摘要:

Earlier data from experiments in rats have shown that administration of retinyl esters (vitamin A) strongly influences the effects of CCl4on the liver. The accumulation of collagen was inhibited, but an increase in CCl4‐toxicity with high mortality was observed. The present study was conducted to examine the effects of β‐carotene (provitamin A) on CCl4‐related general and hepatic toxicity in rats. Oral administration of β‐carotene during CCl4‐treatment resulted, biochemically, in a significantly lower increase in the hydroxyproline liver content and, histopathologically, in less severe liver fibrosis as compared with the liver of rats not treated with β‐carotene. The study also showed that β‐carotene administration could prevent the long‐term loss of retinoids from the CCl4‐injured liver. No significant toxic effects of β‐carotene, as previously found with retinyl esters (vitamin A), were observed. This experimental study suggests that β‐carotene has the therapeutic potential to decrease the severity of liver fibro

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1995.tb00098.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Thirteen cases of combined hepatocellular (HCC) and cholangiocellular carcinoma (CCC) were examined. In addition to routine pathology, immunoreactivities for carcinoembryonic antigen, α‐fetoprotein (AFP), cytokeratin (Cam 5.2 and AE1), epithelial membrane antigen (EMA) and tumor‐associated glycoprotein 72 (B72.3) were also examined. The average age of the 13 cases was 64.8 years, which lay between the average ages of pure HCC and CCC cases. They were categorized as separate type (2), collision type (6), and intermingled type (5). AE1 and EMA were the best markers to differentiate the CCC from the HCC area. B72.3 immunoreactivity was detected only in CCC (46%). There were no transitional features between HCC and CCC in two cases of the separate type and two cases of the collision type. However, focal transitional features from HCC to CCC were observed in all cases of the intermingled type and in four of six cases of the collision type. In one case of the intermingled type, many cancer cells contained both bile and mucus simultaneously, and revealed dual immunoreactivities. The conclusions are: 1) the combined type is generated from two sources; one is the intrahepatic double cancer (thoroughly separate type and a part of the collision type) and another is the stem cell origin with diverse phenotypes (intermingled type and a part of the collision tumor); and 2) AE1 was the most helpful marker to differentiate the CCC area from HCC, and other markers, e.g. AFP for HCC and EMA, CEA, and B72.3 for CCC, were also supportive but somewhat limited in the differential diagn

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1995.tb00099.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

There is evidence that an increase in cytosolic Ca++ concentration is a terminal event in the progression to cell death in toxic liver injury. We have compared the hepatoprotective effects ofN‐acetylcysteine (1 g/kg) and the calcium channel blocking agent, diltiazem (24 mg/kg), when given at 30 min, 3 h and 6 h after single intraperitoneal overdoses of acetaminophen (500 mg/kg) in mice. Overall beneficial effects on mortality, liver necrosis score, and plasma alanine aminotransferase (ALT) activity were found in diltiazem‐treated mice 24 h after acetaminophen overdose. However, the most marked effects were obtained when diltiazem was given 6 h after acetaminophen.N‐acetylcysteine was more effective than diltiazem at 30 min and 3 h, although it was less effective at 6 h. Mean plasma concentrations of the mercapturate metabolite (hepatic oxidative metabolism) were not significantly different among animals receiving acetaminophen alone or in combination with diltiazem, which suggests that the hepatoprotective effects of diltiazem are not exerted by inhibition of drug metabolic en

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1995.tb00100.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Sixty patients of both sexes with biopsy‐proven chronic hepatitis C were randomized to receive lymphoblastoid interferon 3 MU or 6 MU three times weekly for 6 months. A follow‐up period of 3 months at the end of the therapy was scheduled. Thirty‐two patients (53.3%) normalized alanine aminotransferase at the end of the therapy. Of these, 17 received 3 MU (56.7%) and 15 (50%) received 6 MU. Eighteen of the 32 patients (56.2%) relapsed in the follow‐up period after treatment. No significant difference in relapse rate was observed between the two groups. The overall percentage of the non‐responder patients was 36.6%. The treatment was discontinued because of non‐compliance and/or side effects in six patients (10%): three in the 3‐MU group and three in the 6‐MU group. An improvement in liver histology was observed in about a quarter of chronic active hepatitis patients whose overall diagnosis changed to chronic persistent hepatitis. Knodell's score system showed a significant improvement (p<0.05) with regard to peripheral necrosis, fibrosis and total score. HCV‐RNA was positive at the beginning in all patients and it became undetectable in almost all responder patients. In some cases there was no correlation between viraemia and biochemical signs of liver disease. Our study shows that 6 MU does not increase the response rate compared to 3 MU. Moreover, the lower dose is able to improve the liver histology and to abolish the HCV viraemia in r

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1995.tb00101.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

We report three cases of severe hepatotoxicity related to benzarone, a benzofuran derivative. Our cases include a 35‐year‐old woman with (sub)fulminant hepatitis, a 67‐year‐old woman with macronodular cirrhosis, and a 68‐year‐old man with severe chronic active hepatitis and cirrhosis, with positivity of anti‐smooth muscle antibodies. Two patients died. We stress the potential of benzarone to cause hepatotoxicity, which usually resembles severe chronic active hepatitis. Our cases constitute the most severe cases of benzarone hepatotoxicity reported so far, and comprise the first cases of (sub)fulminant hepatitis and cirrhosis related

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1995.tb00102.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

