摘要:

Abstract:A food‐derived mutagenic heterocyclic aromatic amine, 2‐amino‐3‐methylimidazo[4,5‐f]quinoline (IQ), is a potent hepatocarcinogen in cynomolgus monkeys. In an ongoing carcinogenesis study, 34 out of 40 monkeys dosed with IQ have developed malignant liver tumors. The histology and cytokeratin expression was examined in a total of 94 tumors and non‐neoplastic lesions obtained from 34 cases. The majority of the tumors were classified as hepatocellular carcinoma. In some cases, a striking difference in the histological features between individual tumor nodules was suggestive of a multicentric origin. Intrahepatic vascular invasion was seen in 14 (41.2%) and metastases in 6 (17.6%) of the hepatocellular carcinoma cases. There was no evidence of regenerative hyperplasia or fibrosis in the parenchyma of the tumor‐bearing livers. Clear‐cell foci composed of glycogen‐rich hepatocytes were the only macroscopic lesions detected prior to gross tumor development. Other liver lesions included dysplastic hepatocyte foci and areas of proliferating bile ductular like (oval) cells, located around the periportal areas and along the portal tracts. Expression of bile duct type cytokeratin 7 was observed in a few of the oval cells and non‐malignant hepatocytes, as well as in some of the hepatocellular carcinoma nodules. This aberrant cytokeratin expression raises questions concerning the histogenesis of the IQ‐induced hep

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00708.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Upper gastrointestinal bleeding is a leading cause of death in patients with liver cirrhosis. In most cases haemorrhage originates from oesophageal varices or from congestive gastropathy, and the evaluation of the bleeding risk is based on oesophagogastroduodenoscopic data. The aim of this prospective study was to determine whether the measurement of portal flow velocity by Duplex‐Doppler, compared with endoscopic data, can help in detecting patients with cirrhosis at risk of bleeding. One hundred and seventy‐three patients underwent endoscopy to ascertain the size of the varices and the severity of congestive gastropathy. For each patient maximal portal flow velocity measurements were obtained. No difference in portal flow velocity was observed between patients with or without oesophageal varices or congestive gastropathy. During a 2‐year observation period, 27 patients (15.6%) had at least one episode of acute digestive bleeding. Stepwise multiple logistic regression analysis demonstrated a correlation between oesophageal varices and congestive gastropathy endoscopic grading and the incidence of bleeding; only the former was entered into the final regression equation (p>0.001). No relationship between the max portal flow velocity value and incidence of bleeding was found. This study shows that portal flow velocity is unrelated to the degree of the endoscopic abnormalities in patients with liver cirrhosis and that it has no value in the identification of patients with cirrhosis at risk of upper gastrointestinal ble

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00709.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Dideoxycytidine (ddC) is a nucleoside analogue active against human immunodeficiency virus and within vitroactivity against human hepatitis B virus. We investigated the ability of ddC to inhibit one of the Hepadnaviridae, the woodchuck hepatitis virus and compared the results with the effect obtained by a conjugate of lactosaminated human serum albumin 2′,‐3′‐dideoxycytidine monophosphate (L‐HSA ddCMP). This compound specifically enters the hepatocyte via the asialoglycoprotein receptor. We treated five chronic woodchuck hepatitis virus carriers with intravenous injections of 0.5 mg/kg body weight of ddC for 5 consecutive days, and under the same protocol five woodchucks with 10.4 mg/kg L‐HSA ddCMP, a dose equivalent to 0.25 mg/kg of free ddC. A reduction of serum woodchuck hepatitis virus DNA (5–125 fold) was observed during therapy in three out of five animals receiving ddC and in two of the five animals treated with L‐HSA ddCMP. In responding wood‐chucks, virus DNA levels rebounded immediately after stopping therapy. No signs of toxicity were observed during or after the course of therapy. These preliminary results of short‐term treatment indicate that ddC has anti‐viral activity against woodchuck hepatitis virus. When the dose was reduced by 50%, L‐HSA ddCMP showed anti‐viral activity

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00710.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:During a 4‐year period portal vein thrombosis was diagnosed in 20 Child class A patients with cirrhosis by means of ultrasound and ultrasound‐Doppler study. Seventeen of them showed single or multiple focal liver lesions diagnosed as hepatocellular carcinoma by ultrasound‐guided fine‐needle biopsy and the remaining three a coarse liver echo‐pattern without focal lesions. One patient was found to have developed portal vein thrombosis after the fifth ethanol injection of a single hepatocellular carcinoma lesion 17 mm in diameter. Ultrasound‐guided fine‐needle biopsy of the thrombus was performed on all the patients: portal vein thrombosis was neoplastic in 13 cases and non‐neoplastic in seven cases (five patients with a single lesion; one with two lesions; one with coarse liver echo‐pattern). Among the five patients with a single lesion, one had already been treated by percutaneous ethanol injection therapy. There were no complications related to the biopsy procedures. The diagnosis of non‐neoplastic thrombosis allowed five new patients to be recruited for percutaneous ethanol injection treatment and allowed it to continue in the patient with portal vein thrombosis occurring after the fifth ethanol injection. The routine use of ultrasound‐guided fine‐needle biopsy of portal vein thrombosis yields an accurate diagnosis of the nature of the thrombus and can improve the selection for percutaneous ethanol injection treatment of patients with cirrhosis with hepatocel

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00711.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Point mutation of the p53 tumor suppressor gene appears to be an important event in tumor development and progression, and overexpression of the p53 gene product has been widely studied in a variety of neoplasms. Some point mutations of the p53 gene lead to an increase in half‐life in the gene product, which accumulates in the nucleus and can be detected by immunohistochemical means. We studied overexpression of p53 protein in specimens from 12 patients with adenocarcinoma of the gallbladder, two gallbladders with epithelial dysplasia without carcinoma, eight carcinomas of the common bile duct, 13 hilar cholangiocarcinomas, and six peripheral cholangiocarcinomas. The monoclonal antibody Ab‐2 (Oncogene Science) was used in conjunction with citrate microwave antigen retrieval. Nuclear staining was scored as positive (graded 1 to 3, depending on number of positive nuclei) or negative. Overexpression of p53 protein was present in 7/12 (58%) gallbladder carcinomas, and was seen more often in moderately or poorly differentiated tumors. Intramucosal carcinoma adjacent to invasive carcinoma was positive in three cases, although fewer cells stained than in the carcinoma. Two cases of low‐grade dysplasia not associated with carcinoma were negative. Expression of p53 was not an independent prognostic factor when survival was related to grade and stage of tumor. Three of eight (38%) common bile duct carcinomas and 5/13 (38%) hilar cholangiocarcinomas were positive for p53. Slightly fewer (2/6, 33%) peripheral cholangiocarcinomas were positive. No difference in survival relative to p53 expression was demonst

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00712.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:A retrospective study was carried out in 40 patients with chronic viral hepatitis, to assess whether serum alanine aminotransferase reflects the inflammatory process in the liver. Twenty liver biopsy specimens were included for each disease. Five histological aspects were scored: periportal inflammation, lobular inflammation, ballooning, Councilman bodies and lymphocyte follicles. Logarithmic values of alanine aminotransferase were correlated with each aspect using the Spearman correlation coefficient. For the hepatitis B cohort a statistical significant correlation was found between alanine aminotransferase and periportal inflammation (p=0.0001), lobular inflammation (p=0.0002) and Councilman bodies/area (p=0.003). In the hepatitis C study population alanine aminotransferase correlates with both periportal inflammation (p=0.007) and lymphocyte follicles/Area (p=0.02). In conclusion, these results suggest that alanine aminotransferase can be used as an indicator of inflammatory activity. A prospective study is needed, to further analyze the use of alanine aminotransferase, as a monitor of disease activity in patients with chronic viral hepatitis.

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00713.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Serum samples from 9006 women, who delivered in Switzerland in 1990 and 1991, were collected around the country. Of these women, 62.7% were Swiss and 37.3% originated from foreign countries. Samples were first screened for anti‐HBc and those found positive were further tested for HBsAg, anti‐HBs and anti‐HDV Anti‐HBc was found in 640 of the 9006 women (overall prevalence, 7.1%; Swiss, 3.3%; foreigners, 13.5%). Of these 640 positive samples, 61 (9.5%) were positive for HBsAg (without anti‐HBs), 467 (73.0%) positive for anti‐HBs (without HBsAg) and 8 (1.3%) positive for both HBsAg and anti‐HBs. The remaining 104 were thus anti‐HBc positive without HBsAg or anti‐HBs. These 104 specimens with the so‐called “isolated anti‐HBc” reactivity represented 1.2% of the whole population or 16.3% of the 640 anti‐HBc positive mothers. All were HBV DNA negative (PCR). Anti‐HDV antibody was found in only five women. HBsAg was seen in 38 of the cord‐blood samples from the anti‐HBc positive mothers. In this large sampling, we observed a relatively high seroprevalence of HBV infection. Cases with isolated anti‐HBc reactivity, being HBV DNA negative by PCR, were probably non‐infec

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00714.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Two hundred and twenty‐eight patients who underwent orthotopic liver transplantation for hepatitis B‐related cirrhosis in 11 European Liver Transplant Centers were collected. The male/female ratio was 184/44, with a median age of 41 years (13–66). In 55 patients (24%) hepatocellular carcinoma was associated with liver disease. All cases were stratified for pre‐orthotopic liver transplantation viral characteristics: HBV‐DNA neg/HBeAg neg: 106 patients (47%), HBV‐DNA neg/Delta pos: 80 (35.5%), HBV‐DNA pos/HBeAg pos: 28 (12.5%), other 14 (5%). In 49 patients (21.4%) post‐orthotopic liver transplantation passive prophylaxis with anti‐HBs immunoglobulins was not followed, while in 179 patients the anti‐HBs serum titer was kept above 100–200 mU/ml. Overall 5‐year actuarial survival of the series was 54%. One hundred and eighty‐five patients were evaluable for HBsAg reappearance in the serum at various intervals after orthotopic liver transplantation. Overall 3‐year HBV‐free survival of these patients was 55%. There was a significant difference in 3‐year HBV‐free survival between HBV‐DNA neg (52%), HBV‐DNA pos (13%) and Delta pos (73%) patients (p: 0.03). Sixty‐three percent of patients in the prophylaxis group were HBV‐free, compared to only 25% of untreated patients (p>0.001). Three‐year HBV‐free survival in patients with or without HCC was 44% and 59%, respectively. Cox‐multivariate analysis revealed that only post‐transplantation prophylaxis (p: 0.003) and pre‐transplantation viral activity (p: 0.004) can be considered as independent factors affecting HBV recurrence. Candidates with hepatocellular carcinoma in HBV‐cirrhosis should not be excluded from orthotopic liver transplantation, supporting the idea of a h

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00715.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:To investigate the contribution of apoptosis, a major mechanism of cell death, in the growth of hepatocellular carcinoma, we analyzed both apoptosis and cell proliferation in human hepatocellular carcinoma. We used the terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end labeling method and proliferative cell nuclear antigen staining, respectively. Among 21 hepatocellular carcinoma specimens examined, four were well, ten were moderately, and seven were poorly differentiated hepatocellular carcinoma. Terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end labeling‐positive cells in hepatocellular carcinoma were scattered individually or were sometimes clustered in the tumors. The terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end labeling indices were 0.35±0.09, 0.81±0.29, and 1.9±0.94 in well, moderately, and poorly differentiated hepatocellular carcinoma, respectively. The proliferative cell nuclear antigen labeling indices were 6.6±0.9, 13.1±3.5, and 26.7±6.3 in hepatocellular carcinoma in the same respective order of differentiation. The differences in both terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end labelling indices and proliferative cell nuclear antigen labeling indices (p>0.05) were significant between well, moderately and poorly differentiated hepatocellular carcinoma. There was a positive correlation between the terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end labeling and proliferative cell nuclear antigen labeling indices in hepatocellular carcinoma (r=0.84, p>0.001). This study showed that the proliferation rate and the incidence of apoptosis increased as the differentiation grade of hepatocellular carcinoma was lowered, suggesting a rapid turnover of cancer cells in the lower differentiation grades. Apoptosis may thus play an important role in the growth

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00716.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Our previous study demonstrated that apolipoprotein A‐1 (apo A‐1) immunoreactive peptides were located diffusely in the cytoplasm, not only of human normal hepatocytes, but also of intrahepatic bile ducts and peribiliary glands. It is important to determine whether the presence of these immunoreactive peptides in intrahepatic biliary tree is caused by pinocytosis from the bile, or by intracellular protein synthesis. Thus, we investigated whether apo A‐1 is synthesized by cells that line the biliary tree. Normal human liver samples obtained at surgery were used, and the expression and distribution of apo A‐1 mRNA in normal human liver tissues were examined, usingin situhybridization histochemistry with a35S‐labeled oligonucleotide probe specific for apo A‐1. On the autoradiogram, many silver grains were found to be distributed uniformly in hepatocytes. In addition, an appreciable apo A‐1 mRNA signal was also observed in both the surface epithelial lining of the bile ducts and the epithelial cells of the peribiliary glands. In conclusion, these findings suggest that the apo A‐1 found in bile is secreted both by hepatocytes and by intrahepatic bile duct cells and per

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1996.tb00717.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY