摘要:

AbstractCytomegalovirus infection is one factor implicated in the cause of the vanishing bile duct syndrome complicating liver transplantation. To further investigate the role of cytomegalovirus in this syndrome, we studied serial liver biopsy material byin situhybridization for cytomegalovirus DNA using a highly sensitive technique that allows the localization of viral replication.Cytomegalovirus DNA was identified in hepatocytes in 10 of 12 patients with the vanishing bile duct syndrome, 1 of whom had no serological evidence of cytomegalovirus infection. It was also present in all 18 patients with uncomplicated cytomegalovirus infection but was not identified in any of 10 subjects with transplants who had neither complication. Nine of the patients in this series underwent a diagnostic liver biopsy at 1 wk and subsequently had cytomegalovirus infection develop; cytomegalovirus DNA was identified in liver tissue of all nine patients, indicating that cytomegalovirus replication commences at an early stage.In those with uncomplicated cytomegalovirus, infection occurred earlier (p<0.05) but was eliminated more quickly (p<0.0005), and the number of infected hepatocytes was greater (p<0.05) when compared with those with the vanishing bile duct syndrome; in these, cytomegalovirus DNA was detectable until death or retransplantation. Cytomegalovirus DNA was never identified in either biliary or endothelial tissue. These data indicate that the vanishing bile duct syndrome is associated with persistent cytomegalovirus replication within hepatocytes. (HEPATOLOGY1992;16:285–292

ISSN:0270-9139    

DOI:10.1002/hep.1840160202

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractTo investigate the relationship between genotypes of hepatitis C virus and response to interferon‐α therapy, hepatitis C virus RNA was assayed by polymerase chain reaction with three sets of primers and probes in 70 patients with non‐A, non‐B chronic hepatitis who received interferon‐α. Twenty‐four patients sustained long‐term remissions (complete responders). Polymerase chain reaction for 5′‐terminal noncoding region detected hepatitis C virus RNA in 94.3% (66 of 70) of the patients. Polymerase chain reaction for nonstructural region 3, in which primers and a probe were synthesized to be identical to hepatitis C virus‐J, detected hepatitis C virus RNA in 40 patients. Polymerase chain reaction for nonstructural region 5–in which sequences of primers and a probe were derived from hepatitis C virus‐K2, a genotype different from hepatitis C virus‐J–detected hepatitis C virus RNA in 17 patients. Only one patient was positive on both nonstructural region 3 and nonstructural region 5 polymerase chain reaction. Nucleotide sequence of clones obtained from 5′ terminal noncoding region polymerase chain reaction products of two patients positive on polymerase chain reaction for nonstructural region 3 and negative on polymerase chain reaction for nonstructural region 5 (group 1) corresponded to that of the hepatitis C virus‐J group, and those of clones from two patients negative on polymerase chain reaction for nonstructural region 3 and positive on polymerase chain reaction for nonstructural region 5 (group 2) corresponded to that of hepatitis C virus‐K2. A clone from a patient negative on polymerase chain reaction for nonstructural region 3 and polymerase chain reaction for nonstructural region 5 (group 3) showed low nucleotide sequence homology with the hepatitis C virus‐J and hepatitis C virus‐K2 groups. The complete response rates of group 2 (10 of 16 [62.5%]) and group 3 (6 of 10 [60.0%]) were significantly higher than that of group 1 (5 of 39 [12.8%]) (p<0.01 for both). Logarithms of hepatitis C virus RNA concentrations (copies per milliliter) were significantly higher in group 1 (5.0 ± 1.1) than in group 2 (3.8 ± 1.1) or group 3 (3.2 ± 1.1) (p<0.01 for either). These results indicate that detection of hepatitis C virus RNA by polymerase chain reactions with different sets of primers and probes may be valuable in classifying hepatitis C virus into genotypes, and that amount of hepatitis C virus RNA in sera and response to interferon‐α may vary among different ge

ISSN:0270-9139    

DOI:10.1002/hep.1840160203

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractSerum samples from 100 patients with non‐A, non‐B hepatitis–related chronic liver disease and 100 patients with hepatitis B–related chronic liver disease were tested by first‐generation and second‐generation enzyme‐linked immunosorbent assays, a second‐generation recombinant immunoblot assay and the nested polymerase chain reaction. In non‐A, non‐B hepatitis–related chronic liver disease, second‐generation enzyme‐linked immunosorbent assay (anti‐c22 and/or c200) and second‐generation recombinant immunoblot assay showed 98% positivity, whereas first‐generation enzyme‐linked immunosorbent assay (anti‐c100‐3) showed 89% positivity. The two second‐generation recombinant immunoblot assay–negative samples were positive by nested polymerase chain reaction, but one second‐generation recombinant immunoblot assay–positive sample was polymerase chain reaction negative. However, when this second‐generation recombinant immunoblot assay–positive sample was tested by polymerase chain reaction using another set of primers, it was polymerase chain reaction positive. Therefore, 100% of the non‐A, non‐B hepatitis–related chronic liver disease serum samples were hepatitis C virus RNA positive by polymerase chain reaction. Nine hepatitis B–related chronic liver disease samples were first‐generation enzyme‐linked immunosorbent assay positive. Of the eight second‐generation enzyme‐linked immunosorbent assay positive hepatitis B–related chronic liver disease samples, six were first‐generation enzyme‐linked immunosorbent assay positive and five were second‐generation recombinant immunoblot assay positive and polymerase chain reaction positive. One indeterminate secon‐generation recombinant immunoblot assay sample was polymerase chain reaction negative. Therefore, second‐generation recombinant immunoblot assay appears to be as useful as polymerase chain reaction for detecting a chronic hepatitis C virus infection, although some discrepancies were noted. Second‐generation enzyme‐linked immunosorbent assay is also a useful method, but false‐positive results were found in

ISSN:0270-9139    

DOI:10.1002/hep.1840160204

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractThe localization of hepatitis C virus–infected hepatocytes in the human liver remains unclear despite the development of a serological assay for the antibody to hepatitis C virus. We studied their localization immunohistochemically with monoclonal antibodies to core, envelope and NS3 antigens of hepatitis C virus. We examined 48 liver biopsy samples from C100‐3 antibody–positive patients with chronic liver disease (chronic persistent hepatitis, 5 cases; chronic active hepatitis, 41 cases; cirrhosis, 2 cases) and 12 liver biopsy samples from C100‐3 antibody–negative patients with chronic liver disease (type B chronic hepatitis, 8 cases; alcoholic liver disease, 4 cases). In the C100‐3 antibody–positive group, positive immunostaining for core antigen, envelope antigen and NS3 antigen was found in 23% (11 of 48), 24% (11 of 45) and 24% (11 of 46), respectively. Negative results were obtained in the C100‐3 antibody–negative group. Hepatocytes with positive staining were scattered in the lobules, and they were found in the same regions irrespective of whether the antibody to core antigen, to envelope antigen or to NS3 antigen was used. Each positive cell was strongly stained in the cytoplasm; these decorations disappeared after absorption of the primary antibody with purified antigen. Mean ALT levels in the patients with positive immunostaining for core, envelope or NS3 antigen (174.8 ± 105.7 U/L) tended to be higher than in those with negative immunostaining (142.0 ± 93.8 U/L). On histological evaluation of liver specimens with a scoring system of the histological activity index, intralobular inflammation and fibrosis had higher scores for samples with positive rather than negative immunostaining (p<0.05). Our findings suggest that inflammation is more severe in liver tissue with hepatitis C virus infection in which more virus is present and that in more advanced chronic liver disease with hepatitis C virus infection, greater amounts of virus are present. (HEPATOL

ISSN:0270-9139    

DOI:10.1002/hep.1840160205

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractThe derangements of levels of sex hormones and gonadotropins in alcoholic cirrhotic men are well delineated. The countersituation in alcoholic cirrhotic women has not yet been fully described. This study was performed in postmenopausal women among whom menstrual cycle variations in hormones no longer occur; with such a study population, it is possible to control for confounding factors and thus optimize detection of differences in levels of hormones and hormone interrelationships. Both estradiol levels and a rough estimate of aromatization of testosterone to estradiol, the estradiol to testosterone ratio, were significantly elevated in the 20 alcoholic subjects with alcohol‐induced cirrhosis, as compared with the 27 normal controls; similarly, testosterone, luteinizing hormone and follicle‐stimulating hormone were all significantly reduced in the alcoholic cirrhotic women. In addition, the normal relationships of estradiol with luteinizing hormone, follicle‐stimulating hormone, body mass and the estradiol/testosterone ratio were detected in the control group but not in the group of cirrhotic women. Further, among the alcoholic cirrhotic postmenopausal women, testosterone, luteinizing hormone, follicle‐stimulating hormone and the estradiol/testosterone ratio were all significantly correlated with the Child's liver disease severity score. That the hormone levels and their interrelationships differ markedly between normal and alcoholic cirrhotic women extends previous findings in both men and postmenopausal women; the correlations of hormone levels and markers of liver disease will require further investigation. (HEPATOLOGY1992;16:3

ISSN:0270-9139    

DOI:10.1002/hep.1840160206

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractThe objective of this study was to investigate cholesterol metabolism in human gallbladder mucosa, especially in relation to hepatic cholesterol metabolism, gallstone disease and treatment with bile acids. Gallbladder mucosa and liver tissue samples were collected in 44 patients undergoing cholecystectomy; 30 had cholesterol gallstones and the rest were stone free. Ten of the gallstone patients were treated with chenodeoxycholic acid and eight received ursodeoxycholic acid, with a daily dose of 15 mg/kg body wt, for 3 wk before surgery.The 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase activity, governing cholesterol synthesis, was considerably lower in the gallbladder mucosa than in liver tissue (28 ± 6 and 120 ± 40 pmol/min/mg protein). The acyl coenzyme A:acyltransferase activity in the gallbladder mucosa catalyzing the esterification of cholesterol was, on the other hand, several times higher than corresponding activity in the liver (92 ± 23 and 11 ± 2 pmol/min/mg protein). In the presence of exogenous cholesterol, the acyl coenzyme A:acyltransferase activity increased about twofold in the gallbladder mucosa.The acyl coenzyme A:acyltransferase activity of the gallbladder mucosa from untreated gallstone patients was not stimulated further by the addition of exogenous cholesterol. Otherwise, there were no significant differences in acyl coenzyme A:acyltransferase and 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase activities in the gallbladder mucosa of gallstone patients compared with gallstone‐free controls.Treatment with chenodeoxycholic and ursodeoxycholic acids did not affect the 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase activity of the gallbladder mucosa but reduced the acyl coenzyme A:acyltransferase activity by 60% to 65%. A positive correlation was obtained between the cholesterol concentration in bile and the acyl coenzyme A:acyltransferase activity in the gallbladder mucosa in the whole series of patients (Spearman's rank‐order correlation coefficient [rS] = 0.42, p<0.05).We conclude that human gallbladder mucosa has a lower 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase activity but acyl coenzyme A:acyltransferase activity several times higher than that in liver tissue. Disturbance of cholesterol metabolism in the gallbladder mucosa, which might contribute to the high cholesterol content of gallbladder bile in patients with cholesterol gallstones, was not fou

ISSN:0270-9139    

DOI:10.1002/hep.1840160207

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractGiant‐cell hepatitis is a frequent pattern of liver injury in the neonate, but it is rare after infancy. Such cases have been attributed to autoimmune disease, to non‐A, non‐B hepatitis and, most recently, to paramyxovirus infection. To better define the entity of postinfantile (syncytial) giant‐cell hepatitis, we reviewed 24 biopsy specimens from 20 patients with this finding, either alone or in combination with other diagnoses. The number of multinucleated giant cells varied greatly from one specimen to another. Varying degrees of portal inflammation appeared in all but one of the patients, and all had hepatitislike acinar inflammation associated with hepatocellular injury. Fibrosis was a common finding, varying from mild periportal fibrosis to established cirrhosis (33%). The changes were interpreted as acute giant‐cell hepatitis in 25%, as CAH in 42% and as active cirrhosis in the remainder.The patients ranged in age from 2 to 80 yr, with a mean of 35 yr and a male/female ratio of approximately 1:1. The signs and symptoms of liver disease were present for more than 1 mo in most patients. A positive antinuclear antibody titer was found in seven of the patients. Three patients had a direct Coombs reaction and anemia. Overall, evidence of autoimmune disease was found in 40% of the patients. One patient had non‐Hodgkin's lymphoma involving the liver. Only one patient had a history of blood transfusion or risk factors for hepatitis C. No patient underwent serological study for paramyxovirus antibodies. Liver tissue from one patient was examined ultrastructurally, but no viral particles could be identified. Follow‐up information was available in 17 of the patients. Four had died (one of causes unrelated to liver disease); one of the surviving patients underwent successful orthotopic liver transplantation. It would appear that postinfantile giant‐cell hepatitis is best regarded as an unusual reaction pattern that can occur in both acute and chronic hepatitis. The most frequently identified underlying cause in our series was autoimmune disease, which may have significant implications for treatment of many of these patients. (HEPATOLOGY1

ISSN:0270-9139    

DOI:10.1002/hep.1840160208

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractCystic dilatation of peribiliary glands of intrahepatic and extrahepatic bile ducts was investigated in autopsied livers with adult polycystic disease (n = 8), in autopsied livers with solitary nonparasitic cysts (n = 18) and in normal autopsied livers (n = 23). In normal livers, cystic dilatation of intrahepatic peribiliary glands was absent or slight, when present. In livers with solitary nonparasitic cysts, cystic dilatation of intrahepatic peribiliary glands was present in varying degrees. In livers with adult polycystic disease, intrahepatic peribiliary glands showed frequent and severe cystic dilatation so marked that it was grossly recognizable. In contrast, peribiliary glands of the extrahepatic bile ducts showed no cystic dilatation in most cases, regardless of the three conditions examined. Liver parenchymal cysts were numerous in livers with adult polycystic disease, few in livers with solitary nonparasitic cysts and nonexistent in normal livers. Von Meyenburg complexes were present in 87.5% of livers with adult polycystic disease, in 16.7% of livers with solitary nonparasitic cysts and in 4.3% of normal livers. These findings suggest that intrahepatic peribiliary glands undergo cystic dilatation in livers with adult polycystic disease‐and, to a lesser degree and frequency in livers with solitary nonparasitic cysts, probably because of congenital or genetic factors‐and that these cystic changes may comprise a part of numerous cysts of adult polycystic disease. (HEPATOLOGY1992;16:334

ISSN:0270-9139    

DOI:10.1002/hep.1840160209

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractTo assess the hemodynamic status of patients with compensated cirrhosis, mean arterial pressure, cardiac index and peripheral vascular resistance and markers of central (plasma concentrations of atrial natriuretic factor) and arterial volemia (plasma norepinephrine concentration, plasma renin activity) were studied in 10 patients and 10 healthy control subjects under steady‐state conditions (after 2 hr of standing) and after assumption of the supine position (30, 60, and 120 min). After standing, neither hemodynamics nor markers of effective volemia differed significantly between controls and patients. By evaluating the areas under the curve during the 2 hr of supine posture, the increase in cardiac output and plasma natriuretic factor and the decrease in peripheral vascular resistance were greater in patients (2.59 ± 0.43 [S.E.M.] L/min/hr; 32.8 ± 7.2 pg/ml/hr − 1,103 ± 248.4 dyn · sec/cm5/hr, respectively) than in controls (0.53 ± 0.24 L/min/hr, p = 0.005; 17.4 ± 4.7 pg/ml/hr, p = 0.005; − 265.5 ± 206.2 dyn · sec/cm5/hr, p = 0.02). The declines in heart rate, plasma norepinephrine concentration and plasma renin activity did not differ significantly. Mean arterial pressure did not significantly change. Our results suggest that during periods of upright posture, cirrhotic patients in the preascitic stage, who are known to have expanded blood volume, compensate for dilatation of the splanchnic vascular bed through total hypervolemia. The latter becomes excessive during recumbency, leading to supernormal increases in venous return, central volemia and cardiac index. The decline in peripheral vascular resistance appears to be a compensatory mechanism to maintain steady arterial blood pressure. Thus increased cardiac index and reduced peripheral vascular resistance in recumbent compensated cirrhotic patients may represent a physiological adaptation rather than a primitive vascular abnormality. (HEPATOLOGY199

ISSN:0270-9139    

DOI:10.1002/hep.1840160210

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractUrinary15N‐ammonia and15N‐urea were measured by gas chromatography‐mass spectrometry after the intravenous administration of15N‐ammonia (0.2 μmol/kg/hr) to 6 volunteers and 11 patients with cirrhosis. Urinary15N‐nitrogen excretion as ammonia and urea was measured during the 210‐min infusion period, and urea synthesis and ammonia conversion to amino acids were analyzed with a three‐compartment model using the nonlinear least‐squares method. The rate of urea synthesis in control subjects was 14.1 ± 1.2 mg/kg/hr (mean ± S.E.M.), and in cirrhotic patients it was 11.0 ± 3.2 mg/kg/hr. The cirrhotic group was divided into those with compensated cirrhosis (Child class A patients) and those with decompensated cirrhosis (Child classes B and C patients), and the rates of urea synthesis for these groups were 14.5 ± 1.5 and 8.9 ± 1.6 mg/kg/hr, respectively. The difference between decompensated cirrhotic patients and control subjects was statistically significant (p<0.001). The percentage of ammonia reutilization of a given dose of15N‐ammonia was 75.9% ± 2.4% in compensated cirrhotic patients and 82.9% ± 3.6% in decompensated cirrhotic patients (p<0.05). Fasting venous ammonia levels correlated inversely with urea synthesis (p<0.001) and correlated positively with ammonia reutilization (p<0.05). These results are consistent with a decreased capacity to synthesize urea and an increased capacity to convert ammonia to amino acids in chronic liver failure. (H

ISSN:0270-9139    

DOI:10.1002/hep.1840160211

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY