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Biomedical subjects

Mitsuhiko Moriyama

Publications and source records attributed to Mitsuhiko Moriyama.

At least 19 recordsLinked to original sources
PubMed2006

Interferon therapy improves the irregular regeneration of hepatocytes in liver in patients with C-viral chronic hepatitis and liver cirrhosis.

We examined changes in the degree of irregular regeneration (IR) of hepatocytes and the F stage in patients with C-viral chronic hepatitis (CH) and liver cirrhosis (LC) who received interferon (IFN) therapy. The IFN-treated group consisted of 148 C-viral CH and LC patients; the IFN-untreated (UT) group consisted of 42 patients. The liver biopsy specimens were examined histologically, followed by a separate scoring of the degree of IR of hepatocytes which was classified into the following 5 grades and scored (IR score): score 0 (none), 1 (minimal), 2 (mild), 3 (moderate) and 4 (severe). The annual rates of the IR score were -0.593 in sustained virologic responders, -0.188 in sustained biochemical responders, 0.071 in nonresponders and 0.121 in UT patients. The annual rates of the F stage were -0.218 in sustained virologic responders, -0.061 in sustained biochemical responders, 0.123 in nonresponders and 0.157 in UT patients. The cumulative probability of hepatocellular carcinoma (HCC) incidence was significantly higher in groups of IFN-treated patients without improvement of IR scores than in groups with improvement of IR scores. Multivariate analyses revealed that a lack of improvement in the IR score was a cardinal risk factor for the development of HCC in C-viral CH and LC patients. Our data suggest that IFN therapy leads to an improvement in the degree of IR of hepatocytes and thereby influences the development of HCC in patients with CH and LC.

Adult↗
PubMed2006

Clinical significance of evaluation of serum zinc concentrations in C-viral chronic liver disease.

We evaluated zinc concentrations in patients with hepatitis C virus (HCV)-positive chronic liver disease and correlated them with the clinical profiles of the patients. A total of 100 patients with chronic hepatitis (CH), 29 with liver cirrhosis (LC), and 6 who were asymptomatic HCV carriers (ASC) were examined. All of the patients were positive for serum HCV RNA. One hundred eighteen HCV antibody-positive hepatocellear carcinoma (HCC) patients and 11 healthy subjects also were included in this study. Serum zinc concentrations were evaluated using conventional atomic absorption spectrometry. The median concentration of zinc in patients with CH was statistically lower than that in healthy control subjects. The median zinc concentrations of the LC and HCC groups were significantly lower than that of the CH group. A significant correlation was observed between the zinc concentrations and the platelet counts and albumin concentrations. The zinc concentrations did not correlate with tumor size and number and decreased with the development of Child-Pugh stage. The cumulative survival rate after therapy for HCC nodules in the low zinc concentration group was significantly lower than in the high group. We conclude that the serum concentration of zinc influences the clinical profiles in patients with C-viral chronic liver disease.

Adult↗
PubMed2006

Genetic variants of the IgA Fc receptor (FcalphaR, CD89) promoter in chronic hepatitis C patients.

Fc receptor for IgA (FcalphaR, CD89) is capable of triggering IgA-mediated immune responses to pathogens and has been proposed to function in circulating IgA clearance. Because inheritable variations modifying individual immune responses or immunoglobulin catabolism may affect the chronicity of viral infection, we investigated whether promoter polymorphisms of the FcalphaR gene (FCAR) affect chronic hepatitis C virus (HCV) infection and its disease progression. The two -311T/C and -142T/C single-nucleotide polymorphisms (SNPs) were studied by direct DNA sequencing in 177 Japanese patients with chronic hepatitis C (CHC). Both -311CC and -142CC genotypes were more frequent in CHC patients (15.9 and 18.6%) compared with 210 healthy controls (5.7 and 10.0%) [p = 0.001, odds ratio (OR) = 3.10, 95% confidence interval CI) = 1.53-6.30 and p = 0.014, OR = 2.06, 95% CI = 1.14-3.72, respectively], and were associated with infection with HCV genotype 2a/2b (p = 0.019 and p = 0.005, respectively). Conversely, -311CC and -142CC were decreased in 59 patients at advanced stages of disease as assessed on the basis of hepatic fibrosis markers such as decreased platelet count (PLT) (< 150,000/microl) (5.1 and 8.5%) compared with 91 patients with normal PLT (> or = 150,000/microl) (24.2 and 26.4%) (p = 0.006 and p = 0.005, respectively). Moreover, among the patients with normal PLT (but not with decreased PLT), -311CC or -142CC was significantly associated with decreased serum IgA levels (p = 0.023 or p = 0.007, respectively). These results suggest that the FCAR promoter SNPs may be related to chronic HCV infection and disease progression in Japanese CHC, which might be explained by altered FcalphaR expression affecting IgA-mediated immune responses and/or IgA catabolism.

Adult↗
PubMed2006

Measurement of human intercellular adhesion molecule 1 in the blood is useful for predicting the occurrence of hepatocellular carcinomas from chronic hepatitis C and liver cirrhosis.

OBJECTIVE: We measured the concentrations of serum intercellular adhesion molecule 1 (sICAM-1) in patients with C-viral chronic liver diseases and started prospective studies immediately thereafter, in order to determine whether the concentration of sICAM-1 is useful for predicting the occurrence of hepatocellular carcinoma (HCC) following C-viral chronic hepatitis (CH) and liver cirrhosis (LC). METHODS: We studied 74 patients with CH, 18 with LC, and 28 patients with HCC who visited our institute from 1993 through 1996. All were positive for hepatitis C virus RNA in the blood. The concentrations of sICAM-1 were measured using enzyme-linked immunosorbent assay kits. The expression of ICAM-1 in the liver was detected by indirect immunoperoxidase staining. RESULTS: The concentrations of sICAM-1 were significantly higher in patients with LC and HCC than in patients with CH. The sICAM-1 concentrations were high in patients whose platelet counts were low. ICAM-1 in the liver was localized to the endoplasmic reticulum or the membrane of cancer cells. The cumulative rate of occurrence of HCC from CH or LC was significantly higher in the high-sICAM-1 group (>400 ng/ml) than in the low-sICAM-1 group. Multivariate analysis revealed that elevation of the sICAM-1 concentration is a significant risk factor for the occurrence of HCC. CONCLUSION: Evaluation of the sICAM-1 concentration is useful for prediction of the occurrence of HCC in patients with C-viral CH or LC.

Biomarkers↗
PubMed2006

Twenty-four weeks of interferon alpha-2b in combination with ribavirin for Japanese hepatitis C patients: sufficient treatment period for patients with genotype 2 but not for patients with genotype 1.

BACKGROUND: Hepatitis C virus (HCV) RNA titer and HCV genotype are two major determinants of the outcome of interferon (IFN) monotherapy. To clarify the usefulness of combination therapy with IFN and ribavirin in Japanese hepatitis C patients, we treated patients with a relatively high dose of IFN in combination with ribavirin for 24 weeks and examined the effects in relation to the viral parameters. METHODS: Two hundred and ninety-five patients were enrolled in the study. The patients received either 6 or 10 million units (MU) of interferon alpha-2b every day for 2 weeks and then three times a week for 22 weeks with a daily dose of either 600 or 800 mg of ribavirin. The treatment response and safety of this treatment were examined. RESULTS: The sustained virologic response (SVR) rates were 26.8% in genotype 1 and 76.5% in genotype 2 (P < 0.001), and 36.1% with the 6 MU group and 45.8% with the 10 MU group (P = 0.09). Multivariate analysis indicated that SVR was associated with genotype 2, HCV RNA <500 kilointernational unit/ml (kIU/ml), and HCV RNA undetectability at week 8 of treatment. CONCLUSION: Our current study showed that a 24-week course of IFN plus ribavirin combination therapy was effective with respect to virologic response in Japanese hepatitis C patients, particularly in patients with HCV genotype 2.

Adolescent↗
PubMed2006

Treatment of interferon-alpha for chronic hepatitis C.

Combination therapy with polyethylene glycosylated IFN-alpha2a or IFN-alpha2b and ribavirin is currently the standard therapy for chronic hepatitis C. However, even with this therapy, hepatitis C virus cannot be eradicated in 50% of patients with refractory chronic hepatitis C. In addition, withdrawal or dose reduction occurs in approximately 40% of patients due to adverse effects. This treatment is also a contraindication in some patients, such as in patients with coexisting diseases or in elderly patients. For these patients, standard IFN-alpha monotherapy is even safer and more effective. In patients with chronic hepatitis C, IFN-alpha monotherapy results in a significant increase in the cumulative survival rate by suppressing the progression to hepatocellular carcinoma or liver failure. In addition, other efficacious therapeutic regimens have been employed, such as prolonged administration of standard IFN-alpha in elderly patients; prolonged low-dose continuous administration in patients with decompensated cirrhosis or hepatocellular carcinoma postoperative patients; and combination therapy with 5-fluorouracil and standard IFN-alpha for advanced hepatocellular carcinoma. Monotherapy with standard IFN-alpha should thus be recognised as one of the important therapeutic strategies for chronic hepatitis C.

Adult↗
PubMed2005

Decreased risk of hepatocellular carcinoma in patients with chronic hepatitis C whose serum alanine aminotransferase levels became less than twice the upper limit of normal following interferon therapy.

AIM: The incidence of hepatocellular carcinoma (HCC) in C-viral chronic hepatitis (CH) and liver cirrhosis (LC) patients after interferon (IFN) therapy was evaluated according to alanine aminotransferase (ALT) levels. PATIENTS: Two hundred sixty-nine patients with C-viral CH and LC were treated with natural IFN-alpha. The efficacy of IFN therapy was evaluated based on virologic response and ALT levels using the following groups: virologic-sustained responders (VSR); biochemical-sustained responders (BSR); partial responders (PR), which consisted of BSR patients whose serum ALT levels later relapsed; non-responders (NR)1, which included patients with serum ALT levels that were usually less than 80 IU/l; and NR2, NR with ALT levels persistently more than 80 IU/l. RESULTS: Of the 269 patients, 22 (8.2%) developed HCC after IFN therapy. The incidence of HCC (%/patient/year) was 0.78%, 0%, 0%, 0.17%, 4.68% in VSR, BR, PR, NR1, NR2, respectively. Multivariate analysis revealed that an increase in ALT levels to more than 80 IU/l is an important risk factor for the occurrence of HCC. CONCLUSIONS: We concluded that the patients with ALT levels less than twice the upper limit of normal after IFN therapy have a reduced risk of progression to HCC from C-viral chronic liver disease.

Adult↗
PubMed2005

SEN virus infection influences the pathological findings in liver but does not affect the incidence of hepatocellular carcinoma in patients with chronic hepatitis C and liver cirrhosis.

BACKGROUND/AIMS: This investigation compared the histological findings in the livers of chronic hepatitis C patients who were or were not co-infected with SEN virus (SEN-V) to determine the histological and clinical characteristics of SEN-V infection in Japan. METHODS: Three hundred and ninety-two patients with hepatitis C virus-associated chronic hepatitis (CH) or liver cirrhosis (LC) were included in the study. Serum samples were tested for the presence of SEN-V DNA by nested polymerase chain reaction. The liver biopsy specimen of each patient was examined and scores were assigned to indicate the severity of each of the following features: inflammatory cell infiltration in the periportal, parenchymal, and portal areas; F stage; portal sclerotic change; perivenular fibrosis; pericellular fibrosis; damage to the bile ducts; steatosis and irregular regeneration of hepatocytes (IR). RESULTS: Of the 473 patients, 194 (41.0%) were positive for SEN-V DNA. The rate of progression of F stage correlated with SEN-V DNA positivity. The blood biochemical parameters did not differ significantly between the SEN-V DNA-positive and -negative patients. The histological features of the livers of SEN-V DNA-positive patients included more severe parenchymal inflammatory cell infiltration and more IR. In particular, among those at the F2, F3 and F4 stages, the degree of IR of the SEN-V DNA-positive patients was significantly greater than that of the SEN-V DNA-negative patients. The cumulative probability of hepatocellular carcinoma (HCC) incidence and survival rate did not differ between the SEN-V DNA-positive and-negative patients. CONCLUSIONS: SEN-V co-infection may influence the histopathological features of the livers of patients with type C CH and LC but does not affect the outcome of patients with type C chronic liver disease.

Adult↗
PubMed2005

Removal of hepatitis C virus by G-1 beads in sera from patients with chronic hepatitis C.

UNLABELLED: Recently, a new method of extracorporeal granulocyte depletion apheresis has been developed to treat inflammatory systemic diseases using an Adacolumn (Japan Immunoresearch Laboratories, Takasaki, Japan) that is filled with acetate cellulose beads (G-1 beads) to adsorb the granulocytes. We examined whether hepatitis C virus (HCV) is adsorbed after incubation of the Adacolumn with the sera from patients with HCV-RNA-positive chronic hepatitis C. PATIENTS AND METHODS: A total of 10 patients with chronic hepatitis C, whose levels of HCV RNA were greater than 800 kIU/ml were examined. The serum was incubated with 500 G-1 beads in a syringe at 37 degrees C for 1 h. After removal of the serum, the beads were washed with RNase-free water. The G-1 beads were removed from the syringe after centrifugation. RNA was extracted from 200 microl of the wash waste and from 10, 50, 100 and 200 beads, respectively, using TRIZol regent. Detection of HCV RNA was performed using the nested PCR method. RESULTS: HCV RNA was detected from as few as 10 G-1 beads. HCV RNA was not detected from waste fluid collected after the last wash from any of the patients. Further, HCV RNA was detected in the initial waste fluid after the 37 degrees C incubation with serum in all of the patients. Since HCV RNA was detected on the G-1 beads, but not from the last washing solution in the current examination, these results suggest that the G-1 beads adsorbed HCV RNA. CONCLUSIONS: Our in vitro study confirmed that G-1 beads adsorbed HCV; therefore, apheresis using a column filled with G-1 beads may reduce the HCV RNA load in the blood of patients with chronic hepatitis C.

Adsorption↗
PubMed2005

Evaluation of serum concentrations of human hepatocyte growth factor during interferon therapy for chronic hepatitis C.

In this study, the serum concentrations of human hepatocyte growth factor (HGF) were examined to clarify the relationship between HGF and interferon (IFN) therapy for hepatitis C. The subjects were 94 patients with chronic hepatitis C who underwent liver biopsy at our institution from 1994 through 1996. These patients were treated with natural IFN-alpha, IFNalpha(2a) and IFNalpha(2b) for periods varying from 12 to 26 weeks. Serum levels of HGF were determined in individual patients just before and after the administration of IFN and at 6 months and 1 year thereafter. The serum concentration of HGF was evaluated using enzyme-linked immunosorbent assay kits. The intra-hepatic location of HGF was explored using an immunoperoxidase-staining method. A positive correlation was found between the degree of HGF expression in the liver and the serum HGF concentrations. The degree of HGF expression in the liver decreased in the virologically sustained responders (SVRs) following IFN therapy. The serum HGF concentrations immediately after IFN therapy were lower than those before therapy in 83% of the patients. The concentrations gradually rose thereafter in about 45% of the non-responders, while it remained low or declined further in about half of the patients in this group. In the SVRs, the serum HGF concentrations declined in 88% of patients immediately after IFN therapy. Thereafter, it remained equally low or declined further in 60% of the SVRs. The serum HGF concentrations at 6 months and 1 year after IFN therapy were significantly lower in the SVRs than in the non-responders. In conclusions, serum HGF concentrations declined following IFN treatment regardless of the virological outcome of treatment. The decrease in serum HGF concentrations results from a decrease in the number of mesenchymal cells producing HGF. Consequently, evaluation of the serum HGF concentration is of clinical value for assessing changes in liver tissues after IFN therapy.

Adult↗
PubMed2005

Full genomic analysis of hepatitis delta virus prevalent on Miyako Island, Japan.

The aims of this study were to determine the full-length genome sequences of hepatitis delta virus (HDV) in HDV RNA-positive subjects, and to elucidate the molecular specificity of the HDVs that are clustered on a distant island in Japan. This study included 3 subjects with chronic hepatitis who were positive for hepatitis B surface (HBs) antigen and HDV RNA, and who were admitted to the Okinawa Prefectural Miyako Hospital in 1998. The full-length genome sequence of HDV was determined by nested polymerase chain reaction (PCR) using four kinds of primer sets. The genomic length of HDV was 1,675, 1,679 and 1,681 base pairs, respectively. There was 90-92% nucleotide homology between each pair of isolates. In comparison with HDV isolates in geographically neighboring regions, the nucleotide homology of the 3 HDV isolates were 73-75% with the China isolate of genotype I; 77-78% with the Taiwan isolate of genotype I; 83-84% with a Japan isolate of genotype IIa; 85-87% with the Taiwan isolate of genotype IIa, and 87-88% with the Taiwan isolates of genotype IIb. Therefore, the Miyako Island isolates had high homology with the Taiwan isolate of genotype IIa and IIb. Phylogenetic analysis of the full-length genome sequences of HDV revealed that the two Miyako Island isolates were classified into a genotype IIb'. The other one was classified as genotype IIb. In conclusion, the HDV of Miyako Island isolates can be classified as a novel subgroup of genotype IIb, designated type IIb', and genotype IIb.

Aged↗
PubMed2004

Transcription of dbpA, a Y box binding protein, is positively regulated by E2F1: implications in hepatocarcinogenesis.

Human hepatocellular carcinoma is one of the most common cancers in the world. We previously showed that dbpA, a member of the Y box family of proteins, could accelerate the process of inflammation-induced hepatocarcinogenesis, and that dbpA is more abundantly expressed in hepatocellular carcinoma than in non-tumorous tissue. In this study, to clarify the mechanism by which expression of dbpA is enhanced in the proliferative state, we examined the transcriptional activity of the dbpA promoter region. We focused on the sequence 5'-TTTGGGGC-3' (-8 to -1 in the promoter region) resembling the E2F binding site (one base mismatch, TFSEARCH score 86.2). By overexpressing E2F1 in Huh-7 cells, transcriptional activity of dbpA was significantly increased, and this increase was abolished by mutating or deleting this sequence. Thus, expression of dbpA was positively regulated by E2F1, suggesting that one of the effects of E2F1 on cell proliferation might be mediated by dbpA at the carcinogenesis step.

Animals↗
PubMed2004

PBC-AIH overlap syndrome with concomitant ITP and Hashimoto's disease with positivity for anti-centromere antibody.

We report a case of primary biliary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome with concurrent idiopathic thrombocytopenic purpura (ITP) and Hashimoto's disease with positivity for anticentromere antibody. The patient was a 64-year-old woman with symptoms of jaundice and general fatigue. About 30 years earlier, she had been diagnosed as having ITP and had undergone splenectomy. As part of her present history, she had exhibited liver dysfunction in 1995, during the follow-up of Hashimoto's disease, and a liver biopsy led to the diagnosis of PBC. In March 2000, she was admitted to hospital because of general fatigue and jaundice. Blood tests revealed: total protein (TP), 6.6 g/dl; gamma-globulin (glb), 35.9%; total bilirubin (T-bil), 9.41 mg/dl; direct bilirubin (D-bil), 7.52 mg/dl; aspartate aminotransferase (AST), 957 U/l; alanine aminotransferase (ALT), 651 U/l; alkaline phosphatase (ALP), 595 U/l; gamma-guanosine triphosphate (GTP), 129 U/l; IgG, 2620 mg/dl; IgM, 223 mg/dl; hepatitis B surface antigen (HBsAg), negative; anti-hepatitis C virus (HCV), negative; antinuclear antibody, positive; antimitchondrial antibody (AMA), negative (by the immunofluorescence [IF] method); and anti-pyruvate dehydrogenase complex (PDC)-E2 antibody, positive (by Western blotting). Anticentromere antibody (ACA), which is an alternative diagnostic marker for PBC, was detected in this patient. Prednisolone was administered after admission and liver function test results improved markedly. The liver biopsy in 1995 had revealed infiltration of lymphocytes and plasma cells in the portal areas with fibrous expansion and periportal necrosis. Destructive cholangitis was observed, as well as scattered epitheloid cell granulomas in some portal areas. Liver biopsy after the steroid treatment revealed alleviated necrotic inflammatory responses of hepatocytes, while the destructive cholangitis persisted. This is a very rare case of PBC-AIH overlap syndrome accompanied by ITP and Hashimoto's disease which provides a possible insight into the mechanisms and interplay of autoimmune diseases.

Antibodies↗
PubMed2004

Detection of telomerase activity, telomerase RNA component, and telomerase reverse transcriptase in human hepatocellular carcinoma.

The aim of this study was to estimate the correlation between telomerase activity and the expression of human telomerase RNA component (hTERC), human telomerase reverse transcriptase (hTERT) in patients with hepatocellular carcinoma (HCC), and to analyze the influence of the nucleotide homology of the hTERC template region on telomerase activity. Six HCC patients and two chronic hepatitis patients were enrolled in this study. Telomerase activity was determined using the fluorescence-based telomeric repeat amplification protocol (TRAP) method. Quantification of hTERC and hTERTmRNA was performed using a real-time PCR method. Furthermore, a portion of the hTERC gene was amplified using nested RT-PCR methods. After sub-cloning, the nucleotide sequence of the cloned hTERC that contained the template region was determined. Telomerase activity and hTERTmRNA was detected in all cancerous tissues, while hTERC was present in both tumorous and non-tumorous lesions. The level of telomerase activity correlated with expression of hTERTmRNA, but not that of hTERC. The nucleotide sequence of cloned hTERC was similar in both tumorous and non-tumorous lesions. The expression of hTERT may be a definitive factor in the activation of telomerase in hepatocarcinogenesis.

Journal Article↗
PubMed2004

Detection of serum and intrahepatic KL-6 in anti-HCV positive patients with hepatocellular carcinoma.

We investigated the clinical significance of serum and intrahepatic KL-6/MUC1 (KL-6) in patients with hepatitis C virus (HCV) antibody-positive hepatocellular carcinoma (HCC). The subjects included 76 patients diagnosed with anti-HCV positive HCC, 69 with, and 51 without, liver cirrhosis (LC). Frozen serum samples were obtained from each subject to determine the serum KL-6 levels using an enzyme-linked immunosorbent assay. Expression of KL-6 antigen in the liver was also investigated using immunoperoxidase staining. The mean serum KL-6 level in patients with HCC was [Formula: see text] U/ml (319U/ml for HCC with LC, 342.8U/ml for HCC without LC). Serum KL-6 levels in patients with HCC with LC and HCC without LC did not differ. Serum KL-6 levels were elevated with increases in the size of spaces occupied by tumors in the liver. Among patients with HCC, there was no correlation between serum KL-6 levels and alpha-fetoprotein (AFP) levels and protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels. However, some patients with low levels of AFP and PIVKA-II possessed high levels of KL-6. Furthermore, serum KL-6 levels decreased after therapy for HCC nodules. Immunohistochemical staining showed KL-6 antigen was detected within the cell membrane and in the cytoplasm of cancer cells. KL-6 antigen was localized on the membrane and the endoplasmic reticulum of cancer cells in the cancerous foci by electron microscopy. Our results suggest that serum KL-6 levels represent a serological marker of HCC development, because KL-6 expression was localized to the cancer cells in HCC nodules.

Journal Article↗
PubMed2004

Liver cirrhosis and metabolism (sugar, protein, fat and trace elements).

The metabolism of various nutrients in the liver indicates the presence and severity of liver disorder, and can also reveal suitable nutritional treatment strategies. This paper overviews liver cirrhosis, investigates nutritional therapy and the role of malnutrition in patients with liver disease, and analyzes metabolism in the diseased liver of amino acids (BCAA etc.), carbohydrates and fats, with special attention to the metabolism of trace elements for diagnostic, surveillance and treatment. Trace elements play an essential role in maintaining vital functions, and excess or deficiency leads to metabolic disorders. To investigate the effect of trace element concentrations in liver disorders, we conducted tests comparing the concentrations of trace elements among patients at various stages of liver cirrhosis, and found a significant correlation between trace element metabolism and disease presence and progression. There is also a correlation between serum trace element concentrations and metalloprotein concentrations in the body, imbalances in which play a role in liver disease. Excess or deficiency can be rectified for improvement of liver disease. Because trace element concentrations are markers of oxidative stress levels in the liver, analysis of the concentrations can also be used for diagnosis of liver disease as well as indicating the effectiveness of antioxidant therapy.

Journal Article↗