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PubMed2002

Human fetuin/alpha2HS-glycoprotein level as a novel indicator of liver cell function and short-term mortality in patients with liver cirrhosis and liver cancer.

OBJECTIVE: Human fetuin/alpha2HS-glycoprotein (AHSG) is synthesized by hepatocytes. We intended to determine whether liver dysfunction or acute phase reaction is dominant in the regulation of its serum concentrations and to see if decreased AHGS levels are associated with short-term mortality. DESIGN: We determined the serum AHSG levels in patients with acute alcoholic, acute A, B, and Epstein-Barr virus hepatitis, alcoholic cirrhosis, and hepatocellular cancer and correlated them to conventional laboratory parameters of inflammation and liver function. Patients were followed for 1 month. METHODS: Serum AHSG was determined by radial immunodiffusion. RESULTS: Compared to controls, significantly lower AHSG levels were found in patients with liver cirrhosis and hepatocellular cancer but not the acute viral hepatitides. Strong positive correlation with serum transferrin, albumin and prothrombin was found. Febrile episodes were not associated with significantly decreased AHSG levels. Concentrations below 300 microg/ml were associated with high mortality rate (52.0%; relative risk, 5.497; 95% confidence interval, 2.472-12.23; P < 0.0001). Of all laboratory parameters studied serum AHSG levels showed the greatest difference between deceased and survived patients with cirrhosis and cancer. Moreover, other acute phase reactants did not differ significantly. The multiple logistic regression analysis indicated that the decrease of serum AHSG is independent of all other variables that were found decreased in deceased patients. CONCLUSIONS: Decreased serum AHSG concentration is due rather to hepatocellular dysfunction than the acute phase reaction and is an outstanding predictor of short-term mortality in patients with liver cirrhosis and liver cancer.

Acute-Phase Reaction↗

PubMed1975

The diagnostic significance of liver cell inhomogeneity: serum enzymes in patients with central liver necrosis and the distribution of glutamate dehydrogenase in normal human liver.

16 Patients with acute right-sided cardiac failure associated with a high pressure of the central venous system, exhibited a marked increase in glutamate dehydrogenase activity in serum. This increase was 40-fold higher than in patients with acute viral hepatitis. Histological examination of seven deceased patients revealed central necrosis within the liver lobule. This observation led us to determine glutamate dehydrogenase activity in microdissected peripheral and central portions from the unchanged liver lobule. A 1.7-fold higher glutamate dehydrogenase activity was found in the central part of the liver lobule than in the peripheral portion. The diagnostic significance of the glutamate dehydrogenase activity distribution along the cords of liver cells is discussed in view of liver diseases with central necrosis.

Aged↗

PubMed1975

Factors affecting liver fat accumulation and liver hemorrhages associated with fatty liver-hemorrhagic syndrome in laying chickens.

A series of four experiments was conducted with a commercial strain of laying chickens in an attempt to experimentally produce Fatty Liver-Hemorrhagic syndrome (FLHS). Different dietary energy sources, environmental temperatures and feeding schedules were the experimental variables. Increasing the environmental temperature from 12.2 degrees C. (experiment 1) to 27.8 degrees C. (experiment 2) did not drastically alter total liver fat, 2.7 g. (experiment 1) vs. 2.9 g. (experiment 2) or the incidence of FLHS, 0.0% (experiment 1) vs. 1.0% (experiment 2). Likewise, in experiment 4, changing the environmental temperature from 22.2 degrees C. to 30.6 degrees C. or from 30.6 degrees C. to 22.2 degrees C. did not significantly (P greater than .05) alter total liver fat or liver wet weight. The greatest incidence (50%) of FLHS occurred in birds which were restricted in feed intake and exposed to an environmental temperature of 30.6 degrees C. from 32-36 weeks of age followed by ad libitum feeding at a temperature of 22.2 degrees C. from 36-40 weeks of age. These birds ate 26.8% more feed than the control birds during the ad libitum feeding period. Restricted feed schedules (experiment 3) resulted in significantly (P less than .05) lower 40 week liver wet weights and total fat when applied during the growing (14-20 weeks of age) and early lay (20-28 weeks of age) periods.

Age Factors↗

PubMed1989

[NK activity in various liver diseases--especially the relation between NK activity and reserve function of the liver in liver cirrhosis and hepatocellular carcinoma].

NK activity in acute viral hepatitis, chronic hepatitis, liver cirrhosis (LC), metastatic liver cancer and hepatocellular carcinoma (HCC) was preserved and had no significant change compared with the normal control in each disease. In acute hepatitis, NK activity was higher in convalescent phase than in acute phase. Although in LC and HCC, some liver functions such as total bilirubin, the rate of ICG 15' excretion, AFP and IAP did not have significant correlation with NK activity, advanced cases according to Child's classification and E factor which was anatomical extent of HCC in liver showed significantly low NK activity. The low NK activity group advanced much more in Child's classification, performance status, stage and E factor of HCC than high NK activity group significantly. According to those facts, LC or HCC is not a single entity of disease in view point of NK activity. NK activity may change in accordance with the advancement of hepatic disease and reserve function of the liver in LC and HCC.

Adult↗

PubMed1995

[Increased gamma-GT, minimal changes in liver histology, abdominal complaints--a functional liver liver disease].

Of 1,756 liver biopsies performed in the years 1987-1991, in 139 cases the patients exhibited both a nearly normal liver histology and elevated GGT values. After exclusion of patients with known causes for an elevated GGT 15 patients were selected, who over at least one year, were documented as having at least 3 measured GGT values with an average of over 40 U/l. In the follow-up of 1-15 years a typical constellation was detectable: longterm elevation of GGT (average 47-156 U/l, moreover a smaller degree of elevation of GLDH and GPT), minimal deviations from norm in liver histology (periportal fibrosis and/or fatty liver degeneration), and functional abdominal complaints. This triad occurred predominantly in middle-aged males, did not exhibit laboratory-chemical or histological signs of progression or regression tendencies and could be interpreted as a "functional" liver disorder with parelleles to M. Gilbert-Meulengracht.

Abdominal Pain↗

PubMed1975

Effect of cholesterol content on some physical and functional properties of mitochondria isolated from adult rat liver, fetal liver, cholesterol-enriched liver and hepatomas AH-130, 3924A and 5123.

The cholesterol to phospholipid ratio in mitochondria from hepatomas AH-130, 3924A and 5123 is higher than in the particles isolated from adult or fetal rat livers. Nearly all the cholesterol of hepatoma mitochondria is located in membranes. As in liver mitochondria, in the particles isolated from hepatoma AH-130 there is more cholesterol in the outer than in the inner membrane. In mitochondria from cholesterol-enriched liver and hepatomas, there occurs a decrease in extent of hypoosmotic and phosphate-induced swelling and a decrease of conformational changes linked to energy states. The phenomenon is more marked in particles which exhibit higher cholesterol to phospholipid ratios. A statistically significant negative correlation exists between the cholesterol to phospholipid ratio and extent of volume or conformational changes. No significant modifications of these parameters were found in fetal liver mitochondria. Cholesterol content does not influence K+ uptake by cholesterol-enriched or hepatoma mitochondria. Nor does cholesterol content affect the respiratory increment related to this uptake. As a consequence of K+ uptake, total mitochondrial water exchangeable with tritiated water rises 20% while sucrose-impermeable water rises 42-48% in both adult rat liver and hepatoma AH-130 mitochondria. Absorbance changes linked to ion uptake do not correspond merely to variations in mitochondrial water content. Water content is apparently not influenced by the cholesterol to phospholipid ratio. However, the ratio is significantly correlated to both extent and initial rate of absorbance decrease of mitochondrial suspensions during K+ uptake. The higher the ratio, the lower the extent and initial rate of absorbance decrease.

Animals↗

PubMed1984

Isolation of micro- and macro-droplet fractions from needle biopsy specimens of human liver and determination of the subcellular distribution of the accumulating liver lipids in alcoholic fatty liver.

Needle biopsy specimens of liver were obtained from six control subjects with histologically normal liver and 11 chronic alcoholics with fatty liver. Micro- and macro-lipid droplet fractions were isolated by differential flotation. These fractions, together with the sedimenting membranes, were assayed for cholesterol, cholesteryl ester, phospholipid, free fatty acids and triglyceride. Electron microscopy demonstrated marked differences in the range of lipid droplet sizes in the two fractions and biochemical analysis suggested that the microdroplet lipid corresponded to pre-very low density lipoprotein (VLDL) particles. Studies on biopsies from patients with alcoholic fatty liver showed a 2-3-fold increase in triglyceride in both lipid droplet fractions but most of the accumulating triglyceride was sedimentable and membrane-bound. Needle biopsy specimens from two patients with alcoholic fatty liver were fractionated with a vertical pocket re-orientating rotor. The principal organelles were separated and the subcellular distribution of triglyceride, phospholipid and free cholesterol determined. Triglyceride showed a bimodal distribution to a particulate fraction tentatively located to Golgi particles and to droplet-lipid remaining in the sample layer.

Biopsy, Needle↗

PubMed2001

The National Liver Transplantation audit: an overview of patients presenting for liver transplantation from 1994 to 1998. On behalf of the Steering Group of the UK Liver Transplantation Audit.

BACKGROUND: The aim of this study was to describe current clinical practice in liver transplantation in the UK and Ireland, to provide overall 1-year graft and patient survival rates, and to study some preoperative risk factors. METHODS: All patients receiving a liver transplant in the UK or Ireland between 1 March 1994 and 30 September 1998 were included. Data were collected on patients at the time of transplantation, 3 months after grafting and annually thereafter until the patient's death. The main outcome measures were graft and patient survival at 1 year. RESULTS: A total of 3102 liver transplants were carried out, of which 87 per cent were first transplants. The mean age at first transplantation was 42 (range 0-76) years. The most common indications for transplantation were primary biliary cirrhosis, alcoholic cirrhosis and posthepatitis C cirrhosis, but variations existed between sexes and centres. Risk factors associated with lower graft and patient survival were the presence of acute disease, being transplanted from hospital, and the need for renal and/or ventilatory support before operation. CONCLUSION: Donor and recipient demographics are consistent with data held by the European Liver Transplant Registry, as are 1-year graft and patient survival rates. Variation across centres in factors such as the primary indication for liver transplantation, population demographics, the clinical status of each patient, incidence of retransplantation and other risk factors contributes to the problem of adjusting for case mix.

Adolescent↗

PubMed1983

Incidence of hepatitis B virus infection in alcoholic liver disease, HBsAg negative chronic active liver disease and primary liver cell cancer in Britain.

A study has been undertaken to determine the incidence of serum markers of hepatitis B virus (HBV) infection in British caucasian patients with biopsy-proven alcoholic liver disease (n = 56), HBsAg negative chronic active liver disease (CALD) (n = 47) and primary liver cell cancer (PLCC) (n = 27), compared to a hospital control population without liver disease (n = 112). No increased incidence of any serum marker of HBV infection was found in alcoholic liver disease or in 'lupoid' CALD (antinuclear factor positive 1:40 and/or smooth muscle antibody positive greater than 1:40). In contrast, the incidence of antibody to HB surface and core antigens was significantly increased (p less than 0.05) in patients with cryptogenic CALD. The incidence of hepatitis B surface antigen and antibodies to HB core and 'e' antigens was significantly increased (p less than 0.005) in PLCC.

Female↗

PubMed1981

Autoimmunity to a liver membrane lipoprotein and liver damage in alcoholic liver disease.

Antibodies reacting with a liver membrane lipoprotein (LSP) have been detected by radioimmunoassay in the sera of 15 (27%) of 55 patients with alcohol-related liver lesions. There was a close association between the presence of the anti-LSP antibody and the findings on liver biopsy of a lymphocytic infiltrate in the portal tracts together with piecemeal necrosis of periportal hepatocytes. These histological features are characteristically found in the autoimmune disorder of chronic active hepatitis, in which anti-LSP antibodies are almost invariably present. It is suggested that in these cases of alcoholic liver disease there is loss of tolerance, and continued production of anti-LSP could promote periportal inflammation and accelerate the progression to cirrhosis. In the cases of acute alcoholic hepatitis without periportal inflammation studied, anti-LSP was not detected demonstrating that production of this autoantibody is not simply secondary to liver damage.

Autoantibodies↗

PubMed1999

[Mechanisms of rejection in guinea pig (GP)-to-rat liver xenotransplantation: improvement of recoloration of GP liver graft and effects of perfluorochemical (FC43) in GP-to-rat liver xenotransplantation].

The impaired reperfusion after revascularization has not allowed guinea pig (GP)-to-rat liver xenograft model to be widely used for xenotransplant research. This study was designed to clarify mechanisms responsible for the impaired recoloration, and to examine effects of FC43 emulsion, an anti-complement agent. 1) Mechanisms responsible for the impaired recoloration: GP allogeneic and xenogeneic liver grafts flushed with 4 degrees C lactated Ringer's (LR) solution were poorly perfused around the porta hepatis, whereas those flushed with 15 degrees C LR solution were immediately recolored, this being confirmed by portal venography. The recoloration was also ameliorated by reduction of ischemic time. Even recolored GP xenografts, turned uneven dark gray however, and enlarged around 5 min after revascularization. Histological and immunohistological findings of GP livers 1 h after xenografting were characteristic of sinusoidal congestion and hepatocytes necrosis, and the livers had remarkable C3 deposits on sinusoids and central veins, IgM deposits faintly stained on some small vessels but no detectable deposits of IgG. 2) Effects of FC43. Administration with of either a single dose of 10 microliters/g or repeated doses of 5 microliters/g of FC43 resulted in significant prolongation of xenograft survivals compared with controls (8.06 +/- 1.45, 9.45 +/- 3.64 vs. 4.23 +/- 0.89 h; p < 0.02), thereby sustaining almost normal gross appearances until abdominal closures. Thus, the onset of hyperacute rejection (HAR) was postponed by FC43 administration; however, all rats died within 14 h. No deposit of C3 was detected in GP xenografts of FC43 groups, while deposits of granulocytes and macrophages (M phi) were observed from 1 and 3 h after revascularization, respectively. In conclusion, the impaired recoloration in this model may be due to physiological defects during the initial stage of revascularization, which is followed by the immunological responses that probably involved M phi and granulocytes. The present study indicates that discordant GP liver xenotransplantation is feasible as a useful rodent model for either exploration of mechanisms of immunological responses or examination of the immunosuppressive effects of pharmacological agents.

Animals↗

PubMedDate not supplied

Significance of hyperattenuating and contrast-enhancing hepatic nodules detected in the cirrhotic liver during arterial phase helical CT in pre-liver transplant patients: radiologic-histopathologic correlation of explanted livers.

BACKGROUND: Hyperattenuating nodules detected by arterial phase helical computed tomography (HCT) in patients with cirrhosis usually are believed to represent hepatocellular carcinomas (HCCs). We correlated HCT morphology of hyperattenuating hepatic nodules detected during arterial phase scans with the histopathology of explanted livers of patients with hepatic cirrhosis undergoing liver transplantation. METHODS: Three hundred fifty-four patients had arterial and portal phase HCT performed before subsequent hepatic transplantation. Each patient received 180 mL of contrast by power injection at 5 mL/s. All hyperattenuating nodules detected on arterial phase HCT were assessed for morphology and evidence for contrast enhancement. Explanted livers in all patients were then sectioned at 10-mm intervals, and the histology of the nodules was correlated with the HCT findings. RESULTS: Sixty-one hyperattenuating nodules were detected on the arterial phase HCT in 43 patients: 41 nodules were benign regenerating nodules (RN), three were dysplastic nodules (DP), and 17 were HCCs. Most RN/DP nodules were 5-20 mm in diameter, had distinct margins, were homogeneous, and were isoattenuating on precontrast, portal, and delayed scans. Thirty-six showed positive contrast enhancement and displayed a wide range of attenuation profiles. HCC nodules were 6-50 mm. All showed positive contrast enhancement and displayed a wide range of attenuation profiles. CONCLUSION: Hyperattenuating nodules seen on arterial phase HCT are likely to be RN/DP nodules. In many cases, it is not possible to distinguish between RN/DP and HCC. Thus, clinical decisions regarding inclusion criteria for transplantation based on CT morphology of liver lesions may be tenuous.

Carcinoma, Hepatocellular↗

PubMed2001