摘要:

AbstractFifty‐nine patients with prior hepatitis B virus infection underwent orthotopic liver transplantation. During the first 2 mo, mortality was not significantly different in the hepatitis B virus–infected group (25.5%) vs. a hepatitis B virus–immune control group (21%). Beyond 2 mo, the mortality, rate of graft loss, need for retransplantation and incidence of abnormal liver function were significantly higher in the hepatitis B virus–infected group. Treatment of the hepatitis B virus infection was attempted with passive immunization, combined active and passive immunization, α‐interferon or nothing. The clinical outcome was not significantly influenced by any of these therapies. However, of the patients who lived more than 60 days, 6 of 22 treated with active plus passive immunization were cleared of HBsAg, something achieved once in 16 patients treated with α‐interferon, never in 3 patients with passive immunization only and once in 4 patients with no therapy. In patients with recurrent hepatitis B virus infection, the pace of hepatitis development in the graft appeared to be accelerated, and this was particularly striking in patients who underwent multiple retransplantations at progressively shorter intervals. None of the patients who became HBsAg‐negative had HBeAg preoperatively. (HEPATOLOGY1

ISSN:0270-9139    

DOI:10.1002/hep.1840130402

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractTo investigate the incidence, determinants and significance of delayed clearance of serum HBsAg in chronic hepatitis B virus infection, a prospective follow‐up study was conducted in two consecutive groups of patients. Group I consisted of 984 patients (859 men and 125 women) with biopsy‐proven chronic type B hepatitis, whereas group II consisted of 1,598 asymptomatic chronic carriers (998 men and 600 women) with normal serum aminotransferase activity. During a mean follow‐up period of 4.0 ± 2.3 yr, 19 patients (1.9%) of group I cleared HBsAg from their serum, whereas 35 patients (2.2%) in group II did so in a mean follow‐up period of 2.7 ± 1.4 yr. The annual incidence of delayed serum HBsAg clearance was 0.5% in group I and 0.8% in group II (p<0.02). The cumulative probability of HBsAg clearance was also higher in group II than in group I (p<0.007). Antibodies to HBsAg developed in 9 patients (47.4%) with chronic hepatitis and in 11 (31.4%) asymptomatic carriers who cleared serum HBsAg. Those who were HBeAg negative and those older than 40 at entry and those who exhibited cirrhosis during follow‐up had a higher incidence of delayed HBsAg clearance. Gender, initial histological changes and hepatitis delta virus infection did not influence the occurrence of HBsAg clearance. Serum HBV DNA was not detectable by slot‐blot hybridization but was still detectable by polymerase chain reaction in serum specimens collected within 1 yr of HBsAg clearance. Liver biopsy performed later in 10 patients showed no significant hepatitis activity or tissue HBV DNA, HBsAg or HBcAg. The results suggest that the incidence of delayed clearance of HBsAg during chronic HBV infection is low. HBeAg status, age of patients and development of cirrhosis are determinants for HBsAg clearance. (HEPATOLOGY199

ISSN:0270-9139    

DOI:10.1002/hep.1840130403

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractSera from 98 patients with various stages of chronic hepatitis B virus infection were studied to determine the clinical significance of hepatitis B virus DNA in serum detected by the polymerase chain reaction. Patients were divided into three groups according to their HBsAg and HBeAg status. Group I (n = 31) had detectable HBsAg and HBeAg, group II (n = 46) had HBsAg but not HBeAg and group III (n = 21) consisted of patients who were once chronic hepatitis B virus carriers but had lost HBsAg during follow‐up.Group I patients usually had significant liver disease (raised serum aminotransferases), had higher titers of HBsAg and had been infected with hepatitis B virus for a shorter period than patients in the other two groups. All patients in group I had hepatitis B virus DNA detectable by polymerase chain reaction and 94% had sufficient hepatitis B virus DNA present for detection by dot‐blot hybridization. Group II patients had lower mean serum aminotransferase activities and titers of HBsAg than those in group I. Serum hepatitis B virus DNA was detectable by polymerase chain reaction in 78% but in only 30% of group II patients by dot‐blot hybridization. Group II patients who did not have hepatitis B virus DNA detectable by polymerase chain reaction had mean serum aminotransferase levels within the normal range and had a younger mean age than those with hepatitis B virus DNA. Group III patients generally had no evidence of active liver disease. Of five patients in this group seropositive for hepatitis B virus DNA by polymerase chain reaction on initial testing, all eventually became negative for hepatitis B virus DNA on subsequent testing. There was a tendency for those patients in group III with hepatitis B virus DNA detectable by polymerase chain reaction to have elevated serum aminotransferase levels (40% vs. 25%); however, these differences were not statistically significant.Taken together, these data show that the presence of hepatitis B virus DNA in serum as detected by polymerase chain reaction appears to be a good marker of the level of viremia, can be correlated with aminotransferase levels and parallels the presence of HBsAg in serum. (HEPATOLOGY1991;13:632

ISSN:0270-9139    

DOI:10.1002/hep.1840130404

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractThe hepatitis B virus genome encodes a transcriptional transactivator protein designated HBxAg. We have investigated whether this antigen is a target structure for human T‐lymphocytes. Using recombinant HBxAg protein, we found HBxAg‐specific stimulation of peripheral blood mononuclear cells in patients with acute hepatitis B virus infection (6 of 6) and chronic hepatitis B virus infection (6 of 17) but not in healthy individuals. With HBxAg‐specific synthetic polypeptides, several T‐cell epitopes were identified. Most were located in the carboxyterminal half of the HBxAg protein. Five T‐cell clones specific for a T‐cell epitope located at the carboxyterminal region of HBxAg were established and found to belong to the CD2/CD4‐positive, CD8‐negative subtype. These data establish for the first time HBxAg as an antigen in the cellular immune response. (HEPATOLOGY

ISSN:0270-9139    

DOI:10.1002/hep.1840130405

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractInsulin‐like growth factor II is a fetal growth factor structurally and functionally related to insulin and insulin‐like growth factor I. Its mRNA expression is developmentally regulated in human liver, the reexpression of insulin‐like growth factor II fetal transcripts being often observed in primary liver cancer. Insulin‐like growth factor II and α‐fetoprotein mRNAs were studied in 16 human primary liver cancers, most of which were highly differentiated. Hepatitis B virus transcripts were also analyzed in the tumors from hepatitis B virus chronic carriers. α‐Fetoprotein mRNA was detected in only four tumors and in one nontumorous cirrhotic tissue; all these samples also displayed insulin‐like growth factor II fetal transcripts. Furthermore, fetal insulin‐like growth factor II mRNAs were observed in five tumors and six nontumorous cirrhotic areas not expressing α‐fetoprotein mRNA. The presence of hepatitis B virus RNA was only observed in tissues not expressing α‐fetoprotein or fetal insulin‐like growth factor II mRNA. In conclusion, fetal insulin‐like growth factor II transcripts are more frequently observed than α‐fetoprotein mRNA in highly differentiated liver cancers and in surrounding cirrhotic areas. The reexpression of fetal insulin‐like growth factor II transcripts might then be a marker of early steps of liver cell transformat

ISSN:0270-9139    

DOI:10.1002/hep.1840130406

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractThe sex‐specific and age‐specific incidence rates of the major parenchymal liver diseases in a North European population were estimated using a computerized registry of all admissions to somatic hospitals in Denmark.The incidence was calculated by counting all incident cases of these diseases reported to the registry in the 5‐yr period 1981 to 1985 and dividing the number of cases by the number of person‐years at risk in this period.The incidence rates (per million person‐years) were for men and women, respectively: infectious hepatitis, 109 and 71; toxic hepatitis, 19 and 22; chronic hepatitis, 27 and 29; alcoholic cirrhosis, 190 and 85; nonalcoholic nonbiliary cirrhosis, 110 and 82; primary biliary cirrhosis, 4 and 14. The pattern of the age‐specific incidence rates was similar in men and women in infectious hepatitis, alcoholic cirrhosis, nonalcoholic nonbiliary cirrhosis and primary biliary cirrhosis. Toxic and chronic hepatitis had a higher incidence in women than in men only in older age groups. The incidence of idiopathic hemochromatosis, Wilson's disease, secondary biliary cirrhosis, portal vein thrombosis and Budd‐Chiari's syndrome were less than four in both sexes. (HEPATOLOGY199

ISSN:0270-9139    

DOI:10.1002/hep.1840130407

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractRecently the formation of bile acid glucosides has been described as a novel conjugation mechanismin vitroandin vivo. In 10 patients with extrahepatic cholestasis caused by carcinoma of the head of the pancreas we investigated excretion rates and profiles of urinary bile acid glucosides. Urinary bile acid glucosides and, for comparison, bile acid glucuronides were extracted and characterized according to established methods. In controls total urinary bile acid glucoside excretion was 0.22 ± 0.03 μmol/24 hr (mean ± S.E.M.)–in the range of bile acid glucuronide excretion (0.41 ± 0.06 μmol/24 hr; mean ± S.E.M.). A gas chromatography–mass spectrometry–characterized trihydroxy bile acid glucoside of stillunknown hydroxyl positions accounted for 65% of total urinary bile acid glucosides. In extrahepatic cholestasis total urinary bile acid glucoside excretion was 0.52 ± 0.13 μmol/24 hr (mean ± SEM), yet significantly lower than bile acid glucuronide excretion (1.53 ± 0.13 μmol/24 hr; mean ± SEM; p

摘要:

AbstractSerum levels of cholesterol precursors (squalene, Δ8‐cholestenol, desmosterol and lathosterol), plant sterols (campesterol and sitosterol), cholestanol and cholestanol/noncholesterol sterol ratios were related to liver damage and liver transplantation indications in healthy controls (n = 26) and in 31 patients with primary biliary cirrhosis divided into group I (S‐bilirubin<21 μmol/L; n = 14), group II (S‐bilirubin 21 to 108 μmol/L; n = 7) and group III (elected for liver transplantation; S‐bilirubin 109 to 520 μmol/L; n = 10). The mean sérum respective lathosterol levels in controls and in group I were three and two times higher than those in groups II and III, respectively. The plant sterol contents were higher in group II than in groups I and III and the campesterol/sitosterol ratios were lowest in group III. The serum cholestanol levels were high even in group I (i.e., in patients without icterus) and increased progressively to group III, up to 6 and 13 times those in group I and the control group, respectively. The cholestanol/noncholesterol sterol ratios increased progressively from the controls to groups I, II and III. The serum cholestanol levels were positively related to serum bilirubin levels in all primary biliary cirrhosis patients (n = 31, r = 0.906) and to the plant sterol levels in the control group and group I, but significantly negatively in group III. The cholestanol vs. precursor sterol correlations were negative in most cases. In conclusion, our findings suggest that determination of serum cholestanol and lathosterol levels and cholestanol/plant sterol, campesterol/sitosterol and campesterol/lathosterol ratios might aid staging of liver damage in primary biliary cirrhosis. The high serum cholestanol level associated with the low campesterol/sitosterol ratio could be a significant indicator of end‐stage primary biliary cirrhosis and, finally, of the need for liver transplantation. (HEPATOLOGY19

ISSN:0270-9139    

DOI:10.1002/hep.1840130409

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractUnder endotoxin‐free conditions, peripheral blood mononuclear cells and purified monocytes isolated from healthy control subjects and patients with alcoholic cirrhosis disclose elevated tumor necrosis factor α messenger RNA level and produce tumor necrosis factor α in response to stimulation by either soluble polymeric IgA or monomeric IgA bound to the surface of culture dishes but not by soluble monomeric IgA. Polymeric IgA induces tumor necrosis factor α secretion in a dose‐dependent fashion. These results suggest that cross‐linking of Fcα receptors on human monocytes induces the messenger RNA accumulation and the secretion of the cytotoxic and immunoregulatory cytokine tumor necrosis factor α. Furthermore, it is shown that lipopolysaccharide‐induced tumor necrosis factor α secretion by peripheral blood mononuclear cells is synergistically enhanced in the presence of solid phase monomeric IgA but not in the presence of either soluble monomeric or polymeric IgA. Although increased lipopolysaccharide‐induced tumor necrosis factor α secretion is observed at baseline in alcoholic cirrhotic patients, this synergism is also expressed in this group of patients. These observations could be of pathophysiological relevance in alcoholic cirrhosis because monomeric IgA deposits along the liver sinusoids and increased serum levels of polymeric IgA are common even in the early stages of this disease. (HEPATOLOGY

ISSN:0270-9139    

DOI:10.1002/hep.1840130410

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY

摘要:

AbstractThe existence of a marginal lymphocyte population in rat liver sinusoids has already been demonstrated using the sinusoidal lavage method. We used the same technique to study the lymphocyte population in human liver obtainedex vivoafter partial hepatectomy for benign or malignant tumors and compared it with peripheral and portal blood lymphocyte populations. Percentages of lymphocyte surface phenotypes were evaluated by flow cytometry.The lymphocyte population obtained from human liver is mainly made up of CD56+(35%) cells. This percentage is three times greater than that found in peripheral and portal blood. Two‐color flow cytometry analysis showed that within the CD56+liver cell population, at least three distinct subsets could be found: (a) CD3+/CD56+/CD16−; (b) CD3−/CD56+/CD16−; and (c) CD3−/CD56+/CD16+. Although these subsets were also present in peripheral and portal blood, the percentage distribution was completely different because most CD56+cells in peripheral and portal blood belonged to the CD3−/CD56+/CD16+subset.These results show the existence of a heterogeneous natural killer cell population in human livers with tumors. The functional significance of this heterogeneity still needs to be explained. (HEPATOLOGY1991;

ISSN:0270-9139    

DOI:10.1002/hep.1840130411

出版商:W.B. Saunders    

年代:1991

数据来源: WILEY