[Show abstract][Hide abstract] ABSTRACT: Efficacy of interferon-alpha2b (IFN) + ribavirin (IFN/RBV) combination in patients with high plasma hepatitis C virus (HCV) is very poor. Dysregulated CD4+ /CD8+ T cells is involved in both impaired cell-mediated immunity and resistance to IFN. Adsorptive granulocytes and monocytes apheresis (GMA) can remove infected leucocytes which are extrahepatic HCV reservoirs and also has been associated with intriguing immunomodulation and increases in CD4+ T cells. Our aim was to see if GMA enhances the efficacy of IFN/RBV. Twenty-four patients, 13 IFN resistant and 11 IFN naive were enrolled. Seventeen were genotype 1b and 7 were 2a or 2b. Mean plasma HCV-RNA was 612.9 (100-850) kIU/mL and alanine aminotransferase, 108 (41-373) U/L. GMA was performed with Adacolumn at one session/day for five consecutive days and IFN/RBV was started within 24 h after the last GMA session. Daily 6 million units of IFN, six times/week for 2 weeks and then three times/week for 22 weeks were given with RBV (600-800 mg/day/patient). Patients were followed for 6 months. GMA was associated with a significant increase in lymphocyte counts, complement activation fragment C3a and falls in tissue necrosis factor-alpha, and IL-8 produced by peripheral blood leucocytes. At week 24, 20 of 24 patients (83%) were HCV negative and by end of follow-up (week 49), the remission was sustained in 14 of 24 patients (58%) including 100% of patients with 2a or 2b. In conclusion, enhanced efficacy of IFN/RBV following GMA might be attributed to a more efficient immune function and a renewed IFN signaling towards HCV.
[Show abstract][Hide abstract] ABSTRACT: We previously reported three activated and two suppressed genes detected by cDNA microarrays in peripheral lymphocytes from chronic hepatitis C (C-CH) patients. In this report, we investigated whether they could predict the outcome of interferon (IFN) treatment. Ten C-CH patients were treated by β-interferon for 26 weeks (with some variations), and sustained virological response (SVR) was achieved in six. Three activated genes: migration inhibitory factor-related protein 14 (MRP-14), interleukin(IL)-8 precursor, and puromycin-sensitive aminopeptidase (PSA), were detected in 33%, 33% and 67%, respectively in SVR patients, and in 100%, 75% and 50%, respectively in non-SVR patients. Two suppressed genes, platelet basic protein (PBP), precursor and monoamine oxidase (MAO-A), were detected in 67% and 50%, respectively in SVR patients, but in 75% and 50%, respectively in non-SVR patients. Since the statistical analysis did not show significance in this small size pilot study, further study will be needed to prove the hypothesis that these genes would predict non-SVR in IFN teatment.
[Show abstract][Hide abstract] ABSTRACT: By PCR screening, we found an extremely high prevalence of TT virus (TTV) in the general populations from different geographic regions. This suggests that TTV may be a common DNA virus with no clear disease association in humans. TTV genotyping by phylogenetic analysis was also performed.
Journal of Clinical Microbiology 09/1999; 37(8):2703-5. · 3.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sensitive and reliable laboratory parameters are necessary to evaluate the degree of liver regeneration serially in patients after partial hepatectomy for liver cancer. We evaluated the serum levels of transforming growth factor-alpha (TGF-alpha) and hepatocyte growth factor (HGF), both of which are potent mitogens for hepatocytes, in 22 hepatectomized patients with liver cancer: 10 patients with hepatocellular carcinoma and 12 patients with metastatic liver tumors. Ten patients who underwent laparotomy for nonhepatic surgery were also studied as surgical controls. The serum TGF-alpha and HGF levels were measured by sandwich enzyme-linked immunosorbent assay techniques. Both the serum TGF-alpha and HGF levels increased after partial hepatectomy. However, there was no correlation between the levels of TGF-alpha and HGF. The maximal level of TGF-alpha achieved in each case correlated significantly with the resected liver volume and the increased volume of the remaining liver. Hepatocyte growth factor showed no such correlations. After nonhepatic surgery, the HGF level also increased significantly, while the TGF-alpha level did not. These results suggest that the serum TGF-alpha level varies depending on the regenerative stimulus to the liver, and that its increase corresponds with the degree of liver regeneration that occurs in patients after partial hepatectomy for liver cancer. In contrast, it is unlikely that the serum HGF level reflects liver regeneration. In conclusion, the serum TGF-alpha level can be used as a parameter for evaluating liver regeneration in patients who have undergone partial hepatectomy.
[Show abstract][Hide abstract] ABSTRACT: Fifty-one patients with acute A, B, C, and non A-C hepatitis were studied. Alcoholic abusers and drug-induced hepatitis were excluded from non A-C hepatitis. Among 10 patients with acute non A-C hepatitis, 3 were positive for HGV-RNA by nested RT-PCR as primer of 5' non-coding region of HGV. Maximal s-ALT values in acute hepatitis G patients were significantly higher than those in acute hepatitis C(p < 0.05), but not different from those in acute hepatitis A and B. Although HGV-RNA was demonstrated after 9 years of onset of hepatitis in one patient, non of three patients took chronic course. In one patient, route of transmission was assumed to be blood transfusion.
Nippon rinsho. Japanese journal of clinical medicine 04/1997; 55(3):613-6.
[Show abstract][Hide abstract] ABSTRACT: Sjögren's syndrome (SjS) has been well known to complicate autoimmune liver diseases such as autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). In addition, it has been recently described that chronic viral hepatitis type C could be accompanied by a sialadenitis resembling SjS. Among 98 patients with SjS at our clinic, 7 AIH, 1 PBC, and at least 11 hepatitis C virus (HCV) infection were noted. However, occurrence of SjS was not always associated with the severity of chronic liver diseases. Our present study suggested that three mechanisms might contribute to the pathogenesis of HCV-related SjS: 1) direct infection and proliferation of HCV in salivary glands, 2) molecular mimicry between HCV and salivary glands, and 3) formation of immune complex containing HCV. Further investigation would be indispensable to elucidate immunological systems to regulate these phenomena.
Nippon rinsho. Japanese journal of clinical medicine 11/1995; 53(10):2530-5.
[Show abstract][Hide abstract] ABSTRACT: Serum hepatocyte growth factor levels were measured in hepatectomized and nonhepatectomized surgical patients. The levels were significantly increased and reached a maximum within 7 days after surgery in both groups, returning to preoperative levels 28 days after partial hepatectomy and 7 days after other operations. Multiple regression analysis showed that such maximal hepatocyte growth factor levels were significantly related to having liver cirrhosis and postoperative maximal serum total bilirubin and alanine aminotransferase levels and peripheral white blood cell counts in the hepatectomized group and to postoperative maximal peripheral white blood cell counts and serum C-reactive protein levels in the nonhepatectomized group. However, the levels showed no relation to the resected liver volume and increment of the remaining liver volume 28 days after partial hepatectomy. It is concluded that serum hepatocyte growth factor levels were increased after partial hepatectomy in association with hepatocellular dysfunction and necrosis and systemic inflammation. It is unlikely that the increase was related to liver regeneration.
[Show abstract][Hide abstract] ABSTRACT: When prostaglandin (PG) E1 was continuously administered to rats from 24 hours before giving a dose of carbon tetrachloride, deranged serum glutamic pyruvic transaminase levels and prothrombin time were significantly reduced 12 hours after intoxication compared with controls. A similar effect of PGE1 was seen at 24 hours in D-galactosamine-intoxicated rats. Liver histology showed a comparable attenuation of injury in these rats. These results were consistent with reported effects of PGE2, suggesting that both prostaglandins may share a common pathway in protection against liver injury. When PGE1 or 16,16'-dimethyl PGE2 was added to the medium of primary cultured rat hepatocytes, lipid peroxidation-dependent killing of the cells by tert-butyl hydroperoxide was significantly attenuated without affecting the extent of malondialdehyde accumulation compared with controls. Both prostaglandins significantly reduced the extent of increased plasma membrane microviscosity of these cells assessed by 1-[4-(trimethyl-ammonio)phenyl]-6-phenyl-1,3,5-hexatriene. PGE1 and PGE2 may possess cytoprotective effects on liver parenchymal cells through stabilization of membrane microviscosity, which may contribute to protection against liver injury.
[Show abstract][Hide abstract] ABSTRACT: Thirty-six patients with gallbladder stone(s), 21 with solitary stone and 15 with multiple stones up to five in number, were treated by a single session of extracorporeal shock wave lithotripsy. In eight patients (group A), stones were gradually fragmented from the surface, producing fine powderlike fragments which made residual stones invisible, leading to reduced therapeutic efficacy. In 13 patients (group B), residual stones remained visible up to 2,400 shocks, though they showed similar fragments. Such fragments did not appear throughout treatment in 14 patients (group C). Computed tomography (CT) attenuation number, when the region of interest was settled on the whole stone, increased in the order of group A, B, and C. When the distribution of CT density on stones was analyzed, the density was diffusely lower than 50 HU in all patients in group A, higher than 50 HU only on the surface in all patients except for two in group B, and diffusely higher than 50 HU in all patients except for one in group C. CT findings may be useful for predicting the fragmentation mode of gallbladder stones by extracorporeal shock wave lithotripsy.
[Show abstract][Hide abstract] ABSTRACT: When rats received dimethylnitrosamine every 24 h until death, plus hormone treatment after the first 24 h, the survival was enhanced between 100 and 140 h compared with the control rats, with attenuated derangements of prothrombin time and serum albumin levels at 120 h. In rats given a single dose of dimethylnitrosamine, hepatic DNA synthesis peaked at 48 h. The synthesis was increased after hormone treatment when started immediately, but not when delayed for 24 h. Hormone treatment for 3 days starting 24 h after a single dose of dimethylnitrosamine produced a rapid normalization of decreased hepatic protein content on day 9, although hepatic DNA content was not affected. These results suggest that this treatment is effective for hepatic failure, and the promotion of restoration of liver function is a contributing factor to its effect, in addition to the stimulation of hepatocyte proliferation.