[Show abstract][Hide abstract] ABSTRACT: To investigate the duration of fecal shedding and changing loads of hepatitis E virus (HEV) in feces and serum from patients with acute HEV infection, HEV RNA was quantitated in periodic serum and fecal specimens obtained from 11 patients with sporadic acute hepatitis E. All 11 patients had detectable HEV RNA in serum at admission, with the highest viral load being 1.9 x 10(3) to 1.7 x 10(7) copies/ml, and HEV viremia lasted until days 17 to 48 (mean, 28.3) after the onset of hepatitis. Even at the initial examination on days 10 to 29 (mean, 17.6), the HEV load in fecal supernatant was less than 5.7 x 10(4) copies/ml for 10 of the 11 patients, while for the remaining patient (patient 1) it was markedly high, 2.0 x 10(7) copies/ml on day 22. In addition, although HEV RNA in fecal supernatant continued to be positive until days 14 to 33 (mean, 22.4) for patients 2 to 11, that for patient 1 was detectable even on day 121. HEVs in fecal specimens obtained on days 22, 24, 26, 28, and 30, but not day 121, from patient 1 grew efficiently in PLC/PRF/5 cells, reaching the highest titer of up to 10(7) copies/ml in culture medium on day 50 postinoculation. The HEV genome recovered from patient 1 had 29 unique nucleotides that were not seen in any of the 25 reported HEV isolates of the same genotype over the entire genome, with six amino acid substitutions in the ORF1 protein.
Journal of Clinical Microbiology 12/2007; 45(11):3671-9. · 4.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
Our results indicate that HBV/D infections in Japan are heterogeneous.
[Show abstract][Hide abstract] ABSTRACT: To investigate the prevalence of hepatitis B virus (HBV) genotypes and characteristics of HBV isolates among Japanese patients infected with human immunodeficiency virus type 1 (HIV), serum samples collected between September 1990 and March 2002 from 471 HIV-infected patients (age, 38.8 +/- 11.4 [mean +/- standard deviation] years; male, 90%) were tested for hepatitis B surface antigen (HBsAg) and HBV DNA. Positivity for HBsAg and HBV DNA was seen in 42 patients (8.9%), 41 of whom had contracted HIV infection through sexual activity and 1 had hemophilia. Genotypes of HBV were determined by comparative and phylogenetic analyses of the S gene sequence (396 nucleotides [nt]). The distribution of HBV genotypes among the 42 HBV-viremic patients was: A (50%), B (5%), C (24%), D (5%), E (2%), H (10%), A plus D (2%), A plus G (2%). The hemophilia patient had HBV genotype D. Genotypes E, G, and H which had not been reported in Japan, were found in one patient each who had traveled to Zambia, the US, and South America, respectively. Genotypes A and D, which are rare in Japan, were found in patients who had no history of traveling abroad. The entire genome of the HB-JI411 (genotype E [3,212 nt]), HB-JI444G (genotype G [3,248 nt]), and HB-JI260 (genotype H [3,218 nt]) isolates had the highest identity of 98.3%, 99.9%, and 98.5%, respectively, with reported HBV isolates of the same genotype. Most Japanese patients coinfected with HIV and HBV had HBV genotypes that are found rarely or had not been reported in Japan.
Journal of Medical Virology 06/2005; 76(1):24-32. · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: The aim of this study was to clarify the clinical significance of reddish markings appearing on the surface of the liver.Methods: Subjects were patients with Hepatitis B virus-related (n = 232) or Hepatitis C-related (n = 246) chronic liver disease. Reddish lesions were obtained from this population using punch biopsy (n = 30) or wedge biopsy (n = 4), then studied histopathologically. In addition, the incidence and macroscopic forms of reddish markings in each laparoscopic stage for the 478 subjects were examined to determine when reddish markings appeared.Results: Reddish markings on the liver surface appeared only after the appearance of hepatic parenchymal destruction subjacent to the liver capsule, rather than with the appearance of piecemeal necrosis in the portal area. Moreover, following expansion of necrotic hepatic parenchyma subjacent to the liver capsule and distortion of hepatic lobular architecture in this lesion, net-like or hemorrhagic fleck-like reddish markings appeared. Therefore, this was recognized as changes at the liver capsule, such as capillary proliferation and dilatation, and blood flow changes in both the capsule and hepatic parenchymal lesions subjacent to the liver capsule. With regards to timing, reddish markings were most frequently observed in the transition to liver cirrhosis. After the appearance of reddish markings on the liver surface, chronic hepatitis rapidly progressed to liver cirrhosis.Conclusion: Reddish markings correspond to hepatic parenchymal destruction subjacent to the liver capsule, and not to piecemeal necrosis. Reddish markings appear in the transition to liver cirrhosis and might offer a useful marker of the progression to liver cirrhosis.
[Show abstract][Hide abstract] ABSTRACT: Objectives: To investigate the prevalence and relative titre of TT virus (TTV) DNA, and to examine the relationship between the extent of TTV viraemia and the immune status among 144 patients with HIV infection; 178 age- and sex-matched healthy individuals were also studied.
Methods: TTV DNA was detected quantitatively by two distinct polymerase chain reaction (PCR) methods [untranslated region (UTR) and N22]. UTR PCR detects all TTV genotypes, and N22 PCR can primarily detect four major TTV genotypes (1-4).
Results: Using UTR PCR and N22 PCR, respectively, TTV DNA was detected significantly more frequently in HIV-infected patients than in controls (99 versus 91%, P < 0.001; 56 versus 27%, P < 0.0001), and the relative titre (10N/ml) was significantly higher in HIV-infected patients [4.5 ± 1.2 (mean ± SD) versus 3.1 ± 0.9, P < 0.0001; 2.6 ± 1.5 versus 1.5 ± 0.9, P < 0.0001]. Age, sex, co-infection with hepatitis B or C virus, and risk factors for HIV transmission did not appear to be significant factors associated with the titre of TTV viraemia. However, the titre of TTV DNA was significantly higher in HIV-infected patients with AIDS (P < 0.0001), those with low CD4 T cell count (P < 0.0001), or those with high HIV viral loads (P = 0.0047).
Conclusion: TTV is highly prevalent and high-titred in HIV-infected patients. The TTV viral load may reflect the degree of immune status of these immunocompromised hosts.
[Show abstract][Hide abstract] ABSTRACT: TT virus (TTV) has not yet been cultured or visualized. We attempted to recover and visualize TTV-associated particles from the serum samples and feces of infected humans. Serum samples were obtained from 7 human immunodeficiency virus (HIV)-infected patients. Three patients had a high TTV DNA titer (108 copies/ml), three had a low TTV DNA titer (102 copies/ml), and one was negative for TTV DNA. Fecal supernatant was obtained from a different TTV-infected subject. The serum samples were fractionated by high-performance liquid chromatography, and TTV DNA-rich fractions were subjected to floatation ultracentrifugation in cesium chloride. Virus-like particles, 30–32 nm in diameter, were found in the 1.31–1.33 g/cm3 fractions from each of the three serum samples with high TTV DNA titer, but not in any fraction from the four serum samples that either were negative for TTV DNA or had low TTV DNA titer. The TTV particles formed aggregates of various sizes, and immunogold electron microscopy showed that they were bound to human immunoglobulin G. Similar virus-like particles with a diameter of 30–32 nm banding at 1.34–1.35 g/cm3 were visualized in fecal supernatant with TTV genotype 1a by immune electron microscopy using human plasma containing TTV genotype 1a-specific antibody.
Biochemical and Biophysical Research Communications 01/2001; · 2.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It remains unclear whether the hepatitis C virus genotype is associated with the severity and outcome of HCV-related liver disease. The aim of this study was to determine whether hepatitis C virus genotype influenced the risk of developing hepatocelMar carcinoma. Two hundred and sixty nine patients who had chronic hepatitis C and cirrhosis without hepatocellular carcinoma were studied. The stage and activity of hepatitis were determined at laparoscopy and patients were followed up until the development of hepatocellular carcinoma or for a maximum of 16 years. Hepatitis C virus genotypes were determined by a genotyping enzyme-linked immunosorbent assay. A cross-sectional study revealed that the prevalence of hepatitis C virus genotype 1 increased and that of genotype 2 decreased with the progression of liver disease (pc 0.01). A follow-up study using the Kaplan-Meier method showed that hepatocellular carcinoma occurred more frequently in patients with hepatitis C virus genotype 1 (p<0.01), patients with a more advanced disease stage (p<0.01), and patients with reddish markings (p<0.05). Cox multivariate proportional hazards analysis confirmed that these three risk factors were independent. Hepatocellular carcinoma developed more frequently in patients with hepatitis C virus genotype 1 and pre-cirrhosis (stage 3 chronic hepatitis with nodules) or liver cirrhosis, in whom hepatitis showed continued activity and progression. (Dig Endosc 1999; 11: 24–31)
[Show abstract][Hide abstract] ABSTRACT: To clear the efficacy of treatment for large porto-systemic shunts, changes of liver function and portal hemodynamics after obliteration of gastric-renal shunt (GRS) or gastric-inferior phrenic vein shunt (GIS) communicated with gastric fundic varies in 24 patients treated with balloon-occluded retrograde transvenous obliteration (B-RTO) were studied. 1) The wedged hepatic venous pressure and the hepatic venous pressure gradient were statistically not significant changed after obliteration of GRS or GIS. 2) Serum albumin value was significantly increased (p < 0.005) and ICGR15 was significantly improved (p < 0.005) at one year after treatment in patients that, not only whose GRS or GIS were larger than 10mm in diameter, but also whose superior mesenteric arterial venography before treatment showed hepatofugal flow. 3) At a mean follow-up abdominal angiography of 23.3 months in 20 cases, GRS or GIS was yet obliterated respectively. And more, superior mesenteric arterial venography revealed hepatopetal flow alone in 43% of patients that, whose superior mesenteric arterial venography before treatment showed hepatofugal flow. 4) During a mean follow-up of 32.5 months, gastric fundic varies were not recurrent in all patients, but the other hand, cumulative red color sign positive esophageal varies apparent rates were high (16.7% at before treatment, 38.4% at 2-years, 54.4% at 4-years). According to their hemodynamic characteristics, cumulative red color sign positive esophageal varies apparent rates in patients with another collaterals besides GRS or GIS before treatment (26.7% at before treatment, 61.1% at 2-years, 74.1% at 4-years) were significantly higher (p < 0.05) than those in patients without another collateral except GRS or GIS (0% at 2-years, 16.7% at 4-years). We conclude that, 1) Increment of portal flom and improvement of liver function can be expected by obliteration of GRS or GIS in patients that, whose superior mesenteric venous blood flow into large GRS or GIS. 2) After obliteration of GRS or GIS, the incidence of aggravation of esophageal varies in patients with another collaterals besides GRS or GIS before treatment is high, while that in cases without another collateral is low.
Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 08/1998; 95(7):755-63.
[Show abstract][Hide abstract] ABSTRACT: RNA of recently reported, putative non-A to E hepatitis virus designated GB virus C (GBV-C) was determined by reverse-transcription polymerase chain reaction in sera from 231 Japanese patients with primary hepatocellular carcinoma. GBV-C RNA was detected in 21 patients (9% of the total), including two of the 23 patients (8%) with markers of hepatitis B virus infection, 11 of the 114 patients (10%) with markers of hepatitis C virus infection, seven of the 86 patients (8%) with markers of both hepatitis B and C virus infections, and one of the eight patients (13%) without such markers. These results indicate that the contribution of GBV-C infection to the development of hepatocellular carcinoma would be small either by itself or in cooperation with hepatitis B and C viruses.
Hepatology Research 01/1997; 8(1):37-43. · 2.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Two sera obtained from four healthy blood donors, which caused non-A, non-B post-transfusion hepatitis in two recipients, were experimentally inoculated into nine marmosets. Three of seven marmosets developed acute hepatitis characterized by the elevation of serum concentrations of glutamic pyruvic transaminase (GPT) and/or isocitric dehydrogenase (ICD) 8-11 weeks after inoculation. Four of seven showed histopathological changes of acute hepatitis in liver biopsy specimens during the biochemically acute phase. In electron microscopic examination, attached membrane-like structures, which consisted of two-unit membranes of two neighboring endoplasmic reticula with electron-dense material between them, were noted in cytoplasm of hepatocytes during the acute phase of hepatitis. Furthermore, acute-phase sera obtained from two animals were inoculated into four additional marmosets, and non-A, non-B hepatitis was successfully passaged in two of them. The results of this study indicate that certain species of marmoset monkeys are susceptible to human non-A, non-B hepatitis agents and provide a useful animal model for non-A, non-B hepatitis.
Journal of Medical Virology 07/1987; 22(2):143-56. · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Two sera obtained from four healthy blood donors, which caused non-A, non-B post-transfusion hepatitis in two recipients, were experimentally inoculated into nine marmosets. Three of seven marmosets developed acute hepatitis characterized by the elevation of serum concentrations of glutamic pyruvic transaminase (GPT) and/or isocitric dehydrogenase (ICD) 8-11 weeks after inoculation. Four of seven showed histopathological changes of acute hepatitis in liver biopsy specimens during the biochemically acute phase. In electron microscopic examination, attached membrane-like structures, which consisted of two-unit membranes of two neighboring endoplasmic reticula with electron-dense material between them were noted in cytoplasm of hepatocytes during the acute phase of hepatitis. Furthermore, acute-phase sera obtained from two animals were inoculated into four additional marmosets and non-A, non-B hepatitis was successfully passaged in two of them. The results of this study indicate that certain species of marmoset monkeys are susceptible to human non-A, non-B hepatitis agents and provide a useful animal model for non-A, non-B hepatitis.
Journal of Medical Virology 05/1987; 22(2):143 - 156. · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Electron microscopic and virological studies of marmoset liver tissue with acute infection of hepatitis A virus (HAV), especially in the earlier stages of infection, were carried out to characterize the maturation process of HAV. Four marmosets were inoculated intravenously with HAV suspension and sacrificed 1 week, 2 weeks, 3 weeks and 4 weeks after inoculation respectively. Hepatitis A antigen (HAAg) in 10% liver homogenates of marmosets was examined by radioimmunoassay and a large amount of HAAg was detected in the liver homogenate of two marmosets sacrificed 2 weeks and 3 weeks after inoculation respectively. The histodiagnosis of the marmoset sacrificed 2 weeks after HAV inoculation was normal. However, many clusters of virus-like particles about 27 nm in diameter, in both "solid" and "empty" forms were found, mainly in vesicles of Kupffer cells by electron microscopy. In the animal that developed mild hepatitis 3 weeks after inoculation HAV-like particles were found in vesicles of hepatocytes by electron microscopy. By immune electron microscopy using peroxidase-conjugated anti-hepatitis A antibody, HAAg was detected on the particles present within the cytoplasmic vesicles of Kupffer cells or hepatocytes and on the surrounding membrane of the vesicles which contained HAV-like particles.
[Show abstract][Hide abstract] ABSTRACT: Electron microscopic studies of the morphology of hepatitis B surface antigen (HBsAg) produced by PLC/PRF/5 cells in vitro were carried out. Aggregates of 20-nm spherical particles in 3-day culture supernatants were observed by immune electron microscopy (IEM). Aggregates of tubular structures were found with IEM in the extracts of the cells. Tubular structures 18 to 22 nm in diameter were seen by electron microscopy (EM) in the cisternae of the endoplasmic reticulum in 2-3% of the cells. The tubular structures in the cytoplasm and extracts of PLC/PRF/5 cells resembled those observed in the hepatocytes of human carriers of hepatitis B virus (HBV). Intracellular localization of HBsAg in PLC/PRF/5 cells by direct peroxidase-conjugated antibody staining was observed on the tubular structures and the cisternal wall, which contained these structures. Rotation technique analysis indicated that the tubular structures were composed of 11 or 12 subunits.
Journal of Medical Virology 02/1984; 13(3):205-14. · 2.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Five male patients with HbsAg-positive liver disease were treated with ara-A at dosages ranging between 5 mg and 10 mg/kg/day for five days. Before treatment, all of them had detectable DNA polymerase activity and HbeAg in their sera. The five-day course of the drug resulted in a rapid fall in DNA polymerase activity in every patient, the effect being dose-dependent. The amount of circulating Dane particles also decreased simultaneously, or with a short time lag, with the fall of the enzyme activity. The following decrease in HBeAg concentration was observed in all patients, and it was also noteworthy that antiHBe response was found in two of the five. HBsAg titers were significantly diminished in two patients. In the present series of ara-A treatment, these effects were temporary in two patients, while, in the remaining three, they lasted for two to three months. Ara-A had no serious side effects at dosages of 10 mg/kg/day or less, and can thus be counted among the valuable therapeutic drugs against chronic HBV infection.