摘要:

AbstractThe nucleoside analog 2′,3′‐dideoxyinosine, currently being used to treat patients infected with the human immunodeficiency virus, has been shown to inhibit viral replication in certain cell culture systems of hepatitis B virus and the duck model of chronic hepatitis B infection. We studied the effect of dideoxyinosine on viral replication in patients with chronic hepatitis B. In the initial dose‐finding phase, patients received sequential 2‐wk courses of dideoxyinosine in escalating doses of 3,6 and 9 mg/kg/day. In the second, long‐term treatment phase, patients received dideoxyinosine at a dose of 9 mg/kg/day for 12 wk. Dideoxyinosine was given orally in three divided doses. The effects of dideoxyinosine on hepatitis B were assessed by serial measurements of ALT, hepatitis B virus DNA and DNA polymerase activity in serum. Six patients completed the dose‐finding phase, and five patients continued into the long‐term treatment phase. No significant differences were seen in serum aminotransferases, hepatitis B virus DNA levels or DNA polymerase activity at any time during treatment when compared with pretreatment levels. All patients remained positive for HBeAg during treatment and during 6 mo of follow‐up. Thus at the doses tested, dideoxyinosine had no appreciable effect on viral replication in patients with chronic hepatitis B. (HEPATOLOGY

ISSN:0270-9139    

DOI:10.1002/hep.1840160402

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractIn this study we examined multiple serial liver biopsy specimens from liver transplant recipients to determine the pathological features of hepatitis C virus—induced hepatitis. Hepatitis C virus infections acquired after transplantation and previous infections that recurred in patients after transplantation were confirmed by the results of the polymerase chain reaction. Of 43 patients infected with the hepatitis C virus, 18 had a mild form of chronic hepatitis. Four patients had hepatitis that progressed to focal bridging fibrosis or cirrhosis. There were no significant clinical or pathological differences between infections acquired after transplantation and recurrent infections (as determined by polymerase chain reaction) except that acquired infections more often developed into hepatitis. Findings indicative of hepatitis C infection included portal and parenchymal mononuclear infiltrates of varying degrees, acidophilic necrosis and swollen hepatocytes. Other common findings included lymphoid aggregates, bile duct damage and fatty change. Atypical pathological conditions included extensive hepatocyte swelling or acidophilic necrosis with minimal inflammation mimicking ischemia and ductal or ductular damage and proliferation with mixed portal infiltrates mimicking rejection or obstruction. We conclude that in transplant recipients infection by the hepatitis C virus usually produces a mild disease state, but the diagnosis of hepatitis can be difficult to make because indicators of hepatitis may mimic those of rejection, ischemia, obstruction or other hepatic infections. Serial biopsy specimens with persistent pathology and polymerase chain reaction may be necessary to define the presence of a hepatitis C virus lesion. (HEPATOLOGY 1992;16:865–8

ISSN:0270-9139    

DOI:10.1002/hep.1840160403

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractHepatitis C virus RNA, anti—hepatitis C virus immune response and biochemical markers of liver injury were investigated in 17 patients with acute non‐A, non‐B hepatitis. At the first observation, 1 to 3 wk from the clinical onset, all patients had hepatitis C virus RNA in their serum, and most (15 of 17) were positive for second‐generation anti—hepatitis C virus enzyme immunoassay. Follow‐up serum samples were available for 10 patients. The rate of recombinant immunoblot assay—confirmed anti—hepatitis C virus enzyme immunoassay reactivities increased from 67% in the first 3 wk to 86% after 21 wk. Elevated ALT levels were associated with hepatitis C virus RNA positivity in most of cases, but the viral nucleic acid was also detected in sera with normal or slightly increased enzyme values. None of the single antibodies tested were related to hepatitis C virus RNA positivity or to the clinical phase of the infection. Therefore hepatitis C virus RNA determination might provide important additional information as compared with anti—hepatitis C virus markers, allowing earlier diagnosis, discrimination of active infection and, possibly, prognostic evaluation. (HEPATOLOGY

ISSN:0270-9139    

DOI:10.1002/hep.1840160404

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractTwelve children with chronic non‐A, non‐B hepatitis were entered in a pilot trial of recombinant interferon‐α. Although all the children had hepatitis C virus RNA in serum, only five had antibodies against this virus. Children received 3 MU/m2body surface area interferon‐α 3 times/wk for 6 mo; they were followed for 24 mo, including the therapy period. One child was dropped from the study, so the results are from the 11 children who completed the study. At the end of the therapy period, 36% of the children had normal ALT levels; this percentage increased to 90% at mo 15 of follow‐up. Thereafter, relapse occurred in five children; thus ALT normalization was observed in 5 of 11 children at the 24th month. Moreover, two different ALT patterns were found: HCV antibody—negative children had significant peaks of ALT levels with respect to the basal samples (p<0.05) until the third month of the therapy; these levels later decreased. In contrast, HCV antibody—positive children had slight fluctuations of ALT until normal levels were reached. At the end of treatment, three children had HCV RNA; one demonstrated a rebound in ALT levels. Finally, histological activity had decreased significantly in the second liver biopsy specimen in all children. In summary, interferon treatment in children with chronic hepatitis C may be helpful, although these results should be confirmed in controlled trials. (HEPATOLOGY 1

ISSN:0270-9139    

DOI:10.1002/hep.1840160405

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractFour distinct genotypes of hepatitis C virus types I, II, III and IV have been identified by comparison of nucleotide sequences of isolates from different areas of the world. We examined the possibility that hepatitis C virus may have serologically definable subtypes. Enzyme‐linked immunosorbent assay systems were prepared by use of two synthetic peptides deduced from the putative core protein of hepatitis C virus. The following are the two peptides that were used: (a) IPKARRPEGRTWAQPGY (subtype‐1) conserved in hepatitis C virus isolates with type I and type II genotypes; and (b) IPKDRRSTGKSWGKPGY (subtype‐2) conserved in type III and type IV genotypes. With the enzyme‐linked immunosorbent assays, the subtype‐1 antibodies were detected in 26 (68%) of 38 subjects whose hepatitis C virus RNA had been genotyped as type I or type II, whereas subtype‐2 antibodies were not detected. Inversely, the subtype‐2 antibodies were detected in 10 (56%) of 18 subjects with hepatitis C virus RNA genotypes III or IV, whereas subtype‐1 antibodies were detected in none of them. These results suggest that hepatitis C virus has two serologically distinguishable core antigen subtypes, corresponding to either genotype I/II or genotype III/IV. Subtyping of HCV by serological methods would contribute to tracking transmission routes of the virus, especially in cases where serum samples were not stored under conditions to preserve RNA or in infected hosts who have cleared the virus and therefore have only antibodies remaining to identify the infection. (HEPATOLOGY 1

ISSN:0270-9139    

DOI:10.1002/hep.1840160406

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractAn autoantibody to liver cytosol was previously described in childhood autoimmune chronic active hepatitis type 2. The antigen, liver cytosol antigen type 1, was for the first time partially purified using gel filtration and ion exchange chromatography, and it was characterized using immunodiffusion, immunoblot and sodium dodecyl sulfate—polyacrylamide gel electrophoresis analysis of the immunoprecipitate. Immunoblot detected a unique antigenic peptide at 62 kD from human cytosol and at 58 kD from rat cytosol. The same peptides were also detected when immuno‐precipitates of liver cytosol antigen type 1 and autoantibodies to liver cytosol antigen were submitted to sodium dodecyl sulfate—polyacrylamide gel electrophoresis. A polymeric structure, probably a tetramer, is suggested for native liver cytosol antigen type 1 because in gel filtration chromatography liver cytosol antigen type 1 was eluted as a protein of a molecular weight between 240 and 290 kD when human liver cytosol was fractionated and between 220 and 270 kD from rat liver cytosol. Liver cytosol antigen type 1 is probably poor in carbohydrates because it was not stained by periodic acid—Schiff stain. The autoantibodies to liver cytosol were frequently found in association with antiliver kidney microsomal autoantibodies type 1, which are directed against the cytochrome P‐450 of the IID6 subfamily. Antiliver kidney microsomal autoantibodies type 1 but not antiliver cytosol autoantibodies were found in association with antibodies to hepatitis C virus. Autoantibodies to liver cytosol antigen type 1 seem to be a more specific marker for autoimmune hepatitis type 2 than antiliver kidney microsomal antibodies type 1 autoantibodies. (HEPATOLOGY 1992;16

ISSN:0270-9139    

DOI:10.1002/hep.1840160407

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractThe 2‐oxo‐acid dehydrogenase family of enzymes have been identified as the major mitochondrial autoantigens of primary biliary cirrhosis. Using immunoblotting, enzyme‐linked immunosorbent assay and enzyme inhibition with both purified mitochondrial proteins and recombinant autoantigens, we have studied family members and spouses of patients with primary biliary cirrhosis for the presence of antimitochondrial antibodies. Antimitochondrial antibodies and other common autoantigens were also tested for by indirect immunofluorescence. This study included 27 index patients with primary biliary cirrhosis, 15 spouses and 48 first‐ and second‐degree relatives. Overall, 7 relatives (11%) were positive for autoantibodies to nuclear and cytoplasmic antigens by indirect immunofluorescence against mouse liver and stomach sections. However, with immunofluorescence, the reactivity strictly paralleled that of antimitochondrial antibodies in only one of these (1:640)—a sibling with mild pruritus and a liver biopsy specimen diagnostic of primary biliary cirrhosis despite normal levels of serum alkaline phosphatase. In addition, one of the mothers, who had a history of sarcoidosis, was positive by immunoblotting for antibodies to the E2 subunit of the pyruvate dehydrogenase complex and protein X. All other relatives were negative for all of the assays. Antibodies to neither the 2‐oxo‐acid dehydrogenase enzymes nor the recently proposed family of naturally occurring mitochondrial antibodies were found in spouses or healthy relatives. Three other first‐degree relatives suffered from liver disease: two died (one from primary biliary cirrhosis and the other from an unknown type of liver disease) and one (a sibling with primary biliary cirrhosis) was unavailable for testing. Our results are consistent with a familial predisposition to primary biliary cirrhosis. These data do not support a deficiency of naturally occurring mitochondrial antibodies as an explanation for an inherited basis of the disease because none of our samples, patients or relatives, were positive for these putative autoantibodies. Among blood relatives, antimitochondrial antibodies were not detected in the absence of proved or suspected primary biliary cirrhosis. Within primary biliary cirrhosis kindreds, the presence of antimitochondrial antibodies should arouse suspicion of primary biliary cirrhosis even without overt clinical or biochemical disease markers. (HEPATOLOGY

ISSN:0270-9139    

DOI:10.1002/hep.1840160408

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractOf 270 consecutive patients with hepatocellular carcinoma who underwent surgery, 50 who had recurrence and were subsequently treated with transcatheter arterial embolization were analyzed. The longest interval between surgery and recurrence in the 50 patients who underwent transcatheter arterial embolization was 7 yr. Recurrence was initially found in the remnant liver in all patients but one; extrahepatic metastases were detected in 13 patients (26%) during follow‐up. A “multiple” type was the most common (64%) hepatic recurrence pattern on angiography, followed by the “solitary” (16%) and “tumor thrombus” (12%) patterns. Hepatic recurrence was most frequently found in the ipsilateral lobe (48%) relative to the site of the primary hepatocellular carcinoma. Multivariate analysis of the factors affecting survival after transcatheter arterial embolization indicated that recurrence pattern (p = 0.025) and distant metastases (p = 0.011) were significant. Of 13 patients with distant metastases, 11 had the “multiple” pattern of hepatic recurrence. Survival rates for all 50 patients after initial surgery and after transcatheter arterial embolization were 90% and 64%, respectively, at 1 yr; 52% and 24%, respectively, at 3 yr; and 27% and 5%, respectively, at 5 yr. On analysis of survival rates after transcatheter arterial embolization in 37 patients with recurrence only in the liver and of the response of recurrent hepatocellular carcinoma to transcatheter arterial embolization, a significant difference was noted between those with “partial response” and “progressive disease” (p<0.05) and between those with “no change” and “progressive disease” (p<0.

ISSN:0270-9139    

DOI:10.1002/hep.1840160409

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractWe conducted a prospective, multicenter, randomized trial to compare the efficacy of sclerotherapy plus propranolol with that of propranolol alone in the prevention of recurrent gastroesophageal bleeding in severely cirrhotic patients. For 2 yr (1987 to 1988) 131 patients (96% of whom were alcoholic) with Child‐Pugh class B or C cirrhosis (56% were class B and 44% were class C) were randomly assigned to one of our two treatment groups after cessation of variceal bleeding, without hemostatic sclerosis, and were observed for at least 2 yr. Treatment observance was good in 89% of cases; alcohol withdrawal was observed in 62% of cases. Sclerotherapy was performed weekly with 1% polidocanol, and variceal obliteration was obtained in 83% of cases, in a mean number of four sessions. The cumulative percentages (expressed as mean ± S.D.) of recurrent bleeding at 2 yr were 42% ± 6% for propranolol plus sclerotherapy and 59% ± 6% for propranolol alone (a nonsignificant difference). Twentyeight patients from the propranolol group but only 12 patients from the propranolol‐plus‐sclerotherapy group had recurrent bleeding from esophageal variceal rupture (p<0.01). The total number of blood units per patient with recurrent bleeding was slightly but not significantly more important in the propranolol group (8 ± 7) than in the propranolol‐plus‐sclerotherapy group (5 ± 5; p = 0.09). There were no statistical differences in the cumulative survival rate at 2 yr (propranolol plus sclerotherapy, 74% ± 6% and propranolol alone, 64% ± 6%) or in the number of patients who died of repeat bleeding (propranolol plus sclerotherapy, 13% ± 4% and propranolol alone, 17% ± 5%). Among the surviving patients, cirrhosis improved during the follow‐up; Child‐Pugh classification was the following at 1 mo: 35% for class A, 50% for class B and 15% for class C and the following at 2 yr: 58% for class A, 38% for class B and 4% for class C. In conclusion, elective sclerotherapy does not significantly decrease the rate of recurrent bleeding or death in severely cirrhotic patients who are treated with propranolol and who mainly abstain from drinking alcohol. (HEPAT

ISSN:0270-9139    

DOI:10.1002/hep.1840160410

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY

摘要:

AbstractPatients with liver disease have a variety of coagulation abnormalities. These derangements are of uncertain origin and do not always correlate with disease severity or activity. We have measured the levels and proportions of the total fibrin‐related and fibrinogenrelated antigens, the principal fibrin (D‐dimer) and fibrinogen (D‐monomer) degradation fragments and intermediates of fibrin formation (fibrin monomers) in patients with a variety of acute and chronic liver diseases in whom all known other precipitating causes of disseminated intravascular coagulation had been excluded. Fibrin‐related and fibrinogen‐related antigens were extracted from serum using antihuman fibrinogen‐IgG covalently bound to activated aminophenylthioether paper disks and were subjected to 4% to 11% sodium dodecyl sulfate—polyacrylamide gel electrophoresis under nonreducing conditions. Fibrinrelated and fibrinogen‐related antigen proportions were determined by densitometry, and their levels were measured by radioimmunoassay. Levels of total fibrin‐related and fibrinogen‐related antigens (and D‐dimer) were significantly elevated (p<0.01) in patients with cirrhosis (121 to 641 ng/ml) and hepatocellular carcinoma (416 to 8,786 ng/ml) when compared with patients with acute viral hepatitis (84 to 322 ng/ml) and control subjects (38 to 186 ng/ml). In addition, D‐monomer levels were elevated. These findings strongly suggest that disseminated intravascular coagulation is a component of the coagulopathy of certain liver diseases. Because fibrin‐related and fibrinogen‐related antigens have anticoagulant, vasoactive and immunosuppressive properties, their elevated presence may be biologically significant in these patients. (

ISSN:0270-9139    

DOI:10.1002/hep.1840160411

出版商:W.B. Saunders    

年代:1992

数据来源: WILEY