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Norio Horiike

Publications and source records attributed to Norio Horiike.

At least 19 recordsLinked to original sources

Clinicopathologic features of the severe form of acute type 1 autoimmune hepatitis.

BACKGROUND & AIMS: Acute onset autoimmune hepatitis (acute AIH) is difficult to diagnose by using serologic data. In addition, some patients with the severe form of acute AIH do not respond to immunosuppressive therapy and have a poor outcome. In this study, we analyzed the clinicopathologic features of patients who were diagnosed as having acute AIH. METHODS: Retrospective review of patients with presumed acute AIH at Ehime University Graduate School of Medicine was performed. RESULTS: In liver tissue, infiltrates in the portal area and plasma cell infiltration are more common in acute AIH compared with acute hepatitis caused by other causes. Patients with acute AIH who did not have severe jaundice at the time of diagnosis exhibited a very good response to corticosteroid therapy, despite lower titers of antinuclear antibody (ANA). Most patients with acute AIH with higher levels of bilirubin and titers of ANA in sera respond poorly to corticosteroid therapy. CONCLUSIONS: Histologic findings might be useful for the early diagnosis of acute AIH. Acute AIH patients with high levels of bilirubin and high titers of ANA in sera often do not respond to corticosteroid therapy.

Acute Disease↗

Development of hepatocellular carcinoma (HCC) in a patient 17 years after recovery from chronic hepatitis B and seroconversion to anti-HBs.

A 63-year-old man was admitted to hospital in 2003 for treatment of a hepatocellular carcinoma (HCC). He was negative for HBs antigen (HBsAg) and anti-HCV antibody, and positive for anti-HBs. He had a past history of chronic hepatitis B. In 1986, HBsAg had become negative with the development of anti-HBs. In 2003, an HCC was detected and liver resection was carried out. Histological examination revealed moderately differentiated HCC and slightly fibrotic liver. It is suggested that a diagnosis of HCC, combined with negativity for HBsAg and anti-HCV antibody, may include cases of past recovery from chronic hepatitis B, such as this case.

Antibodies, Viral↗

Heterogeneity of hepatitis B virus genotype D in Japan.

OBJECTIVE: Hepatitis B virus (HBV) genotypes B and C are predominant in Japan. Previously, we reported that approximately 9% of HBV carriers in the Ehime area of western Japan were infected with genotype D (HBV/D) and their sequences closely related. Recently, serum samples from 3 patients with chronic HBV/D infections living in Tokyo and the surrounding area became available for testing. The purpose of this study was to determine whether the HBV/D isolates from these different areas of Japan are closely related. METHODS: Of the 3 Tokyo area patients infected with HBV/D, 2 had chronic hepatitis, and 1 had hemophilia with a history of frequent coagulation factor injections. The complete HBV/D genome sequences of each were determined, and compared with those of subjects from the Ehime area. RESULTS: All 3 HBV/D sequences had a genomic length of 3,182 bases, and the hepatitis B surface antigen subtype was ayw3. Phylogenetic analysis revealed that the 1 of the HBV/D isolates was closely related to the isolates from Ehime Prefecture, while 1 was similar and 1 was clearly distinct. CONCLUSION: Our results indicate that HBV/D infections in Japan are heterogeneous.

Adult↗

Clinical characteristics of autoimmune hepatitis in older aged patients.

BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) is an inflammatory disease of the liver that usually develops in middle-aged women. However, due to the increasing aging of the population and better diagnostic facilities, AIH is now diagnosed in older patients as well. This analysis compared the clinical and pathologic characteristics of older and middle-aged patients with AIH. PATIENTS AND METHODS: Thirteen older patients with AIH (mean age, 75.0+/-5.3 years; range, 70-89 years) and 27 middle-aged patients (mean age, 51.3+/-5.8 years; range, 41-60 years) were included in this study. In addition, the use of different treatment regimens, including prednisolone therapy and ursodeoxycholic acid (UDCA), was examined. RESULTS: There were no significant differences in gender, complications of other autoimmune diseases, and liver function tests between groups. However, the degree of hepatic fibrosis was significantly higher in older patients compared with middle-aged patients (P<0.05). Four patients with AIH in the older age group were successfully managed by UDCA alone. CONCLUSION: This study shows that older patients with abnormal liver function should be checked for AIH. In addition, UDCA may be an effective drug for management of older patients with AIH.

Journal Article↗

Anti-HBs-positive liver failure due to hepatitis B virus reactivation induced by rituximab.

A 59-year-old man developed acute hepatitis with reactivated hepatitis B virus (HBV) following administration of rituximab (anti-CD20 monoclonal antibody). The patient was diagnosed with malignant lymphoma in 1998, and virus marker testing indicated HBV surface antigen (HBsAg)-negative and anti-HBs antibody (anti-HBs)-positive results when chemotherapy including rituximab was started. Levels of aminotransferases were elevated, and HBsAg results turned positive. Despite therapy for late-onset hepatic failure, the patient died. Rituximab appears likely to have induced HBV reactivation in this case. Anti-viral agents should be administered for both HBsAg-positive and anti-HBs-positive patients who are scheduled to receive rituximab.

Antibodies, Monoclonal↗

Immune therapy including dendritic cell based therapy in chronic hepatitis B virus infection.

Hepatitis B virus (HBV) infection is a global public health problem. Of the approximately 2 billion people who have been infected worldwide, more than 400 million are chronic carriers of HBV. Considerable numbers of chronic HBV carriers suffer from progressive liver diseases. In addition, all HBV carriers are permanent source of this virus. There is no curative therapy for chronic HBV carriers. Antiviral drugs are recommended for about 10% patients, however, these drugs are costly, have limited efficacy, and possess considerable side effects. Recent studies have shown that immune responses of the host to the HBV are critically involved at every stage of chronic HBV infection: (1) These influence acquisition of chronic HBV carrier state, (2) They are important in the context of liver damages, (3) Recovery from chronic HBV-related liver diseases is dependent on nature and extent of HBV-specific immune responses. However, induction of adequate levels of HBV-specific immune responses in chronic HBV carriers is difficult. During the last one decade, hepatitis B vaccine has been administered to chronic HBV carriers as a therapeutic approach (vaccine therapy). The present regimen of vaccine therapy is safe and cheap, but not so effective. A dendritic cell-based therapeutic vaccine has recently been developed for treating chronic HBV infection. In this review, we will discuss about the concept, scientific logics, strategies and techniques of development of HBV-specific immune therapies including vaccine therapy and dendritic cell-based vaccine therapy for treating chronic HBV infection.

Antiviral Agents↗

Prognosis following transcatheter arterial embolization for 121 patients with unresectable hepatocellular carcinoma with or without a history of treatment.

AIM: To retrospectively evaluate the prognosis of patients with hepatocellular carcinoma (HCC) with or without a history of therapy for HCC following transcatheter arterial embolization (TAE). METHODS: One hundred and twenty-one patients with HCC treated with TAE from 1992 to 2004 in our hospital were enrolled in this study. Eighty-four patients had a history of treatment for HCC, while 37 did not. At the time of entry, patients with extra-hepatic metastasis, portal vein tumor thrombosis, or Child-Pugh class C were excluded. TAE was repeated when recurrence of HCC was diagnosed by elevated tumor markers, or ultrasonography or dynamic computed tomography findings. RESULTS: Tumor size was larger and the number of tumors was fewer in patients without past treatment (P<0.01). However, there were no differences in tumor node metastasis (TNM) stage or survival rate between the 2 groups. A bilobular tumor and high level of alpha-fetoprotein (AFP) (>100 ng/mL) were factors related to a poor prognosis in patients with a history of HCC. CONCLUSION: The prognosis following TAE is similar between HCC patients with and without past treatment. Early diagnosis of HCC or recurrent HCC and obtaining good local control against HCC before entry to a repeated TAE course can improve prognosis.

Aged↗

Tracing the history of hepatitis B virus genotype D in western Japan.

The major hepatitis B virus (HBV) genotypes in Japan are B and C. HBV genotype D (HBV/D), however, is widespread in a small area of Western Japan, where the Gianotti-Crosti syndrome caused by HBV subtype ayw, which is suspected to be HBV/D, was endemic in the 1970s. The aim of the study was to elucidate its origin, time of transmission, and spread in this area. Genotyping of HBV-DNA was done in 363 patients with HBV infection. The year of birth was checked in patients with HBV/D. The full genome sequences of 20 HBV/D strains, 2 of which were obtained from a single carrier with a 19-year-interval, were analyzed. An evolutionary rate, the date of the most recent common ancestor, and the effective number of HBV/D infections were calculated. Fifty-two of 363 patients were infected with HBV/D, and 39 were born in 1970s. In a phylogenetic tree, the 20 HBV/D strains produced a definite cluster, and the evolutionary rate was calculated to be 5.4 x 10(-5) nucleotide substitutions/site/year. The root of the tree was estimated to be in approximately 1,900 and began to spread from the 1940s, leading to a rapid increase of infected patients in the 1970s. From these results, it is suspected that HBV/D was likely transmitted to the area investigated approximately 100 years ago and then spread widely in the 1970s. From the history of the area and the genetic analysis, HBV/D in this area was speculated to be of Russian origin.

Acrodermatitis↗

Usefulness of contrast-enhanced ultrasonography with abdominal virtual ultrasonography in assessing therapeutic response in hepatocellular carcinoma treated with radiofrequency ablation.

OBJECTIVE: Contrast-enhanced computed tomography (CECT) is regarded as the gold standard for assessing the efficacy of radiofrequency ablation (RFA) against hepatocellular carcinoma (HCC). We evaluated the efficacy of virtual ultrasonography (VUS) with contrast-enhanced ultrasonography (CEUS) vs. CECT for assessing the response to RFA. MATERIALS AND METHODS: Study 1: The therapeutic responses in 22 patients with 26 HCC nodules were assessed by CEUS with VUS as well as by CECT. The efficacy of treatment was based on whether the safety margin was greater than 5 mm after RFA. Study 2: In seven patients with seven HCC nodules, the nodules were treated by RFA and the therapeutic efficacy was assessed by CEUS with VUS. The number of RFA sessions was assessed. RESULTS: Compared with CECT, CEUS with VUS had a specificity of 77%, a sensitivity of 91.6%, and an accuracy of 84%. When the therapeutic response to RFA was analyzed by CECT only, 1.86 +/- 0.69 assessments (mean) were required, while when response was assessed by CEUS with VUS, 1.14 +/- 0.38 CECT assessments were required (P = 0.03). CONCLUSION: CEUS with VUS is effective in assessing the therapeutic response to RFA of HCC. Moreover, the number of CECT scans required is reduced by this approach.

Abdomen↗

Virtual sonographic radiofrequency ablation of hepatocellular carcinoma visualized on CT but not on conventional sonography.

OBJECTIVE: Some nodules cannot be visualized clearly on conventional sonography but can be visualized on CT. In the present study, we evaluated the usefulness of real-time percutaneous ablation therapy under virtual sonographic guidance for these nodules. SUBJECTS AND METHODS: In vitro experiments were performed with gelatin gel to evaluate the accuracy of virtual sonography. We also studied 50 patients with 58 hepatocellular carcinoma nodules, of whom 18 patients (21 nodules) underwent radiofrequency ablation by virtual sonography. This was the initial treatment for seven of these patients and an additional treatment for 11 patients. Thirty-two patients (37 nodules) received radiofrequency ablation without virtual imaging. The patients receiving standard radiofrequency ablation were retrospectively selected as the historical control group under the same conditions as the study group. RESULTS: The in vitro gelatin gel study revealed that all punctures had been performed accurately. In both the initial-treatment group and the additional-treatment group, the mean number of treatments with virtual sonography was significantly lower than that without virtual sonography (p = 0.003 for both groups). The rates of local recurrence and complications did not differ significantly between the two groups. CONCLUSION: In the treatment of nodules not depicted on sonography, radiofrequency ablation assisted by virtual sonography is an efficacious alternative.

Aged↗

Cell-based models of sustained, interferon-sensitive hepatitis C virus genotype 1 replication.

We have previously reported hepatitis C virus (HCV) replication using a novel binary expression system in which mammalian cells were transfected with a T7 polymerase-driven full-length genotype 1a HCV cDNA plasmid (pT7-flHCV-Rz) and infected with vaccinia-T7 polymerase. We hypothesized that the use of replication-defective adenoviral vectors expressing T7 (Ad-T7pol) or cell lines stably transfected with T7 (Huh-T7) would alleviate cell toxicity and allow for more sustained HCV replication. CV-1, Huh7, and Huh-T7 cells were transfected with pT7-flHCV-Rz and treated with Ad-T7pol (CV-1 and Huh7 only). Protein and RNA were harvested from cells on days 1, 2, 3, 5, 7, and 9 post-infection. No cytotoxicity was observed at 9 days post-infection in any cell type. HCV positive- and negative-strand RNA expression were strongest during days 1-3 post-infection; however, HCV RNA remained detectable throughout the 9-day observation period. Furthermore, transfection with a replication-incompetent plasmid suggested that efficient HCV replication is dependent upon NS5B gene expression. Finally, after 1-2 days of IFN treatment, HCV positive-strand levels decreased significantly compared to HCV-infected but untreated samples (p<0.05). In conclusion, these refined binary systems offer more durable and authentic models for identification of host cellular processes critical to HCV replication and will permit longer-term analysis of virus-host interactions critical to HCV pathogenesis and the treatment of genotype 1 infections.

Antiviral Agents↗

Detection of hepatitis C virus (HCV) in serum and peripheral-blood mononuclear cells from HCV-monoinfected and HIV/HCV-coinfected persons.

It has been speculated that hepatitis C virus (HCV) replicates in peripheral-blood mononuclear cells (PBMCs), which, therefore, may be a site for interaction with human immunodeficiency virus (HIV). We used strand-specific real-time polymerase chain reaction to detect HCV RNA in 28 HCV-monoinfected and 20 HIV/HCV-coinfected women. At the first visit, positive-strand HCV RNA was detected in serum samples from 89% of the women, whereas positive-strand HCV RNA was detected in PBMC samples from 32% and 55% of the HCV-monoinfected and HIV/HCV-coinfected women, respectively. After initiation of antiretroviral therapy, the HIV/HCV-coinfected women were significantly more likely to have detectable positive- and negative-strand HCV RNA in the PBMC compartment than were the HCV-monoinfected women. HIV and HCV RNA levels were not correlated. Serum HCV RNA levels were correlated over time; HCV RNA levels in the serum and PBMC compartments were not. These data suggest differential regulation of HCV RNA in the serum and PBMC compartments and may partially explain the limited HCV antiviral response rates observed in coinfected persons.

Adult↗

Soluble CD163 in patients with liver diseases: very high levels of soluble CD163 in patients with fulminant hepatic failure.

BACKGROUND: The levels of several cytokines and chemokines are elevated in various liver diseases, especially in fulminant hepatic failure (FHF). Activated macrophages may have a role in the production of these immune modulators. CD163 is a member of a scavenger receptor family and is expressed mainly on activated macrophages, and a soluble form of CD163 (sCD163) is released from activated macrophages. The aim of this study was to assess sCD163 levels in patients with FHF and to evaluate their clinical significance. METHODS: The levels of sCD163 in the sera were measured in 21 patients with FHF, 17 patients with acute hepatitis (AH), 22 patients with chronic hepatitis (CH), and 14 normal healthy controls (NC), by an enzyme-linked immunosorbent assay. The levels of sCD163 were observed serially in patients with FHF and AH. RESULTS: The levels of sCD163 in the sera from patients with FHF were significantly higher than those in patients with AH and CH and the NC group (P < 0.0001). There was a good correlation between serum levels of sCD163 and prothrombin time (r = -0.677; P < 0.0001). A kinetic study revealed that the levels of sCD163 decreased in patients with AH and in survivors of FHF, whereas the levels of sCD163 progressively increased in nonsurvivors of FHF. CONCLUSIONS: This study shows that the products of activated macrophages may be involved in the pathogenesis of FHF. This study also inspires optimism that sCD163 may possess prognostic importance in FHF.

Adolescent↗

Therapeutic efficacy of decreased nitrite production by bezafibrate in patients with primary biliary cirrhosis.

BACKGROUND: The therapeutic efficacy of bezafibrate, a hypolipidemic drug, has been shown in patients with primary biliary cirrhosis (PBC) in some pilot studies; however, little is known regarding the mechanism of action of bezafibrate in PBC. This study was conducted to evaluate the therapeutic efficacy, as well as to gain insight about the possible mechanism of action, of bezafibrate in PBC. METHODS: Sixteen patients with PBC were administered with bezafibrate (400 mg/day) either with (n = 10) or without ursodeoxycholic acid (UDCA; n = 6). The peripheral blood of these patients was collected before and at different times after therapy commencement, and antigen-presenting dendritic cells (DCs) were then cultured. The DCs were enriched and cultured with Staphylococcus aureus Cowan strain-1 for 48 h to evaluate their capacity to produce nitrite. RESULTS: One month after the start of bezafibrate therapy, the serum levels of alkaline phosphatase (P = 0.0005), gamma-glutamyl transpeptidase (P = 0.0006), total cholesterol (P = 0.0072), and immunoglobulin M (P = 0.0281) were decreased significantly compared to those before patients started bezafibrate therapy. The levels of nitrite produced by DCs decreased in all patients with PBC within 1 month of commencement of bezafibrate therapy. Moreover, decreased nitrite production by DCs was also seen when nitrite production was evaluated 1 year after the start of bezafibrate therapy. CONCLUSIONS: This study reconfirms the therapeutic efficacy of bezafibrate in patients with PBC, including those with UDCA-resistant PBC. Downregulation of nitrite production by DCs may have some relationship with the therapeutic efficacy of bezafibrate; however, further study will be needed to clarify whether or not the antiinflammatory activity of bezafibrate is mediated through nitrite production.

Adult↗

The quantification of cytochrome P-450 (CYP 3A4) mRNA in the blood of patients with viral liver diseases.

OBJECTIVE: We quantified cytochrome P-450 (CYP) 3A4 mRNA in the blood and liver of patients with viral liver diseases to determine whether CYP 3A4 expression is related to disease progression. DESIGN AND METHODS: Total RNA was extracted from 10 mL of blood from 12 normal volunteers, from 6 patients with acute hepatitis, 17 with chronic hepatitis, 12 with liver cirrhosis, and 16 with hepatocellular carcinoma. Total RNA from 1 mg of liver tissue was extracted simultaneously in 10 patients. CYP 3A4 mRNA was quantified by competitive reverse-transcription polymerase chain reaction and expressed as log copies/microliter. RESULTS: The CYP 3A4 mRNA titer in blood correlated with that of the liver (r = 0.65, P < 0.05). The CYP 3A4 mRNA titer was 1.6 +/- 0.4 in normal controls, 1.0 +/- 0.5 in acute hepatitis, 0.7 +/- 0.2 in chronic hepatitis, 0.5 +/- 0.2 in liver cirrhosis, 0.5 +/- 0.2 in hepatocellular carcinoma, and decreased with progression of liver disease (P < 0.05). CONCLUSION: These data suggest that the CYP 3A4 mRNA level in blood relates to progression of liver disease.

Adult↗

Abdominal virtual ultrasonographic images reconstructed by multi-detector row helical computed tomography.

BACKGROUND: Three-dimensional (3D) images can be generated using thin sections from multi-detector row computed tomography (CT) and computer software, simulating images obtained using conventional ultrasonography (US). This software allows easy diagnosis of abdominal lesions and subsequent treatment of focal liver lesions such as hepatocellular carcinoma (HCC). The present study used newly developed virtual US software for diagnose and treatment of hepatobiliary disease. METHODS: The software was used to create virtual US images in 10 subjects. Radiofrequency ablation (RFA) was performed by virtual US in seven patients with HCC. RESULTS: Slices were easily reconstructed from various angles, and each slice was continuously animated as with conventional US in all subjects. Moreover, when seven patients with HCC were examined using virtual US, HCC nodules were visualized and could be treated with RFA. CONCLUSIONS: Virtual US should prove useful for visualization of HCC nodules that cannot be seen under conventional US. Virtual US is a useful tool for US-guided treatment of HCC.

Aged↗

In vivo immunization by vaccine therapy following virus suppression by lamivudine: a novel approach for treating patients with chronic hepatitis B.

BACKGROUND: Both the hepatitis B virus (HBV) and the immune response of the hosts to HBV play important roles in the pathogenesis of chronic hepatitis B (CHB). Lamivudine is a potent antiviral agent with minimal immune modulator capacity. Moreover, lamivudine causes severe side effects like breakthrough of HBV DNA and breakthrough hepatitis in patients with CHB. On the other hand, vaccine therapy, a recently-developed immune therapy, exhibits potent immune modulatory potentials and almost no side effects, but possesses little antiviral capacity in patients with CHB. OBJECTIVES: The aim of this clinical trial is to evaluate the efficacy of a combination therapy of lamivudine and vaccine in patients with CHB. STUDY DESIGN: Seventy-two patients with CHB (hepatitis B e antigen (HBeAg)-positive, 40; antibody to HBeAg (anti-HBe)-positive, 32). All patients received lamivudine at a dose of 100 mg daily for 12 months. Fifteen patients (HBeAg+, 9; anti-HBe+, 6) receiving oral lamivudine were also given a vaccine containing 20 microg of hepatitis B surface antigen, intradermally, once every 2 weeks for 12 times (combination therapy). RESULTS: Twelve months after the start of therapy, serum HBV DNA became negative in 9 of 9 (100%) HBeAg+ CHB patients receiving combination therapy and in 15 of 31 (48%) HBeAg+ CHB patients receiving lamivudine monotherapy (P < 0.05). The rate of seroconversion from HBeAg to anti-HBe was also significantly higher in patients receiving combination therapy (56% versus lamivudine monotherapy, 16%, P < 0.05). Of the 57 patients receiving lamivudine monotherapy, breakthrough of HBV DNA was found in 10 and breakthrough hepatitis was found in 4; however, these were not seen in any patient receiving combination therapy. CONCLUSIONS: Combination therapy represents a better therapeutic regimen with few complications in patients with CHB.

Adult↗