Variety Of Liver Diseases Research Articles

HBsAg-associated albumin receptors and antialbumin antibodies in sera of patients with liver disease

Several investigators reported that sera from patients with liver disease react with polymerized human serum albumin. This reactivity may be mediated by antibodies to polymerized albumin or polymerized albumin receptor sites on HBsAg. We tested sera from 114 patients with a variety of liver diseases by techniques which differentiate polymerized albumin binding activity mediated by HBsAg-associated receptors from that due to immunoglobulins. Total polymerized albumin binding activity was detected by passive hemagglutination of polymerized albumin-coated red blood cells, in 62.3% of patients with liver disease. The specificity for polymerized albumin was proven by hemagglutination inhibition of 18 sera using polymeric, monomeric, and native albumin as inhibiting antigens. Indirect immunofluorescence of polymerized albumin coated red blood cells after incubation with serum revealed that antibodies, HBsAg or both mediated polymerized albumin binding. The predominant immunoglobulin class with polymerized albumin binding activity was IgG in sera from patients with chronic active hepatitis and alcoholic liver disease, and IgM in acute viral hepatitis, chronic persistent hepatitis, and primary biliary cirrhosis. HBsAg-mediated polymerized albumin binding activity was frequently associated with antibodies to polymerized albumin. The attachment of hepatitis B virus to hepatocytes may be facilitated by polymerized albumin via polymerized albumin receptors. Antibodies to polymerized albumin may interfere with this binding and may result in reduced infectivity.

Oxyphilic granular hepatocytes. Mitochondrion-rich liver cells in hepatic disease.

In the course of examining liver biopsy specimens, certain larger than normal liver cells whose cytoplasm is finely granular and strikingly acidophilic have been seen. These cells are called "oxyphilic granular hepatocytes" (oxyphils) because of their similarities to the "oncocytes" of the salivary glands and other endocrine organs. Oxyphilic liver cells can be readily differentiated from acidophilic bodies and groundglass hepatocytes by light and electron microscpy, the latter showing them to be extraordinarily rich in mitochondria. A retrospective study of 214 consecutive liver biopsies was undertaken to determine the prevalence of oxyphilic cells in a variety of liver diseases. Oxyphils were identified in 15% of the biopsy specimens, and were most strongly associated with chronic active hepatitis and cirrhosis in hepatitis B surface antigen (HBsAg)-positive patients. Subsequent reevaluation of 77 biopsy specimens from HBsAg-positive patients showed oxyphils in 28.6%. Their pathogenesis and significance in chronic liver disease are unknown.

Measurement of colloid clearance rate as an adjunct to static liver imaging.

A technique for the measurement of the rate of uptake of 99mTc labelled sulphur colloid in the liver using a gamma camera and computer is described. The mathematical model showing the factors affecting the rate of uptake, and the results of the measurements in a series of normals and patients with a variety of liver diseases are presented. The range in cirrhosis was found to be significantly lower than normal and the range in acute liver injury significantly higher. The technique can easily be incorporated into a standard colloid liver imaging procedure and is considered to be a valuable adjunct to diagnosis using the static images.

Antibodies to Ribosomes in Chronic Active Hepatitis

A recently developed Farr-type radioimmunoassay for the detection of antibodies to tritium-labeled HeLa cell cytoplasmic ribosomes was evaluated as a serologic test in a variety of liver diseases. Ribosomal antibodies were detected in the sera of 31.4% of 70 patients with chronic active hepatitis (CAH) and primary biliary cirrhosis compared with only 4.2% of patients with chronic persistent hepatitis, acute viral hepatitis, alcoholic liver disease, and miscellaneous liver diseases (X2 = 17.89, P less than 0.001). The level of ribosomal binding activity was also significantly higher in sera of patients with CAH and primary biliary cirrhosis (15.4% vs 6.5%; t = 5.61, P less than 0.001). The antibodies were observed almost exclusively in HBsAg-negative CAH with autoimmune features and infrequently at lower titer in HBsAg-positive CAH or CAH without HBsAg or autoantibodies. Inhibition experiments with purified ribosomal RNA suggested that the ribosomal antibodies are in part reactive with ribosomal RNA. Ribosomal antibodies appear to represent another example of the exaggerated immune response associated with CAH and primary biliary cirrhosis.

Hepatitis B surface antigen and antibody status in biopsy proven chronic hepatitis in Singapore

During the period between January 1975 and August 1976, 203 liver biopsies were received at the Singapore General Hospital from patients with a variety of liver diseases. A histological diagnosis of chronic hepatitis was made in 29 patients: 13 cases of Chronic Aggressive Hepatitis (C.A.H.). 10 cases Chronic Persistent Hepatitis (C.P.H.) and 6 of Chronic Lobular Hepatitis (C.L.H.). C.P.H. and C.L.H. were found mainly in the third and fourth decades. C.A.H. was more common in the fifth to seventh decades and occurred principally in females. Hepatitis B antigenaemia was detected in 48.3% of these cases using the immunoelectroosmophoresis (EOP) technique and showed an even scatter in all histological sub-types. Using the reverse passive haemagglutination (rPHA) method for detection by HBs antigen and the radioelectrocomplexing (REC) method for anti-HBs, an immune sub-group (HBs Ag+/anti-HBs+) was identified in greater proportions in C.A.H. and C.P.H. compared to normal controls. This was interpreted to mean that these patients suffered from a primary immunodeficiency characterized by failure of production of high avidity anti-HBs with resulting failure to clear HBsAg leading to perpetuation of liver damage due to circulating immune complexes. It is also suggested that patients with C.P.H. belonging to this immune sub-group may progress to C.A.H. with its more ominous prognosis.

Erythrocyte lipid composition and sodium transport in human liver disease

In patients with liver disease there are usually increases in erythrocyte cholesterol and phosphatidylcholine concentrations. This increase in membrane lipid changes the shape of the erythrocyte and “spur” or “target” cells may be present. Sodium fluxes were measured in erythrocytes from 17 patients with a variety of liver diseases and from 17 normal subjects and the values related to the lipid content of the membrane. Ouabain-insensitive and ouabain-sensitive effluxes were lower in patients than in normal subjects and the reduction in ouabain-insensitive efflux was more marked. Sodium influx was also significantly lower in erythrocytes from patients than controls. Ouabain-sensitive and ouabain-insensitive effluxes and sodium influx did not correlate with the cholesterol content of erythrocytes from patients. Significant negative correlations were noted between ouabain-insensitive sodium efflux ( r = −0.63, P < 0.01), sodium influx ( r = −0.61, P < 0.01) and intracellular sodium concentration ( r = −0.66, P < 0.01) and the cholesterol : phospholipid molar ratio of the cell but there was no significant correlation between this ratio and the ouabain-sensitive sodium efflux ( r = 0.41, P > 0.05). These results support the hypothesis that an altered lipid composition may affect the permeability of the erythrocyte membrane in patients with liver disease.

Simultaneous measurement of mitochondrial and microsomal cytochrome levels in human liver biopsy

The mitochondrial and microsomal cytochromes in patients' livers obtained from needle biopsies have been analyzed using a sensitive spectrophotometric method. To determine simultaneously the concentration of these cytochromes from hemoglobin-contaminated liver, difference spectra of liver homogenates were taken at the temperature of liquid nitrogen before and after photolysis of carbon monoxide molecules from various hemoprotein-CO complexes. This method utilizes a characteristic property of hemoprotein-CO complexes, in which the reassociation of CO molecules with photolyzed hemoglobin, cytochrome P-450 and cytochrome a 3 is temperature-dependent. The results in 69 cases with a variety of liver diseases have revealed that the concentrations of cytochromes aa 3, P-450 and b 5 showed a huge variation in the injured livers as compared with those in the normal controls. The significance of the measurement of these cytochrome concentrations and their ratios is discussed.

Effects of jaundiced plasma on vascular sensitivity to noradrenalin

Alterations in renal perfusion have been shown in a variety of liver diseases. We have examined the possibility that the syndrome is due to a renal vascular hypersensitivity to noradrenalin (NA). Isolated perfused kidneys and segments of rabbit femoral artery were used. Potentiation of the pressor effects of injected NA occurred in all (five artery and five kidney) preparations when jaundiced baboon plasma was perfused. These changes were significant (P less than 0.05) in nine out of the ten experiments. Controls to which normal baboon plasma was administered showed no such change. No correlation was found between the degree of NA potentiation and the plasma concentrations of bilirubin (total and conjugated), serum glutamic oxaloacetic transaminase, blood urea nitrogen, serum glutamic pyruvic transaminase, alkaline phosphatase, Na+ ions or K+ ions in the jaundiced plasma. Plasma renin levels were not significantly changed. When arteris were perfused with Krebtentiation of NA was found. Perfusion of sodium taurocholate or sodium deoxycholate (400 mug/ml) yielded no potentiation. Thus, the altered renal perfusion associated with jaundice may be attributed to a potentiated pressor response to NA which may be caused by an increased level of cholesterol carried on the beta-lipoprotein.

Demonstration of bile canaliculi by an immunofluorescent staining technique.

AbstractUsing an indirect immunofluorescent technique sera from a group of patients suffering from a variety of liver diseases have been shown to contain an antibody which will specifically stain the bile canaliculi of a wide variety of mammals, birds and amphibia. It is suggested that this method is an effective alternative to the methods presently available for demonstration of bile canaliculi.

The mercuric chloride turbidity test

1. 1. Some of the factors concerned with the Takata-Ara reaction have been investigated. It is suggested that the test is best conducted in the neighbourhood of pH 12.3 in phosphate buffer at a final ionic strength of 1.0. 2. 2. Of the common metallic salts which can be used under these conditions only those of mercury and silver have shown any differentiation between hepatitis and normal sera. This may be correlated with the instability of the hydroxides of these two metals. 3. 3. On the basis of these experiments, a new technique for the determination of HgCl 2 turbidity is proposed which gives normal limits of from 0–4 units. 4. 4. Experiments with bovine and human serum proteins have shown that the reagent is precipitated by the β- and γ-globulin fractions. The influence of albumen may be either inhibitory or enhancing according to its relative concentration. 5. 5. The results of the test have been tabulated in 279 patients suffering from a variety of diseases. It appears to be a sensitive indicator of hepatic cirrhosis, but is also positive in a variety of liver diseases and in certain other conditions. 6. 6. The test shows a fairly close correlation with the zinc sulphate test; it is, however, more sensitive and less specifically related to liver damage. There is a definite but less close correlation with the thymol turbidity test, and with the A/G ratio. 7. 7. The mercuric chloride turbidity test appears to be of value in the diagnosis of hepatic cirrhosis, and in the investigation of liver damage in other conditions.