ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb01836.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract We performed prophylactic sclerotherapy in 350 patients with ‘high risk’ oesophageal varices (F2 or F3 with a moderate or severe red colour sign). Of these patients, eight exhibited sclerotherapy resistance (i.e. no significant reduction in the size of varices after five sessions of sclerotherapy). Thus, the prevalence of sclerotherapy resistant varices was 2%. Of 350 patients, 97 underwent haemodynamic investigation before sclerotherapy. This group consisted of seven patients with sclerotherapy resistant varices and 90 patients with non‐resistant varices. Portal pressure, assessed by portal venous pressure gradient, was similar in these two groups (21.5±4.8vs19.8±5.0 mmHg, respectively; NS). However, the prevalence of the ‘pipe‐line’ form of variceal feeding pattern (a large dilated left gastric vein running up the oesophagus) was higher in patients with resistant varices than in those with non‐resistant varices (100vs3%, respectively;P<0.01) and the diameter of the left gastric vein was larger in patients with resistant varices than in those with non‐resistant varices (12.4±2.0vs7.8±2.3 mm, respectively;P<0.01). Moreover, the extravariceal portosystemic shunt was poorly developed in patients with resistant varices compared with non‐resistant varices (0vs52%, respectively;P<0.05). We conclude that the pipe‐line pattern, fed by a large left gastric vein and associated with poorly developed extravariceal portosystemic shunt, is a distinctive portal venographic feature of sclero

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb01837.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract Several clinical events have a rhythmicity over the 24 h period. We assessed the presence of periodic rhythm in the occurrence of haematemesis in patients with liver cirrhosis under different daylight regimens, namely during standard time and during daylight savings. Over a 48 month period there were 212 consecutive admissions of 118 cirrhotics with variceal bleeding. Complete data were available for 181 episodes of bleeding: 121 (66.9%) started with haematemesis and 60 (33.1%) started with melaena. One hundred and two (56%) episodes occurred during daylight savings and 79 (44%) occurred during standard time. The cosinor test showed a 24 h biphasic peak for the occurrence of haematemesis (09.45 and 21.45 h). Moreover, a biphasic diurnal asymmetric frequency was also found by multiple component rhythmometry. The time peaks of onset of variceal haemorrhage did not change significantly during standard time and daylight savings. Patients with more than one haematemesis episode significantly bled over the same time interval. The present study confirms that over the 24 h period variceal bleeding in cirrhotic patients occurs with a predictable rhythmicity that does not seem to be under the control of the light‐dark cycle. The finding of a chronorisk for variceal haemorrhage addresses specific questions for pathophysiological studies as well as for new treatment strateg

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb01838.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract Recent research has led to an improved understanding of the aetiology of Budd‐Chiari syndrome in some patients. Fresh approaches and technical developments within methods of radiological intervention have added more effective options to its treatment. In this editorial we aim to summarize our understanding of the role of new aetiologies and new therapeutic approaches in the Budd‐Chiari syn

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb01839.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract The pathogenesis of liver fibrosis in genetic haemochromatosis and other iron overload states remains enigmatic. Recent advances in the cellular and molecular pathogenesis of liver fibrosis have determined a central role for hepatic stellate cells. These become activated to a myofibroblastic phenotype following most forms of liver injury and are the major cellular source of collagens and other matrix proteins laid down in fibrotic liver. Similar changes have now been reported in the liver in genetic haemochromatosis, with activation of stellate cells becoming more prominent with increasing hepatic iron concentration. In contrast to other liver diseases, this apparently occurs in the absence of significant necroinflammatory change. Unravelling the mechanism of liver fibrogenesis in iron overload states may, therefore, provide important general insights into the pathogenesis of liver fibrosis. The present article reviews current knowledge of this field with emphasis on the role of lipid peroxidation, sideronecrosis of hepatocytes and spillover of iron to Kupffer cells. An attempt is made to draw these observations together with previous studies of the mechanisms of stellate cell activation in other models and diseases. A unifying hypothesis emerges that helps to define some of the next research questions in the pathogenic mechanisms of liver fibrosis in iron overloa

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb01840.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract In both acute and chronic liver disease in man, elimination of drugs metabolized by the cytochrome P450 (CYP) enzymes is impaired. In contrast, those drugs metabolized by UDP‐glucuronosyltransferase (UGT) have a relatively normal elimination. Studies in rats with experimentally induced liver injury also show this relative preservation of glucuronidation. In liver disease, a number of factors, including inflammation, fibrosis and regeneration, may be associated with this differential effect on drug metabolism. Partial hepatectomy provides a model in which to isolate the effects of liver regeneration on drug metabolism. Partial hepatectomy or sham operation was performed in 24 male Sprague‐Dawley rats and three rats from each group were studied at days 1, 2, 4 and 6. Comparison between CYP and UGT was made at the protein level using immunohistochemistry and immuoblotting probed with a polyclonal antibody to UGT, identifying both family 1 and family 2 isoforms, and an antibody to the CYP isoform CYP2C11. Steady state messenger RNA levels of four isoforms of UGT were assessed by northern blot analysis. By both immunohistochemistry and immunoblotting, the level of CYP protein decreased from day 2 to 6 after hepatectomy. In contrast, the UGT protein level was not altered by partial hepatectomy. Northern blot analysis of UGT isoforms demonstrated differential regulation of isoforms from the two major families. The UGT family 1 isoforms were initially markedly depressed following partial hepatectomy and then steadily rose over 6 days to greater than the level in controls. In contrast, there was an apparent increase in UGT2B1 mRNA (not significant) on day 2, while UGT2B3 mRNA was maintained over the six days. These results demonstrate that during hepatic regeneration the protein content of total UGT is normal, while CYP2C11 protein is markedly reduced. Northern blot analysis suggests that individual isoforms of UGT are differentially regulated during the regeneration pr

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb01841.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract Albumin immunoreactivity in the liver was examined on days 2, 5 and 10 after two‐thirds partial hepatectomy by light and ultrastructural immunoperoxidase methods and the ultrastructural area of the rough endoplasmic reticulum (ER) in hepatocytes was measured. Albumin immunoreactivity was seen in the rough ER and Golgi apparatus of all hepatocytes in the hepatectomized liver and ultrastructural analysis showed a significantly greater area of rough ER on day 5 than on days 2 or 10. Albumin mRNA was studied by thein situhybridization technique using radioisotopes and their numbers were determined visually. Albumin mRNA was present as grains in all hepatocytes and the grains varied in number during regeneration of the liver, being more abundant on day 5 than on days 2 or 10. The activity of [3H]‐leucine incorporated into albumin synthesis, an indicator of translational activity, was higher on days 5 and 10 than on day 2 and was highest on day 5. In conclusion, albumin synthesis varied during liver regeneration after partial hepatectomy, being reduced at the peak of cell proliferation on day 2 and being most active on

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb01842.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract To investigate the pathogenesis of hepatic osteodystrophy (HOD) in parenchymal liver disease, we developed a laboratory model in animals using carbon tetrachloride (CCl4) and thioacetamide. Biochemical and histological parameters in the model were measured. In rats with both chronic non‐cirrhotic liver injury and CCl4‐induced cirrhosis, tibial bone volume was significantly lower than in controls. In CCl4‐treated cirrhotic rats, the osteoid volume decreased while the urinary calcium/creatinine ratio increased. In all CCl4‐treated rats, bone volume was significantly correlated with both the serum albumin concentration and the number of goblet cells reflecting intestinal villous atrophy. The serum concentration of vitamin D metabolites was not correlated with bone volume. Whole body retention of47Ca was significantly lower in CCl4‐treated cirrhotic rats than in controls. Furthermore, the bone volume in thioacetamide‐treated cirrhotic rats was significantly lower than in controls. These data demonstrate that chronic parenchymal liver injury itself causes osteoporosis (i.e. HOD) due to a combination of low bone formation rates and high resorption rates, that HOD begins at the stage of chronic non‐cirrhotic liver injury, that bone volume in HOD parallels liver damage and that the principal pathogenesis of HOD seems to be intestinal Ca malabsorption due to lower serum albumin and villous atrophy, while serum levels of vitamin D metabolites have little influence on the path

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb01843.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract Ursodeoxycholic acid (UDCA) has recently been combined with interferon (IFN) in the treatment of individuals with chronic hepatitis C. However, whether its addition results in a long‐term favourable response to IFN remains unclear. A prospective randomized trial of IFN alone versus IFN plus UDCA was therefore undertaken in 52 patients with chronic hepatitis C. All patients received a 24 week course of IFN‐α (6 × 106U/day for 2 weeks and then three times a week for 22 weeks) and half also received UDCA (600 mg/day) with IFN and then alone for 48 additional weeks. Normalization of serum alanine transaminase (ALT) concentrations at 0, 24 and 48 weeks after cessation of IFN therapy was apparent in 77, 42 and 42% of patients in the IFN‐alone group and in 77, 54 and 42% of patients in the IFN plus UDCA group, respectively. There was no significant difference between the two groups with regard to response rate to IFN and the addition of UDCA to IFN treatment had no significant effect on hepatitis C virus (HCV) viraemia. During the follow‐up period, 10 of 20 patients with normal serum ALT at the end of IFN treatment relapsed in the IFN‐alone group compared with 11 of 20 patients in the IFN plus UDCA group. Among these relapsed patients, serum ALT concentration was significantly lower in the IFN plus UDCA group than in the IFN‐alone group during the follow‐up period. Twenty‐four weeks after cessation of IFN therapy, the percentage of patients with HCV‐RNA in their serum who showed a normalization of serum ALT concentrations was significantly higher in the IFN plus UDCA group than in the IFN‐alone group (44vs6%). Thus, although the addition of UDCA was not associated with a favourable long‐term response to HCV viraemia, it did reduce the risk and the severity of relapse following the

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb01844.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract Primary sclerosing cholangitis is rare among Chinese. We report on a 71 year old male patient who presented with clinical features consistent with the disorder. Subsequent investigations confirmed the diagnosis. The patient was found to have anti‐neutrophil cytoplasmic antibodies with specificity against proteinase 3. Treatment with ursodeoxycholic acid resulted in clinical remission and disappearance of the antibod

ISSN:0815-9319    

DOI:10.1111/j.1440-1746.1996.tb01845.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY