摘要:

AbstractTo investigate the antibody titer necessary to prevent hepatitis A virus infection, either 15 or 7.5 mg/kg of immune serum globulin was injected into 10 antihepatitis A virus negative volunteers and their serum antihepatitis A virus titers were observed for 28 wk. In addition, antibody titers were observed for 96 wk in a phase 1 clinical trial of a hepatitis A vaccine. The two studies were then compared to assess the immunogenicity of the vaccine and the persistence of the antibody. Serum‐neutralizing antibody titers that were greater than or equal to 4 (considered as positive) persisted for 18 wk and 14 wk after the injection of 15 and 7.5 mg/kg of globulin, respectively. Hepatitis A virus vaccine recipients showed adequate neutralizing antibody titers, with the groups receiving 1, 0.5 and 0.25 μg/dose showing titers of 45.5, 44.7and 44, respectively, at 18 mo after the third inoculation. These findings suggested that effective blood antibody titers were likely to be retained in the 1.0 μg or 0.5 μg/dose groups for at least several years. Moreover, the serum antihepatitis A virus titers demonstrated by a modified radioimmunoassay changed in parallel with the neutralizing antibody titers in the volunteers injected with globulin. (HEPATOLOGY1992;15:983

ISSN:0270-9139    

DOI:10.1002/hep.1840150602

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractOpen fenestrations are a conspicuous feature of sinusoidal endothelial cells and allow free movement of plasma into the space of Disse. In hepatic fibrosis, the number of fenestrations decreases as interstitial collagen increases in the liver, a change that correlates with deposition of extracellular matrix in the space of Disse. In this study, the possibility of a causal relationship between altered fenestral morphology and perisinusoidal matrix has been examined by culturing rat sinusoidal endothelial cells on individual matrix proteins or on a native matrix consisting of human amniotic membrane with interstitial collagen (types I and III) on one side and basement membrane proteins (collagen types IV and V and laminin) on the other. Under culture conditions, individual components of the extracellular matrix failed to maintain fenestrations. A basement‐membranelike gel matrix derived from the Engelbreth‐Holm‐Swarm tumor was similarly ineffective. Fenestral density and porosity (percentage of cell surface occupied by fenestrations) were significantly enhanced, however, when endothelial cells were cultured on the basement‐membrane side of human amnion. These data suggest that support of endothelial fenestrations requires a complex matrix. In particular, physiologically derived basement membrane maintains fenestrations, whereas interstitial collagen matrix does not. The loss of fenestrations associated with hepatic fibrosis may be related in part to an accumulation of interstitial collagens in the space of Disse. (HEPATOLOGY1992;15:9

ISSN:0270-9139    

DOI:10.1002/hep.1840150603

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractWe assessed the correlation between the positivity for serum IgM antibody to hepatitis C virus and the activity of liver disease in patients with chronic hepatitis C virus infection. Serum samples were taken from 10 antibody to hepatitis C virus‐positive asymptomatic patients with normal serum ALT levels, from 14 untreated patients with clinically and histologically proven chronic hepatitis C and from 26 patients with clinically and histologically proven chronic hepatitis C assigned to receive recombinant interferon α‐2a (6 million IU three times a week for 6 mo). Each serum specimen was tested for IgM antibody to hepatitis C virus‐associated C 100‐3 antigen by enzyme‐linked immunosorbent assay. Patients were observed for at least 12 mo.All 10 patients with normal ALT values tested negative for IgM antibody to hepatitis C virus. In contrast, 33 of 40 (82%) patients with chronic hepatitis C had IgM antibody to hepatitis C virus, and a positive correlation was seen between the ALT level and the level of IgM antibody to hepatitis C virus (r = 0.803, p<0.001).During interferon treatment, ALT levels declined into the normal range in 18 of 26 treated patients (69%) and remained normal after stopping treatment in 8 patients (31%). In untreated patients, in treated patients who did not respond to interferon treatment and in responder patients who relapsed, no significant changes in IgM antibody to hepatitis C virus levels were seen during the study period. In contrast, IgM antibody to hepatitis C virus became undetectable by the end of interferon treatment in seven of eight patients with a sustained response.In conclusion, we found a positive correlation between the presence of serum IgM antibody to hepatitis C virus and the activity of the hepatitis C‐induced liver disease. In patients with chronic hepatitis C showing a response to α‐interferon treatment, the disappearance of IgM antibody to hepatitis C virus predicted that the response would be sustained. (HEPATOLOGY19

ISSN:0270-9139    

DOI:10.1002/hep.1840150604

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractPrecore defective HBV mutants may gradually prevail because of immune selection and explain spontaneous seroconversion from HBeAg to anti‐HBe in HBV carriers. We have analyzed whether the presence of precore HBV mutants is a determinant of responsiveness to interferon‐α therapy. Fifteen carriers (nine responders and six nonresponders)who were treated with interferon‐α were examined. Serum samples were collected before and after therapy. After extraction of DNA, the precore region was amplified by the polymerase chain reaction, and the product was identified by gel electrophoresis and ethidium bromide staining and then Southern blotting and molecular hybridization. The amplified products in all patients were asymmetrically amplified by a modified polymerase chain reaction, and the precore region was directly sequenced. All patients were HBV DNA positive initially. Circulating HBeAg‐negative mutants were not identified before treatment in either responders or nonresponders. All nine responders were negative for HBV DNA in serum by dot blot during or after treatment, but seven remained positive by polymerase chain amplification and Southern‐blot hybridization. All of the nonresponders remained positive for HBV DNA by dot blot. A silent mutation involving the substitution of an A for G at position 1888 was found in seven carriers; however, no HBeAg‐negative mutants were detected in the follow‐up of either responders or nonresponders to interferon‐α. These results suggest that HBV DNA is detectable by polymerase chain reaction for a period after clearance of HBsAg. A predominance of HBeAg‐negative HBV virions cannot be considered a pivotal determinant of response to treatment. The role of other mutations in the precore region in determining response to therapy is uncertain. (HEPATOLO

ISSN:0270-9139    

DOI:10.1002/hep.1840150605

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractSera from 103 patients were tested for hepatitis C virus RNA by nested polymerase chain reaction assay. Using primers from the highly conserved 5′untranslated region, we detected hepatitis C virus RNA in 67 (88.2%) of 76 patients positive for antibody to hepatitis C virus by both second‐generation and neutralization enzyme immunoassays. Hepatitis C virus RNA was detected in 93% of patients who had been infected for 10 yr or less and in 89% of those who had been infected for longer than 10 yr. Hepatitis C virus RNA was detected in all patients with chronic hepatitis, active cirrhosis or hepatocellular carcinoma and in 50% of those with nonspecific reactive hepatitis or inactive cirrhosis. Hepatitis C virus RNA was not detected in sera from 22 patients negative for antibody to hepatitis C virus or in 5 patients positive for antibody to hepatitis C virus by second‐generation but not by neutralization enzyme immunoassay. Using primers from the less conserved nonstructural region 4, we detected hepatitis C virus RNA at a lower frequency, in 66% of patients who were positive for antibody to hepatitis C virus by both secondgeneration and neutralization enzyme immunoassays. The detection rate was higher in patients with frequent parenteral exposure.Our study showed that hepatitis C viremia can be detected in most patients with hepatitis C virus infection, including those with long‐standing infection or advanced liver disease. (HEPATOLOGY1992;15:100

ISSN:0270-9139    

DOI:10.1002/hep.1840150606

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractWe reanalyzed the results of a pilot study of recombinant α‐interferon therapy for chronic non‐A, non‐B hepatitis in light of the recent discovery of the hepatitis C virus and the development of diagnostic assays for this agent. Stored serum samples from 10 patients treated between 1984 and 1986 were tested for antibody to hepatitis C virus and hepatitis C virus RNA before, during and after therapy. In addition, the current clinical, serum biochemical and virological statuses of these patients were evaluated to determine the long‐term effects of interferon therapy. All patients had evidence of hepatitis C virus infection, with hepatitis C viral RNA, antibody to hepatitis C virus or both markers detectable in serum. Serum hepatitis C virus RNA was found to disappear in seven of eight patients whose aminotransferase levels became normal with interferon therapy but remained present in two patients who did not respond to therapy. Levels of hepatitis C virus RNA decreased and disappeared when serum aminotransferases fell to normal levels but rose with subsequent elevation of aminotransfrase levels in two patients who had relapses in disease when interferon was stopped. During a follow‐up of 3 to 6 yr, hepatitis C virus RNA remained undetectable in the six patients whose serum aminotransferase levels remained normal after interferon therapy. However, neither initial titers of hepatitis C virus RNA nor disappearance of viral RNA from serum during treatment predicted a sustained response. Thus long‐term beneficial responses to α‐interferon can occur in patients with chronic hepatitis C and are associated with sustained loss of hepatitis C virus RNA from serum. (HEPATOLOGY199

ISSN:0270-9139    

DOI:10.1002/hep.1840150607

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractTwo types of factors can theoretically modulate alcohol metabolism toward increased acetaldehyde production. These factors are the following: (a) individual, genetically determined isoenzymes with distinct catalytic properties, and (b) modifications of enzyme activity induced by alcohol itself or liver damage. To investigate the respective roles of these factors in white individuals, we studied the alcohol dehydrogenase phenotype, together with liver alcohol dehydrogenase and aldehyde dehydrogenase activities, in 161 patients. Patients with alcoholic cirrhosis (n = 31) were compared with three types of controls: patients with nonalcoholic cirrhosis (n = 25) and excessive (n = 62) and moderate drinkers (n = 43) without liver disease. No association between alcohol dehydrogenase—3 phenotype and alcoholic cirrhosis was found. The prevalence of atypical alcohol dehydrogenase in the four groups was less than 1%. Patients with cirrhosis, regardless of its cause, had significantly lower alcohol dehydrogenase activity than the patients without cirrhosis (p<0.05 and p<0.01 vs. excessive and moderate drinkers, respectively). Among the noncirrhotic patients, alcohol dehydrogenase activity was significantly lower in the excessive drinkers than in the moderate drinkers (p<0.001). Aldehyde dehydrogenase activity was not different between cirrhosis‐free excessive and moderate drinkers; in contrast, compared with these two groups, it was significantly lower in the two cirrhosis groups (p<0.01).These results suggest that no phenotypic pattern of alcohol dehydrogenase—3 associated with alcoholic cirrhosis in white patients exists, that liver alcohol dehydrogenase activity falls as a consequence of both alcohol abuse and cirrhosis and that liver aldehyde dehydrogenase activity is unaffected by alcohol abuse and only falls after the onset of cirrhosis. (HEPATOLOGY1992;15:1017

ISSN:0270-9139    

DOI:10.1002/hep.1840150608

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractFifty episodes of bleeding from esophageal or gastric varices in 33 patients with cirrhosis were randomized to treatment with either intravenous terlipressin (2 mg initially and 1 mg every 4 hr for 24 hr together with bolus injection and continuous infusion of placebo) or with somatostatin (250 μg as a bolus and continuous infusion of 250 μg/hr somatostatin for 24 hr and placebo injections). Standard therapy with transfusions, fluid and electrolyte correction and lactulose was administered in both groups.In the terlipressin group, 22 of 25 bleeding episodes (88%) were initially stopped by the vasoactive drugs, and in the somatostatin group 19 of 25 bleeding episodes (76%) were initially stopped by the vasoactive drugs. Two of the three bleeding episodes not arrested by terlipressin and five of the six bleeding episodes not arrested by somatostatin were controlled by balloon tamponade. In one patient in each group variceal bleeding initially could not be stopped, and the patients died. The failure rate of the vasoactive treatment alone, including rebleeding episodes within the study period, was 20% in the terlipressin group and 32% in the somatostatin group. The control rate, including balloon tamponade, was 96% in both groups. The hospital mortality rate was 16% (4 of 25) in the terlipressin group and 24% (6 of 25) in the somatostatin group. Blood transfusions, use of balloon tamponade and duration of bleeding did not differ significantly.This interim analysis of the ongoing study indicates that a large proportion of bleeding episodes from esophageal and fundic varices can be stopped initially (82%) and definitively controlled (74%) by vasoactive drugs alone. Differences in the effectiveness of terlipressin and somatostatin were not observed. (HEPATOLOGY1992;15:1023‐10

ISSN:0270-9139    

DOI:10.1002/hep.1840150609

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractEsophageal staple transection effectively controls acute variceal bleeding, but up to 50% of these patients will have recurrent upper gastrointestinal bleeding. In our experience, most of these bleeding episodes are caused by total or partial circumferential ulceration at the level of the staple transection: staple line erosion. It caused rebleeding in 29 (40%) of our patients. Whereas the pathogenesis of this lesion is unknown, acid reflux is a consequence of transection surgery. Assuming that staple line erosion could be healed by acid suppression therapy, thereby preventing recurrent bleeding, an acid suppression regimen was evaluated prospectively in 24 patients. Only six (25%) healed with daily standard (300 mg) or high‐dose (1,200 mg) ranitidine combined with sucralfate (4 gm). The remaining 18 (75%) healed after omeprazole administration (40 mg/day) for 1 mo. Maintenance ranitidine alone (300 mg/day) was introduced, but 11 (48%) had relapse of erosions. All 11 healed with omeprazole (40 mg/day) for 2 mo, but again on maintenance ranitidine, 10 relapsed. All healed with further omeprazole and healing persisted with long‐term administration (20 mg/day). Fifteen rebleeding episodes occurred in eight patients on maintenance ranitidine. Whereas relapse of staple line erosions did occur in the absence of rebleeding, all rebleeding episodes were associated with the relapse of staple line erosion.Omeprazole is more effective than ranitidine alone and combined with sucralfate in healing staple line erosion. Omeprazole prevents rebleeding, which may enhance the long‐term benefits of staple transection for acute variceal bleeding. (HEPATOLOGY1992;15:1031

ISSN:0270-9139    

DOI:10.1002/hep.1840150610

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractTransjugular liver biopsy is widely used in adult patients with liver disease when transthoracic needle liver biopsy is contraindicated by severe coagulopathy or ascites. It has not been used extensively in children. We report our experience with 30 consecutive transjugular liver biopsy procedures performed in 27 young patients at the Hospital for Sick Children in Toronto. Patient weights ranged from 14 to 91 kg (median = 42 kg); most patients had not yet attained adult size. A 9F catheter was used except in very small children, for whom we developed a 7F biopsy needle catheter. Most procedures were done with patients under general anesthesia. Specimens were obtained in all patients, and the procedure was tolerated well. A major complication occurred only once: perforation of the inferior vena cava, which was later repaired at liver transplantation. Minor complications included subcapsular extravasation of contrast agent in five patients and a small intrahepatic hematoma in one. Results of transjugular liver biopsy changed the diagnosis in 30% of patients and added valuable information about the disease process in most patients. Transjugular liver biopsy was an important component of emergency assessment for liver transplantation. Our results indicate that transjugular liver biopsy can be performed safely in children with liver disease if a skilled interventional radiologist and a well‐equipped angiography suite are available. Histological studies in these patients enhance our understanding of the natural history of pediatric liver diseases. (HEPATOLOGY1992;15:1036–10

ISSN:0270-9139    

DOI:10.1002/hep.1840150611

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY