摘要:

ABSTRACT—Hepatocytes isolated from patients with chronic liver disease are often covered by immunoglobulin. The aim of the present study was to establish whether this surface immunoglobulin (SIg) mediates liver cell damage. Freshly isolated hepatocytes from percutaneous liver biopsy of 16 patients with chronic active hepatitis (CAH) (6 HBsAg positive), 3 with HBsAg‐positive chronic lobular hepatitis (CLH), 5 with HBsAg‐positive chronic persistent hepatitis (CPH) and 12 with minor histological abnormalities (MHA) (5 HBsAg positive) were divided into two aliquots. One was studied for the presence of membrane‐bound immunoglobulin and the third component of complement by direct immunofluorescence and the other was incubated, in an allogeneic cytotoxic assay, with peripheral blood mononuclear cells prepared from healthy volunteers as a source of effectors for antibody‐dependent cell‐mediated cytotoxicity (ADCC). Liver biopsies were scored for portal and parenchymal inflammatory activity. The percentage of SIg positive hepatocytes was significantly higher in patients with CAH (median 52.5%) than in patients with CLH/CPH (20.5%) or in patients with MHA (1%). Percentages of SIg‐positive liver cells were significantly correlated with total liver biopsy scores and with both portal or parenchymal scores considered independently. SIg were found to belong to the IgG class in all groups of patients. When hepatocytes were cultured with normal human lymphocytes, allogeneic cytotoxicity values were significantly higher in patients with CAH (median 34%) than in patients with CLH and CPH (18%) or in those with MHA (12%). Percentage cytotoxicity was positively correlated with total biopsy scores and with portal activity but not with parenchymal activity, suggesting that ADCC might play a damaging role mainly in the portal areas. Our results show that in HBsAg‐positive and in HBsAg‐negative chronic liver disease IgG on the liver cell membrane is associated with increased susceptibility toin vitrocytotoxicity by killer cells and with increased severity of histological liver damage, suggesting a direct role for these antibodies in the generation of

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1987.tb00361.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

ABSTRACT—A long‐term follow‐up study of liver cirrhosis (LC) was performed in 582 patients diagnosed by peritoneoscopy and liver biopsy in the 26 years from 1958 to 1984. The etiology of LC consisted of hepatitis B virus (HBV) in 21%, alcoholic in 39% and cryptogenic in 39%. Fifty‐nine percent of patients had died. Causes of death were hepatocellular carcinoma (HCC 44%), liver failure (30%), rupture of esophageal varices (14%), gastrointestinal bleeding (4%) and non‐liver‐related causes (8%). HCC accounted for increasing percentages (68%) since 1980. In all groups classified by the etiology, the causes of death had the same order in incidence. The age of onset of LC increased by 10 years from 42 to 52 years old and the age of death by 15 years from 43 to 58 in the 26‐year period. The cumulative survival rate improved over the period. The 50% survival year was 7.9 in total patients, and 7.0, 8.5 and 10.0 in the three periods 1958–64, 1965–74 and 1975–84, respectively. It was 9.5, 6.3 and 9.8 in HBV, alcoholic and cryptogenic, respectively. LC patients survived 40–44% of the life expectancy of the general population in Japan in all age groups. Cox's multiregression life‐table method selected three important prognostic factors from 7 parameters: a poor prognosis with a history of heavy alcohol consumption and old age at onset, and a better prog

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1987.tb00362.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

ABSTRACT—Twelve hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B virus DNA polymerase (HBV‐DNAp) and hepatitis B virus DNA (HBV‐DNA) positive patients with chronic active hepatitis (CAH) were treated with doses of either 20 times 106IU/m2or 10 times 106IU/m2body surface of recombinant interferon (rIFN)‐alpha‐2A, I.M., twice a week, during a period of 6 months. No appreciable differences with respect to clinical history, liver function tests and markers of HBV replication between the two groups were apparent at the time of entry into the trial. At the third month of treatment HBV‐DNAp became negative in 10 out of 12 patients (83%). After a 15‐month follow‐up, HBV‐DNAp, HBV‐DNA and HBeAg were negative in 7 out of 12 patients (38%) (responders). Furthermore, at 24 months, 2 non‐responder patients became HBV‐DNA and HBV‐DNAp negative and one responder lost serum HBsAg. In addition, HBsAg concentration, GPT level and histological Knodell's index decreased significantly in the responder patients, while no changes were observed in non‐responders. Five out of six patients who received a low rIFN dose responded to the treatment, and only 2 out of 6 with a higher dose. No unacceptable toxicity was noted in any of the 12 patients. All of them completed the course of treatment. The results suggest that long‐term rIFN‐alpha‐2A therapy has an antiviral effect in CAH due to HB

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1987.tb00363.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

ABSTRACT—Originally published in 1984, the Copenhagen Pocket Chart for early differentiation between causes of jaundice has been tested with success in centres outside Denmark. Using a logistic discrimination model, it estimates probabilities of obstruction and non‐obstruction in each case (and provides a further subdivision if desired). Here we evaluate its performance in the hands of young clinicians on a consecutive series of 173 jaundiced patients from two Danish hospitals. The chart performed as well as in the original series: confident diagnoses (probability ≥ 0.80) were assigned to 124 patients; of these 115 proved correct (93%). In 46 patients diagnostic probabilities were<0.80, and 3 patients had an unknown cause of jaundice. There were 108 cases in which physician and chart were in agreement, both with a confident diagnosis, and only one of these cases was wrong. In one hospital, contributing 107 cases, each patient was independently examined by a medical student in addition to the physician's examination. Student performance was equally good, practically speaking, in particular when taking the scores on the chart into consideration. As to observer disagreement, the student and the physician typically differed on 0–2 of the chart's 21 items. In no case, however, did this lead to a confident obstructive diagnosis being changed into a confident diagnosis of non‐obstruction, orv

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1987.tb00364.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

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 thecurrentfibrotic 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 propeptid

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1987.tb00365.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

ABSTRACT—Ultrastructural examination was carried out in 13 liver biopsies from patients with alcoholic hepatitis, with special reference to the relationship between alcoholic hyaline (AH)‐containing hepatocytes and inflammatory cell infiltration. In as many as one third of the cases, polymorphonuclear leucocyte (PMN) migration into the cytoplasm of AH‐containing hepatocytes was noted. The migrating PMNs often had discontinuous cell membranes and their primary and secondary granules were demonstrated to be released into the liver cell cytoplasm. Finally, migrating PMNs appeared collapsed and dying. These PMNs appeared to gather around AH, presumably due to the strong chemoattractive action of AH. The hepatocytes invaded by PMNs revealed various degrees of degeneration and cell necrosis. Occasionally, some lymphocytes infiltrated into hepatocytes and had a direct contact with AH. However, the occurrence of lymphocyte migration was much less than that of PMNs. Kupffer cells were also intermingled with these PMNs and often possessed AH in degraded forms in their phagosomes or phagolysosomes. Based on these results, it is postulated that acute hepatocellular damage in patients with alcoholic hepatitis might be caused by this peculiar type of degranulation and collapse of migrating PMNs against AH‐containing hepatocytes in addition to the various causes previously

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1987.tb00366.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

ABSTRACT—To demonstrate DNA clonal heterogeneity of hepatocellular carcinomas (HCC), the DNA histographic pattern of both primary HCCs and their recurrent or metastatic lesions were studied among 36 patients (33 men and 3 women). Thirty‐six paired aspirations or imprints taken from primary, recurrent or metastatic lesions were stained, using the modified Feulgen method, and the DNA content was measured with a scanning microdensitometer at a wavelength of 550 nm. Paired aspirations or imprints taken from different parts of the same HCC were examined in 17 cases; the DNA distribution patterns were similar in 15 (88%) and differed in only two (12%). A similar DNA histogram was also shown among different tumors in 10 (71%) of 14 patients with multiple HCCs, with a DNA ploidy discrepancy in only four (29%). Two of two subcutaneous metastases and two of three recurrent tumors showed DNA distribution patterns similar to those in their primary HCCs. In summary, a DNA clonal heterogeneity of HCC was found in 19% (7/36). In contrast, the similar DNA histographic patterns found in most instances among different parts of the HCC and between the primary and recurrent or metastatic lesions suggest that HCC may derive from a single cell clone in the majority of ca

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1987.tb00367.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

ABSTRACT—In order to assess whether acetaldehyde adducts with liver plasma membrane proteins are formedin vivoduring 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 formationin 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 bindingin v

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1987.tb00368.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

ISSN:0106-9543    

DOI:10.1111/j.1600-0676.1987.tb00369.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY