摘要:

AbstractHepatitis C virus (HCV) RNA polymerase chain reaction (PCR) is widely used for diagnosis of HCV infection and evaluation of therapy. The sensitive hepatitis B virus (HBV) DNA PCR is often reserved for detection of quantities of HBV DNA that are insufficient for hybridization. Application of both PCR techniques is limited by their labor‐intensity, potential for contamination, and substantial time required for analysis. To study HCV and HBV infections, occurring alone or in combination, we developed a combined one‐step PCR method to detect HCV RNA and HBV DNA in a single serum specimen using oligoprimers from the HCV 5′ untranslated region and the HBV preS/S region. Specificity of the HBV and HCV PCR products was confirmed on the basis of their molecular sizes in positive samples, Southern blot hybridization, and negative controls. The sensitivities of the combined PCR were assessed using samples containing a wide range of defined amounts of HBV DNA and HCV RNA and were comparable with those obtained with conventional HBV DNA or HCV RNA PCR methods. The sensitivity of the combined method was further validated by the 100% concordance between results of its HBV and HCV components and those of conventional PCR methods in patients with HBV and/or HCV infections. The combined one‐step HBV/HCV PCR is a sensitive, specific, rapid, and cost‐effective method, especially suited for epidemiological screening and clinical diagnosis of HBV and HCV infections occurring alone or in combination. (HEPATOLOGY1995; 21

ISSN:0270-9139    

DOI:10.1002/hep.1840210402

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractSeveral lines of evidence have suggested that immune mechanisms are involved in the pathogenesis of hepatitis B virus (HBV)— and hepatitis C virus (HCV)‐related hepatitis. Study of patients with dual HBV and HCV infection raises the question of which is etiologically more relevant in determining the liver cell damage. To address this issue, proliferation of peripheral blood mononuclear cells (PBMCs) in response to a panel of HBV and HCV antigens was assayed in 13 patients with chronic dual hepatitis B and C, 7 patients with chronic hepatitis B, 7 patients with chronic hepatitis C, and 6 patients with hepatitis B surface antigen (HBsAg) carrier state. Although HBV or HCV hepatitis patients had a significant response to HBV or HCV antigens, respectively, the patients with dual hepatitis B and C exclusively responded to HCV antigens, but not to HBV antigens. One patient who was seropositive for both HBV‐DNA and HCV‐RNA showed a low response to HBV antigens initially but lost the response 3 months later and became responsive to more HCV antigens. These findings suggest that HCV has a dominant role in the immune response of the patients with dual HBV and HCV infection. (HEPATOLOGY1995; 21:9

ISSN:0270-9139    

DOI:10.1002/hep.1840210403

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractThe clinical significance of single band reactivity (indeterminate pattern) at anti‐hepatitis C virus (HCV) second‐generation recombinant immunoblot assay (RIBA‐2) was investigated in symptomless subjects with normal liver function tests to obtain data for their counseling and clinical management. Serum and hepatic HCV RNA were determined by the nested polymerase chain reaction, and liver histology was evaluated in 40 symptomless blood donors with stable indeterminate RIBA‐2 pattern, including 38 reactive to c22‐3. All but one had normal alanine aminotransferase (ALT) levels. Two new immunoblot tests, RIBA‐3 and INNO‐LIA HCV Ab III (LIA‐III), which incorporate additional HCV antigens, were also done to assess whether they could identify the viremic subjects. Ten cases (25%, confidence interval 12 to 38) were HCV RNA positive. Three of the HCV RNA‐positive and none of the HCV RNA‐negative subjects had chronic hepatitis. RIBA‐2 strong intensity of reaction (score>2+) was observed in all the HCV RNA‐positive and in 12 HCV RNA‐negative subjects. RIBA‐3 and LIA‐III gave positive results in 9 of 10 and 10 of 10 HCV RNA‐positive, but also in 8 of 30 and 24 of 30 HCV RNA‐negative subjects. A c‐22‐3 reactivity score of 4+ by RIBA‐3 and E2/NS1 reactivity by LIA‐III were both strongly associated with HCV RNA (P<.001). Based on relatively high prevalence of chronic hepatitis in our series (30%), apparently healthy subjects with stable indeterminate RIBA‐2 pattern and HCV RNA positivity should be considered for liver biopsy independently of ALT profile. Reactivity to particular HCV antigens by third‐generation tests helped to identify the subjects with cu

ISSN:0270-9139    

DOI:10.1002/hep.1840210404

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractFourteen patients with chronic hepatitis C who had a sustained response to a 60‐week interferon alfa‐2b treatment course were followed, biochemically and virologically, 2 years after treatment cessation. Biopsies were repeated in 12 of 14 for histological and virological evaluation at 2‐year follow‐up. All 14 patients had normal serum alanine transaminase (s‐ALT) levels and were negative for hepatitis C virus (HCV) RNA in serum during treatment and at short‐term follow‐up 6 months posttreatment. At 2‐year follow‐up, 13 patients still had normal ALT levels (<0.6 μkat/L for women;<0.8 μkat/L for men), 1 a near normal level (0.76 μkat/L); all were HCV RNA negative in serum, and 11 of 12 also in the liver. Liver histology improved during treatment and remained stable during the 2‐year follow‐up. The authors conclude that most sustained responders, who have normal ALT levels and are nonviremic at short‐term follow‐up 6 months after interferon treatment, will continue to have a durable long‐term response without relapse of the viremia

ISSN:0270-9139    

DOI:10.1002/hep.1840210405

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractThe impact of hepatic dysfunction on the elimination and hydrolysis of three potential tyrosine sources for total parenteral nutrition, the dipeptides L‐alanyl‐L‐tyrosine (Ala‐Tyr) and glycyl‐L‐tyrosine (Gly‐Tyr), and N‐acetyl‐L‐tyrosine (Nac‐Tyr) were evaluated in six patients with hepatic failure (five chronic, one acute) and seven healthy subjects. In controls, whole‐body clearance (Cltot) of Ala‐Tyr was higher than of Gly‐Tyr (3,169 ± 214 vs. 1,780 ± 199 mL/kg/min,P.01). Both dipeptides were hydrolyzed and released tyrosine immediately. In hepatic failure, elimination and hydrolysis of Ala‐Tyr and Gly‐Tyr were comparable to controls, but Cltotof Nac‐Tyr was reduced (236 ± 26 mL/kg/min). Neither in controls nor in patients an increase in plasma tyrosine concentration was seen after Nac‐Tyr, and the major part of Nac‐Tyr infused was lost in urine. The Cltotof tyrosine as evaluated after Ala‐Tyr infusion (with the immediate release of tyrosine) was severely reduced in hepatic failure (152.7 ± 38.4 vs. 484.4 ± 41.4 mL/kg/min,P.03). The authors conclude that acute and chronic hepatic dysfunction does not affect elimination and hydrolysis of the dipeptides Ala‐Tyr and Gly‐Tyr and the constituent amino acids are released immediately. Nac‐Tyr elimination was not grossly affected by hepatic failure, but neither in healthy subjects nor in hepatic failure patients was an increase of tyrosine seen. Both dipeptides but not Nac‐Tyr may serve as a tyrosine source in parenteral nutrition. Moreover, by its rapid hydrolysis, the use of Ala‐Tyr, for the first time, enables a simple rapid nonisotope evalution of tyrosine kinetics fo

ISSN:0270-9139    

DOI:10.1002/hep.1840210406

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractIsoniazid and pyrazinamide are well‐known hepatotoxic drugs, often used in combination. The aim of this study was to assess the prognostic influence of pyrazinamide on the outcome of fulminant or subfulminant liver failure caused by antituberculous therapy. Eighteen patients with fulminant or subfulminant liver failure due to antituberculous therapy were studied. Nine patients received isoniazid and rifampicin without pyrazinamide (group 1), and nine patients received isoniazid and rifampicin together with pyrazinamide (group 2). The severity of fulminant and subfulminant liver failure, as judged by the prevalence of coma and the lowest level of factor V, was similar in the two groups. Spontaneous survival was greater in group 1 (eight of nine) than in group 2 (two of nine) (P<.02). The authors conclude that pyrazinamide co‐administration was associated with an increased mortality in patients with fulminant or subfulminant hepatitis occurring during antituberculous therapy. In these patients, pyrazinamide administration and an interval of more than 15 days between the onset of antituberculous treatment and jaundice, combined with grade III encephalopathy and factor V below 20%, predicted death without liver transplantation. (HEPATOLOGY1995; 21:929

