Publications (17)23.85 Total impact
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Article: Alcohol, postprandial plasma glucose, and prognosis of hepatocellular carcinoma.
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ABSTRACT: To identify factors associated with prognosis of hepatocellular carcinoma (HCC) after initial therapy. A total of 377 HCC patients who were newly treated at Katsushika Medical Center, Japan from January 2000 to December 2009 and followed up for > 2 years, or died during follow-up, were enrolled. The factors related to survival were first analyzed in 377 patients with HCC tumor stage T1-T4 using multivariate Cox proportional hazards regression analysis. A similar analysis was performed in 282 patients with tumor stage T1-T3. Additionally, factors associated with the period between initial and subsequent therapy were examined in 144 patients who did not show local recurrence. Finally, 214 HCC stage T1-T3 patients who died during the observation period were classified into four groups according to their alcohol consumption and postprandial glucose levels, and differences in their causes of death were examined. On multivariate Cox proportional hazards regression analysis, the following were significantly associated with survival: underlying liver disease stage [non-cirrhosis/Child-Pugh A vs B/C, hazard ratio (HR): 0.603, 95% CI: 0.417-0.874, P = 0.0079], HCC stage (T1/T2 vs T3/T4, HR: 0.447, 95% CI: 0.347-0.576, P < 0.0001), and mean postprandial plasma glucose after initial therapy (< 200 vs ≥ 200 mg/dL, HR: 0.181, 95% CI: 0.067-0.488, P = 0.0008). In T1-T3 patients, uninterrupted alcohol consumption after initial therapy (no vs yes, HR: 0.641, 95% CI: 0.469-0.877, P = 0.0055) was significant in addition to underlying liver disease stage (non-cirrhosis/Child-Pugh A vs B/C, HR: 0649, 95% CI: 0.476-0.885, P = 0.0068), HCC stage (T1 vs T2/T3, HR: 0.788, 95% CI: 0.653-0.945, P = 0.0108), and mean postprandial plasma glucose after initial therapy (< 200 mg/dL vs ≥ 200 mg/dL, HR: 0.502, 95% CI: 0.337-0.747, P = 0.0005). In patients without local recurrence, time from initial to subsequent therapy for newly emerging HCC was significantly longer in the "postprandial glucose within 200 mg/dL group" than the "postprandial glucose > 200 mg/dL group" (log-rank test, P < 0.05), whereas there was no difference in the period between the "non-alcohol group" (patients who did not drink regularly or those who could reduce their daily consumption to < 20 g) and the "continuation group" (drinkers who continued to drink > 20 g daily). Of 214 T1-T3 patients who died during the observation period, death caused by other than HCC progression was significantly more frequent in "group AL" (patients in the continuation and postprandial glucose within 200 mg/dL groups) than "group N" (patients in the non-alcohol and postprandial glucose within 200 mg/dL groups) (P = 0.0016). This study found that abstinence from habitual alcohol consumption and intensive care for diabetes mellitus were related to improved prognosis in HCC patients.World Journal of Gastroenterology 01/2013; 19(1):78-85. · 2.47 Impact Factor -
Article: Several factors including ITPA polymorphism influence ribavirin-induced anemia in chronic hepatitis C.
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ABSTRACT: To construct formulae for predicting the likelihood of ribavirin-induced anemia in pegylated interferon α plus ribavirin for chronic hepatitis C. Five hundred and sixty-one Japanese patients with hepatitis C virus genotype 1b who had received combination treatment were enrolled and assigned randomly to the derivation and confirmatory groups. Single nucleotide polymorphisms at or nearby ITPA were genotyped by real-time detection polymerase chain reaction. Factors influencing significant anemia (hemoglobin concentration < 10.0 g/dL at week 4 of treatment) and significant hemoglobin decline (declining concentrations > 3.0 g/dL at week 4) were analyzed using multiple regression analyses. Prediction formulae were constructed by significantly independent factors. Multivariate analysis for the derivation group identified four independent factors associated with significant hemoglobin decline: hemoglobin decline at week 2 [P = 3.29 × 10(-17), odds ratio (OR) = 7.54 (g/dL)], estimated glomerular filtration rate [P = 2.16 × 10(-4), OR = 0.962 (mL/min/1.73 m(2))], rs1127354 (P = 5.75 × 10(-4), OR = 10.94) and baseline hemoglobin [P = 7.86 × 10(-4), OR = 1.50 (g/dL)]. Using the model constructed by these factors, positive and negative predictive values and predictive accuracy were 79.8%, 88.8% and 86.2%, respectively. For the confirmatory group, they were 83.3%, 91.0% and 88.3%. These factors were closely correlated with significant anemia. However, the model could not be constructed, because no patients with rs1127354 minor genotype CA/AA had significant anemia. Reliable formulae for predicting the likelihood of ribavirin-induced anemia were constructed. Such modeling may be useful in developing individual tailoring and optimization of ribavirin dosage.World Journal of Gastroenterology 11/2012; 18(41):5879-88. · 2.47 Impact Factor -
Book: Dyslipoproteinemia in Chronic HCV Infection
edited by Sasa Frank and Gerhard Kostner, 09/2012; INTECH., ISBN: 978-953-51-0773-6 -
Article: Viral Factors Associated with Response to Antiviral Therapy for Chronic Hepatitis C Virus Infection
Journal of Antivirals and Antiretrovirals 04/2012; jaa.S3-003. -
Article: Contribution of ribavirin transporter gene polymorphism to treatment response in peginterferon plus ribavirin therapy for HCV genotype 1b patients.
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ABSTRACT: Standard-dose ribavirin is crucial for the standard-of-care treatment of chronic hepatitis C virus (HCV) infection. Equilibrative nucleoside transporter 1 (ENT1), encoded by SLC29A1 gene, is the main transporter that imports ribavirin into human hepatocytes. Aims: To determine whether single nucleotide polymorphisms (SNPs) at the SLC29A1 gene could influence the probability of treatment response compared with other baseline and host genetic factors. A total of 526 East Asian patients monoinfected with HCV genotype 1b who had received pegylated interferon alpha plus ribavirin therapy were enrolled in this study. They were assigned randomly to the derivation and confirmatory groups. SNPs related to the IL28B, ITPA and SLC29A1 genes were genotyped using real-time detection polymerase chain reaction. Factors associated with sustained virological response (SVR) were analysed using multiple logistic regression analysis. Multivariate analysis for the derivation group identified six baseline variables significantly and independently associated with SVR: age [P = 0.023, odds ratio (OR) = 0.97], gender (P = 0.0047, OR = 2.25), platelet count (P = 0.00017, OR = 1.11), viral load (P = 0.00026, OR = 0.54), IL28B SNP rs12979860 (P = 1.09 × 10(-7) , OR = 8.68) and SLC29A1 SNP rs6932345 (P = 0.030, OR = 1.85). Using the model constructed by these independent variables, positive and negative predictive values and predictive accuracy were 73.3, 70.1 and 71.9% respectively. For the confirmatory group, they were 71.4, 84.6 and 75.3% respectively. The SLC29A1 and IL28B SNPs were also significantly associated with rapid virological response. The SNP at the major ribavirin transporter ENT1 gene SLC29A1 was one of significantly independent factors influencing treatment response, although the impact on the prediction was small.Liver international: official journal of the International Association for the Study of the Liver 12/2011; 32(5):826-36. · 3.82 Impact Factor -
Article: Genotype rs8099917 near the IL28B gene and amino acid substitution at position 70 in the core region of the hepatitis C virus are determinants of serum apolipoprotein B-100 concentration in chronic hepatitis C.
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ABSTRACT: The life cycle of the hepatitis C virus (HCV) is closely related to host lipoprotein metabolism. Serum levels of lipid are associated with the response to pegylated interferon plus ribavirin (PEG-IFN/RBV) therapy, while single nucleotide polymorphisms (SNPs) around the human interleukin 28B (IL28B) gene locus and amino acid substitutions in the core region of the HCV have been reported to affect the efficacy of PEG-IFN/RBV therapy in chronic hepatitis with HCV genotype 1b infection. The aim of this study was to elucidate the relationship between serum lipid and factors that are able to predict the efficacy of PEG-IFN/RB therapy, with specific focus on apolipoprotein B-100 (apoB-100) in 148 subjects with chronic HCV G1b infection. Our results demonstrated that both the aa 70 substitution in the core region of the HCV and the rs8099917 SNP located proximal to the IL28B were independent factors in determining serum apoB-100 and low-density lipoprotein (LDL) cholesterol levels. A significant association was noted between higher levels of apoB-100 (P = 1.1 × 10(-3)) and LDL cholesterol (P = 0.02) and the subjects having Arg70. A significant association was also observed between subjects carrying the rs8099917 TT responder genotype and higher levels of apoB-100 (P = 6.4 × 10(-3)) and LDL cholesterol (P = 4.2 × 10(-3)). Our results suggest that apoB-100 and LDL cholesterol are markers of impaired cellular lipoprotein pathways and/or host endogenous interferon response to HCV in chronic HCV infection. In particular, serum apoB-100 concentration might be an informative marker for judging changes in HCV-associated intracellular lipoprotein metabolism in patients carrying the rs8099917 responder genotype.Molecular and Cellular Biochemistry 08/2011; 360(1-2):9-14. · 2.06 Impact Factor -
Article: Expansion of CD4(+)CD25(+)FoxP3(+) regulatory T cells in hepatitis C virus-related chronic hepatitis, cirrhosis and hepatocellular carcinoma.
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ABSTRACT: Aim: Regulatory T (Treg) cells may play a pivotal role in the persistence of hepatitis C virus (HCV) infection and the development of hepatocellular carcinoma (HCC). Therefore, we examined their frequency in peripheral blood from patients with HCV-positive chronic hepatitis (CH), cirrhosis (LC) and HCC. Methods: Treg cells were identified as CD4(+), CD25(+) and FoxP3(+) T lymphocytes using three-color FACS. The frequency of Treg cells was expressed as a percentage of the total CD4(+) T lymphocytes, and the phenotype of Treg cells was examined using CD45RA. Results: Treg cells were significantly increased in CH (5.88 +/- 0.19%, n = 76; P < 0.01), LC (6.10 +/- 0.28%, n = 40; P < 0.001) and HCC (6.80 +/- 0.30%, n = 57; P < 0.0001) compared to healthy control (5.13 +/- 0.25%, n = 31). However, Treg cells were not increased with the progression of fibrosis or the grade of inflammations. Treg cells were slightly increased in early-stage HCC (6.91 +/- 0.40%) compared with advanced-stage HCC (6.58 +/- 0.39%), but these results were not statistically significant. In a serial examination, a distinct increase in Treg cells after local therapy for early-stage HCC was a hallmark of early recurrence. Most expanded Treg cells in HCC were CD45RA(-), suggesting that a memory-type Treg population had differentiated in the periphery and not in the thymus. Conclusion: We observed an increase in Treg cells in HCV-related chronic liver disease, particularly in HCC, and these cells were shown to be memory-type Treg cells.Hepatology Research 02/2010; 40(2):179-87. · 2.20 Impact Factor -
Article: [A case of primary small cell carcinoma of the esophagus responding remarkably to carboplatin (CBDCA) + etoposide (VP-16) combination therapy and radiation therapy].
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ABSTRACT: A 78-year-old man was admitted to hour hospital because of dysphagia, and primary small cell carcinoma of the esophagus was diagnosed. Carboplatin (CBDCA) + etoposide (VP-16) combination chemotherapy and radiation therapy was performed. After this therapy, endoscopic examination and computed tomographic scan showed the disappearance of the primary esophageal tumor. Endoscopic examination with biopsy confirmed the disappearance of malignant cells. Severe adverse reactions were not observed during this therapy. This patient is alive without recurrence for 6 years and 3 months. This case seems to provide suggestions on deciding on the operative indications for small cell carcinoma of esophagus.Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 10/2009; 106(9):1334-42. -
Article: Etiology of non-B non-C hepatocellular carcinoma in the eastern district of Tokyo.
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ABSTRACT: This study was carried out to clarify the carcinogenic factors associated with nonviral hepatocellular carcinoma (HCC). A total of 320 HCC patients diagnosed and treated from January 2000 to December 2006 were enrolled. The clinical characteristics of non-B non-C HCC patients were examined to determine possible carcinogenic factors. Of 320 HCC patients, 64 were classified as having non-B non-C HCC. The proportion of non-B non-C HCC increased from 17.8% in 2000 to 28.6% in 2006. Non-B non-C HCC patients had a significantly higher rate of early stage cirrhosis (Child-Pugh classification) than viral HCC patients. Significantly fewer non-B non-C HCC patients had periodic intensive medical assessments than viral HCC patients. Forty-five non-B non-C HCC patients were habitual alcohol drinkers, ten had nonalcoholic fatty liver disease (NAFLD), and seven had no apparent etiology. In habitual drinkers, the stage of underlying liver disease varied widely, while most NAFLD patients had early stage cirrhosis. On the other hand, more than half of the patients with HCC of undetermined etiology had noncirrhotic liver disease. Among habitual drinkers, the underlying liver disease was more progressive, and the T stage was more advanced in those with high daily alcohol intake than in those with low daily alcohol intake. Periodic intensive medical assessments were crucial for detecting early stage HCC. Alcohol consumption and NAFLD may be important etiological factors in non-B non-C HCC. Periodic medical assessments for all patients with non-B non-C cirrhosis are crucial for early diagnosis and curative therapy.Journal of Gastroenterology 02/2008; 43(12):967-74. · 4.16 Impact Factor -
Article: [Hepatitis A].
Nippon rinsho. Japanese journal of clinical medicine 04/2007; 65 Suppl 3:139-43. -
Article: Treatment effects and predictors of a 24-week course of interferon alpha-2b plus ribavirin combination therapy for patients with chronic hepatitis C.
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ABSTRACT: In chronic hepatitis C patients with genotype 1b and a high viral load, the sustained virological response (SVR) rate remained as low as 2-3% with conventional interferon (IFN) monotherapy, but improved to more than 20% with IFN alpha-2b plus ribavirin combination therapy. This study examined the therapeutic effects and predictors of this combination therapy. Subjects were 105 patients with chronic hepatitis C (73 males, 32 females) with a median age of 53 years (range 19-70 years). Seventy-two patients had genotype lb and 33 patients had genotype 2 (2a or 2b). Six million units (MU) or 10 MU of IFN alpha-2b was administered by intramuscular injection six times a week for the first 2 weeks, and the same amount of IFN was administered three times a week for the following 22 weeks. During the IFN administration period, 600-800 mg of oral ribavirin was administered daily. Patients who were hepatitis C virus (HCV)-RNA negative 24 weeks after the completion of administration were defined as SVR. The overall SVR rate was 39%; 22.2% for the genotype 1b group and 75.8% for the genotype 2 group, and the difference between the groups was significant (P < 0.0001). Multivariate logistic regression analysis indicated that the factors that contributed to SVR include genotype 2, age (younger than 53 years), and an increase in Th2 measured by flow cytometry before and 4 weeks after start of treatment. The overall SVR rate of IFN alpha-2b plus ribavirin combination therapy for 24 weeks was 39%, and contributing factors for SVR rate include genotype 2, age younger than 53 years and elevated Th2.Journal of Gastroenterology and Hepatology 08/2006; 21(7):1177-83. · 2.87 Impact Factor -
Article: Treatment effects and predictors of a 24‐week course of interferon α‐2b plus ribavirin combination therapy for patients with chronic hepatitis C
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ABSTRACT: Background and Aims: In chronic hepatitis C patients with genotype 1b and a high viral load, the sustained virological response (SVR) rate remained as low as 2-3% with conventional interferon (IFN) monotherapy, but improved to more than 20% with IFN α-2b plus ribavirin combination therapy. This study examined the therapeutic effects and predictors of this combination therapy.Methods: Subjects were 105 patients with chronic hepatitis C (73 males, 32 females) with a median age of 53 years (range 19–70 years). Seventy-two patients had genotype lb and 33 patients had genotype 2 (2a or 2b). Six million units (MU) or 10 MU of IFN α-2b was administered by intramuscular injection six times a week for the first 2 weeks, and the same amount of IFN was administered three times a week for the following 22 weeks. During the IFN administration period, 600–800 mg of oral ribavirin was administered daily. Patients who were hepatitis C virus (HCV)-RNA negative 24 weeks after the completion of administration were defined as SVR.Results: The overall SVR rate was 39%; 22.2% for the genotype 1b group and 75.8% for the genotype 2 group, and the difference between the groups was significant (P < 0.0001). Multivariate logistic regression analysis indicated that the factors that contributed to SVR include genotype 2, age (younger than 53 years), and an increase in Th2 measured by flow cytometry before and 4 weeks after start of treatment.Conclusions: The overall SVR rate of IFN α-2b plus ribavirin combination therapy for 24 weeks was 39%, and contributing factors for SVR rate include genotype 2, age younger than 53 years and elevated Th2.Journal of Gastroenterology and Hepatology 04/2006; 21(7):1177 - 1183. · 2.87 Impact Factor -
Article: [A case of cholangiocellular cacinoma associated with autosomal dominant polycystic kidney disease].
Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 12/2005; 102(11):1434-8. -
Article: [A case of agenesis of the left hepatic lobe complicated with hypogenesis of the anterior segment of the right hepatic lobe].
Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 02/2005; 102(1):48-52. -
Article: [A case report of diffuse hepatic angiosarcoma].
Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 01/2005; 101(12):1325-31. -
Article: [A case of Caroli's disease which DIC-CT was useful to a definite diagnosis].
Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 10/2003; 100(9):1129-33. -
Article: Analysis of risk factors for hepatocellular carcinoma that is negative for hepatitis B surface antigen (HBsAg).
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ABSTRACT: To clarify risk factors for hepatocellular carcinoma (HCC) other than hepatitis B surface antigen (HBsAg). We investigated serum HBV-DNA and other factors in 146 patients with liver cirrhosis (LC) or HCC who were HBsAg negative. We analyzed the clinical background of the patients, status of hepatitis B (HBV) viral markers and platelet count as well as the presence of an HBV-DNA fragment by PCR and elucidated risk factors for HCC generation using a logistic regression model. Among ten factors, we determined that four represented a significant risk for HBsAg negative HCC: male gender, total alcohol consumption, total cigarettes smoked, and the presence of an HBV-DNA fragment. Multivariate analysis showed that among the four factors, the HBV-DNA fragment was an independent factor associated with HCC. The presence of an HBV-DNA fragment irrespective of the status of antibodies to either HBsAg (anti-HBs) or hepatitis B core antigen (anti-HBc) is a pivotal factor associated with the development of HCC.Internal Medicine 06/2003; 42(5):389-93. · 0.94 Impact Factor
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2003–2013
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The Jikei University School of Medicine
- Department of Internal Medicine H
Tokyo, Tokyo-to, Japan
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