Wiley

Tóm tắt: Mẫu huyết thanh từ 9006 phụ nữ sinh đẻ tại Thụy Sĩ trong các năm 1990 và 1991 được thu thập trên khắp cả nước. Trong số phụ nữ này, 62,7% là người Thụy Sĩ và 37,3% có nguồn gốc từ các quốc gia khác. Các mẫu được sàng lọc ban đầu cho anti-HBc và nếu dương tính, thì được xét nghiệm thêm cho HBsAg, anti-HBs và anti-HDV. Anti-HBc được phát hiện ở 640 trong số 9006 phụ nữ (tỷ lệ chung là 7,1%; người Thụy Sĩ là 3,3%; người nước ngoài là 13,5%). Trong số 640 mẫu có anti-HBc dương tính, 61 mẫu (9,5%) dương tính với HBsAg (không có anti-HBs), 467 mẫu (73,0%) dương tính với anti-HBs (không có HBsAg) và 8 mẫu (1,3%) dương tính với cả HBsAg và anti-HBs. Còn lại 104 mẫu có anti-HBc dương tính mà không có HBsAg hoặc anti-HBs. 104 mẫu này, với phản ứng được gọi là “anti-HBc đơn độc”, chiếm 1,2% của toàn bộ dân số hoặc 16,3% của những người mẹ có anti-HBc dương tính. Tất cả đều âm tính với HBV DNA (PCR). Kháng thể anti-HDV chỉ được tìm thấy ở 5 phụ nữ. HBsAg được thấy trong 38 mẫu máu dây rốn từ những người mẹ có anti-HBc dương. Trong mẫu lớn này, chúng tôi đã quan sát thấy tỷ lệ lưu hành huyết thanh của nhiễm HBV khá cao. Các trường hợp chỉ phản ứng anti-HBc đơn độc, khi âm tính với HBV DNA qua PCR, có lẽ không truyền nhiễm tại thời điểm thu thập máu.

ABSTRACT— A hitherto undescribed industrial liver injury of fulminant form induced by dichloropropanol is reported. Two middle‐aged men developed severe hepatic injury just after cleaning a dichloropropanol tank at a plant producing dichloropropanol. They died from hepatic failure 4 and 11 days respectively, after carrying out the work. Liver specimens taken at autopsy from one of the cases showed submassive hepatic necrosis. This accident prompted us to undertake an experimental study in rats of intraperitoneal one‐shot injection of two isomeric substances of dichloropropanol, that is, 2,3‐dichloro‐l‐propanol (DCIP) and 1,3‐dichloro‐2‐propanol (DC2P). Saline was injected into the control rats. One, two, four, six, 24, 48, 72 h, and 1 week after the injection, rats in each group were sacrificed. Neither control nor DC IP‐injected rats showed significant biochemical or histopathological abnormalities. DC2P‐injected rats revealed elevations of transaminase from 6 h after the injections, and submassive necrosis of the liver was observed in many rats. It was concluded that the severe liver injuries in both the human cases and rats in our study were caused by DC2P.

ABSTRACT— The pathogenetic role of lipid peroxidation in ethanol‐induced liver injury was previously supported by demonstration of increased formation of diene conjugates and decreased hepatic levels of reduced glutathione in ethanol‐fed animals and alcoholic patients with liver injury. The present study was carried out to investigate whether these findings can be extended to a rat model that was shown to produce a spontaneous ethanol‐induced liver injury progressing from steatosis to necrosis and fibrosis (Hepatology 6: 814, 1986). Despite the histological evidence of progression from hepatic steatosis to centrilobular necrosis in these animals, diene conjugate formation in mitochondrial and microsomal lipids was not enhanced when compared to pair‐fed controls. In addition, hepatic levels of neither methionine nor glutathione were decreased in the ethanol‐fed animals. The fatty acid composition of mitochondrial phospholipids from these animals was similar to that in the controls. However, in the microsomal phospholipids, the level of arachidonate (20:4) was depressed by about 50% as compared to the controls. These results demonstrate the lack of evidence for a pathogenetic relationship between lipid peroxidation and ethanol‐induced liver injury progressing to centrilobular necrosis. They further suggest that the decreased levels of 20:4 commonly seen after chronic ethanol intake may not be due to a peroxidative loss.

Abstract: Background: Gut‐derived endotoxin is insufficiently cleared by the diseased liver, and thus, is elevated in plasma of patients with chronic liver disease (CLD). Endotoxin action might be modified by binding to soluble CD14 (sCD14) and lipopolysaccharide‐binding protein (LBP), both of which have not yet been sufficiently studied in CLD.

Methods: Endotoxin, sCD14 and LBP have been determined in peripheral blood of 72 patients and 39 control subjects, and in portal and hepatic venous blood of 12 patients during transjugular intrahepatic portosystemic shunt (TIPS) implantation.

Results: Peripheral endotoxin (average 3‐fold increased compared to controls), LBP, and sCD14 plasma levels were elevated in chronic liver disease irrespective of Child stage m, preserve/absence of cirrhosis or aetiology. LBP, and sCD14. Furthermore, endotoxin levels in the portal vein (38.1 ± 6.1 pg/ml) were only slightly elevated compared to the hepatic vein (29.2 ± 4.4 pg/ml), and peripheral endotoxin levels did not increase after TIPS.

Conclusions: Decreased hepatocellular function rather than hepatic blood shunting might be responsible for endotoxemia. The elevation in LBP and sCD14 levels may be a consequence of endotoxemia.

ABSTRACT— Hepatic stellate cells (HSC) are presently regarded as one of the key cell types involved in the progression of liver fibrosis and in the related pathophysiological and clinical complications. Following acute or chronic liver tissue damage, HSC undergo a process of activation towards a phenotype characterised by increased proliferation, motility, contractility and synthesis of extracellular matrix (ECM) components. Several factors have been shown to play a key role in the promotion of the full‐blown picture of activated HSC. These include extensive changes in the composition and organisation of the ECM, the secretion of several growth factors, cytokines, chemokines, products of oxidative stress and other soluble factors. It is evident that each cellular response to extracellular stimuli must be framed in a scenario where different forces modulate one another and result in a prevalent biological effect. Along these lines, the identification and characterisation of intracellular signalling pathways activated by different stimuli in HSC represent a mandatory step. In this review article we have made an attempt to summarise recent acquisitions to our knowledge of the involvement of different intracellular signalling pathways in key aspects of HSC biology.

Abstract: Immune responses to dihydrolipoamide dehydrogenase, the E3 subunit which is a common component of 2‐oxoacid dehydrogenase complexes, have been suggested to be associated with the etiology of primary biliary cirrhosis (PBC). However, since an antibody to E3 could be detected in Caucasian patients with PBC, but was not specific for the disease, the proposal is not evident at the antibody level. We have identified the antibody also in Japanese patients with PBC by immunoblotting with sera at a 1: 100 dilution and have assessed cellular immune responses to E3 by proliferation assay of peripheral blood lymphocytes. Anti‐E3 antibody was detected more frequently in 25 of 43 PBC (58.1%) than in normal controls (p>0.01) and in chronic liver diseases (p>0.05), but the antibody was not specific for PBC as reported in Caucasian PBC. Anti‐E3 antibody‐positive sera of PBC patients or normal controls and their IgG fraction did not inhibit the enzyme activity of E3. Lymphocyte blastogenesis to E3 in PBC was significantly greater than normal controls (p>0.05), but was not significant as compared with chronic liver disease or non‐hepatic autoimmune diseases. Thus, these data do not support the hypothesis that the immune response to the E3 subunit is associated with etiology of PBC.

Abstract: A high prevalence of HCV infection has been reported in patients with hepatocellular carcinoma. The progression from acute transfusion‐associated hepatitis to hepatic cirrhosis and hepatocellular carcinoma has been suggested in several studies to be very long. We have investigated the prevalence of anti‐HCV and the interval between HCV infection and hepatocellular carcinoma among 191 consecutive patients with cirrhosis and liver‐cell carcinoma. Serum samples from 191 patients with cirrhosis and hepatocellular carcinoma, consecutively diagnosed in our hospital between 1988 and 1993, were tested for serological markers of HBV and HCV infection. One hundred and forty‐eight patients (77.5%; 95% confidence interval (c.i): 76% to 80%) were anti‐HCV positive by 2nd generation enzyme immunoassay (confirmed by 2nd generation recombinant immunoblot assay) and 152 patients (79.5%; 95% c.i: 76% to 80%) were anti‐HCV positive by 3rd generation enzyme immunoassay, while only 14 (7.4%; 95% c.i: 5% to 10%) were HBsAg positive. Of the 29 anti‐HCV positive patients with previous transfusion, the interval between the date of blood transfusion and the diagnosis of hepatic cirrhosis was 24±12.5 years and that of hepatocellular carcinoma was 26.8±12.4 years. These results confirm the high prevalence of HCV infection in patients with hepatocellular carcinoma and the slow sequential progression from HCV infection through cirrhosis and hepatocellular carcinoma.

ABSTRACT— In order to assess whether acetaldehyde adducts with liver plasma membrane proteins are formed in vivo during alcohol ingestion, liver plasma membranes were prepared from control rats and rats fed on 10% ethanol from weaning and the amino acid constituents of liver plasma membrane proteins were assessed by reversed phase liquid chromatography of an acid hydrolysate of the membranes. The retention time of acetaldehyde/lysine adduct after stabilisation through reduction was determined by chromatography of an acid hydrolysate of polylysine pretreated with acetaldehyde. The presence of a peak with identical retention time to the acetaldehyde/lysine adduct was detected in liver plasma membranes isolated from alcohol‐fed rats indicating adduct formation in vivo. The adduct was detectable only when the membranes were prepared by a rapid (Percoll) method, suggesting that the adduct may be unstable. The findings are consistent with the hypothesis that the inflammation of acute alcoholic liver disease may be initiated by the product of acetaldehyde/membrane binding in vivo.

ABSTRACT— Serum concentrations of the aminoterminal propeptide of type III procollagen and of the 7S domain of type IV collagen, presumed to reflect fibrotic activity in liver tissue, and of the glycosamonoglycan hyaluronan, were obtained from 40 alcohol abusers, at the time of liver biopsy. The serological results were related to morphological findings in liver tissue, i.e. no fibrosis, fibrosis without cirrhosis, micronodular cirrhosis and macronodular cirrhosis, and to ultrastructural indications of perisinusoidal fibrosis in the acinar zone 3. All patients with fibrosis and cirrhosis on light microscopy had elevated serum levels of the type III procollagen peptide as well as of the 7S domain of type IV collagen. However, due to a considerable overlap between the groups, no relations could be demonstrated to the severity of the fibrosis, supporting the assumption that these serological markers reflect the current fibrotic activity and not the amount of fibrotic tissue previously deposited. Among patients without fibrosis on light microscopy, a relation between the propeptide levels and ultrastructural perisinusoidal zone 3 fibrosis was observed, suggesting that type III procollagen peptide may be valuable in detecting very early liver fibrosis. A positive correlation was demonstrated between the serum concentrations of type III procollagen peptide and hyaluronan. As hyaluronan is degraded in the liver endothelial cells, it is suggested that the liver is involved, not only in the synthesis, but also in the degradation of the propeptide.