摘要:

AbstractTo investigate the presence of serum hepatitis delta virus antigen by immunoblot and its correlation with other markers of active viral replication (intrahepatic hepatitis D antigen, IgM antibody to hepatitis D and serum hepatitis D virus RNA), we studied serum samples from 50 patients with chronic hepatitis D virus infection (38 with and 12 without intrahepatic hepatitis D antigen). Of the 38 patients with intrahepatic hepatitis D antigen, 27 (71%) had antigen detectable in seurm by immunoblot, whereas only two were reactive by conventional enzyme‐linked immunosorbent assay. Thirty‐one (82%) patients were also positive for serum hepatitis D virus RNA by spot hybridization and 33 (87%) were positive for IgM anti‐hepatitis D virus. All markers were simultaneously present in 24 patients. Circulating hepatitis D antigen was detected in one (8%), IgM antihepatitis D in seven (58%) and hepatitis D virus RNA in two (17%) of the 12 patients who had anti‐hepatitis D in serum but not detectable hepatitis D antigen in liver. Hepatitis D antigen was not detected in serum of any of the 15 control patients.The results suggest that serum hepatitis D antigen as detected by immunoblot and serum hepatitis D virus RNA are similar in sensitivity for detection of active hepatitis D virus replication during chronic infection and constitute useful, sensitive and noninvasive tests for the diagnosis and monitoring of chronic hepatitis D virus in

ISSN:0270-9139    

DOI:10.1002/hep.1840100602

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractTo evaluate the immune process involved in the pathogenesis of liver cell damage in chronic hepatitis delta virus infection, a panel of monoclonal antibodies against pan T cells (Leu 4), inducer/helper T cells (Leu 3a+3b), suppressor/cytotoxic T cells (Lue 2a), B cell (Leu 12), monocyts/macrophages (Leu M3) and NK/K cells (Leu 7) was used to characterize the subsets of the mononuclear cell infiltrates in livers from 12 patients with chronic type D hepatitis, with special emphasis on the areas of periportal piecemeal necrosis and intralobular necrosis. A control group of 12 patients with chronic type B hepatitis was also studied for comparison. The results revealed that the livers from patients with chronic type D hepatitis showed a prominent mononuclear cell infiltration in portal/periportal and intralobular areas. Furthermore, the vast majority of the mononuclear cell infiltrates in liver were T cells, which constituted more than 80% of the cells in the areas of periportal piecemeal necrosis and intralobular necrosis and about 60% of the cells in the portal tract, whereas B cells, monocytes/macrophages and NK/K cells were relatively uncommon. Among T cell populations, the inducer/helper T cells were predominant in the portal tract, and, by contrast, the suppressor/cytotoxic T cells were predominant in the areas of piecemeal necrosis and intralobular necrosis. The distribution of the mononuclear cell subsets in relation to the different topographical areas of the liver in patients with chronic type B hepatitis was essentially the same as that observed in chronic type D hepatitis. Our findings therefore suggest that T cell‐mediated immunity might play a role in the pathogenesis of chronic type D hepatitis, similar to that suggested for chronic type B hepatiti

ISSN:0270-9139    

DOI:10.1002/hep.1840100603

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractThe intrahepatic distribution of hepatitis delta virus RNA was studied byin situhybridization in 33 formalin‐fixed, paraffin‐embedded biopsies from 17 chronic hepatitis B virus carriers superinfected with hepatitis delta virus. The findings were correlated with the expression of the hepatitis delta antigen, the duration of the hepatitis delta virus infection and the eosinophilic degeneration of the hepatocytes. Intranuclear hepatitis delta virus RNA and antigen were found in 28 specimens, whereas the remaining five were negative for both markers. Hepatitis delta virus RNA and antigen were mostly found within the same cell. In 20 specimens, however, a variable number of hepatocytes showed the presence of hepatitis delta virus RNA alone. The percentage of these over the total number of infected cells was higher in the specimens taken within 1 year from the acute delta hepatitis, whereas their absence was invariably associated with a long‐established hepatitis delta virus infection. Interestingly, the vast majority of hepatocytes undergoing eosinophilic degeneration, a change significantly associated with hepatitis delta virus infection, did not show the presence of either hepatitis delta virus RNA or the viral antigen, suggesting a lack of association, at the cellular level, between viral replication and cytopathological change. The specificity of the detection of hepatitis delta virus RNA was confirmed by negative findings in nine specimens from seven chronic hepatitis B virus carriers without evidence of past or current hepatitis delta virus infection. The loss in sensitivity due to the formalin fixation was estimated to be 50% of that obtained in frozen biopsies, as determined by counting autoradiographic grains over infected cells. Consistent results were obtained when sections from the same biopsies were hybridized in separate experiments. Detection of hepatitis delta virus RNA byin situhybridization in formalin‐fixed, paraffin‐embedded sections is therefore a rapid, specific, sensitive and reproducible assay for monitoring intrahepatic hepatitis delta virus replication and might have diagnostic

ISSN:0270-9139    

DOI:10.1002/hep.1840100604

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractPrimary chimpanzee hepatocytes were maintainedin vitroutilizing a serum‐free medium. Hepatocyte functions were sustained throughout the culture period as demonstrated by the synthesis and secretion of liver‐specific plasma proteins characteristic for differentiated hepatocytes. Hepatocyte cultures established from a chimpanzee chronically infected with human hepatitis B virus exhibited the synthesis and secretion of hepatitis B virus proteins into the medium. In addition, thede novoreplication of hepatitis B virus was documented by the recovery of virus, exhibiting an endogenous DNA polymerase activity, from the tissue culture medium. Therefore, both the long‐term maintenance of differentiated hepatocytes and the expression of hepatitis B virus from these primary cultures were sustained in the serum‐free

ISSN:0270-9139    

DOI:10.1002/hep.1840100605

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractSerum levels of soluble interleukin 2 receptor were determined in patients with acute viral hepatitis and patients with various chronic liver diseases. In addition, the ability of peripheral blood mononuclear cells of patients with alcoholic cirrhosis to generate soluble interleukin 2 receptor following mitogenic stimulation was studiedin vitro.Serum soluble interleukin 2 receptor concentrations in all patients with acute viral hepatitis were found to be significantly elevated (1,319 ± 527 units per ml) during the first week after onset of disease, as compared to healthy control individuals (375 ± 102 units per ml; p<0.0005) and declined toward normal levels during the course of the illness. Similarly, patients suffering from chronic liver disease such as alcoholic liver cirrhosis (1,172 ± 507 units per ml), primary biliary cirrhosis (619 ± 190 units per ml) or chronic active HBsAg+ hepatitis (941 ± 357 units per ml) showed increased serum soluble interleukin 2 receptor concentrations (p<0.0005 vs. controls, respectively).In vitromitogen stimulation of peripheral mononuclear cells derived from patients with alcoholic cirrhosis resulted in a soluble interleukin 2 receptor production not different from that seen in healthy individuals, suggesting that elevated soluble interleukin 2 receptor production not different from that seen in healthy individuals, suggesting that elevated soluble interleukin 2 receptor serum levels seen in this disease are not the result of an increased synthesis by circulating lymphocytes. Due to the ability of soluble interleukin 2 receptor to bind free interleukin 2—thus making it a potential immunoregulatory molecule—its high serum levels could explain some of the immunologic abnormalities observed in acute and chronic liver

ISSN:0270-9139    

DOI:10.1002/hep.1840100606

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractAcetaldehyde, a product of ethanol oxidation which forms adducts with proteins, has been incriminated in the pathogenesis of alcoholic liver injury. High serum antibody titers against acetaldehyde‐protein adducts have been found not only in alcoholics but also in patients with nonalcoholic liver disease, suggesting a contribution of acetaldehyde derived from sources other than exogenous ethanol. To investigate the effect of liver injury on the removal and the production of acetaldehyde, we produced fibrosis and cirrhosis (by chronic administration of carbon tetrachloride) and fatty liver (with very small doses of dimethylnitrosamine) in rats. Endogenous blood acetaldehyde levels increased by 38% in rats with severe liver injury (p<0.005), but not significantly in rats with fatty liver. However, an i.v. load of threonine (a physiological source of acetaldehyde), in amounts equivalent to the daily intake of this amino acid, increased blood and hepatic acetaldehyde levels in the rats with both types of liver injury more than in controls. Threonine dehydrogenase and dehydratase activities, involved in the major pathways for threonine degradation in mitochondria and cytosol, respectively, were markedly decreased in rats with liver injury with a resulting increase in hepatic threonine concentration. Moreover, the threonine aldolase activity, which splits threonine into glycine and acetaldehyde, remained unaffected or even slightly increased. Liver injury was also associated with impaired mitochondrial functions, including a 10 to 23% decrease in acetaldehyde oxidation (depending upon the severity of the lesions). As a consequence, administration of ethanol (an exogenous source of acetaldehyde) resulted in striking elevations in the levels of acetaldehyde in carbon tetrachloride‐treated rats. Thus, liver injury promotes the accumulation of acetaldehyde from either physiological sources or from ethanol by decreasing acetaldehyde oxidation and by enhancing its production from threon

ISSN:0270-9139    

DOI:10.1002/hep.1840100607

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractIt has been suggested that hepatocyte enlargement can lead to compression of the extracellular space (sinusoidal and interstitial) and induce portal hypertension. However, this hypothesis has never been tested by measuring the vascular and extravascular spaces in the intact liver. The aim of the present study was to investigate the effects of chronic alcohol intake on the hepatic microcirculation using Goresky's multiple‐indicator dilution technique in the isolated perfused rat liver. Female rat littermates were pair‐fed either ethanol (n = 7) or an isocaloric carbohydrate diet (n = 7) for 21 days. As expected, chronic alcohol intake produced a significant increase in liver/body weight ratio (+32%, p<0.01) and hepatocyte size (+45%, p<0.001), which was accompanied by a marked increase in the cellular water space (control: 3.3 ± 0.6 ml; ethanol‐fed: 4.9 ± 0.9 ml; p<0.001). When expressing data per total liver, the sinusoidal space was similar in the two groups (control: 1.87 ± 0.2; ethanol‐fed: 1.95 ± 0.2 ml; not significant), whereas the interstitial space was increased in alcohol rats compared to controls (albumin space +58%, p<0.01; sucrose space +51%, p<0.01). In alcoholic rats, the sinusoidal space was probably stretched, with an overall reduced transversal diameter, as suggested by the reduced values found when data were expressed per gm of liver weight. However, despite this finding and the enlargement of the liver and hepatocytes observed in alcoholic rats, similar values were obtained between the two groups for the portal perfusion pressure and thus the intrahepatic vascular resistance. The present data show that the enlargement of the liver and hepatocytes due to chronic alcoholic intake: (i) does not develop at the expense of the total vascular space and unexpectedly increases the interstitial space, and (ii) under our experimental conditions, does not modify the overall resistance o

ISSN:0270-9139    

DOI:10.1002/hep.1840100608

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractAlcoholic liver disease is frequently accompanied by portal hypertension. We have previously shown that alcohol intake in awake, unrestrained rats is followed by an increase in portal tributary blood flow. In this study, the effect of ethanol on splanchnic hemodynamics in rats with portal hypertension was analyzed. Portal hypertension was induced by partial ligation of the portal vein. This procedure resulted in an increase in portal tributary and hepatic arterial blood flows compared to sham‐operated animals. Ethanol (2 gm per kg, oral) increased portal tributary blood flow in both sham‐operated and portal vein‐ligated rats (sham + water = 37.6 ± 1.4; sham + ethanol = 63.1 ± 1.9; p<0.01; partial portal vein stenosis + water = 53.2 ± 3.3; partial portal vein stenosis + ethanol = 69.5 ± 2.2 ml · kg−1. min−1; p<0.01). In sham‐operated rats, hepatic artery blood flow was unchanged following ethanol (sham + water = 6.6 ± 0.7; sham + ethanol = 7.1 ± 1.0 ml · kg−1. min−1), whereas in portal vein‐ligated rats, flow was increased (partial portal vein stenosis + water = 13.7 ± 1.4; partial portal vein stenosis + ethanol = 19.8 ± 1.1 ml · kg−1· min−1; p<0.025). The adenosine receptor blocker 8‐phenyltheophylline suppressed only the ethanol‐induced increase in both portal tributary and hepatic artery blood flows in portal vein‐ligated rats. The increases in hepatic artery and portal tributary blood flows observed in portal vein‐ligated rats without ethanol were not influenced by 8‐phenyltheophylline. In conclusion, the increase in portal tributary and hepatic artery blood flow following partial portal vein ligation is not adenosine mediated. We have now shown that, in portal hypertension, ethanol further increases portal tributary blood flow. Contrary to what is seen in normal and sham‐operated rats, in portal hypertension, ethanol also increases hepatic arterial blood flow. Both the portal and arterial blood flow effec

ISSN:0270-9139    

DOI:10.1002/hep.1840100609

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractPropranolol decreases portal pressure by reducing portal blood inflow. Studies in rats with prehepatic portal hypertension due to portal vein stenosis (a model with extensive portosystemic shunting) have shown that propranolol increases the portocollateral resistance, which hinders the fall in portal pressure. The present study examined the effects of propranolol on splanchnic and systemic hemodynamics in rats with portal hypertension due to cirrhosis of the liver, a model which is characterized by mild portosystemic shunting. Two groups of rats with CCl4‐induced cirrhosis were studied: the propranolol group (n = 8), which received a propranolol infusion of 2 mg per 15 min, and controls (n = 9), which received a placebo (saline) infusion. Hemodynamic measurements were done using radiolabeled microspheres. Propranolol‐treated rats had signficantly lower cardiac output (−31%) and heart rate (−26%) than controls (p<0.001). Hepatic artery flow was not modified by propranolol. Propranolol caused splanchnic vasoconstriction, manifested by increased splanchnic resistance (+57%) and by a significant fall in portal blood inflow (4.8 ± 0.4 vs. 6.3 ± 0.5 ml per min · 100 gm in controls, p<0.05). In contrast with rats with prehepatic portal hypertension, propranolol did not increase portal resistance in cirrhotic rats [2.0 ± 0.2 vs. 2.0 ± 0.1 mmHg per ml per min · 100 gm body weight (not significant)]. Hence, the fall in portal pressure (−19%) was expected from the decrease in portal inflow (−24%). These results suggest that increased portal resistance in rats with prehepatic portal hypertension may represent an intrinsic effect of propranolol on the portocollateral an intrinsic effect of propranolol on the portocollateral vessels, since β‐blockade does not modify portal vascular res

ISSN:0270-9139    

DOI:10.1002/hep.1840100610

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractA prospective, randomized, placebo‐controlled, double‐blind, multicenter clinical trial of intravenous somatostatin (Stilamin®; Serono Laboratories, Inc., Randolph, MA) was performed in 102 patients with actively bleeding esophageal varices from August, 1985, to November, 1986. Patients had major hemorrhage indicated by hematemesis or melena and evidence of significant blood loss. For entry, patients had to have endoscopic demonstration of active bleeding from esophageal varices or stigmata of recent hemorrhage and bright red blood in the gastric aspirate with no other source of bleeding found. Randomized patients received identical appearing somatostatin or placebo for a 30‐hr study period. Those given somatostatin received a 250‐μg bolus and a 250‐μg per hr infusion with repeat bolus and doubling of the infusion if the bleeding was not controlled. In retrospect, 18 patients could not be evaluated.Of the 84 evaluable patients, 48 received somatostatin and 36 placebo. They were comparable in age, gender, severity of liver disease and history of variceal bleeding. Transfusion requirements were similar in both groups. Bleeding stopped for 12 consecutive hr during 30 hr of the study period in 31 (65%) of the somatostatin group vs. 30 (83%) of the placebo group (p = 0.06). The median time to cessation of bleeding was 2 hr in the placebo group and 3 hr in the somatostatin group. Deaths following the study period were nine (25%) in the placebo group and 15 (31%) in the somatostatin group. Within the limitations of the present study, we conclude that somatostatin was ineffective in the management of active bleeding of esopha

ISSN:0270-9139    

DOI:10.1002/hep.1840100611

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY