compared the sustained viral response (SVR) rates of patients with NALT and elevated ALT who received at least 80% or more of the target dosage of PEG-IFN α-2b and 60% or more of the target RBV (minimum acceptable dosage). Results:  No significant difference was found in the overall SVR rate between the NALT (42.1%) and elevated ALT groups (37.3%). No significant difference in the SVR rates was found between NALT (63.3%) and elevated ALT group (61.6%) patients who received minimum acceptable dosage. Multivariate analysis showed that age (<65 years old) and total cholesterol (≧220 mg/dL) were significantly independent positive factors associated with an SVR in the NALT group. Twenty-four weeks after treatment, an ALT increase above the normal range was observed for 34.0% (18 of 53) of the non-responsive group of NALT patients. Conclusions:  The efficacy and safety of PEG-IFN α-2b plus RBV combination therapy for patients with chronic HCV infection are similar for patients with NALT and those with elevated ALT levels. These results indicate that patients with NALT should be considered for treatment with PEG-IFN α-2b plus RBV.
    Hepatology Research 11/2011; 42(1):33-41. · 2.07 Impact Factor
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    ABSTRACT: Pegylated interferon (PEG-IFN) α-2b and ribavirin (RBV) treatment of chronic hepatitis C virus (HCV) infection is associated with a substantially elevated risk of discontinuation. The aim of this study is to evaluate the reason for premature discontinuation during PEG-IFN α-2b and RBV treatment due to adverse effects in patients with chronic HCV infection. A total of 2871 Japanese patients who had chronic HCV infection treated with PEG-IFN α-2b and RBV were screened. We prospectively investigated the reasons for premature discontinuation of treatment classified by sex and age, and analyzed the timing of discontinuation. Of the 2871 patients, 250 (8.7%) discontinued treatment because of adverse effects. The main reasons for premature discontinuation were neurovegetative symptoms (n = 77, 30.8%), depression-related syndrome (n = 46, 18.4%), hematologic effects (n = 41, 16.4%) and dermatologic effects (n = 27, 10.8%). The rate of discontinuation of treatment for patients aged ≥ 65 years was significantly higher than for patients aged < 65 years, for both men (P < 0.0001) and women (P = 0.0121). Moreover, the frequency of discontinuation due to neurovegetative symptoms, depression-related syndrome, and hematologic effects for men aged ≥ 65 years was significantly higher than for those aged < 65 years (P = 0.0001, P = 0.0016, and P = 0.0170, respectively), but not for women. Premature discontinuation due to the adverse effects of PEG-IFN α-2b and RBV treatment by patients with chronic HCV infection is mainly due to neuropsychiatric symptoms and is more common for older than for younger patients.
    Journal of Gastroenterology and Hepatology 11/2011; 27(7):1233-40. · 3.33 Impact Factor
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    ABSTRACT: To analyze the efficacy and safety of a combination therapy of pegylated interferon (PEG-IFN) α-2b plus ribavirin (RBV) in older Japanese patients (65 years or older) infected with hepatitis C virus (HCV). This multicenter study included 938 patients with HCV genotype 1 who received 1.5 μg/kg per week PEG-IFN α-2b plus RBV 600-1000 mg/d for 48 wk and 313 HCV genotype 2 patients who received this treatment for 24 wk. At 24 wk after the end of combination therapy, the overall sustained virological response (SVR) for genotypes 1 and 2 were 40.7% and 79.6%, respectively. The SVR rate decreased significantly with age in each genotype, and was markedly reduced in genotype 1 (P < 0.001). Moreover, the SVR was significantly higher in patients with genotype 1 who were less than 65 years (47.3% of 685) than in those 65 years or older (22.9% of 253) (P < 0.001) and was higher in patients with genotype 2 who were less than 65 years (82.9% of 252) than in those 65 years or older (65.6% of 61) (P = 0.004). When patients received a dosage at least 80% or more of the target dosage of PEG-IFN α-2b and 60% or more of the target dosage of RBV, the SVR rate significantly increased to 66.5% in patients less than 65 years and to 45.2% in those 65 years or older (P < 0.001). Adverse effects resulted in treatment discontinuation more often in patients with genotype 1 (14.4%) than in patients with genotype 2 (7.3%), especially by patients 65 years or older (24.1%). PEG-IFN α-2b plus RBV treatment was effective in chronic hepatitis C patients 65 years or older who completed treatment with at least the minimum acceptable treatment dosage.
    World Journal of Gastroenterology 09/2010; 16(35):4400-9. · 2.55 Impact Factor
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    ABSTRACT: The aim of the present study was to investigate the association between the length of the treatment period and the cumulative dose of pegylated interferon alpha-2b (peg-IFN alpha-2b) plus ribavirin (RBV) and their effectiveness in the treatment of chronic hepatitis C. Seven hundred and fifteen patients received peg-IFN alpha-2b plus RBV treatment for 48 weeks and 24 weeks for genotypes 1 (n = 586) and 2 (n = 129), respectively. Sustained virological responses (SVR), defined as serum hepatitis C virus (HCV)-RNA undetectable at 24 weeks after the end of treatment, were 42.4% and 74.4% in genotypes 1 and 2, respectively, on an intention-to-treat analysis. SVR significantly increased with treatment length (4.7%, 36.4%, and 51.8% for < 24 weeks, 24-47 weeks, and 48 weeks, respectively, for genotype 1; and 28.6%, 57.1%, 78.3% for < 12 weeks, 12-23 weeks, and 24 weeks, respectively, for genotype 2). SVR significantly increased with total cumulative treatment dose (21.1%, 36.5%, and 52.9% with < 60%, 60-79%, and >or= 80% in peg-IFN dose; 29.6%, 51.1%, and 59.2% with < 60%, 60-79%, and >or= 80% in RBV dose) in genotype 1, although it did not differ significantly for genotype 2. In peg-IFN alpha-2b plus RBV treatment for chronic hepatitis C, it is important to complete the target length of treatment and to continue the target dosage to achieve SVR, especially for genotype 1 patients.
    Journal of Gastroenterology and Hepatology 02/2008; 23(7 Pt 1):1094-104. · 3.33 Impact Factor
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    ABSTRACT: Lamivudine treatment has been recently demonstrated to increase the serum albumin levels in cirrhotic patients with hepatitis B virus (HBV) infection, but the precise mechanism remains unclear. We hypothesized that the improvement of hypoalbuminemia by lamivudine may be attributable to the reduction of HBV replication itself, rather than to cessation of hepatitis. In order to confirm this hypothesis, in this study we evaluated factors which correlated with the increase in serum albumin levels. Fifty-four patients (Child-Pugh A/B/C, 35/9/10) with HBV-related liver cirrhosis who had been treated with lamivudine for more than 12 months were evaluated. We analyzed the correlation between the increase in serum albumin levels at month 12 after starting treatment (Delta-albumin) and various pretreatment variables. We also analyzed the correlation between Delta-albumin and the reduction in serum levels of HBV-DNA (Delta-HBV-DNA) or alanine aminotransferase (Delta-ALT) at month 12. The average Delta-albumin was 0.38 g/dL and only serum HBV-DNA levels before treatment correlated significantly with Delta-albumin. We also analyzed the correlation in patients whose alanine aminotransferase levels were normalized after 12 months so that the possible influence of breakthrough hepatitis could be excluded. Even among this subgroup of patients, there was no significant correlation between Delta-albumin and either pretreatment alanine aminotransferase levels or Delta-ALT. In contrast, in patients whose serum HBV-DNA was undetectable at month 12, we found a significant correlation between Delta-albumin and both pretreatment serum HBV-DNA levels and Delta-HBV-DNA. Our results demonstrated that albumin levels are associated with pretreatment HBV-DNA but not with alanine aminotransferase levels.
    Comparative Hepatology 02/2007; 6:3. · 1.88 Impact Factor
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    ABSTRACT: To determine the efficacy of an interferon alpha and ribavirin combination treatment for Japanese patients infected with hepatitis C virus (HCV) of genotype 2, a multi-center study was retrospectively analyzed. In total, 173 patients with HCV genotype 2 started to receive interferon-alpha subcutaneously thrice a week and 600-800 mg of ribavirin daily for 24 wk. The overall sustained virological response (SVR), defined as undetectable HCV RNA in serum, 24 wk after the end of treatment, was remarkably high by 84.4%, (146/173) by an intention-to-treat analysis. A significant difference in SVR was found between patients with and without the discontinuation of ribavirin (46.9% vs 92.9%), but no difference was found between those with and without a dose reduction of ribavirin. A significant difference in SVR was also found between patients with less than 16 wk and patients with 16 or more weeks of ribavirin treatment (34.8% vs 92.0%). The 24-wk interferon and ribavirin treatment is highly effective for Japanese patients with HCV genotype 2. The significant predictor of SVR is continuation of the ribavirin treatment for up to 16 weeks.
    World Journal of Gastroenterology 03/2006; 12(5):784-90. · 2.55 Impact Factor