Showing papers by "Masashi Mizokami published in 1995"
TL;DR: Serum samples from 139 US patients with chronic hepatitis C virus (HCV) infection were studied using six different genotyping systems, including both molecular and serologic methods, to determine the applicability of these approaches and the prevalence of various HCV subtypes.
Abstract: Serum samples from 139 US patients with chronic hepatitis C virus (HCV) infection were studied using six different genotyping systems, including both molecular and serologic methods, to determine the applicability of these approaches and the prevalence of various HCV subtypes. The concordance of genotyping results based on the various systems (except for core polymerase chain reaction genotyping) was good (93.5%). Subtypes 1a and 1b were prevalent (37.4%). Subtypes 2a (2.2%), 2b (8.6%), and 3a (5.8%) were less common. HCV genotypes could not be determined in 3.4%-16.5% of samples depending on the method used. HCV type 2 was associated with greater histologic activity but lower serum HCV RNA levels (P < .05), whereas type 3 was associated with lower serum alanine aminotransferase levels (P < .05). These data demonstrate a high concordance between HCV genotyping systems and provide a foundation for comparison of genotyping data between studies using different systems. HCV types 1a and 1b are both prevalent in the United States.
205 citations
TL;DR: Similar levels of hepatitis C virus core protein were detected in patients with chronic hepatitis and cirrhosis, but patients with hepatitis-C-virus-related hepatocellular carcinoma tended to have a lower level of hepatitisC virus coreprotein.
123 citations
TL;DR: To determine the virological factors associated with a favorable long‐term response to interferon‐α (IFN) therapy in chronic hepatitis C virus (HCV) infection, 61 Japanese patients with chronic HCV infection were treated with IFN for 24 weeks and followed for 8 to 16 months after cessation of therapy.
Abstract: To determine the virological factors associated with a favorable long-term response to interferon-alpha (IFN) therapy in chronic hepatitis C virus (HCV) infection, 61 Japanese patients with chronic HCV infection were treated with IFN for 24 weeks (780 million units in total) and followed for 8 to 16 months after cessation of therapy. Ten patients dropped out because of severe side effects. Of the 51 patients who completed IFN therapy, 23 showed complete and sustained response (CR --> SR), 13 complete response with early relapse (CR --> Rel), and 15 no response to IFN (NR). For the pretreatment serum HCV RNA level, 20/23 who had CR --> SR had Rel and 1/15 NR (P SR compared to CR --> Rel of NR (P SR were HCV RNA negative compared to 3/11 CR --> Rel (P SR compared to 8/11 CR --> Rel (P = NS), and 0/13 in NR (P SR patients were HCV RNA positive despite normalization of serum ALT levels. These data indicated that in addition to pretreatment serum HCV RNA levels and HCV type, the kinetics of response to IFN (at week 4) were also predictive of subsequent long-term response to IFN in patients with chronic HCV infection.
104 citations
TL;DR: Responses of patients infected with chronic hepatitis C virus to interferon-alpha (IFN-alpha) treatment were studied and levels of HCV viremia levels were determined by quantitative reverse transcription-polymerase chain reaction.
Abstract: Responses of patients infected with chronic hepatitis C virus (HCV) to interferon-alpha (IFN-alpha) treatment were studied. HCV genotypes were determined by molecular and serologic techniques. Levels of HCV viremia were determined by quantitative reverse transcription-polymerase chain reaction. Infection with HCV genotype 2 or low pretreatment HCV viremia levels in subjects infected with genotype 1 were associated with favorable (complete and sustained) responses (CR-SR; P < .001) to IFN-alpha treatment. HCV viremia levels in genotype 2 infection were significantly lower (P < .05) than in genotype 1 infection. The reduction rates of serum HCV RNA levels were four times higher in patients with genotype 2 infection than in those infected with genotype 1. The proportion of patients with CR-SR who experienced virologic relapse after completion of IFN-alpha treatment was higher for those infected with genotype 1. The proportion of patients with CR-SR and genotype 1 infection increased linearly in accordance with increases in single or total IFN-alpha dose.
70 citations
Shinshu University1, Hokkaido University2, Iwate Medical University3, National Defense Medical College4, St. Marianna University School of Medicine5, Niigata University6, Kanazawa University7, Nagoya City University8, Kyoto Prefectural University of Medicine9, Osaka City University10, Okayama University11, Institute of Medical Science12
TL;DR: SG‐1 HCV was found to predominate in Japan, and the HCV genotypes were found to be related to the stage of hepatitis C disease.
Abstract: Sixteen medical institutions in Japan collaborated in this study of the epidemiology of hepatitis C virus (HCV) genotypes. A total of 4176 patients with type C chronic liver disease, from the four main islands of Japan, were evaluated. Of those evaluated, 2794 had chronic hepatitis, 727 had liver cirrhosis and 655 had hepatocellular carcinoma. The HCV genotype of the patients was determined by an enzyme-linked immunosorbent assay based on serological genotype 1- and 2-specific recombinant peptides (SG-1 and SG-2, respectively) of the NS4 region. The prevalence of SG-1 and SG-2 HCV was similar in the four main islands of Japan. SG-1 HCV predominated in each disease category (69-76%). The percentage of patients with SG-1 HCV increased by 7%, while that of patients with SG-2 HCV decreased by 7%, as liver disease progressed in severity from chronic hepatitis to carcinoma (P < 0.001). Patients with either SG-1 or SG-2 had a similar mean age and history of blood transfusion. In conclusion, SG-1 HCV was found to predominate in Japan, and the HCV genotype was found to be related to the stage of hepatitis C disease.
62 citations
TL;DR: Cryostat sections, using polyclonal IgG against HCV antigens, exhibited greater immunohistochemical staining, suggesting that the fixation and processing of the tissue may be a major factor in the conservation and the outcome of HCV antigen(s) findings, however, the results using monoclonal antibodies may reflect the specificity of antigen expression.
Abstract: Localization of hepatitis C virus (HCV) antigens was studied in fresh frozen and formalin-fixed, paraffin-embedded liver tissue by immunoperoxidase using monoclonal antibodies to nucleocapsid protein and polyclonal human immunoglobulin G purified from plasma containing antibodies to structural and non-structural antigens of hepatitis C virus. The results observed using monoclonal antibody to HCV core were similar to those of polyclonal IgG against HCV antigens in the majority of cases and both correlated well with HCV status as defined by 'nested' polymerase chain reaction. HCV antigens were detected in both hepatocytes and mononuclear cells. Using polyclonal human IgG, a small proportion of biliary epithelial cells were also positive in 6/29 patients. In most of the specimens examined, relatively few cells (1-5 per cent) were found to be positive for HCV antigens. The cryostat sections, using polyclonal IgG against HCV antigens, exhibited greater immunohistochemical staining, suggesting that the fixation and processing of the tissue may be a major factor in the conservation and the outcome of HCV antigen(s) findings. However, the results using monoclonal antibodies may reflect the specificity of antigen expression.
54 citations
TL;DR: Molecular evolutionary analysis was applied to determine the number of hepatitis C virus types and subtypes based on all the HCV nucleotide sequences available from the DNA data banks, and there was an excellent concordance among the types andSubtypes assigned based on different HCV genomic regions.
35 citations
TL;DR: The phylogenetic trees constructed showed that all isolates were grouped into 4 genotypes, which did not necessarily correspond to the conventional serotypes and gave more accurate information about genetic variation of HBV.
34 citations
TL;DR: A case of acute hepatitis C that developed after a needlestick injury, despite short duration interferon treatment performed just after the accident in a trial effort to prevent HCV transmission is reported.
Abstract: Hepatitis C virus (HCV) transmission by needlestick accidents involving hospital employees has become an important problem. The present report is of a case of acute hepatitis C that developed after a needlestick injury, despite short duration interferon treatment performed just after the accident in a trial effort to prevent HCV transmission. Nosocomial infection of HCV in medical employees is reviewed, and the current prospects for protecting them from HCV transmission after needlestick accident are discussed.
30 citations
TL;DR: Histological findings obtained intra‐operatively were consistent with a cystic lymphangioma and its characteristic histology was observed in the subserous layer of the gall‐bladder.
Abstract: Intra-abdominal cystic lymphangiomas are rare lesions that can be difficult to diagnose. We present a report of a patient with a giant multilocular cystic lesion in the abdomen. Ultrasonography and computed tomography scans of the abdomen revealed that the cyst had originated in the gall- bladder fossa. There was some calcification and thickening of the cyst wall. Endoscopic retrograde cholangiopancreatography demonstrated a medially deviated common bile duct, an elongated cystic duct and an inferior compressed gallbladder. There was no apparent communication between the cyst and the biliary tract; however, an abdominal angiogram revealed that the lesion was supplied by a branch of the cystic artery. Histological findings obtained intra-operatively were consistent with a cystic lymphangioma. Its characteristic histology was observed in the subserous layer of the gall-bladder. This case is a rare instance of a cystic lymphangioma originating in the gall-bladder.
24 citations
TL;DR: Sequencing of the HCV core region from two patients showed that the assignment of HCV genotype by genotype‐specific primers for PCR matched well with the genotyping results based on sequence comparison and molecular evolutionary analysis.
Abstract: The seroprevalence of hepatitis C virus (HCV) infection in Lanzhou, Western China was studied. HCV genotypes in 20 patients with HCV infection was determined by genotype-specific primer for polymerase chain reaction (PCR) based on HCV core region and compared with the genotype assigned by sequence comparison and molecular evolutionary analysis based on the same region. Antibody to HCV (anti-HCV) was present in 2.5% of volunteer blood donors and in 35.0% of paid blood donors (P < 0.01). HCV infection is uncommon in patients with liver disease who attended liver clinics in this locality; 4.0% with acute hepatitis and 4.0% with chronic hepatitis, 10.0% with liver cirrhosis, and none with hepatocellular carcinoma were seropositive for anti-HCV. Genotype 1b and 2a were both found to be prevalent. Together, they accounted for 19 of 20 (95%) patients with HCV infection. Sequencing of the HCV core region from two patients showed that the assignment of HCV genotype by genotype-specific primers for PCR matched well with the genotyping results based on sequence comparison and molecular evolutionary analysis. These data showed that HCV is present in Western China, HCV infection is more common in paid blood donors, and HCV genotypes 1b and 2a are both prevalent in Western China. © 1995 Wiley-Liss, Inc.
TL;DR: It is concluded that hepatic expression of HCV core and NS4 antigens parallels serum HCV-RNA levels and IFN therapy reduces hepaticexpression of these viral antigen.
Abstract: To determine the significance of hepatic expression of hepatitis C viral (HCV) antigens, HCV core and NS4 antigens were detected by immunohistochemistry in 46 patients with chronic HCV infection. Serum HCV RNA was quantitated by branched DNA assay in 41 and HCV genotype determined in 30 patients. HCV core and NS4 antigens were detected exclusively in the cytoplasm of hepatocytes in 83% and 61% of patients, respectively. There was no correlation between the expression of HCV antigens and clinical, biochemical, histological parameters and HCV genotype. Hepatic expression of HCV antigens was positively associated with serum HCV-RNA levels (P<0.02). At the end of interferon-α (IFN) therapy, expression of HCV antigens remained either unchanged or decreased in 11/12 patients studied (undetectable in all four patients who had complete and sustained response). We conclude that hepatic expression of HCV core and NS4 antigens parallels serum HCV-RNA levels and IFN therapy reduces hepatic expression of these viral antigens.
TL;DR: The results suggest that genotype 3a is rare among Japanese patients with HCV; thus, when classifying Japaneses isolates, the authors should take more care because genotype3a is not determined by current typing systems.
Abstract: We evaluated hepatitis C virus (HCV) genotype distribution among Japanese patients in the city of Nagoya and the possible existence of any other genotype not determined by Okamoto's method. Eighty-five of 93 (91.4%) anti-HCV-positive patients had detectable HCV RNA. The genotype of the HCV isolate was determined in 84 of 85 (98.8%) of these HCV RNA-positive patients by Okamoto's method but determination was not possible in one (1.2%). Genotype 1b was detected in 58 of the 85 patients (68.2%), genotype 2a in 20 (23.5%), genotype 2b in 3 (3.5%), and genotype 1b+2a in 3 (3.5%). In the remaining 1 patient in whom the genotype could not be determined, we determined the nucleotide sequence of the core region in HCV RNA extracted from this patient and evaluated it by molecular evolutionary analysis. This HCV isolate was then classified as genotype 3a. These results suggest that genotype 3a is rare among Japanese patients with HCV; thus, when classifying Japaneses isolates, we should take more care because genotype 3a is not determined by current typing systems.
TL;DR: No response group‐specific nucleotide or encoded amino acid substitution was identified in pretreatment serum samples from 40 patients with chronic HCV infection who were subsequently treated with IFN, and data suggest that these substitutions were selective rather than spontaneous events.
Abstract: Hepatitis C virus (HCV) is an RNA virus with the NS5B gene encoding an RNA-dependent RNA polymerase. Interferon-alpha (IFN-alpha) is effective against HCV and its effect is believed to be related to its antiviral activity. To determine whether sequence variations of the HCV NS5B region correlate with response to IFN therapy, pretreatment serum samples from 40 patients with chronic HCV infection who were subsequently treated with IFN (> or = 3 MU thrice weekly for 24 weeks) and had well-characterized biochemical responses were studied. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to generate an approximately 365-bp fragment from which nucleotide sequence and genotypes were determined. By comparing the nucleotide sequences and the encoded amino acid sequences of samples from each group, no response group-specific nucleotide or encoded amino acid substitution was identified. Most of the substitutions identified were synonymous (usually by changes at the third position of the codon). These data suggest that these substitutions were selective rather than spontaneous events. Of the few non-synonymous substitutions identified, none was correlated with subsequent response to IFN, either within or across genotypes.
TL;DR: Serotype analysis of the HCV isolates using C 14‐1 and C14‐2 recombinant peptides revealed that HCV‐3a was likely to carry an antigenic determinant(s) different from those of the major types 1 and 2 (HCV‐2a and −2b).
Abstract: By means of a polymerase chain reaction (PCR) method using subtype-specific primers for hepatitis C virus (HCV) subtypes 1a, 1b, 2a, 2b and 3a, the prevalence of each subtype among HCV isolates in Chiang Mai, Thailand, was determined. HCV-3a appeared to be the most common subtype in blood donors, and was also frequently found in patients with liver disease. HCV-1b, but not HCV-2a or −2b, was also commonly found in this area, while a considerable percentage of the total HCV isolates still remained unclassifiable by the above methods. Serotype analysis of the HCV isolates using C14-1 and C14-2 recombinant peptides revealed that HCV-3a was likely to carry an antigenic determinant(s) different from those of the major types 1 (HCV-1a and −1b) and 2 (HCV-2a and −2b).
TL;DR: It is suggested that interferon-gamma has an antiviral effect in patients with chronic hepatitis B and that the main mechanism of the therapeutic effect may be associated with the elimination of HBV-infected hepatocytes due to the immunopotentiating effect of the substance.
Abstract: Natural interferon-γ at a dose of 0.5×106 or 1×106 IU daily was intramuscularly administered daily for 4 weeks to 15 patients with chronic hepatitis B. The efficacy and safety of the treatment were evaluated for 24 weeks following the completion of the 4-week treatment period. Persistent disappearance of HBeAg was observed in 5 of 15 patients. Serum hepatitis B virus (HBV)-related DNA polymerase disappeared in 5 of 13 patients at the end of interferon therapy. On the other hand, serum ALT and β2-microglob-ulin levels showed a significant increase during the interferon therapy period. The side effects were completely reversible. These findings suggest that interferon-γ has an antiviral effect in patients with chronic hepatitis B and that the main mechanism of the therapeutic effect may be associated with the elimination of HBV-infected hepatocytes due to the immunopoten-tiating effect of the substance.
TL;DR: The case of a 40-year-old man with AIDS who was admitted to hospital with severe abdominal pain, fever, and chills and underwent an emergency laparotomy which revealed a perforated appendix with suppurative peritonitis demonstrates the effectiveness of this treatment regimen for patients with AIDS complicated by infection without an increase in the white blood cell count.
Abstract: We report herein the case of a 40-year-old man with AIDS who was admitted to hospital with severe abdominal pain, fever, and chills. He underwent an emergency laparotomy which revealed a perforated appendix with suppurative peritonitis. An appendectomy with peritoneal drainage was carried out, but the postoperative course was complicated by fever without leukocytosis; however, he gradually improved following treatment with intravenous antibiotics, granulocyte colony-stimulating factor (G-CSF) and immunoglobulins, and made a complete recovery. His postoperative course demonstrates the effectiveness of this treatment regimen for patients with AIDS complicated by infection without an increase in the white blood cell count (WBC).