We have explored the relationship of serum alpha‐fetoprotein and macroregenerative nodules (MRNs), possible precursor lesions of hepatocellular carcinoma (HCC), and sought to demonstrate alpha‐fetoprotein (AFP) expression in these nodules. One hundred and sixty‐eight sequential adult cirrhotic resected livers were examined and MRNs were identified by standard criteria. Pretransplant serum AFP was available for 158 of these patients (normal<20 ng/ml). One hundred and seventy‐two randomly selected lesions, including ordinary and atypical MRNs, some containing microfoci of HCC, and HCCs were stained for AFP by immunohistochemistry. In the series, 12 cases had grossly apparent HCCs, four associated with high serum alpha‐fetoprotein (p<0.006). Forty‐four cases had MRNs, 32 without grossly apparent HCC. Five of these 32 cases were associated with high serum AFP (not significant). Immuno‐staining for AFP was seen in three specimens of HCC and in a cirrhotic nodule from a patient without HCC, but not in MRNs. 1) Neither the presence of MRNs – whether ordinary, atypical, or containing micro‐foci of HCC – nor that of gross HCC is ruled out by a normal serum AFP. 2) Elevated serum AFP is not associated with the presence of MRNs. 3) MRNs rarely s

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1995.tb00103.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

In these experiments, the role of the spleen in endotoxin‐induced liver injury was evaluated, using rats which underwent splenectomy or splenic vein ligation with antecedent spleno‐systemic shunt. Male Wistar rats were divided into three groups: a sham‐operated group, a splenectomy group, and a splenic vein ligation group. In each animal, 48 h after surgery, 5 mg/kg lipopolysaccharide (LPS) were injected intravenously. Six rats from each group were sacrificed 6 or 12 h after LPS administration. Bronchoalveolar lavage fluid (BALF) and arterial blood were also collected. Splenectomy reduced the liver injury as indicated by the serum lactate dehydrogenase level. A decrease in liver tissue adenosine triphosphate and increase in lipid peroxide were induced by LPS administration and inhibited by splenectomy. Splenectomy also reduced alveolar protein release as indicated by the protein level in BALF. Splenic vein ligation provided similar protective effects on the liver, but did not affect lung injury. From these results, it appears that the spleen plays a significant role in endotoxin‐induced liver injury, and a mediator derived from the spleen is likely associated with development of liver injury. This mediator may be cleared or inactivated by not only splenectomy but also splenic vein l

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1995.tb00104.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Mannan‐binding protein is synthesized by the liver and functions in first‐line host defence by opsonizing mannose‐rich microorganisms due to activation of the classical complement pathway independent of Clq, and by an intrinsic ability to opsonize and mediate phagocytosis. We have investigated whether the increased susceptibility to bacterial infections in patients with cirrhosis could be explained by low plasma concentrations of mannan‐binding protein and impaired complement‐dependent opsonization. We examined 51 patients with compensated alcoholic cirrhosis, 34 who were decompensated and 16 healthy controls. Irrespective of group, we found a significant correlation (p<0.05) between plasma mannan‐binding protein concentration and deposition of the complement opsonin C4 on mannan from baker's yeast. In contrast to what was expected, this kind of opsonization and plasma levels of mannan‐binding protein were significantly increased in the patients with decompensated cirrhosis (p=0.01 and p=0.007, respectively). A significant correlation (0<0.05) was found between mannan‐binding protein and erythrocyte sedimentation rate, fibrinogen and haptoglobin in these patients. Though the correlations were weak (rho=0.49, rho=0.48 and rho=0.40, respectively), the elevated levels of mannan‐binding protein in the patients with decompensated cirrhosis may reflect an acute phase reaction. It is concluded that plasma levels of mannan‐binding protein are increased in patients with decompensated cirrhosis and that complement‐dependent opsonization of mannan does not seem to be compromized in patients wit

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1995.tb00105.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Hepatitis due to hepatitis delta virus (HDV) infection is generally associated with severe histological abnormalities and rapid progression of the disease. To assess the efficacy of recombinant interferon‐a2b in treatment of chronic delta hepatitis, 22 patients were entered into a randomized controlled trial: 11 received interferon‐a2b subcutaneously three times weekly for 12 months (5 MU/m2for 4 months and then 3 MU/ m2for a further 8 months) and 11 were untreated. All patients were followed up for 6 months after the completion of therapy. Nine treated patients completed the trial: one was withdrawn with hyperthyroidism and one committed suicide. Serum ALT levels were normalized or significantly reduced, always within 3 months of initiating treatment, and remained so in 73% of treated patients at the 4th month and in 54.5% at the 12th month, compared with 18% and 18%, respectively, in the untreated group. Moreover, in seven of nine treated patients, interferon was associated with the clearance of serum HDV‐RNA, associated with amelioration of the histological picture, whereas this occurred in only four of 11 untreated patients. On cessation of therapy, all patients but one experienced a biological and/ or virological relapse over the 6‐month follow up. In conclusion, our data confirm that HDV is sensitive to inhibition by interferon‐a2b, although the schedule used did not achieve permanent control of the disease. The adverse effects of interferon require consideration; in particular, care will be needed to avoid serious psychiatric sid

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1995.tb00106.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

A 64‐year‐old Japanese woman with thymoma has been suffering from diarrhea and increased alkaline phosphatase levels without jaundice. Her serum immunoglobulin levels of IgM and IgG were less than half of the normal levels, with an increase in CD8 (suppressor/cytotoxic) T cell percentage and a decrease in CD4 (helper) T cell percentage, resulting in a lower CD4/CD8 ratio of 0.31. These immunological features are in accordance with those of hypogammaglobulinemia complicating thymoma. Cholangiography and a liver biopsy specimen disclosed the presence of primary sclerosing cholangitis (PSC). PSC has been recognized in various immunodeficiency syndromes and this case shows that thymoma complicated by hypogammaglobulinemia is associated with

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1995.tb00107.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY