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Norihiro Furusyo,
Eiichi Ogawa,
Makoto Nakamuta, Eiji Kajiwara,
Hideyuki Nomura,
Kazufumi Dohmen,
Kazuhiro Takahashi,
Takeaki Satoh,
Koichi Azuma,
Akira Kawano,
Yuichi Tanabe,
Kazuhiro Kotoh,
Shinji Shimoda,
Jun Hayashi
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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; · 9.26 Impact Factor
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Eiichi Ogawa,
Norihiro Furusyo, Eiji Kajiwara,
Kazuhiro Takahashi,
Hideyuki Nomura,
Toshihiro Maruyama,
Yuichi Tanabe,
Takeaki Satoh,
Makoto Nakamuta,
Kazuhiro Kotoh,
Koichi Azuma,
Kazufumi Dohmen,
Shinji Shimoda,
Jun Hayashi
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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; · 9.26 Impact Factor
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Norihiro Furusyo,
Eiichi Ogawa,
Masayuki Sudoh,
Masayuki Murata,
Takeshi Ihara,
Takeo Hayashi,
Hiroaki Ikezaki,
Satoshi Hiramine,
Haru Mukae,
Kazuhiro Toyoda,
Hiroaki Taniai,
Kyoko Okada,
Mosaburo Kainuma, Eiji Kajiwara,
Jun Hayashi
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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; · 9.26 Impact Factor
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Eiichi Ogawa,
Norihiro Furusyo, Eiji Kajiwara,
Kazuhiro Takahashi,
Hideyuki Nomura,
Yuichi Tanabe,
Takeaki Satoh,
Toshihiro Maruyama,
Makoto Nakamuta,
Kazuhiro Kotoh,
Koichi Azuma,
Kazufumi Dohmen,
Shinji Shimoda,
Jun Hayashi
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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; · 1.80 Impact Factor
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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. · 2.20 Impact Factor
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Mosaburo Kainuma,
Norihiro Furusyo,
Koichi Azuma, Eiji Kajiwara,
Kazuhiro Takahashi,
Hideyuki Nomura,
Yuichi Tanabe,
Takeaki Satoh,
Toshihiro Maruyama,
Makoto Nakamuta,
Kazuhiro Kotoh,
Shinji Shimoda,
Jun Hayashi
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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. · 2.20 Impact Factor
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Eiichi Ogawa,
Norihiro Furusyo, Eiji Kajiwara,
Kazuhiro Takahashi,
Hideyuki Nomura,
Yuichi Tanabe,
Takeaki Satoh,
Toshihiro Maruyama,
Makoto Nakamuta,
Kazuhiro Kotoh,
Koichi Azuma,
Kazufumi Dohmen,
Shinji Shimoda,
Jun Hayashi
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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. · 2.87 Impact Factor
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Mosaburo Kainuma,
Norihiro Furusyo, Eiji Kajiwara,
Kazuhiro Takahashi,
Hideyuki Nomura,
Yuichi Tanabe,
Takeaki Satoh,
Toshihiro Maruyama,
Makoto Nakamuta,
Kazuhiro Kotoh,
Koichi Azuma,
Junya Shimono,
Shinji Shimoda,
Jun Hayashi
[show abstract]
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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. · 2.47 Impact Factor
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Norihiro Furusyo, Eiji Kajiwara,
Kazuhiro Takahashi,
Hideyuki Nomura,
Yuichi Tanabe,
Akihide Masumoto,
Toshihiro Maruyama,
Makoto Nakamuta,
Munechika Enjoji,
Koichi Azuma,
Junya Shimono,
Hironori Sakai,
Shinji Shimoda,
Jun Hayashi
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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. · 2.87 Impact Factor
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ABSTRACT: Amino acid substitutions within the S gene involving the major antigenic a determinant of the hepatitis B virus (HBV) surface antigen (HBsAg) have been detected in cases of failure of immunization against the virus. Our report showed development of clinical hepatitis in presence of antibody to HBsAg in a healthy individual. A single amino acid substitution (G145R) within the a determinant of the HBsAg was determined by sequencing of the isolated HBV strain. Lamivudine treatment efficiently cleared the peripheral HBV DNA, HBsAg, and hepatitis B e antigen. In conclusion, the immune escape mutant in the S gene can cause hepatitis despite pre-existing naturally acquired immunity.
Journal of Gastroenterology 02/2008; 43(3):243-7. · 4.16 Impact Factor
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Makoto Nakamuta,
Kazuhiro Kotoh,
Munechika Enjoji, Eiji Kajiwara,
Junya Shimono,
Akihide Masumoto,
Toshihiro Maruyama,
Norihiro Furusyo,
Hideyuki Nomura,
Hironori Sakai,
Kazuhiro Takahashi,
Koichi Azuma,
Shinji Shimoda,
Yuichi Tanabe,
Jun Hayashi
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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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Norihiro Furusyo,
Masaki Katoh,
Yuichi Tanabe, Eiji Kajiwara,
Toshihiro Maruyama,
Junya Shimono,
Hironori Sakai,
Makoto Nakamuta,
Hideyuki Nomura,
Akihide Masumoto,
Shinji Shimoda,
Kazuhiro Takahashi,
Koichi Azuma,
Jun Hayashi
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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. · 2.47 Impact Factor
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Norihiro Furusyo,
Hiroaki Takeoka,
Kazuhiro Toyoda,
Masayuki Murata,
Yuichi Tanabe, Eiji Kajiwara,
Junya Shimono,
Akihide Masumoto,
Toshihiro Maruyama,
Hideyuki Nomura,
Makoto Nakamuta,
Kazuhiro Takahashi,
Shinji Shimoda,
Koichi Azuma,
Hironori Sakai,
Jun Hayashi
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ABSTRACT: To determine the efficacy of long-term lamivudine treatment of a large number of Japanese patients with chronic hepatitis B.
In this retrospective, multi-center trial, 318 Japanese patients with chronic hepatitis B received 100 mg of lamivudine daily for up to 36 (median 21) mo. Virological response was a decline to a serum HBV DNA level less than 3.7 log copies/mL. Virological breakthrough was defined as the reappearance of a serum HBV DNA level to more than 10-fold the minimum during treatment.
Lamivudine produced virological response in 86.8% of the 318 patients at 6 mo, in 80.2% of 252 patients at 12 mo, in 69.2% of 133 patients at 24 mo, and in 53.6% of 28 patients at 36 mo. Forward stepwise logistic regression analysis showed an HBV DNA level less than 6.8 log copies/mL (P<0.0001), HBeAg negativity (P<0.0001), a platelet count of 100 x 10(9)/L or more (P=0.0162) at baseline, and a decline of the HBV DNA level of more than 3.2 log copies/mL as compared with the baseline level at 3 mo after the start of treatment (P=0.0003) to be significantly associated with virological response. Among patients with a virological response, virological breakthrough was seen in 5.3% of 19 patients who responded virologically at 1 mo, in 20.7% of 203 patients at 3 mo, in 27.5% of 51 patients at 6 mo, in 33.3% of 12 patients at 9 mo, and in 100% of 3 patients at >=5 mo. A virological breakthrough was found significantly more often in patients with delayed virological response.
Lamivudine treatment could suppress serum HBV DNA in most of the tested Japanese patients. Long-term efficacy might be seen in patients without HBeAg at baseline, in the absence of cirrhosis, and in patients with a decline in HBV DNA level soon after the start of treatment.
World Journal of Gastroenterology 01/2006; 12(4):561-7. · 2.47 Impact Factor
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Makoto Nakamuta,
Shusuke Morizono,
Yuichi Tanabe, Eiji Kajiwara,
Junya Shimono,
Akihide Masumoto,
Toshihiro Maruyama,
Norihiro Furusyo,
Hideyuki Nomura,
Hironori Sakai,
Kazuhiro Takahashi,
Koichi Azuma,
Shinji Shimoda,
Kazuhiro Kotoh,
Munechika Enjoji,
Jun Hayashi
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ABSTRACT: To further evaluate the relationship between BSA and the effects of lamivudine in a greater number of cases and over a longer period of observation than in our previous evaluation.
We evaluated 249 patients with chronic hepatitis B. The effects of treatment for one year (n = 249), two years (n = 147), and three years (n = 72) were evaluated from the levels of serum ALT and HBV-DNA, as biological and virological effects (undetectable levels by PCR), respectively. Moreover, several variables that could influence the response to treatment, including ALT, albumin, bilirubin, platelet counts, BSA, HBV-DNA, and HBeAg were analyzed.
For 1-year treatment, multivariate analysis revealed that BSA (P = 0.0002) was the only factor for the biological effect, and that ALT (P = 0.0017), HBV-DNA (P = 0.0004), and HBeAg (P = 0.0021) were independent factors for the virological effect. For 2-year treatment, multivariate analysis again showed that BSA (P = 0.0147) was the only factor for the biological effect, and that ALT (P = 0.0192) and HBeAg (P = 0.0428) were independent factors for the virological effect. For 3-year treatment, multivariate analysis, however, could not reveal BSA (P = 0.0730) as a factor for the normalization of ALT levels.
BSA is a significant predictor for the normalizing the effect of lamivudine therapy on ALT for an initial 2-year period, suggesting that lamivudine dosage should be based on the individual BSA.
World Journal of Gastroenterology 12/2005; 11(44):6948-53. · 2.47 Impact Factor
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ABSTRACT: We report a case of intestinal obstruction due to intramural hematoma of the duodenum following therapeutic endoscopy for a bleeding duodenal ulcer in a patient with liver cirrhosis. A 44-year-old man was admitted to our hospital with severe epigastralgia, nausea and tarry stool. Two years previously he had undergone endoscopic sclerotherapy for esophageal varices caused by alcoholic liver cirrhosis. Endoscopy revealed an open ulcer with a bleeding vessel in the duodenal bulb, and sclerotherapy was performed by clipping the vessel and injecting 20 ml of 0.2% epinephrine. His platelet count was 3.5x10(4)/mul. Twelve hours later, he again developed epigastralgia and hypotension. Emergency computed tomography and ultrasonography revealed an intramural hematoma, 15x18 cm in diameter, at the dorsal and lateral duodenum. Endoscopy and upper gastrointestinal series revealed severe stenosis of the duodenal lumen caused by intramural hematoma. He received parenteral feeding for 22 days and within 8 weeks the hematoma was gradually absorbed using conservative management. Intramural duodenal hematoma may be diagnosed as a complication of the endoscopic procedure in a patient with a bleeding tendency, such as liver cirrhosis.
Internal Medicine 10/2005; 44(9):954-7. · 0.94 Impact Factor
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Hideyuki Nomura,
Yoichiro Kashiwagi,
Hisashi Nakashima,
Hironori Tanimoto,
Junya Shimono, Eiji Kajiwara,
Toshihiro Maruyama,
Nobuyuki Yamashita,
Masanori Nagano,
Masashi Higashi,
Tamotsu Mukai,
Yutaka Matsui,
Jun Hayashi,
Seizaburo Kashiwagi,
Hiromi Ishibashi
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ABSTRACT: The aim of the present study was to assess the efficacy of the prolonged interferon monotherapy following combination treatment. Seventy-six patients were enrolled. Of these, 7 were withdrawn while undergoing treatment with interferon combined with ribavirin, and 12 remained positive for HCV-RNA at the completion of the combination treatment. We studied 57 Japanese patients with chronic hepatitis C due to genotype 1b HCV of a high viral load. These patients tested negative for HCV-RNA at the completion of the combination treatment for 24 weeks. After the combination treatment, 29 patients of the prolonged treatment group successively received interferon-alpha monotherapy for 24 weeks, while 28 patients in the combination treatment alone group received no medication. The rate of a sustained virologic response (SVR) was higher in the prolonged treatment group (41%, 12/29) than in the combination treatment alone group (25%, 7/28), but not significantly. Patients who became HCV-RNA negative by 4 weeks after the start of the combination treatment showed an SVR rate of 86%. The prolonged treatment resulted in SVR in all five patients who newly became HCV-RNA negative at 12 weeks. In conclusion, the prolonged treatment was effective for patients who newly became HCV-RNA negative at 12 weeks.
Hepatology Research 05/2005; 31(4):211-6. · 2.20 Impact Factor
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Makoto Nakamuta,
Kazuhiro Kotoh,
Yuichi Tanabe, Eiji Kajiwara,
Junya Shimono,
Akihide Masumoto,
Toshihiro Maruyama,
Norihiro Furusyo,
Hideyuki Nomura,
Hironori Sakai,
Kazuhiro Takahashi,
Koichi Azuma,
Shinji Shimoda,
Munechika Enjoji,
Jun Hayashi
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ABSTRACT: BACKGROUND:: It has been suggested that lamivudine therapy may be even more effective if administered at higher doses than is dictated by the current standard regimen. We analyzed the correlation between the effects of lamivudine and body surface area (BSA). METHOD:: We evaluated 134 patients with chronic hepatitis B who had been treated with lamivudine for more than 12 months. The effect of the treatment was evaluated from the levels of serum alanine aminotransferase (ALT) and HBV-DNA. Several variables that could influence the response to treatment, including ALT, albumin, and bilirubin levels, platelet counts, BSA, HBV-DNA, and HBeAg were analyzed. RESULTS:: Univariate logistic analysis selected platelet counts, BSA, HBV-DNA and HBeAg in the biological evaluation, and bilirubin, BSA, HBV-DNA and HBeAg in the virological evaluation (chi(2)>1.0). Using these factors, multivariate analysis revealed that BSA (chi(2)=12.8, p=0.0004) was the only factor that could contribute significantly to the improvement of ALT levels, and that BSA (chi(2)=4.4, p=0.0354) and HBeAg (chi(2)=8.1, p=0.0044) were independent factors that could influence the suppression of HBV-DNA. CONCLUSION:: We revealed that BSA is a significantly predictor of the effect of lamivudine therapy, suggesting that lamivudine dosage should be based on the individual BSA.
Hepatology Research 01/2005; 31(1):13-17. · 2.20 Impact Factor
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Hideyuki Nomura,
Hironori Tanimoto, Eiji Kajiwara,
Junya Shimono,
Toshihiro Maruyama,
Nobuyuki Yamashita,
Masanori Nagano,
Masashi Higashi,
Tamotsu Mukai,
Yutaka Matsui,
Jun Hayashi,
Seizaburo Kashiwagi,
Hiromi Ishibashi
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ABSTRACT: Interferon and ribavirin combination therapy for chronic hepatitis C produces hemolytic anemia. This study was conducted to identify the factors contributing to ribavirin-induced anemia.
Eighty-eight patients with chronic hepatitis C who received interferon-alpha-2b at a dose of 6 MU administered intramuscularly for 24 weeks in combination with ribavirin administered orally at a dose of 600 mg or 800 mg participated in the study. A hemoglobin concentration of <10 g/dL was defined as ribavirin-induced anemia.
Ribavirin-induced anemia occurred in 18 (20.5%) patients during treatment. A 2 g/dL decrease in hemoglobin concentrations in patients with anemia was observed at week 2 after the start of treatment. The hemoglobin concentration in patients with > or =2 g/dL decrease at week 2 was observed to be significantly lower even after week 2 than in patients with <2 g/dL decrease (P < 0.01). A significant relationship was observed between the rate of reduction of hemoglobin concentrations at week 2 and the severity of anemia (P < 0.01). Such factors as sex (female), age (> or =60 years old), and the ribavirin dose by body weight (12 mg/kg or more) were significant by univariate analysis.
Careful administration is necessary in patients > or =60 years old, in female patients, and in patients receiving a ribavirin dose of 12 mg/kg or more. Patients who experience a fall in hemoglobin concentrations of 2 g/dL or more at week 2 after the start of treatment should be monitored with particular care.
Journal of Gastroenterology and Hepatology 12/2004; 19(11):1312-7. · 2.87 Impact Factor
