摘要:

AbstractThe serological responses to two different hepatitis C virus antigens were studied by enzyme‐linked immunosorbent assay in a variety of chronic liver diseases and in healthy blood donors. The study population comprised 97 cases of cryptogenic chronic liver disease (40% with a history suggestive of parenterally transmitted non‐A, non‐B hepatitis and 60% without such a history), 87 cases of other well‐characterized chronic liver diseases and 96 voluntary blood donors. The commercially available C100‐3 assay and a new assay utilizing a 22 kD recombinant protein (c22) from the nucleocapsid region of the virus were used for antibody detection. Overall in the non‐A, non‐B hepatitis group, 77% were positive for anti‐c22, 55% were positive for anti‐C100‐3 and 24% were negative by both tests. In the parenterally transmitted chronic liver disease group, 82% were positive for anti‐C100‐3 and 90% were positive for anti‐c22 (not significant). In the cryptogenic chronic liver disease cases 36% were positive for anti‐C100‐3 and 67% were positive for anti‐c22 (p<0.001). Only in one case (a patient with hepatitis B virus infection) was anti‐C100‐3 detected without concomitant anti‐c22. None of the voluntary blood donors had detectable hepatitis C virus antibodies. The new enzyme‐linked immunosorbent assay test for anti‐c22 would appear to be a more sensitive indicator of chronic hepatitis C virus infection than the existing commercial test, suggesting a useful diagnostic role in both cases of cryptogenic chronic non‐A, non‐B hepatitis liver disease and for the screening of blood products for prevention of hepatitis a

ISSN:0270-9139    

DOI:10.1002/hep.1840150202

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractImmunoassays were developed to detect antibodies against oligopeptides deduced from the putative core gene of hepatitis C virus, and their performances were compared with that of the commercial immunoassay for antibodies against the product of nonstructural regions of hepatitis C virus (anti‐C100‐3). A 19‐mer oligopeptide (CP10) and a 36‐mer oligopeptide (CP9) were chemically synthesized, which represented hydrophilic regions of the product of the hepatitis C virus core gene. They were used to capture corresponding antibodies, anti‐CP10 and anti‐CP9, by enzyme‐linked immunosorbent assay in sera from patients with acute or chronic non‐A, non‐B liver disease and in blood donations. At the onset of acute non‐A, non‐B hepatitis, anti‐CP10 was detected in 15 of 20 patients (75%), and anti‐CP9 was detected in 14 patients (70%). This was more frequent than anti‐C100‐3, which was found in only 9 patients (45%). In 186 patients with chronic non‐A, non‐B liver disease, anti‐CP9, anti‐CP10 or both were detected in 170 patients (91%). This was more frequent than anti‐C100‐3, which was found in 138 patients (74%). Blood with anti‐CP10 as the single serological marker for hepatitis C virus infection transmitted non‐A, non‐B hepatitis by needlestick exposure. In sera from 558 apparently healthy blood donors, anti‐CP10 was detected in 55 donors (9.9%), anti‐CP9 was detected in 26 donors (4.7%) and anti‐C100‐3 was detected in 7 donors (1.3%). Among sera positive by at least one test, 14 were found to contain hepatitis C virus RNA; 7 of them were negative for anti‐C100‐3 but positive for anti‐CP10 and/or anti‐CP9 in high titers. These results indicate that antibodies against antigenic determinants of the hepatitis C virus core would complement anti‐C100‐3 for the diagnosis of non‐A, non‐B liver disease and contribute toward further decreasing the incidence

ISSN:0270-9139    

DOI:10.1002/hep.1840150203

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractMany cases of chronic hepatitis and cirrhosis cannot be attributed to a known cause and are collectively referred to as cryptogenic chronic liver disease. We have evaluated the role of the hepatitis C virus in the pathogenesis of this condition in a retrospective serum analysis for antibody to hepatitis C virus in 129 patients with cryptogenic liver disease. Other causes of chronic hepatitis and cirrhosis were ruled out by clinical, serum biochemical and serological techniques. All 129 patients were HBsAg negative, but 28 (22%) had antibody to HBcAg. Sera were tested by radioimmunoassays using recombinant peptides for antibodies to nonstructural (C 100‐3 and C33c) and structural regions (C22) of HCV. Among the 129 patients, 61 (47%) had antibody to C100‐3, 76 (59%) had antibody to C33c and 74 (57%) had antibody to C22. Seventy‐nine (61%) were reactive with at least one and 76 (59%) were reactive with at least two HCV peptides (this is the criterion used for hepatitis C virus antibody reactivity). A proportion of patients with chronic hepatitis and cirrhosis (55 of 91; 60%) similar to that of patients without cirrhosis (21 of 38; 55%) had hepatitis C virus antibody. No significant clinical, serum biochemical or histological differences were noted between the group of patients with hepatitis C virus antibody and those without this antibody reactivity. Thus more than half the patients with cryptogenic chronic liver disease had hepatitis C virus antibody, suggesting that chronic HCV infection plays a major role in the origin of cryptogenic chronic hepatitis and cirrhosis. (HEPATOLOGY1992;15: 187

ISSN:0270-9139    

DOI:10.1002/hep.1840150204

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractFibroproliferation was measured as the uptake of [3H]thymidine into fibroblasts. Human fibroblasts were incubated with 200 μl monocyte‐conditioned medium, the 0.22 μm filtrate from cultured monocytes, in Dulbecco's modified Eagle medium supplemented with controlled process serum replacement 2, a fetal calf serum substitute with low mitogenic activity. Increasing the numbers of fibroblasts resulted in a parallel increase in thymidine uptake to a maximal level. Fibroblasts (2 × 103) were plated into microwell plates and incubated with monocyte‐conditioned medium for 72 hr. At 16 hr before harvest, 1 μCi [3H]thymidine was added. Cells were harvested with phosphate‐buffered saline and washed, and the filters were counted. Fibroblasts incubated with Dulbecco's modified Eagle medium and controlled process serum replacement 2 showed minimal thymidine uptake. Fibroblasts incubated with Dulbecco's modified Eagle medium plus monocyte‐conditioned medium from monocytes stimulated with 10 μg/ml lipopolysaccharides showed a sixfold increase in thymidine uptake over fibroblasts in Dulbecco's modified Eagle medium and controlled process serum replacement 2 alone. Fibroblasts incubated with Dulbecco's modified Eagle medium plus monocyte‐conditioned medium from monocytes of patients with liver disease (n = 20) showed a 10‐fold elevation in thymidine uptake compared with Dulbecco's modified Eagle medium and controlled process serum replacement 2. Results indicated that preincubation of monocyte‐conditioned medium with either anti‐interleukin‐1β (12.5 halfmaximal units, 4° C, 16 hr) or catalase (1,870 IU, 25° C, 1 hr) did not alter the fibroproliferative activity of the monocyte‐conditioned medium, suggesting that neither interleukin‐1β nor activated oxygen intermediates were involved in fibroproliferation. Fibroblasts were incubated with platelet‐derived growth factor in increasing concentrations to produce a dose‐response relationship. Platelet‐derived growth factor was found to significantly enhance fibroproliferation. The addition of antibody to platelet‐derived growth factor reduced the fibroproliferation activity of plateletderived growth factor. Samples of monocyteconditioned medium were then preincubated with anti—platelet‐derived growth factor to determine whether platelet‐derived growth factor in the monocyte‐conditioned medium was mediating fibroproliferation. Anti—platelet‐derived growth factor reduced the fibroproliferative activity of the monocyteconditioned medium, suggesting that platelet‐derived growth factor probably plays a role in the fibroproliferation observed with monocyte‐conditioned medium obtained from pa

ISSN:0270-9139    

DOI:10.1002/hep.1840150205

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractThe cerebrohepatorenal syndrome of Zellweger is a congenital syndrome of multiple manifestations, including hepatomegaly and liver dysfunction. Treatment is generally of a supportive nature, aimed at improving nutrition and growth, controlling the central nervous system symptoms and limiting progression of liver disease. Because the liver disease in Zellweger syndrome may be attributed to an overproduction and accumulation of cholestanoic acids, exacerbated by diminished primary bile acid synthesis, we hypothesized that primary bile acid administration would be beneficial in improving liver function by a mechanism involving down‐regulation in the synthesis of these atypical bile acids. We report here the clinical and biochemical responses to primary bile acid administration in a 2‐mo‐old boy who was seen with the typical signs of Zellweger syndrome. Liver disease was evident from hepatomegaly and elevated serum liver enzymes and bilirubin. The diagnosis was supported by markedly elevated serum very long chain fatty acids and the bile acids dihydroxycholestanoic acid and trihydroxycholestanoic acid. Confirmation of the lack of peroxisomes was established by electron microscopy. When the patient was 6 mo old, the primary bile acids cholic acid and chenodeoxycholic acid, (100 mg each/day) were administered orally. A significant improvement in biochemical indices of liver function occurred with a normalization of the serum bilirubin and liver enzymes and a histological improvement in the extent of inflammation and bile duct proliferation and disappearance of cannalicular plugs. Serum and urinary cholestanoic acids showed a significant decrease within a few days. A striking and sustained increase in growth was observed after therapy, and an improvement in neurological symptoms was noted. In conclusion, this study indicates that primary bile acid therapy improves liver function and growth in the patient with peroxisomal dysfunction and should be considered in the supportive therapies for this condition. (Hepatology 1992;15:198

ISSN:0270-9139    

DOI:10.1002/hep.1840150206

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractOver 5 yr, 103 elderly patients (mean age = 70 yr) with bile duct stones (mainly not amenable to endoscopic extraction) underwent adjuvant extracorporeal shock‐wave lithotripsy using a first‐generation kidney lithotripter. Disintegration of stones was achieved after a mean of 1.4 sessions in 92% of the patients. Spontaneous passage of fragments into the duodenum occurred in one fourth of the patients, and endoscopic extraction of fragments was necessary in 75% of the patients, resulting in complete clearance of the bile duct stones in 91 (88%) of 103 patients. The most important adverse effect was septic disease after extracorporeal shock‐wave lithotripsy in 4% of the patients. The 30‐day mortality rate was 1% (one patient), and another 15 patients died during a mean follow‐up of 26 ± 14 mo (mainly of causes unrelated to biliary tract disease). Two of 91 patients who had been rendered stone free were readmitted because of recurrent stone disease during the follow‐up period. Of the 43 patients who still had their gallbladders during extracorporeal shock‐wave lithotripsy, 14% subsequently underwent cholecystectomy.These data show that extracorporeal shock‐wave lithotripsy of bile duct stones is a useful and safe adjunct to nonsurgical procedures for the removal of calculi in the biliary tree. (HEPATOLOGY

ISSN:0270-9139    

DOI:10.1002/hep.1840150207

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractTo identify prognostic features and to define the role of liver transplantation in severe autoimmune chronic active hepatitis, findings before and after corticosteroid therapy in 111 patients were correlated with outcome and compared with the findings in 24 patients who had been selected independently for liver transplantation. Patients whose condition deteriorated during corticosteroid treatment were younger (32 ± 3 yr vs. 43 ± 2 yr; p<0.02) than those who experienced remission, but no individual features predicted outcome. Patients in whom therapy failed required longer durations of continuous treatment than did those who experienced remission (60 ± 14 mo vs. 20 ± 12 mo; p = 0.001). Of 13 patients who did not experience remission within 4 yr, 9 (69%) ultimately deteriorated. Ascites developed more often in those patients whose therapy failed and who died of liver failure than in counterparts who survived (86% vs. 33%). Patients undergoing transplantation were similar to those whose treatment failed, but they died less frequently (8% vs. 56%, p<0.01). Indeed, the 5‐yr survival rate after transplantation was comparable to that of patients who had entered remission (92% vs. 100%). Successive biopsy samples failed to disclose recurrent autoimmune hepatitis after transplantation. Human leukocyte antigens Al, B8 occurred more commonly in patients in whom treatment failed or who underwent transplantation (70% vs. 41%, p<0.05). We conclude that failure to achieve remission within 4 yr and the human leukocyte antigen Al, B8 phenotype are associated with poor prognosis. Manifestations of liver decompensation, such as ascites, in patients who have been unable to experience remission justify consideration of transplantation. Transplantation improves the survival of patients with features of treatment failure, and it is not associated with recurrent disease. (HEPATOLOGY1991;15:215

ISSN:0270-9139    

DOI:10.1002/hep.1840150208

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractLactitol (β‐galactosido‐sorbitol) has been recently compared with lactulose for the treatment of chronic hepatic encephalopathy in a few studies, each comprising a small number of patients. The results are controversial. We studied the efficiency and tolerance of both compounds by using a meta‐analysis on the basis of published controlled trials. Our study only included controlled or randomized trials comprising cirrhotic patients with chronic hepatic encephalopathy. Analyzed parameters were the portosystemic encephalopathy index of Conn after treatment, the percentage of improved patients and the percentage of patients who had ill effects related to the treatment (flatulence, diarrhea). Bibliographical screening revealed five studies comparing the effects of lactitol and lactulose in chronic hepatic encephalopathy. Four crossover studies were done that included 48 patients and one parallel study that included 29 patients. The duration of the treatment ranged from 3 to 6 mo. All studies found a similar efficiency with both drugs. However, they exhibited some discrepancies in the relative frequency of adverse reactions (flatulence). Meta‐analysis showed no statistical differences in the portosystemic encephalopathy index after lactitol or lactulose treatment. The percentage of improved patients after lactitol or lactulose was similar. In contrast, the analysis revealed a higher frequency (p<0.01) of flatulence in patients treated with lactulose compared with those treated with lactitol. Inconclusion, this meta‐analysis shows no statistical difference between therapeutic effects of lactitol and lactulose, but it does show a higher frequency of flatulence with lactulose. This suggests that lactitol should be preferred to lactulose for the treatment of chronic hepatic encephalopathy. (HEPATOLOGY1992;1

ISSN:0270-9139    

DOI:10.1002/hep.1840150209

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractThe portal vein is the main source of blood and hepatotrophic factors to the liver. Partial portal‐vein ligation in rats results in reduced growth compared with that in control rats. To investigate whether extrahepatic portal vein obstruction occurring in early childhood influences growth in humans, anthropometric and nutritional assessments were prospectively carried out in 61 patients with extrahepatic portal vein obstruction. Comparisons were made with 183 matched healthy controls using National Center of Health Statistics reference. Fifty‐one percent of children with extrahepatic portal vein obstruction had stunted growth (height for age<90% of normal), compared with 16% of controls (p5 yr) than with shorter (<2.5 yr) duration of clinical portal hypertension (height for age, 88.0 ± 3.2 vs. 95.1 ± 3.0; p<0.01). Little difference was seen in the energy intake (1,302 ± 463 kcal/day vs. 1,335 ± 449 kcal/day; p = not significant) and weight for height index (83.6 ± 9.3 vs. 88.0 ± 7.9; p = not significant) between extrahepatic portal vein obstruction patients and controls. This suggested that despite comparable nutrition, marked growth retardation occurred in extrahepatic portal vein obstruction patients. Incremental growth velocity was studied in 31 patients; in 24 (73%) the baseline Z score (‐2.1 ± 0.2) had decreased further (‐2.4 ± 0.2) at the end of follow‐up (15.5 ± 1.6 mo). Although the incremental height velocity was only 56% of the expected height, incremental weight gain was 98% of the expected weight for the attained height. This indicates linear growth failure despite optimal nutrition. In conclusion, our results demonstrate that most children with extrahepatic portal vein obstruction have marked growth retardation and diminished growth velocity. The roles of hemodynamic and hormonal factors in modulation of growth in young extrahepatic portal vein obstruction patients must be studied. (HEPATOLO

ISSN:0270-9139    

DOI:10.1002/hep.1840150210

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractThe development of techniques for isolating hepatic lipocytes (Ito, stellate or fat‐storing cells) from rodents has been instrumental in defining their role in hepatic vitamin A storage and fibrogenesis. In this study, we developed a method for the purification of lipocytes and Kupffer cell from wedge sections of normal human liver and examined their properties in primary culture. Sections of donor liver (400 to 600 gm) harvested but not used for transplantation were perfusedin situwith University of Wisconsin solution and used for lipocyte isolation within 48 hr. Cells were isolated by catheter perfusion of the wedge through several large vessels with L‐15 salts, Pronase and collagenase, followed by Larex density gradient centrifugation. Lipocytes were plated on either uncoated plastic or a basement membrane‐like gel. Lipocyte and Kupffer cell yields were 2.3 ± 0.6 × 105and 8.6 ± 1.4 × 105cells, respectively, per gram of liver (n = 5). Lipocyte purity was 91% as assessed by vitamin A autofluorescence, and Kupffer cell purity was 83% as determined by uptake of fluorescinated staphylococci. Lipocytes cultured on the plastic spread within 48 to 72 hr, displaying slightly more heterogeneous retinoid droplet size than comparable rat cells; on a basement‐membrane gel, the cells remained aggregated and spherical with occasional spindlelike extensions. Lipocytes on plastic expressed procollagens I and III, collagen IV and laminin by immunocytochemistry, and types I, III and IV procollagen messenger RNAs by RNAse protection, Northern blot and polymerase chain reaction, respectively. Transmission electron microscopy of lipocytes at 7 days demonstrated a prominent rough endoplasmic reticulum and contractile filaments. Scanning electron microscopy revealed a smooth cell surface with perinuclear droplets beneath the cell membrane. With continued primary culture on plastic (more than 7 days), cells appeared “activated” (i.e., increased spreading and diminished retinoid droplets) and began proliferating as assessed by nuclear autoradiography and [3H]thymidine incorporation. Kupffer cells observed by scanning electron microscopy in early primary culture displayed prominent membrane ruffling and lamellipodia. In summary, we have established a reproducible method for the isolation and primary culture of human lipocytes and Kupffer cells. (HEPATOLOGY1

ISSN:0270-9139    

DOI:10.1002/hep.1840150211

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY