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Biomedical subjects

Shigetoshi Fujiyama

Publications and source records attributed to Shigetoshi Fujiyama.

At least 19 recordsLinked to original sources
PubMed2006

Randomized, double-blind, placebo-controlled trial of bovine lactoferrin in patients with chronic hepatitis C.

Several studies have suggested that lactoferrin administration may decrease the serum level of hepatitis C virus (HCV) RNA in patients with chronic hepatitis C. The aim of the present study was to confirm the efficacy of orally administered bovine lactoferrin (bLF) in patients with chronic hepatitis C. The patients with chronic hepatitis C randomly received either oral bLF at a dose of 1.8 g daily for 12 weeks, or an oral placebo. The primary endpoint was the virologic response, defined as a 50% or greater decrease in serum HCV RNA level at 12 weeks compared with the baseline. The secondary endpoint was the biochemical response, which was defined as a 50% or greater decrease in the serum alanine aminotransferase (ALT) level at 12 weeks compared with the baseline. One hundred and ninety-eight of 199 patients were evaluable for efficacy and safety. bLF treatment was well tolerated and no serious toxicities were observed. A virologic response was achieved in 14 of 97 patients (14.4%) in the bLF group, and 19 of 101 (18.8%) in the placebo group. There was no significant difference in virologic response rates between the two groups (-4.4%, 95% confidence interval -14.8, 6.1). In addition, bLF intake did not have any favorable effect on the serum ALT level. The virologic responses were not different between two groups in any subgroup analysis. In conclusion, orally administered bLF does not demonstrate any significant efficacy in patients with chronic hepatitis C.

Administration, Oral↗
PubMed2006

Clinical features of hepatocellular carcinoma that occur after sustained virological response to interferon for chronic hepatitis C.

BACKGROUND AND AIM: This study investigated the clinical features of hepatocellular carcinoma in patients with sustained virological response to interferon for hepatitis C viral (HCV) infection. METHODS: A total of 7,715 patients with HCV infection were treated with interferon and followed up for more than 1 year after withdrawal of interferon in 64 Japanese hospitals and clinics between July 1988 and August 2001. Sustained virological response was obtained in 2,515 (32.6%) patients. Of these 2,515 patients, clinical data were collected for 38 patients in whom hepatocellular carcinoma developed. Sustained virological response was defined as HCV RNA negativity more than 6 months after the termination of interferon. RESULTS: All patients were HCV RNA negative at the time of diagnosis of hepatocellular carcinoma. The median period until the detection of hepatocellular carcinoma was 4.7 years (range 1.4-9.0 years). There were significant improvements in hepatic function including serum albumin, aspartate aminotransferase, alanine aminotransferase, indocyanine green test, platelet count and histological activity grade in comparison with those before interferon therapy and at the onset of hepatocellular carcinoma. The maximum tumor size in patients without medical follow-up for 1 year or more (median: 60 mm) was significantly larger than in patients who were periodically followed up for 6 months or less (median: 25 mm) (P=0.002). CONCLUSIONS: The present findings emphasize the importance of regular medical follow up of patients with HCV infection, as even patients showing a sustained virological response to interferon and in whom hepatic function has improved have the potential to develop hepatocellular carcinoma.

Adult↗
PubMed2005

Risk factors for development of hepatocellular carcinoma in patients with chronic hepatitis C after sustained response to interferon.

BACKGROUND: Interferon (IFN) is expected to prevent the progression of hepatitis C virus infection to cirrhosis and the development of hepatocellular carcinoma (HCC), but there have been several reports of the development of HCC after a sustained response to IFN. Our aim was to elucidate the incidence and clinical features of, and risk factors for, HCC in sustained responders to IFN, taken for the treatment of chronic hepatitis C. METHODS: We designed a retrospective cohort study conducted at 16 major Hospitals. The subjects were a total of 1056 patients showing sustained responses, 29 of whom developed HCC. RESULTS: The incidence of HCC per 100 person-years was 0.56 (95% confidence interval, 0.35-0.76) in sustained responders. By the Cox proportional hazard model, we found that older age, higher serum aspartate aminotransferase level, and lower platelet count before IFN therapy were independent risk factors associated with the development of HCC. A risk index of HCC development, based on the coefficients of these risk factors, was used to classify patients into three groups, with low, intermediate, and high risk. The incidence rates of HCC for these three groups were 0.11, 0.44, and 1.98 per 100 person-years, respectively. The median period to the development of HCC was 4.6 years (range, 1.4-9.0 years), and there were no other specific clinical features of the HCC that developed in these patients. CONCLUSIONS: This study suggests that the risk of development of HCC is not completely eliminated in sustained responders to IFN. These findings may be useful in determining a follow-up strategy after a sustained response to IFN.

Adolescent↗
PubMed2005

Ursodiol use is possibly associated with lower incidence of hepatocellular carcinoma in hepatitis C virus-associated liver cirrhosis.

In a previous study of patients with hepatitis C virus (HCV)-associated liver cirrhosis (HCV-LC), we showed that increased liver inflammation, as assessed by higher serum alanine aminotransferase (ALT), was associated with increased risk for the development of hepatocellular carcinoma (HCC). This suggested that suppression of inflammation might inhibit HCC development in HCV-LC. Several agents have been suggested to possess chemopreventive potential against the development of HCC in chronic HCV-associated liver disease, including herbal medicines, such as Stronger-Neo-Minophagen C (glycyrrhizin) and Sho-saiko-to (TJ-9). Ursodiol [ursodeoxycholic acid (UDCA)], a bile acid widely used to treat cholestatic liver diseases, also possesses anti-inflammatory properties in liver disease. We hypothesized that suppression of liver inflammation, as assessed by decreases in serum ALT, might inhibit HCC occurrence in patients with HCV-LC. In this study, the preventive effect of UDCA on HCC was examined in patients with early-stage HCV-LC. One hundred two patients with HCV-LC (Child stage A) were treated with anti-inflammatory drugs, Stronger-Neo-Minophagen C,Sho-saiko-to, or UDCA, with the goal of lowering the average serum ALT level to <80 IU. Iftheaverage ALT level did not remain <80 IU after treatment with one agent, multiagent therapy was initiated. The patients were followed up for >5 years and were retrospectively subdivided into two groups: 56 UDCA users (group A) and 46 UDCA nonusers (group B). The mean +/- SD dosage of UDCA administered in group A was 473.7 +/- 183.0 mg/d. The average duration of UDCA administration in group A was 37.3 +/- 15.9 months over the 5-year study period. The cumulative incidence of HCC was recorded. The 5-year incidence of HCC in group A was 17.9% (10 of 56) and was significantly lower than that in group B (39.1%, 18 of 46; P = 0.025). The risk for HCC incidence, calculated by a logistic regression model, showed that the administration of UDCA significantly decreased hepatocarcinogenesis (P = 0.036). The herbal medicines used were comparable in dosage and treatment duration in the UDCA and non-UDCA groups. In conclusion, UDCA might prevent HCC development in HCV-LC. Interestingly, because the serum ALT trends over time were nearly the same in both groups, the chemopreventive effectiveness of UDCA was not accompanied by greater reductions in ALT compared with the UDCA nonusers.

Alanine Transaminase↗
PubMed2004

Phase II trial of intra-arterial chemotherapy using a novel lipophilic platinum derivative (SM-11355) in patients with hepatocellular carcinoma.

SM-11355, a lipophilic platinum derivative, is a novel intra-arterial chemotherapeutic agent for hepatocellular carcinoma (HCC). A phase II study of SM-11355 was conducted to evaluate the antitumor activities and the toxicity in chemotherapy-naive patients with HCC. Sixteen patients were treated with transcatheter arterial injection of SM-11355-lipiodol emulsion (20-120 mg/body). The responses were evaluated by computed tomography 3 months after treatment. Complete response (CR) was defined as disappearance or 100% necrosis of all tumors, and lipiodol accumulation in tumors was regarded as indicating necrosis. Nine patients achieved CR (56%; 95% confidence interval, 29.9-80.2%). The grade 3 toxicities were neutropenia (19%), total bilirubin elevation (19%), AST elevation (44%), and ALT elevation (19%). None of the patients showed grade 4 toxicities or episodes of renal dysfunction. Other common adverse effects were eosinophilia (100%) and pyrexia (94%). Intra-arterial chemotherapy with SM-11355, which was well tolerated, showed promising antitumor activity in patients with HCC.

Aged↗
PubMed2004

Clinical usefulness of a new hepatitis C virus RNA extraction method using specific capture probe and magnetic particle in hemodialysis patients.

Hemodialysis patients are a high-risk group for hepatitis C virus (HCV) infection. Assessment of HCV infection using HCV-RNA assay among dialysis patients is important for the issue of safety and environmental protection. However, polymerase chain reaction (PCR)-based methods are unsuitable for analyzing samples from dialysis patients because the conventional centrifugal extraction method fails to eliminate heparin, a potent inhibitor of PCR. In this study, we evaluated the usefulness of a HCV-RNA extraction method using probes and magnetic particles for hemodialysis patients in comparison with the centrifugal method. The study population consisted of 17 HCV antibody-positive patients undergoing hemodialysis. These 17 patients consisted of 12 HCV carrier patients and five patients with past HCV infection. One hundred and two samples from these patients were measured using the centrifugal and magnetic methods. Moreover, we prepared five standards that included theoretically 5 KIU/mL of HCV. One was made from non-HD patient's serum and the other four were from hemodialysis patients' serum. These standards were measured using the two methods. False-negative results were not observed with the magnetic method, but were observed in five out of 102 samples with the centrifugal method. Studies using standard samples revealed that accurate HCV-RNA measurement is achieved using the magnetic method. In conclusion, the present study showed that this magnetic extraction method is a highly reproducible and reliable assay to obtain correct information about the presence of the infective virus itself in the hemodialysis setting. Precise identification of HCV-RNA using this specific method is considered to be useful in preventing HCV infection in hemodialysis units.

Aged↗
PubMed2004

Transcatheter arterial chemotherapy with and without embolization in patients with hepatocellular carcinoma.

OBJECTIVE: This study compared the antitumor effect, adverse effects and survival between transcatheter arterial embolization (TAE) and transcatheter arterial infusion chemotherapy (TAI) in patients with hepatocellular carcinoma (HCC). METHODS: The study population consisted of 168 consecutive patients with advanced HCC treated with transcatheter arterial treatments using cisplatin suspended in lipiodol. Among these, 74 patients were treated with TAE, and the remaining 94 patients were treated with TAI. RESULTS: There were no significant differences in any baseline characteristics except hemoglobin, platelets, albumin, and glutamic pyruvic transaminase. Complete or partial tumor response was achieved in 54 patients (73%) in the TAE group and in 48 patients (51%) in the TAI group (p < 0.01). There were two treatment-related deaths caused by acute hepatic failure and acute renal failure in the TAE group. Nausea and deterioration of serum transaminase after TAE were significantly more severe than after TAI. Median survival time and survival rates at 5 years were 3.1 years and 25% in the TAE group, and 2.5 years and 18% in the TAI group (p = 0.37). CONCLUSION: TAE has a higher antitumor effect than TAI, but does not significantly improve the survival of patients with HCC.

Adult↗
PubMed2004

Assessment of adverse reactions and pharmacokinetics of ribavirin in combination with interferon alpha-2b in patients with chronic hepatitis C.

Ribavirin has recently been demonstrated to be efficacious in combination with interferon (IFN) alpha-2b for the treatment of relapsed hepatitis C infections. The aim of this study was to evaluate the relationship between the pharmacokinetics and adverse reactions of ribavirin when ribavirin plus IFN alpha-2b were administered to patients affected with chronic hepatitis C. Nineteen patients received intramuscular IFN alpha-2b at a dose of 6 or 10 million units and oral ribavirin at 600 mg or 800 mg daily for 24 weeks. The pharmacokinetic profiles of ribavirin were assessed by the measurement of plasma concentrations. Twelve patients were continuously given both ribavirin and IFN alpha-2b, whereas in 7 patients the therapy was discontinued due to severe adverse drug reactions such as skin eruption, anemia and depression. There were no significant differences in ribavirin dose, Hb, ALT and AST values between the continued and the discontinued therapy groups. In contrast, the pretreatment platelet level and patient age of the discontinued therapy group were significantly different to the continued group. The trough plasma concentration of ribavirin in the discontinued therapy group was significantly higher than that in the continued group at week 1. These results suggest that the monitoring of plasma ribavirin concentrations may be valid for predicting the early phase of adverse drug reactions, thereby providing useful information for the adjustment of the ribavirin dosing for each patient.

Adult↗
PubMed2003

Glypican-3, overexpressed specifically in human hepatocellular carcinoma, is a novel tumor marker.

With the global pandemic of hepatitis B and C infections, the incidence of Hepatocellular carcinoma (HCC) is rapidly increasing world wide. We identified glypican-3 (GPC3), a novel oncofetal gene over-expressed specifically in human HCC, as based on data of cDNA microarrays. As GPC3 is a GPI-anchored membrane protein and could be secreted, we attempted to detect secreted GPC3 protein in sera from HCC patients using Western blotting and ELISA. GPC3 protein was positive in sera of 40.0% (16/40) of HCC patients, and negative in sera from subjects with liver cirrhosis (LC) (0/13), chronic hepatitis (CH) (0/34), and healthy donors (0/60). All subjects were Japanese. Although 12 of 40 HCC patients were negative for both alpha-fetoprotein (AFP) and PIVKA-II well known tumor markers of HCC, four of these were GPC3-positive in the sera. We also observed vanishing GPC3 protein in the sera of three patients after the surgical treatment for HCC. On the other hand, immunohistochemical analysis revealed that HCC expressed GPC3 protein in all 14 HCC patients tested. In conclusion, GPC3, as defined in this study was shown to be a useful tumor marker for cancer-diagnosis for large numbers of patients with HCC.

Adult↗
PubMed2003

Impaired hepatic granuloma formation in mice deficient in C-C chemokine receptor 2.

Granulomas are characterized histologically by a nodular collection of macrophages with occasional admixture of epithelioid cells, multinucleate giant cells, and other immunocompetent cells. Chemokines are considered to play an important role in the recruitment of these constituent cells of granulomas. The present study has examined the effect of a deficiency of C-C chemokine receptor-2 (CCR2) on hepatic granuloma formation induced by a single injection of Zymosan A. In CCR2+/+ mice, the number and the size of granulomas gradually increased until they reached peak values at 10 days after the injection. In contrast, both the number and the size of granulomas were smaller in CCR2-/- mice than in CCR2+/+ mice from days 5 to 21. They showed low peaks at day 5, after which the number and the size of the granulomas gradually decreased. Immunohistochemical analysis of the constituent granuloma cells using cell type-specific monoclonal antibodies revealed rapid accumulation of blood monocytes, with subsequent differentiation to macrophages, in CCR2+/+ mice during days 2-10. This process was greatly impaired in CCR2-/- mice and granulomas remained small. At all time points, the percentage of polymorphonuclear cells in granulomas was higher in CCR2-/- mice than in CCR2+/+ mice. Interestingly, multinucleate giant cells were frequently observed in granulomas in CCR2-/- mice, whereas they rarely appeared in CCR2+/+ mice. Profiles of liver cytokine RNA levels as well as serum cytokine levels revealed reduced expression of the Th1 cytokine IFN-gamma in CCR2-/- mice. These data clearly indicate that signalling through CCR2 has many effects on the normal growth and development of hepatic granulomas.

Animals↗
PubMed2003

[Examination of HCV infection in hemodialysis patients with HCV-RNA assay using a magnetic extraction method (AmpliCap GT HCV MONITOR Test Kit v2.0 and AmpliCap GT HCV Specimen Preparation Kit v2.0)].

Hemodialysis(HD) patients are a high-risk group for hepatitis C virus(HCV) infection. Detection of HCV-RNA is important for safety and environmental protection in HD units. PCR-based methods are unsuitable for analyzing large samples of HD patients, because conventional centrifugal extraction method fails to eliminate heparin, a potent inhibitor of PCR. We have reported the usefulness of a new HCV-RNA extraction method using specific capture probes and magnetic particles in comparison with conventional centrifugal extraction method in hemodialysis patients. In this study, we evaluated the rate of HCV infection and HCV-RNA positivity by using a magnetic extraction method. As a result, the rate of HCV infection in dialysis patients was significantly higher than that of healthy people, and positivity for HCV infection was found to be related to the duration of hemodialysis. It has been assumed that the rate of new HCV infection is decreased as the result of improvement in dialysis equipment, a decrease in the need for blood transfusion due to the availability of erythropoietin for renal anemia, and the introduction of anti-HCV screening for blood donors. Hospital infection was strongly suggested from the evidence that the correlation with the rate of HCV infection and duration of dialysis was not significantly changed. HCV-RNA positivity was observed in two among 435 HCV antibody-negative patients. Since HCV-RNA positivity has been observed in HCV antibody-negative patients in HD units, combination with HCV-RNA by the magnetic extraction method and anti-HCV antibodies should be useful for the treatment of HCV infection. In this study, the effectiveness of IFN therapy was expected in 56.7%(38/67) that were genotype2 and/or had a low viral load. A precise diagnosis using HCV-RNA assay by the magnetic extraction method and precise medication including IFN therapy is desired for improving the long-term prognosis of dialysis patients.

Aged↗
PubMed2003

[Multidisciplinary treatment for hepatocellular carcinoma invading the stomach].

The patient was a 69-year-old man who was found to be positive for the hepatitis C antibody in 1996. Hepatocellular carcinoma (HCC) was found in S4 and S7 in April 2000. He received treatment by transcatheter arterial chemoembolization (TACE) 3 times and by percutaneous ethanol injection therapy 1 time. At that point pulmonary metastasis was found. In November 2001 he was urgently admitted with hematemesis to the Department of Gastroenterology and Hepatology of our hospital. Bleeding from the HCC invading the stomach was found by endoscopy. Bleeding was successfully stopped by TACE. Because of the dangerousness of severe bleeding due to the disintegration of the HCC, we carried out a partial hepatectomy with partial gastrectomy and partial excision of the diaphragm. He recuperated at home after being discharged from the hospital, and sufficient QOL was maintained. In April of the same year, he vomited blood again and was readmitted. Endoscopy showed bleeding from a recurrence of the HCC in the stomach and a metastatic tumor at the lower esophagus. Bleeding was controlled by TACE and endoscopic procedures. The patient could maintain QOL under multidisciplinary therapy including surgery for the HCC, which was impossible to treat curatively. In such cases, it is important to use IVR or endoscopic procedures or a combination including them. Furthermore, in case of good hepatic reserve, surgery may then be added.

Aged↗
PubMed2002

The role of hepatitis B virus-specific memory CD8 T cells in the control of viral replication.

BACKGROUND/AIMS: The aim of this study is to clarify the differences of host immune responses between acute self-limited and chronic persistent hepatitis B virus (HBV) infections by quantitative and qualitative analysis of HLA-A*2402-restricted HBV-specific CD8+ T cells. METHODS: HBV-specific CD8+ T cells in peripheral blood mononuclear cells (PBMCs) from patients infected with HBV were analyzed by flow cytometry using two HLA-A*2402-HBV peptide tetrameric complexes. RESULTS: High numbers of HBV-specific CD8+ T cells were detected in acute phase PBMCs from most individuals with acute HBV infection while the number of these cells was greatly reduced in recovery phase PBMCs. HBV-specific CD8+ T cells were not detected in PBMCs from individuals with chronic HBV infection except for one patient during acute exacerbation. HBV-specific CD8+ T cells were induced by in vitro peptide stimulation in PBMCs from chronic HBV carriers with a low level of serum HBV-DNA but not from those with a high level of serum HBV-DNA. CD28CD45RA phenotype analysis showed that HBV-specific CD8+ T cells in acute phase PBMCs predominantly express a memory T cell phenotype. CONCLUSIONS: HBV-specific memory CD8+ T cells may play a crucial role in complete clearance of HBV from patients with acute HBV hepatitis.

Acute Disease↗
PubMed2002

Survival and local recurrence rates of hepatocellular carcinoma patients treated by transarterial chemolipiodolization with and without embolization.

The factors contributing to local recurrence and survival rates of patients with hepatocellular carcinoma (HCC) were analyzed by univariate and multivariate analysis using the Cox proportional hazard model in 356 patients treated by transcatheter arterial chemoembolization (TAE) or transcatheter arterial chemolipiodolization (TAI). Potential predictors of recurrence and survival analyzed included: patient characteristics (gender and age), basal liver disease, tumor characteristics (number of tumors, size of tumor nodule and presence of vascular invasion), Child classification, serum albumin and total bilirubin level, prothrombin time, treatment modality (TAE or TAI) and serum levels of the tumor markers [alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (PIVKA-II)]. In 259 patients (72.5%) with confirmed complete necrosis of the primary lesion, the local recurrence rate in the TAE group was significantly lower than that of the TAI group (P<0.05). Size of tumor nodule, vascular invasion, treatment modality (TAE or TAI) and serum PIVKA-II level were significant independent risk factors contributing to local recurrence. Serum albumin level, size of tumor nodule, vascular invasion and serum AFP level were significantly independent prognostic factors contributing to survival. When size of tumor nodule was greater than 30 mm in diameter and without vascular invasion, TAE had a survival benefit superior to TAI.

Journal Article↗