GB virus infection in acute and chronic cryptogenic liver disease.
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Adolescent↗
Biomedical subjects
K Tanikawa
Publications and source records attributed to K Tanikawa.
Hepatic iron stainings in chronic hepatitis C patients with low HCV RNA levels: a predictive marker for IFN therapy.
OBJECTIVES: Interferon (IFN) therapy is ineffective in about 20-30% of chronic hepatitis C (CH-C) patients who have low HCV RNA levels. Besides the serum HCV RNA level or HCV genotype, hepatic iron concentrations are thought to be correlated with the subsequent response to IFN therapy. Our objective in the present study was to evaluate serum iron, ferritin, and hepatic iron staining in patients with low HCV RNA levels, as predictive markers for IFN therapy. METHODS: We evaluated 75 CH-C patients whose serum HCV RNA levels were below 1 million genome equivalent (mEq)/ml as shown by a bDNA assay. RESULTS: There were no significant differences in age, sex, serum aminotransferase levels, or serum iron concentrations between responders and nonresponders. The total iron scores (TIS) were significantly higher in responders (p < 0.01). The TIS was an independent factor relating to the response to IFN therapy by multivariate analysis (p = 0.0062). The TIS significantly correlated with serum ferritin levels (r = 0.637, p < 0.001), but not with any other parameter. bi] CONCLUSIONS: Among CH-C patients within the limits of low HCV RNA levels, TIS of the liver may be used as a predictive marker for IFN therapy.
Adult↗
Evaluation of magnetic resonance angiography on portosystemic collaterals in cirrhotic patients.
OBJECTIVE: We examined the usefulness of imaging portosystemic collaterals accompanying liver cirrhosis by magnetic resonance angiography (MRA), which facilitates imaging of the vascular system without contrast medium. METHODS: MRA was performed in 30 patients with liver cirrhosis. Of the 30 patients, percutaneous transhepatic portography (PTP) was performed in 10 patients, and conventional arterial portography (CAP) was performed in 20 patients. The three-dimensional (3D) phase contrast method was used for MRA. Study 1: The ability to image portosystemic collaterals was compared between PTP or CAP and MRA. Study 2: The usefulness of MRA for evaluating the effect of treatment on gastric and esophageal varices was examined. RESULTS: Study 1: In comparing PTP and MRA (n = 10), the left gastric vein (n = 10), splenorenal (gastrorenal) shunt (n = 5), and paraumbilical vein (n = 2) were imaged similarly. However, MRA did not reveal any esophageal varices (n = 10). In comparing CAP and MRA (n = 20), the left gastric vein (n = 17), splenorenal (gastrorenal) shunt (n = 10), and paraumbilical vein (n = 4) were imaged similarly. Whereas CAP revealed esophageal varices (n = 4) in four patients, MRA revealed esophageal varices in only one patient. Study 2: When the effect of treatment for varices was evaluated, MRA 3 wk after embolization therapy for gastric varices (n = 4) confirmed the disappearance of gastrorenal shunt. However, it was impossible to evaluate esophageal varices by MRA. CONCLUSIONS: It was possible to image portosystemic collaterals accompanying liver cirrhosis by MRA. MRA was useful as a routine examination. Furthermore, it was useful for evaluating the effect of embolization therapy on gastric varices.
Adult↗
Splanchnic hemodynamic pattern and liver function in patients with cirrhosis and esophageal or gastric varices.
OBJECTIVES: This study was designed to characterize the splanchnic hemodynamic pattern and liver function in patients with cirrhosis and esophageal or gastric varices. METHODS: Forty control subjects and 112 patients with cirrhosis were studied. Portal inflow (the sum of superior mesenteric arterial and splenic arterial flows), portal venous flow, and collateral flow (the difference between portal inflow and portal venous flow) were measured using duplex ultrasonography. Endoscopic examination showed that 45 patients had no varices or small esophageal or gastric varices, 49 had large esophageal varices, and 18 had large gastric varices. Liver function was assessed by Pugh-Child score. RESULTS: Portal inflow was significantly greater in patients with large esophageal varices or large gastric varices than in control subjects and patients with no varices or small esophageal or gastric varices. Portal venous flow was significantly lower in patients with large gastric varices than in the other three groups. Collateral flow was significantly greater in patients with large gastric varices than in patients with large esophageal varices. The Pugh-Child score was significantly higher in patients with large gastric varices than in patients with large esophageal varices. The Pugh-Child score was also inversely correlated with portal venous flow (r = -0.35, p < 0.01) and directly correlated with collateral flow (r = 0.59, p < 0.01). CONCLUSIONS: Both patients with esophageal varices and those with gastric varices have increased portal inflow. However, patients with gastric varices, in contrast to patients with esophageal varices, have a reduced portal venous flow associated with an increased collateral flow. Such a portal outflow pattern may contribute to the worse liver function seen in patients with gastric varices.
Endoscopy, Digestive System↗
[Continuous arterial infusion of low-dose cisplatin, 5-fluorouracil as adjuvant therapy in cytoreductive surgery for advanced hepatocellular carcinoma].
We investigated the effectiveness of continuous arterial infusion of low-dose CDDP, 5-FU for residual cancer after cytoreductive surgery for advanced hepatocellular carcinoma. Thirty-one patients with unresectable advanced hepatocellular carcinoma were classified into two groups by adjuvant therapy after reduction surgery: 1) Low-dose FP Group: 17 patients; continuous arterial infusion of low-dose CDDP, 5-FU via implanted port system; 2) Conventional group: 8 patients; Lipiodolization (6 cases) and transcatheter arterial embolization (2 cases). The five-year survival rate in the low-dose FP group was 34.8%, the efficacy was 64.7%, CR: 6 (35.3%); PR: 5; NC: 4; PD: 2. Thus, continuous arterial infusion of low-dose CDDP, 5-FU was effective as adjuvant therapy in cytoreductive surgery for advanced hepatocellular carcinoma.
Antineoplastic Combined Chemotherapy Protocols↗
Effects of glucagon on superior mesenteric artery and femoral artery haemodynamics in humans.
OBJECTIVE: It remains unclear whether glucagon is a localized splanchnic arterial vasodilator in humans. This study examined this issue by assessing the haemodynamic effect of exogenous glucagon on splanchnic and extrasplanchnic arteries. METHODS: After an overnight fast, flow velocity of superior mesenteric artery and femoral artery was recorded by means of echo-Doppler in 10 controls and 10 patients with cirrhosis. Mean arterial pressure, heart rate and plasma glucagon level were also determined. These measurements were repeated after intramuscular injection of glucagon (1 mg) at 15 min and 30 min. RESULTS: Patients with cirrhosis had much higher glucagon levels than controls (P < 0.01). Plasma glucagon level rose following glucagon administration in controls (P < 0.01) and patients with cirrhosis (P < 0.01). Glucagon administration had no effect on mean arterial pressure, heart rate and femoral artery velocity in controls and patients with cirrhosis. In contrast, superior mesenteric artery velocity significantly increased after glucagon administration in both groups (P < 0.01, P < 0.01), although the effect was less pronounced in patients with cirrhosis than in controls (P < 0.05). CONCLUSION: These data suggest that glucagon might be a localized splanchnic arterial vasodilator. Thus, glucagon may be one of the factors contributing to the pathogenesis of the splanchnic hyperdynamic circulation seen in patients with cirrhosis.
Aged↗
Comparison of carbohydrate structures of serum alpha-fetoprotein by sequential glycosidase digestion and lectin affinity electrophoresis.
Serum alpha-fetoprotein (AFP) is a glycoprotein of which the sugar chain is considered to show structural changes with malignancies. Microheterogeneity of the serum AFP carbohydrate structure was studied in samples from 35 patients with benign and malignant diseases. Sera were digested directly, extensively, and sequentially with sialidase. beta-galactosidase and beta-N-acetylhexosaminidase. Before and after digestion, sera were examined by means of lectin affinity electrophoresis using eight lectins. Relationships between AFP carbohydrate structures and liver diseases were elucidated by the lectin-reactive profiles and the effect of glycosidase digestion. More than 94% of the AFP carbohydrate structures found in patients with benign and malignant liver diseases were biantennary complex-type oligosaccharides. Changes in the AFP carbohydrate structures at the early stage of hepatocellular carcinoma revealed the addition of alpha 1-->6 fucose to the reducing terminal N-acetylglucosamine and monosialylated AFPs. In both advanced hepatocellular carcinoma and AFP producing extrahepatic malignancies, AFP carbohydrate structures were characterized as the further addition of beta 1-->4 N-acetylglucosamine and heterogeneity in the galactose and N-acetylglucosamine residues. Sequential glycosidase digestion and lectin affinity electrophoresis is useful for analysing the carbohydrate structures of serum glycoprotein.
Carbohydrate Conformation↗
Gastric mucus generation in cirrhotic patients with portal hypertension. Effects of tetraprenylacetone.
We have evaluated gastric mucus generation (study 1) and the effects of tetraprenylacetone on gastric mucus generation (study 2) in cirrhotic patients with portal hypertension. Study 1: Included were 50 noncirrhotics (group A), 25 cirrhotics without portal hypertension (group B), and 25 cirrhotics with portal hypertension (group C). The antrum, corpus, and fundus mucus generation was assessed by hexosamine concentration using biopsy specimens. In groups A and B, the antrum hexosamine concentration was significantly higher compared with the corpus (P < 0.01, P < 0.01) and the fundus (P < 0.01). In contrast, the hexosamine concentration at each location was similar in group C. Furthermore, the antrum hexosamine concentration of group C was significantly lower compared with that of group A (P < 0.05). In study 2, a double-blind design, 300 mg of tetraprenylacetone was administered for four weeks in 10 cirrhotics with portal hypertension and placebo in 10. The regional hexosamine concentrations were measured before and after drug administration. Placebo administration did not change hexosamine concentration at each location. In contrast, tetraprenylacetone increased the antrum and corpus hexosamine concentration (P < 0.01, P < 0.05), although the fundus concentration did not change. These data suggest that cirrhotics with portal hypertension have reduced gastric antral mucus generation and tetraprenylacetone normalizes this.
Anti-Ulcer Agents↗
Effectiveness of glycyrrhizin for oral lichen planus in patients with chronic HCV infection.
Oral lichen planus (OLP), an intractable inflammatory disease characterized by a band-like lymphocytic invasion under the oral mucosa, is frequently associated with hepatitis C virus (HCV) infection. We investigated the effects of glycyrrhizin, which is used to treat chronic liver dysfunction, in nine patients with OLP who were positive for HCV antibody and HCV RNA. A control group, eight patients with OLP who were also positive for HCV antibody and HCV RNA, was given only dental cleaning. Glycyrrhizin (GL) was given intravenously, at a dose of 40 ml (0.2% solution) daily, for 4 consecutive weeks. Six (66.7%) of the nine patients given GL improved clinically (P = 0.0141 vs non-GL group), suggesting that GL is useful in treating OLP.
Adult↗
Evaluation of patient outcome following sclerotherapy for esophageal varices.
After excluding terminally all patients, we evaluated a total of 718 patients treated with endoscopic injection sclerotherapy. They involved 350 episodes of acute hemorrhage and 368 prophylactic procedures in patients with risky varices. The 1-year cumulative survival rate was significantly lower in the acute hemorrhage group than in the prophylactic group (P < 0.05). The difference in survival between the two groups was primarily due to the number of deaths in the first 2 months after sclerotherapy (20.1% vs 0.8%, P < 0.0005). Improvements in the sclerotherapy technique significantly reduced the number of deaths from bleeding (9.3% vs 3.4%, P < 0.05), but not those from liver failure following variceal hemorrhage. Prophylactic EIS is advantageous in the treatment of esophageal varices, i.e. it may prevent deaths from liver failure attributed to variceal hemorrhages. The present study shows that preliminary prevention of variceal hemorrhage provides favorable hemostatic efficacy in patients with risky varices.
Cause of Death↗
Analysis of serum hepatitis A virus antibody response in different courses of hepatitis A virus infection.
Changes in the serum hepatitis A virus antibody (anti-HAV) response in patients with different clinical courses of HAV infection were examined using immune adherence hemagglutination (IAHA). Anti-HAV was detected 2-6 weeks after the onset of clinical symptoms in patients with the typical course of acute hepatitis A and 1-4 weeks after the onset in those with fulminant hepatitis A. Maximal anti-HAV titers were observed 8-20 weeks after the onset of clinical symptoms, and changes in anti-HAV were similar in the typical and the prolonged course of acute hepatitis A, but maximal antibody titers were higher in the prolonged course. Maximal anti-HAV titers in patients with subclinical HAV infection were significantly lower than titers in patients with the typical and prolonged courses of acute hepatitis A, and in those with fulminant hepatitis A. High titers of anti-HAV remained positive for at least 6 years after infection in patients with clinical infection and for at least 4 years in patients with subclinical infection on follow-up. These findings suggest that the maximum anti-HAV titer correlates with the clinical severity of HAV infection; knowledge of the antibody response should be useful for analyzing the pathogenesis of HAV infection.
Acute Disease↗
Serum type IV collagen in various liver diseases in comparison with serum 7S collagen, laminin, and type III procollagen peptide.
The clinical significance of the immunoreactive triple helical domain of type IV collagen in serum was evaluated in 73 healthy controls and 161 patients with various biopsy-proven liver diseases. Although serum levels of type III procollagen peptide were increased in all liver diseases, those of type IV collagen, 7S collagen, and laminin were principally increased in chronic liver diseases associated with hepatic fibrogenesis/fibrosis. In both non-alcoholic and alcoholic liver diseases, 7S collagen was increased in serum, while type IV collagen and laminin in serum were particularly increased in alcoholic liver diseases and in hepatocellular carcinoma, in which latter the sensitivity was greater for type IV collagen than for laminin. Gel filtration analysis in Sephacryl S-400 revealed type IV collagen in serum to be a single molecular form with a molecular weight that correspond to type IV collagen, whereas 7S collagen was recognized as several heterogeneous macromolecules. These findings indicate that serum type IV collagen is derived from the type IV protocollagen pool, and is a sensitive marker for the fibrogenetic process in hepatic basement membranes.
Adult↗
Prognostic significance of Lens culinaris agglutinin A-reactive alpha-fetoprotein in small hepatocellular carcinomas.
BACKGROUND & AIMS: Lens culinaris agglutinin A-reactive fraction of alpha-fetoprotein (AFP-L3) has been reported to be a useful marker in the early diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to evaluate the prognostic value of AFP-L3 for HCC. METHODS: Fifty-five patients with HCC whose AFP-L3 levels were negative before initial therapy were studied. AFP-L3 levels were measured by lectin-affinity electrophoresis coupled with antibody-affinity blotting. RESULTS: Of the 55 patients, 28, 15, and 12 underwent percutaneous ethanol injection, transcatheter arterial embolization, and hepatectomy, respectively. Thirty-two (58.2%) of the 55 patients maintained a negative AFP-L3 status during the study, and 23 patients (41.8%) became positive for AFP-L3 during posttreatment observation. Multiple recurrences of HCC and portal vein tumor thrombus were observed significantly more often in patients with positive AFP-L3 than in those with negative AFP-L3 status (P < 0.0001). In contrast, most patients with negative AFP-L3 had solitary recurrences of HCC without portal vein tumor thrombus. Overall survival was significantly lower in patients with positive AFP-L3 than in those with negative AFP-L3 status (P = 0.0006). Cox's proportional hazards model identified that AFP-L3 was an independent prognostic factor (P = 0.0005). CONCLUSIONS: AFP-L3 seems to be a significant marker of poor prognosis for HCC.
Adult↗
Evaluation of hyaluronic acid binding ability of hepatic sinusoidal endothelial cells in rats with liver cirrhosis.
BACKGROUND & AIMS: In liver cirrhosis, the binding and degradation of hyaluronic acid in the hepatic sinusoidal endothelial cells are considered to be reduced by development of hepatic sinusoidal capillarization, resulting in high serum hyaluronic acid concentration. The aim of this study is to clarify the cause of high blood hyaluronic acid concentration in liver cirrhosis. METHODS: Liver cirrhosis was induced in rats by thioacetamide administration. In vivo observation of sinusoidal capillarization, in vitro immunolocalization of factor VIII-related antigen and CD44, and [14C]hyaluronic acid binding in cultured sinusoidal endothelial cells were determined. RESULTS: Basement membranes were observed on the basal side of sinusoidal endothelial cells. The fenestrae and fluorescent intensity of anti-CD44 bound to the cells decreased with progression of hepatic fibrosis. Immunofluorescent reactive products of factor VIII-related antigen were more abundant in the cirrhotic rats compared with the controls. Amount of [14C]hyaluronic acid binding was significantly decreased in the cirrhotic group compared with the controls. CONCLUSIONS: One reason that the blood hyaluronic acid concentration increases markedly in liver cirrhosis is considered to be the reduction in hyaluronic acid receptors of hepatic sinusoidal endothelial cells and in the amount of hyaluronic acid binding to the cells.
Animals↗
Significance of serum tissue inhibitor of metalloproteinases-1 in various liver diseases.
BACKGROUND/AIMS: This study was performed to assess the significance of elevated serum tissue inhibitor of metalloproteinases-1 concentration in various liver diseases. METHODS: Tissue inhibitor of metalloproteinases-1 levels were measured in patients with various liver diseases, and were compared with serum type III procollagen-N-peptide (P III P), type IV collagen and laminin P1 levels, as well as with the histology of liver biopsy specimens. RESULTS: Mean tissue inhibitor of metalloproteinases-1 levels were significantly higher in subjects with acute viral hepatitis, cirrhosis, alcoholic hepatitis, and alcoholic cirrhosis than in the control group (p < 0.05). Serum tissue inhibitor of metalloproteinases-1 levels in the various liver diseases showed positive correlation with serum type IV collagen, P III P, and laminin P1 levels. Regarding the relationship between tissue inhibitor of metalloproteinases-1 and liver histology, serum tissue inhibitor of metalloproteinases-1 levels correlated with the degree of hepatic fibrosis and inflammation, such as focal necrosis and cell infiltration. Furthermore, elevated serum tissue inhibitor of metalloproteinases-1 levels were especially related to the cell infiltration, focal necrosis, portal fibrosis, and serum type IV collagen level. CONCLUSIONS: These findings suggest that the measurement of the serum tissue inhibitor of metalloproteinases-1 level in various liver diseases may be useful to estimate the active hepatic fibrogenesis associated with the active inflammatory stage of the liver injury.
Adult↗
Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPases, inhibits the receptor-mediated endocytosis of asialoglycoproteins in isolated rat hepatocytes.
BACKGROUND/METHODS: The role of vacuolar type H(+)-ATPases (v-ATPases) and pH gradient between the endocytic compartments and cytoplasm in the endocytosis of asialoglycoproteins was morphologically investigated in isolated rat hepatocytes using bafilomycin A1, a specific inhibitor of v-ATPases. RESULTS: Fluorescent staining by acridine orange showed that bafilomycin A2 inhibited the acidification of the endocytic compartments. Uptake of gold-conjugated asialofetuin was significantly inhibited by bafilomycin A1. However, bafilomycin A1 did not significantly inhibit uptake of a fluid phase marker, horseradish peroxidase. The number of autophagic vacuoles increased after the bafilomycin A1 treatment. However, materials in the autophagic vacuoles were rapidly degraded after the removal of bafilomycin A1. CONCLUSIONS: Results suggest that: (a) v-ATPases are necessary for acidification of the endocytic compartments; (b) the pH gradient between the endocytic compartments and the cytoplasm which is generated by v-ATPases is necessary for the receptor-mediated endocytosis of asialoglycoproteins, and (c) v-ATPases may contribute to the degradation of the materials in autophagic vacuoles.
Animals↗
Effect of vasopressin on esophageal varices blood flow in patients with cirrhosis: comparisons with the effects on portal vein and superior mesenteric artery blood flow.
BACKGROUND/AIMS: Vasopressin reduces portal pressure which may be due to decreased portal inflow. However, it remains unclear whether vasopressin is able to selectively reduce esophageal varices blood flow. The aim of this study was to address this question. METHODS: Fifteen patients with cirrhosis and esophageal varices were included in this prospective study. Portal vein and superior mesenteric artery flow velocity were measured with a percutaneous echo-Doppler. Esophageal varices flow velocity was measured using a transesophageal echo-Doppler technique. Mean arterial pressure and heart rate were also recorded. These measurements were performed at baseline condition and 15 min after observer blind drug administration. In this study, two groups, six patients receiving placebo and nine patients receiving 0.3 U/min of vasopressin, were randomized according to the coded number. RESULTS: Placebo administration had no effect on systemic and splanchnic circulation. In contrast, vasopressin administration increased mean arterial pressure (p < 0.05) associated with a bradycardia (p < 0.01). In splanchnic circulation, vasopressin decreased portal vein (-32 +/- 3%, p < 0.01), superior mesenteric artery (-30 +/- 2%, p < 0.01), and esophageal varices flow velocity (-48 +/- 5%, p < 0.01). When the magnitude of these reductions was compared, ANOVA showed a significant difference (p < 0.01). Furthermore, the reduction in esophageal varices flow velocity was significantly higher than that in portal vein flow velocity (p < 0.01) and that in superior mesenteric artery flow velocity (p < 0.01). CONCLUSIONS: These data support the view that vasopressin is able to selectively reduce esophageal varices blood flow. This effect, in addition to its well-established portal pressure reducing action, may play a role in its therapeutic efficacy in the treatment of variceal bleeding.
Aged↗
Quantitative analysis of HCV RNA and genotype in patients with chronic hepatitis C accompanied by oral lichen planus.
Lichen planus (LP) is a common oral disorder that may represent a mucosal reaction to a variety of factors, including hepatitis C virus (HCV). To determine whether viral factors play a role in oral lichen planus (OLP) pathogenesis, we measured serum HCV RNA and determined HCV genotype in patients with chronic hepatitis C accompanied by OLP. The subjects included 43 patients with chronic hepatitis C: 23 with OLP (group 1) and 20 without OLP (group 2). Serum was collected from all subjects and used to quantify HCV RNA by the branched DNA signal amplification assay; HCV genotypes were classified by the reverse transcription-polymerase chain reaction (RT-PCR) method into types I, II, III and IV. Comparison of patient characteristics disclosed that the mean age of group 1, 60.7 years, was significantly higher (P = 0.001) than that of group 2 (46.4 years). No significant differences were seen between sexes in values of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein (T protein), albumin and gamma-globulin. There were also no significant differences in HCV RNA levels or HCV genotypes between groups. The findings suggested that OLP pathogenesis was a result of host factors rather than viral factors.
Adolescent↗