ISSN:0270-9139    

DOI:10.1002/hep.1840210407

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractA blunted initial insulin secretory response may contribute to oral glucose intolerance in cirrhosis. Oral glucose is a better stimulant to insulin secretion than intravenous (IV) glucose in part because of release of gut peptides, notably glucose‐dependent insulinotropic peptide (GIP) and glucagon‐like peptide 1 [7‐36 amide] (GLP‐1 [7‐36 amide]). Because impaired release of or resistance to these gut peptides could explain impaired insulin secretion after oral glucose, we measured insulin secretion, plasma GIP, and GLP‐1 [7‐36 amide] levels, basally and after 75 g oral glucose, in 10 cirrhotics and 10 controls. Insulin secretion was calculated from a two‐compartment analysis of serum C‐peptide levels using kinetic parameters derived from IV injection of recombinant human C‐peptide. C‐peptide metabolic clearance rate, and the fractional rate constants for C‐peptide (using the two‐compartment model) were not significantly different, but the volume of the central compartment was 15% greater in cirrhotics (P<.01). Fasting blood glucose levels were similar (cirrhotics, 4.9 ± 0.2; controls, 4.6 ± 0.1 mmol/L) but serum insulin was six times higher in cirrhotics (P<.001). Cirrhotics had higher fasting GIP (215 ± 72 vs. 42 ± 18 pmol/L) and GLP‐1 [7‐36 amide] levels (25 ± 3 vs. 16 ± 1 pmol/L) (bothP<.05). After oral glucose, blood glucose levels were significantly higher in cirrhotics. The timing of the gut peptide response to oral glucose was similar in the two groups, but peak levels of both peptides were ∼ × 2 higher in the cirrhotics. For the 1st 30 minutes, C‐peptide levels and insulin secretion were similar in the two groups. In controls, insulin secretion peaked at 20 to 25 minutes and coincided with the GLP‐1 [7‐36 amide] peak; insulin secretion then decreased despite a persistent elevation in plasma GIP and glucose levels. In cirrhotics, peak insulin secretion was delayed until 50 to 55 minutes (coincident with the glucose peak). Total insulin secretion during the 4 hours after glucose ingestion was 55% higher in the cirrhotics, but peak insulin secretion rates were similar despite higher gut peptide and glucose levels in cirrhotics. The study shows that, after oral glucose, cirrhotics have a blunted serum C‐peptide response and insulin secretion rate. This is not attributable to reduced levels of GIP or GLP‐1 [7‐36 amide]but could be attributable to resis

ISSN:0270-9139    

DOI:10.1002/hep.1840210408

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractPrevious studies have shown that plasma levels of high‐density lipoprotein (HDL) cholesterol and the two major protein components of HDLs, i.e., apolipoproteins AI and AII, were elevated in male alcoholic patients without serious liver injury. By contrast, alcohol effect on apolipoprotein E remains unclear. Apolipoprotein E is a major component of very low—density lipoprotein (VLDL) and a minor component of human high‐density lipoprotein. It plays a critical role in lipoprotein metabolism through cellular lipoprotein receptors. Furthermore, previous works were carried out mostly with male subjects, whereas alcohol effects on serum apolipoproteins in female subjects have not yet been adequately addressed. In this study, we have raised antibodies specifically to recognize human apolipoprotein AI, AII, and E, respectively, to quantify apolipoprotein concentrations in plasma and lipoprotein fractions of male and female alcoholic patients. We have also measured plasma apolipoprotein concentrations in patients who had abstained from alcohol while in the hospital. Our results showed the following: (1) plasma concentrations of apolipoprotein AI and AII were significantly elevated yet plasma apolipoprotein E decreased (33%) significantly (P<.01) in male alcoholic patients; (2) apolipoprotein AI concentrations in female nondrinking control subjects were higher than in male controls, and the concentrations of apolipoprotein AI in female alcoholic patients were not significantly elevated over those of female controls; (3) similar to their male counterparts, female alcoholic patients exhibited higher plasma apolipoprotein AII and lower apolipoprotein E; (4) changes in plasma apolipoproteins seen here were most likely attributable to a direct effect of alcohol but not a secondary effect of mild liver injury; (5) changes in plasma apolipoprotein levels in alcoholic patients were reversible in 1 week after alcohol abstinence; and (6) the decrease of plasma apo E in alcoholic patients was indicated by the presence of apo E—deficient VLDL particles whereas the concentration of apo E in HDL particles of alcoholic patients remained unaffected.(HEPATOLOGY1995; 21:9

ISSN:0270-9139    

DOI:10.1002/hep.1840210409

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractBecause increasing evidence implicates heparan sulfate proteoglycans (HSPGs) as essential cofactors in receptor‐growth factor interactions, in cell‐cell recognition systems, and in cell‐matrix adhesion processes and yet little is known about their cellular distribution pattern and cellular sources in liver tissue, we used monoclonal antibodies specific for the core proteins of syndecan1, 2, 3, 4, glypican, and perlecan to investigate their immunohistochemical expression in normal adult human liver biopsy specimens. Syndecan1 was expressed in sinusoidal endothelial cells, whereas the endothelium of the portal tract vessels was negative. Hepatocytes showed a membranous staining pattern of the sinusoidal and intercellular domain. Bile duct epithelial cells showed basolateral membrane positivity. Immunoreactivity for syndecan2 was seen in mesenchymal cells, accentuated around bile ducts. Syndecan3 showed intense staining of hepatic arterial and portal venous endothelial cells, of mesenchymal cells, and of Ito cells. Immunohistochemistry for syndecan4 showed a granular staining pattern of hepatocytes at their bile canalicular pole. Glypican showed weak positivity in portal tract mesenchymal cells and clear positivity in nerve bundles. Perlecan was present in Disse's space, in endothelial cells, in basement membranes surrounding bile ducts and vessels, in vessel walls, and in mesenchymal cells. The highly differential expression of these HSPGs in the different cell compartments of the liver, as well as in basement membranes and in Disse's space, suggests that each of these proteoglycans has a specific function in the interplay of cells, matrix molecules, growth factors, and proteinases.(HEPATOLOGY1995; 21:950

ISSN:0270-9139    

DOI:10.1002/hep.1840210410

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractIn recent years there has been an increasing interest in the link between susceptibility to autoimmune liver disease and genes of the HLA system, although the role of the DPB1 locus in British patients has only been investigated in autoimmune hepatitis. The aim of the current study was to determine the distribution of DPB1 alleles in a large series of British patients with the two other autoimmune liver diseases, primary biliary cirrhosis and primary sclerosing cholangitis, and compare the allele frequencies obtained with those of a geographically matched control group. Polymerase chain reaction sequence‐specific oligonucleotide probing was used to assign 18 DPB1 alleles in 82 patients with primary biliary cirrhosis (PBC), 71 patients with primary sclerosing cholangitis (PSC), and 103 controls. The frequencies of the DPB1 alleles were not significantly different comparing patients and controls. However, two important observations were made. Firstly, in primary sclerosing cholangitis, the previously reported association with the haplotype A1‐B8‐DR3‐DQ2 does not extend to the DPB1 locus, suggesting that the genetic determinants of susceptibility for this disease lie closer to the DRB loci. Secondly, in primary biliary cirrhosis there is evidence that the reported association with DR8‐DQB1*0402 includes the DPB1*0301 allele. The weak HLA association reported here is in contrast with recent data from Japan, where susceptibility is strongly linked to a particular amino acid residue encoded by the DPB1*0501 allele. These data clearly demonstrate that the alleles of the DPB1 locus are not associated with susceptibility to or protection from either primary biliary cirrhosis or primary sclerosing cholangitis in British patients. (HEPATOLOGY1995; 21

ISSN:0270-9139    

DOI:10.1002/hep.1840210411

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY