摘要:

AbstractChronic hepatitis B is a severe and frequently progressive disease. We assessed the safety and efficacy of thymosin fraction 5 and thymosin‐α1in a prospective, placebo‐controlled trial in 12 patients with chronic hepatitis B. All patients had histological and biochemical evidence of active liver disease for at least 6 mo before treatment and were positive for serum hepatitis B virus DNA and HBsAg. Seven patients received thymosin fraction 5 or thymosin‐α1and five patients received placebo twice weekly for 6 mo. By the conclusion of the study (1 yr), serum aminotransferase levels had improved significantly in thymosin‐treated patients, but not in the placebo group. Six (86%) of the thymosin treated patients and one (20%) patient given placebo cleared hepatitis B virus DNA from serum (p<0.04, Fisher's exact test). After treatment, replicative forms of hepatitis B virus DNA were present in the liver specimens of four of five placebo‐treated patients but in only one of seven thymosin‐treated patients (p<0.04, Fisher's exact test). Response to thymosin therapy was associated with significant improvements in peripheral blood lymphocyte and CD3 and CD4 counts and inin vitroproduction of interferon‐γ over initial values. No significant side effects were observed in patients given thymosin or in placebo‐treated patients. Clinical, biochemical and serological improvement in patients responding to thymosin were sustained during 26 ± 3 mo of follow‐up. The results of this pilot trial suggest that thymosin therapy promotes disease remission and cessation of hepatitis B virus replication in patients with ch

ISSN:0270-9139    

DOI:10.1002/hep.1840140302

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractSerum and liver HBsAg bear an inverse relation to each other during the evolution of chronic hepatitis B virus infection and the quantity of HBsAg in tissue rises gradually with time. In this study, intracellular and extracellular levels of HBsAg were measured by radioimmunoassay in primary culture of hepatocytes from 30 patients with chronic hepatitis B virus infection to determine a possible relationship with hepatitis B virus replication.Serum levels of HBsAg correlated with markers of active viral replication (serum hepatitis B virus DNA, p<0.005, and tissue HBcAg, p<0.02) but inversely with tissue HBsAg (p<0.05). In similar fashion,in vitroexport of HBsAg was also related to the presence of active viral replication markers (serum hepatitis B virus DNA, p<0.02, and tissue HBcAg, p<0.05) and negatively with tissue HBsAg (p<0.001). Export of HBeAg also correlated positively with markers of active viral replication (serum hepatitis B virus DNA, p<0.05 and tissue HBcAg, p<0.05). Further experiments indicated that intrahepatic pre‐S1 and pre‐S2 correlated closely with intrahepatic HBsAg, indicating that a failure to export HBsAg was unlikely to be attributable to deficient intracellular expression of pre‐S1 or pre‐S2.These data indicate thatin vitroprimary hepatocyte culture of hepatitis B virus—infected cells provides an accurate reflection ofin vivoexport of HBsAg and that this is closely related to the presence of active viral re

ISSN:0270-9139    

DOI:10.1002/hep.1840140303

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractA 56‐yr‐old woman with long‐standing rheumatoid arthritis exhibited jaundice, pruritus and abdominal discomfort after 8 yr of periodic gold sodium thiomalate injections amounting to a cumulative dose in excess of 2.5 gm. Histopathological examination of the liver biopsy specimen showed submassive loss of parenchyma, collapse of reticulin and mixed cellular inflammatory infiltrates. Macrophages contained dark granules, which displayed the characteristics of aurosomes when examined by transmission electron microscopy and electron microprobe analysis. It is likely that hepatocellular injury occurred when the lysosomal storage capacity for gold was exc

ISSN:0270-9139    

DOI:10.1002/hep.1840140304

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractIt has been suggested that immunological mechanisms involving lymphocyte‐mediated damage are important in the characteristic bile‐duct damage that occurs in primary biliary cirrhosis and primary sclerosing cholangitis. Because adhesion is necessary for the interaction of lymphocytes with their target structures, we have studied the expression of intercellular adhesion molecule 1, a ligand for the leukocyte adhesion receptor lymphocyte function—associated antigen 1 in the liver of patients with primary biiary cirrhosis and primary sclerosing cholangitis. Strong expression of intercellular adhesion molecule 1 was seen on interlobular bile ducts and proliferating bile ductules in both conditions. In primary biliary cirrhosis, medium‐sized ducts, which are spared by the disease, were negative. Minimal bile‐duct staining was seen in conditions in which bile‐duct damage is not a major feature, such as nonbiliary cirrhosis and acute liver diseases. In patients with cirrhosis from any cause, strong expression of intercellular adhesion molecule 1 was detected on the periseptal hepatocytes adjacent to new connective tissue. The intensity of immunohistochemical staining was recorded using a semiquantitative visual scoring system that was subsequently validated quantitatively by confocal laser scanning microscopy.The expression/induction of intercellular adhesion molecule 1 on bile ducts may be important in the pathogenesis of bile‐duct damage in primary biliary cirrhosis and primary sclerosing cholangitis and is further evidence to support an immune pathogenesis in these two conditions. Furthermore, the induction of intercellular adhesion molecule 1 on hepatocytes may be an important factor in the liver‐cell damage and fibrosis that occur during the developme

ISSN:0270-9139    

DOI:10.1002/hep.1840140305

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractClinically stable patients with cirrhosis demonstrate insulin resistance with regard to glucose metabolism. However, much less is known about the two major factors, insulin and plasma amino acid concentration, that regulate protein metabolism in cirrhotic patients. To examine this question, we performed paired euglycemic insulin clamp studies in combination with14Cleucine and indirect calorimetry. In the first study insulin alone was infused, and the plasma amino acid concentration was allowed to decline, During the second study a balanced amino acid solution was infused with insulin to increase the total plasma amino acid concentration approximately twofold. Insulinmediated glucose disposal (4.68 vs. 6.45 mg/kg‐min, p<0.01) was significantly impaired by 30% in cirrhotic patients during both insulin clamp studies. In the postabsorptive state, cirrhotic patients manifested low plasma leucine (76 vs. 102 μmol/L) and α‐ketoisocaproate (19 vs. 30 μmol/L) concentrations, but all parameters of leucine turnover were normal. When insulin alone was infused, the endogenous leucine flux (an index of protein degradation) declined similarly in cirrhotic patients (30.8 μmol/m2‐min) and control (26.9) subjects, and this was accompanied by a similar decrease in plasma leucine concentration (31% vs. 33%). The decline in circulating leucine concentration was accompanied by a parallel decline in leucine oxidation (5.1 vs. 4.6 μmol/m2‐min) and nonoxidative (28.9 vs. 26.0 μmol/m2‐min) leucine disposal, which were of similar magnitude in cirrhotic patients and control subjects, respectively. In both cirrhotic patients and control subjects, combined hyperinsulinemia/hyperaminoacidemia elicited a similar stimulation of nonoxidative leucine disposal (an index of protein synthesis) and leucine oxidation while causing a greater suppression of endogenous leucine flux than observed with insulin alone. Thus the suppressive effect of insulin on protein degradation and the stimulatory effect of insulin/amino acid infusion on protein synthesis are not impaired in cirrhotic patients, demonstrating a clear‐cut dissociation between the effects of insulin on protein and g

ISSN:0270-9139    

DOI:10.1002/hep.1840140306

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractThe reason for the close association between primary biliary cirrhosis and the appearance of antibodies that recognize the E2 component of pyruvate dehydrogenase complex is not understood. The distribution of the three pyruvate dehydrogenase complex subunits was examined in the liver and lymph nodes of patients with primary biliary cirrhosis, patients with other liver diseases and normal subjects by immunohistochemistry using affinity‐purified antibodies. Intensity of staining was assessed semiquantitatively and validated by scanning laser confocal microscopy. In primary biliary cirrhosis tissue, the E2 staining pattern did not parallel the reported distribution of mitochondria. E2 staining in biliary epithelial cells was consistently stronger than in hepatocytes. In primary biliary cirrhotic liver, staining of biliary epithelium was significantly stronger than in normal or other liver disease controls; many bile ducts in primary biliary cirrhotic liver demonstrated very high intensity, diffuse distribution of stain. No differences in staining intensity were seen between perivenular hepatocytes in primary biliary cirrhotic liver and those in controls; periportal hepatocytes in primary biliary cirrhotic liver were, however, more intensely stained than perivenular cells. In primary biliary cirrhotic portal lymph nodes, a subset of macrophages showed highintensity, diffuse distribution of stain. By contrast, staining with antibodies to E1 and E3 (other components of pyruvate dehydrogenase complex) produced uniform‐intensity, mitochondrial distribution both in primary biliary cirrhosis and control tissue. The increased intensity of E2 in primary biliary cirrhotic tissue could be explained in terms of abnormal metabolism of E2 by biliary epithelial cells. Release of E2 during biliary‐tract damage and drainage through the lymphatics could result in uptake by macrophages and the presentation of antigen to lymphocytes in portal lymph

ISSN:0270-9139    

DOI:10.1002/hep.1840140307

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractA simple morphometrical method was developed using a color image analyzing system, which allowed quantitative evaluation of parenchymal liver cell volume and total hepatocyte number in cirrhotic patients. With this method, we estimated these values in 29 cirrhotic patients who underwent hepatic resection (nine cases) or nonshunting operation (20 cases). Liver volume, calculated from computed tomographic images, was 976 ± 196 cm3(range = 602 to 1,376 cm3); the parenchymal cell volume ratio, obtained based on liver histological appearance with silver stain, was 0.665 ± 0.092 (range = 0.510 to 0.881); and the parenchymal cell volume, calculated by multiplying the liver volume with the parenchymal cell volume ratio, was 645 ± 140 cm3(range = 403 to 936 cm3). The total hepatocyte number obtained in a similar manner using hematoxylin‐stained specimens was 1.72 ± 0.56 × 1011(range = 0.74 to 2.94 × 1011). The validity and applicability of the method is discussed, and the data are compared with those reported in other

ISSN:0270-9139    

DOI:10.1002/hep.1840140308

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractTo test whether hepatotoxicity occurring in National Cooperative Gallstone Study patients was caused by a toxic effect of chenodiolper seor of lithocholate caused by defective sulfation, bile samples were analyzed using a new high‐performance liquid chromatography method that measures the proportions of the four individual lithocholate amidates (sulfated and unsulfated lithocholylglycine and lithocholyltaurine) and all common bile acid amidates. Samples were obtained from National Cooperative Gallstone Study patients (n = 17) with abnormal light microscopic liver biopsy results or major aminotransferase elevations and from a matched control group of patients (n = 14) who received similar chenodiol doses but had no evidence of liver injury. Bile samples from 45 healthy subjects were also analyzed. The analytical method was validated by showing that the percentage of chenodiol and cholic and deoxycholic acid obtained by highperformance liquid chromatography correlated highly (r>0.94) with previous gas‐liquid chromatography analyses of these samples by the National Cooperative Gallstone Study Reference Laboratory. No significant differences were seen between gallstone patients with and without evidence of liver injury for percent total lithocholate amidates, percent sulfated or unsulfated lithocholate amidates or percent chenodiol amidates. Lithocholate was partially sulfated in all bile samples (52% ± 17% [mean ± S.D., n = 50]), but the extent of sulfation varied widely between and within patients during the course of therapy. Mean values of healthy subjects were similar and also showed a wide range in the extent of lithocholate sulfation. It is concluded that (a) liver injury caused by these doses of chenodiol could not be attributed to the accumulation of unsulfated lithocholateper sein circulating bile acids; (b) liver injury appeared to be, directly or indirectly, caused by enrichment in circulating bile acids with chenodiol or chenodiol together with lithocholate, suggesting that the hepatocytes of those patients with hepatotoxicity were injured by the change induced in bile‐acid metabolism by the feeding of chenodiol; and (c) about half of lithocholate amidates in bile samples were sulfated, but the extent of sulfation was highly variable both in gallstone patients and healthy s

ISSN:0270-9139    

DOI:10.1002/hep.1840140309

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractWasting is common in end‐stage primary biliary cirrhosis and causes concern in patients facing liver transplantation. We have quantified resting metabolic rate and diet‐induced thermogenesis in seven patients with primary biliary cirrhosis, in seven patients after liver transplantation who had previously been diagnosed as having primary biliary cirrhosis and in seven controls.Resting metabolic rate was elevated in the primary biliary cirrhosis group (4.44 ± 0.81 kJ/hr/kg body wt; mean ± S.D.) compared with the post‐liver‐transplantation group (3.39 ± 0.40 kJ/hr/kg body wt) (p<0.005) and compared with control subjects (3.65 ± 0.23 kJ/hr/kg body wt) (p<0.01). A highly significant relationship was found between the severity of liver disease in the primary biliary cirrhosis group, as assessed by Child‐Pugh score, and the resting metabolic rate group (r = 0.93; p<0.005).After a liquid meal (41 kJ/kg body wt), the metabolic rate increased, with similar peak changes from baseline occurring in all three groups. However, the rise persisted significantly longer in the primary biliar cirrhosis patients, and thus the integrated mean postprandial energy expenditure over the 4‐hr postprandial observation period was greater in the primary biliary cirrhosis group than in the other two groups (p<0.001).Fasting glucose and protein oxidation rates were similar between groups, but fasting fat oxidation rate was higher in the primary biliary cirrhosis group (3.90 ± 0.83 kJ/hr/kg body wt) than in the post‐liver‐transplantation group (2.11 ± 0.90 kJ/hr/kg body wt) (p<0.025) and than in the control group (2.49 ± 1.19 kJ/hr/kg body wt) (p<0.05). Postprandial glucose oxidation rates were similar in all groups, but the protein oxidation rate was lower in the primary biliary cirrhosis group than in the other two groups (p<0.01). The fat oxidation rate remained higher after food intake in the primary biliary cirrhosis group than in the post‐liver‐transplantation group (p<0.05), but no significant differences were found between the primary biliary cirrhosis and control groups or between the post‐liver‐transplantation and control groups. No differences in total fasting plasma free fatty acids were seen between groups, but the level of stearic acid was higher in the control group (41.3 ± 10.3 μmol/L) than in the primary biliary cirrhosis group (27.5 ± 9.2 μmol/L) (p<0.05) or than the post‐liver‐transplantation group (26.9 ± 6.6 μmol/L) (p<0.05).These data suggest that, as liver disease progresses, resting. metabolic rate increases. This, together with the greater overall diet‐induced thermogenesis in these patients, could make a significant contribution to increased energy expen

ISSN:0270-9139    

DOI:10.1002/hep.1840140310

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractAmong 597 patients with nodular hepatic lesions who underwent ultrasonically guided needle biopsy, 305 were histologically confirmed as having hepatocellular carcinoma, and 37 patients had borderline lesions. Histological reexamination was correlated with morphometrical analysis on selected cases of well‐differentiated, microtrabecular hepatocellular carcinomas (n = 29), borderline lesion (n = 10), typical (mid‐sized and macrotrabecular) hepatocellular carcinomas (n = 15) and cirrhotic liver tissue obtained from extranodular hepatic parenchyma of hepatocellular carcinoma patients (n = 47). Morphometrical analyses revealed that the mean cell size and nucleocytoplasmic ratio were most useful for distinguishing well‐differentiated, microtrabecular hepatocellular carcinoma from cirrhosis. These two parameters were well correlated with nuclear density. The grade of nuclear density, therefore, seemed to be a convenient semiquantitative indicator for diagnosing well‐differentiated hepatocellular carcinoma. A comparison between intranodular and extranodular hepatic tissues was particularly important for its assessment. It is concluded from the results that hepatic nodules presenting a nuclear density larger than two times that of controls could be classified into the overt hepatocellular carcinoma group. From the statistical aspect, the possibility of microtrabecular hepatocellular carcinoma should be considered when a nodule has a nuclear density exceeding 1.3 times that of the extranodular

ISSN:0270-9139    

DOI:10.1002/hep.1840140311

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY