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1.  Elevated serum levels of Wisteria floribunda agglutinin-positive human Mac-2 binding protein predict the development of hepatocellular carcinoma in hepatitis C patients 
Hepatology (Baltimore, Md.)  2014;60(5):1563-1570.
The Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA+-M2BP) was recently shown to be a liver fibrosis glycobiomarker with a unique fibrosis-related glycoalteration. We evaluated the ability of WFA+-M2BP to predict the development of hepatocellular carcinoma (HCC) in patients who were infected with the hepatitis C virus (HCV). A total of 707 patients who had been admitted to our hospital with chronic HCV infection without other potential risk factors were evaluated to determine the ability of WFA+-M2BP to predict the development of HCC; factors evaluated included age, sex, viral load, genotypes, fibrosis stage, aspartate and alanine aminotransferase levels, bilirubin, albumin, platelet count, alpha-fetoprotein (AFP), WFA+-M2BP, and the response to interferon (IFN) therapy. Serum WFA+-M2BP levels were significantly increased according to the progression of liver fibrosis stage (P < 0.001). In each distinctive stage of fibrosis (F0-F1, F2, F3, and F4), the risk of development of HCC was increased according to the elevation of WFA+-M2BP. Multivariate analysis identified age >57 years, F4, AFP >20 ng/mL, WFA+-M2BP ≥4, and WFA+-M2BP 1-4 as well as the response to IFN (no therapy vs. sustained virological response) as independent risk factors for the development of HCC. The time-dependent areas under the receiver operating characteristic curve demonstrated that the WFA+-M2BP assay predicted the development of HCC with higher diagnostic accuracy than AFP. Conclusion: WFA+-M2BP can be applied as a useful surrogate marker for the risk of HCC development, in addition to liver biopsy. (Hepatology 2014;60:1563–1570)
PMCID: PMC4278450  PMID: 25042054
2.  Association of STAT4 Polymorphisms with Susceptibility to Type-1 Autoimmune Hepatitis in the Japanese Population 
PLoS ONE  2013;8(8):e71382.
Recent studies demonstrated an association of STAT4 polymorphisms with autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, indicating multiple autoimmune diseases share common susceptibility genes. We therefore investigated the influence of STAT4 polymorphisms on the susceptibility and phenotype of type-1 autoimmune hepatitis in a Japanese National Hospital Organization (NHO) AIH multicenter cohort study.
Methodology/Principal Findings
Genomic DNA from 460 individuals of Japanese origin including 230 patients with type-1 autoimmune hepatitis and 230 healthy controls was analyzed for two single nucleotide polymorphisms in the STAT4 gene (rs7574865, rs7582694). The STAT4 rs7574865T allele conferred risk for type-1 autoimmune hepatitis (OR = 1.61, 95% CI = 1.23–2.11; P = 0.001), and patients without accompanying autoimmune diseases exhibited an association with the rs7574865T allele (OR = 1.50, 95%CI = 1.13–1.99; P = 0.005). Detailed genotype-phenotype analysis of type-1 autoimmune hepatitis patients with (n = 44) or without liver cirrhosis (n = 186) demonstrated that rs7574865 was not associated with the development of liver cirrhosis and phenotype (biochemical data and the presence of auto-antibodies).
This is the first study to show a positive association between a STAT4 polymorphism and type-1 autoimmune hepatitis, suggesting that autoimmune hepatitis shares a gene commonly associated with risk for other autoimmune diseases.
PMCID: PMC3750035  PMID: 23990947
3.  Effects and Outcomes of Interferon Treatment in Japanese Hepatitis C Patients 
BMC Gastroenterology  2012;12:139.
No study has compared the long-term prognoses of hepatitis C patients with hepatitis C virus (HCV) antibody-negative individuals and investigated the effects of interferon (IFN) treatment. To clarify the long-term prognosis of HCV-positive residents of an isolated Japanese island and prospectively investigate the effects of IFN treatment in comparison with the HCV-negative general population.
HCV antibody was positive in 1,343 (7.6%) of the 17,712 individuals screened. 792 HCV RNA-positive, HBsAg-negative subjects were enrolled. 1,584 HCV antibody-negative, HBsAg-negative general residents were sex- and age-matched to the 792 subjects. A total of 154 <70-year-old patients without liver cirrhosis (LC) or hepatocellular carcinoma (HCC) underwent IFN treatment. The survival rate with all-cause death as the endpoint was determined and causes of death were compared.
The 10- and 20-year survival rates of the hepatitis C and general resident groups were 65.4% and 87.8%, and 40.8% and 62.5%, respectively (p < 0.001; hazard risk ratio, 0.444; 95% confidence interval (CI): 0.389–0.507). There were 167 liver disease-related deaths and 223 deaths from other causes in the hepatitis C group, and 7 and 451, respectively, in the general resident group. Liver disease-related death accounted for 43.8% and 1.5% of deaths in the hepatitis C and general resident groups (p < 0.0001). The cumulative survival rate of the hepatitis C patients without IFN (n = 328) was significantly lower than the gender- and age-matched general resident group (n = 656) (p < 0.0001) but there was no significant difference between the IFN-treated (n = 154) and general resident groups (n = 308).
In the hepatitis C group, the proportion of liver disease-related death was markedly higher, and the survival rate lower, than the general resident group. Introduction of IFN treatment in <70-year-old patients with hepatitis C without LC or HCC improved the survival rate to a level comparable to that of the general residents.
PMCID: PMC3502559  PMID: 23057417
Hepatitis C virus; Hepatocellular carcinoma; Prospective cohort study; Interferon; Life expectancy
4.  Results of mass endoscopic examination for gastric cancer in Kamigoto Hospital, Nagasaki Prefecture 
AIM: To examine how the introduction of endoscopy to gastric cancer screening affected survival prognosis in a regional population.
METHODS: The subjects comprised 4261 residents of Kamigoto, Nagasaki Prefecture, who underwent gastric X-ray examination for gastric cancer screening from 1991 to 1995, and all 7178 residents who underwent endoscopic examination for the same purpose from 1996 to 2003. The analysis evaluated trends in age-adjusted gastric cancer mortality rates and standard mortality ratios (SMRs) among the Kamigoto residents.
RESULTS: According to demographic statistics, the 1995 and 2000 age-adjusted gastric cancer mortality rates in Nagasaki Prefecture (per 100 000 population) were 42.6 and 37.3 for males and 18.6 and 16.0 for females, while the corresponding rates in Kamigoto before and after the introduction of endoscopic screening were respectively 51.9 and 28.0, and 26.6 and 6.9. The data obtained in this study were divided into those for two periods, 1990-1996 and 1997-2006, and SMRs were calculated separately for males and females. For the first period, the SMR was 1.04 (95% CI 0.50-1.58) for males and 1.54 (95% CI 0.71-2.38) for females, while for the second period the SMR was 0.71 (95% CI 0.33-1.10) for males and 0.62 (95% CI 0.19-1.05) for females.
CONCLUSION: Following the introduction of endoscopic examination, gastric cancer death rates decreased in Kamigoto.
PMCID: PMC4250856  PMID: 17708603
Endoscopy; Mass screening; Gastric cancer; Age-adjusted mortality rate; Standard mortality ratio

Results 1-4 (4)