摘要:

AbstractThe ideal mathematical model for predicting survival for individual patients with primary biliary cirrhosis should be based on a small number of inexpensive, noninvasive measurements that are universally available. Such a model would be useful in medical management by aiding in the selection of patients for and timing of orthotopic liver transplantation. This paper describes the development, testing and use of a mathematical model for predicting survival. The Cox regression method and comprehensive data from 312 Mayo Clinic patients with primary biliary cirrhosis were used to derive a model based on patient's age, total serum bilirubin and serum albumin concentrations, prothrombin time and severity of edema. When cross‐validated on an independent set of 106 Mayo Clinic primary biliary cirrhosis patients, the model predicted survival accurately. Our model was found to be comparable in quality to two other primary biliary cirrhosis survival models reported in the literature and to have the advantage of not requiring liver biops

ISSN:0270-9139    

DOI:10.1002/hep.1840100102

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractThe role of hormones in the regulation of bile secretion is not known; however vasoactive agents, which act via the phosphoinositide signal transduction pathway, may mediate changes in bile flow by altering the hepatic microvasculature. We therefore examined the effects of phorbol esters and diacylglycerol, agonists of the protein kinase C branch of the phosphoinositide cascade, on perfusion pressure and bile flow in a single‐pass, hemoglobin‐free, isolated perfused rat liver system with constant perfusate flow.The active phorbol ester, 12,13‐phorbol dibutyrate, produced a dose‐dependent (maximal effect at 10−6M), sustained and reversible decrease in bile flow from 1.09 ± 0.18 to 0.61 ± 0.09 μl per min per gm liver (37.2 ± 5.9%) while simultaneously increasing perfusion pressure from 12.3 ± 0.7 to 21.5 ± 2.5 cm H2O (74.0 ± 4.3%). Both effects were inhibited by the synthetic protein kinase C antagonist H‐7. 1,2‐Dioctanoyl‐sn‐glycerol, a diacylglycerol, produced changes in bile flow and perfusion pressure that were similar to, but more marked than, those caused by 12,13‐phorbol dibutyrate, whereas the inactive phorbol ester 4α‐phorbol didecanoate and the vehicle dimethyl sulfoxide had no effects on either parameter. 12,13‐Phorbol dibutyrate infusion resulted in reversible decreases in oxygen consumption (23.3%) and a reversible vascular redistribution of trypan blue dye but did not alter hepatic venous effluent concentrations of K+. Increases in perfusion pressure produced by mechanical constrictions of the hepatic venous cannulae did not reproduce phorbol‐induced changes in bile flow, suggesting that the cholestasis is not mediated by postsinusoidal increases in hepatic outflow resistance. Furthermore, the nonspecific vasodilators sodium nitroprusside (10−3M) and papaverine (40 μM) prevented the phorbol‐induced increases in perfusion pressure (p<0.01) but did not block 12,13‐phorbol dibutyrate's cholestatic effects.We conclude from this study that protein kinase C agonists have both vascular and nonvascular effects in the isolated perfused rat liver and that the cholestasis caused by these agents is independent of

ISSN:0270-9139    

DOI:10.1002/hep.1840100103

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractThe rate‐limiting step in the overall plasma‐to‐bile transport of a saturating load of bilirubin is still a matter of controversy. We reassessed the apparent maximal biliary bilirubin excretion following i.v. infusion of unconjugated bilirubin and—for the first time—of highly purified bilirubin diglucuronide in the rat. The bilirubin diglucuronide preparation could be kept in a stable form at −20°C for at least 2 months after addition of 3 mMsodium ascorbate. The biliary bilirubin excretion rates in animals with and without bile depletion in order to induce different flow rates were comparable after infusion of unconjugated bilirubin and of bilirubin diglucuronide. No significant hydrolysis of bilirubin diglucuronide seemed to occur during the hepatic transport of the pigment. Injection of bilirubin diglucuronide into rats which were already being infused with saturating doses of unconjugated bilirubin did not result in increased biliary bilirubin excretion. In contrast, a reversible inhibition of bilirubin output and bile aciddependent bile flow was observed. If unconjugated and diglucuronidated bilirubin follow the same intracellular routes, the present results would suggest that conjugation did not restrict maximal biliary excretion. However, if exogenously administered diglucuronide utilizes a separate pathway, as was recently proposed, the biliary secretion of this exogenous conjugate might be restricted, presumably due to a toxic effect of the high local concentration of diglucuronide. The pathways utilized by the unconjugated pigment, on the other hand, could be primarily determined by the conjugat

ISSN:0270-9139    

DOI:10.1002/hep.1840100104

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractPaucity of interlobular bile ducts is a common feature of cholestatic liver disease in premature infants. Whereas a bile duct to portal space ratio of 0.9 to 1.8 is cited by Alagille as the norm for children, there are no data regarding the normal bile duct to portal space ratio in preterm infants. In this study, by examining liver tissue obtained from autopsied fetuses and infants, we have determined that the bile duct to portal space ratio increases as a function of postconceptional age. After 38 weeks postconception, a ratio equal to or greater than 0.9 was seen in eight of nine subjects. Therefore, in evaluating premature infants for duct paucity, liver biopsies should be obtained only after 38 weeks. Prior to 38 weeks postconception, a bile duct to portal space ratio less than 0.9 may be physiologic.

ISSN:0270-9139    

DOI:10.1002/hep.1840100105

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractRecombinant human α‐interferon is now under intensive investigation as therapy for chronic Type B hepatitis. Recent reports have suggested that prolonged α‐interferon therapy may induce autoimmune reactions. We have evaluated the problem of autoimmunity related to α‐interferon therapy by testing for 15 different antibodies in the sera of 31 patients treated with α‐interferon. No patient had autoantibodies before treatment; 27 (87%) of 31 patients developed at least one autoantibody. Eleven patients had antinuclear antibodies and 21 had smooth muscle antibodies, both of which usually developed during α‐interferon therapy. In contrast, antibodies to endocrine organs such as thyroid microsomal, thyroglobulin and parietal cell antibodies arose in 12 patients, but usually several months after α‐interferon treatment. The appearance of these autoantibodies did not correlate with disease activity or response to α‐interferon. No patient developed autoantibodies specifically associated with autoimmune liver diseases such as liver kidney microsomal antibodies, autoantibodies to soluble liver antigen and the primary billiary cirrhosis‐specific subtypes of antimitochondrial antibodies.These results suggest that prolonged α‐interferon therapy can induce autoantibody production and, in susceptible patients, may lea

ISSN:0270-9139    

DOI:10.1002/hep.1840100106

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractTwo years or more after 35 patients (29 men and six women) with chronic hepatitis B were treated by interferon, we studied relationships of age, ALT activity, activity of serum DNA polymerase associated with the hepatitis B virus, serum levels of hepatitis B e antigen and activity of 2′, 5′‐oligoadenylate synthetase in peripheral blood mononuclear cells when treatment started in comparison with treatment results. Seventeen patients were given human lymphoblastoid interferon‐α; the other 18 patients were given interferon‐β. We measured the activity of 2′, 5′‐oligoadenylate synthetase in these mononuclear cells and found the rate of increase invivoandin vitro; the correlation between the two was r = 0.68. This enzyme activity in the patients who became negative for DNA polymerase after interferon treatment increased more bothin vivoandin vitrothan in patients who did not became negative. Also, both thein vivoandin vitroactivity increased more in patients who became negative for the e antigen after interferon therapy than in those who remained positive. In the first group, interferon was considered to be effective; in the second, ineffective. Of the patients who became negative, some developed e antibodies and some did not; the increase in this enzyme activity in the two groups was not significantly different. The increase in the activity of 2′, 5′‐oligoadenylate synthetase activity could be used to predict the results of interferon treatment and is an index that can be used before treatment

ISSN:0270-9139    

DOI:10.1002/hep.1840100107

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractOne hundred forty‐four serum samples from 52 patients with chronic hepatitis D virus infection were analyzed for hepatitis D virus RNA by dot‐blot hybridization using hepatitis D virus cDNA probe labeled with32p. The results were correlated with the presence of serum IgM anti‐hepatitis D virus and hepatitis D antigen in liver biopsy specimens when available. Although there was a trend of positive correlation between serum hepatitis D virus RNA and IgM anti‐hepatitis D virus, no statistical significance could be found. In the serum samples with hepatitis D virus RNA, 32% were found to be negative for IgM anti‐hepatitis D virus. Therefore, in chronic hepatitis D virus, absence of IgM anti‐hepatitis D virus does not rule out active viral infection, as suggested by previous studies. There was a strong correlation between serum hepatitis D virus RNA and hepatic hepatitis D virus antigen. These data indicate that detection of hepatitis D virus RNA in serum samples is a reliable noninvasive marker of active vira

ISSN:0270-9139    

DOI:10.1002/hep.1840100108

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractIn a randomized, dose‐response study among 305 health care workers, we examined whether the immunogenicity of a heat‐inactivated hepatitis B vaccine could be enhanced when HBsAg was complexed by anti‐HBs contained in hepatitis B immunoglobulin either at equivalent proportions or at 10‐fold antigen excess. The dose of HBsAg in the control vaccine as well as in the two complexed vaccine preparations could be reduced from the standard value (3 μg) to 0.6 μg per injection without affecting the antibody response in the vaccinees. Still lower dosages of HBsAg in the three vaccine preparations induced significantly lower but comparable anti‐HBs responses. These results indicate that, in man, using a heat‐inactivated plasma vaccine, addition of anti‐HBs contained in hepatitis B immunoglobulin does not potentiate the immunoge

ISSN:0270-9139    

DOI:10.1002/hep.1840100109

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractTo determine the frequency, predisposing factors and consequences of extrahepatic malignancy following long‐term immunosuppressive therapy of severe HBsAg‐negative chronic active hepatitis, 149 patients who had received prednisone (20 mg daily) or prednisone (10 mg daily) in combination with azathioprine (50 mg daily) for at least 6 months were evaluated systematically for 109 ± 5 months (range: 7 to 223 months). Seven neoplasms involving cervix (2), lymphatic tissue (1), breast (1), bladder (1), soft tissue (1) and unknown site (1) developed in seven patients after 116 ± 23 months (range: 18 to 164 months). The incidence of extrahepatic neoplasm was 1 per 194 patient–years of surveillance, and the probability of tumor occurrence was 3% after 10 years. Tumor frequency was similar in men and women and the risk was 1.4‐fold greater than that in an age‐and sex‐matched normal population (95% confidence interval, 0.6‐ to 2.9‐fold normal). Patients with extrahepatic malignancy were not distinguished by age, sex, treatment regimen, cumulative duration of treatment (42 ± 9 vs. 60 ± 4 months, p = 0.7) or individual features of the liver disease. Five of the seven patients survived during 48 ± 25 months of follow‐up, including two patients who have lived for at least 5 years after the diagnosis of malignancy. We conclude that extrahepatic malignancy develops infrequently during long‐term immunosuppressive therapy. Its occurrence is not related to the type or duration of treatment, and long‐term survival after tumor detection is possible. The low but probably increased risk of extrahepatic neoplasm does not militate against the use of immunosuppressive

ISSN:0270-9139    

DOI:10.1002/hep.1840100110

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY

摘要:

AbstractInteraction between woodchuck hepatitis virus surface antigen and proteins of hepatocyte plasma membranes were examined in the course of woodchuck hepatitis virus infection. Membranes purified from animals with histologically confirmed acute hepatitis, active or persistent chronic hepatitis and the virus‐related hepatocellular carcinoma were evaluated for the virus surface antigen contents, treated with agents eluting plasma membrane‐bound antigen to test the extent of the antigen‐membrane associations and incubated with purified, particulate woodchuck hepatitis virus surface antigen to determine membrane potential for the antigen adsorption.Hepatocyte plasma membranes originating from woodchucks chronically infected with the virus showed the highest quantities of the incorporated virus surface antigen among membranes studied, the behavior of bound antigen as an integral and a peripheral membrane protein and the resistance to bind an exogenous antigen. Similar properties were expressed by plasma membranes prepared from hepatocytes of nontumor parenchyma displaying chronic active hepatitis of a woodchuck hepatitis virus carrier with hepatoma. Furthermore, plasma membranes originating from animals with active or persistent chronic hepatitis demonstrated identical properties, implicating that histologic activity of the chronic liver inflammatory process is not dependent on the quantity of the virus surface antigen insertion into the membrane. In contrast, hepatocyte plasma membranes from animals with acute hepatitis showed significantly lower antigen quantities, presence of the antigen specificity exclusively behaving as an integral membrane protein and noticeable ability to bind an exogenous surface antigen of the virus. Comparable, but not identical, features were observed for hepatocyte membranes purified from nodules of hepatocellular carcinoma, suggesting that neoplastic transformation of infected hepatocytes is associated with loss of the membrane‐bound antigen and with simultaneous, partial recovery of the membrane potential for the antigen binding.Comparative analysis of the properties on the woodchuck hepatitis virus surface antigen incorporation into hepatocyte plasma membranes in studied cases indicated that sustained infection with woodchuck hepatitis virus leads to an increase in the quantity of the membrane‐incorporated antigen and to the appearance of the virus surface antigen specificity behaving as a peripheral membrane protein. In conclusion, this study demonstrated that the extent and the character of the antigen interaction with hepatocyte plasma membranes undergoes significant variations in the natural course of hepadna viral infection in woodchucks and that histologically distinct forms of the virus‐induced liver disease express specific properties on the

ISSN:0270-9139    

DOI:10.1002/hep.1840100111

出版商:W.B. Saunders    

年代:1989

数据来源: WILEY