Precirrhotic Liver Research Articles

The Use of a Combination of Peripheral Markers for Diagnosing Alcoholism and Monitoring for Continued Abuse

Values for serum aspartate transaminase, gamma glutamyl transpeptidase and mean corpuscular volume were followed in twenty actively drinking alcoholics with pre-cirrhotic liver disease over a three-month period to assess the usefulness of these markers for detecting and monitoring alcohol abuse. At first assessment, values for one or more of these markers were elevated in all twenty patients. Thus measuring all three markers together enabled the diagnosis of alcohol abuse in all patients. At the end of three months, during which time alcohol intake had been changing, values for the markers used singly or in combination did not clearly differentiate patients who ceased, decreased or continued alcohol abuse. In individual patients, however, values of one or more markers clearly mirrored changes in alcohol intake. Values of the markers changed at different rates in relation to changes in alcohol intake and, in certain patients, values remained normal until a given daily alcohol intake was attained.

Topological analysis of the morphogenesis of liver cirrhosis.

Cirrhotic and precirrhotic livers consist of three-dimensional parenchymal networks. Topological analysis has been carried out using the total connectivity number p1 on the livers from 6 autopsy cases of chronic liver diseases of different types. The total p1 amounts to 6,100,000 in chronic hepatitis of periportal type and 6,350,000 in portal cirrhosis, but to only 100,000 in posthepatitic cirrhosis of coarse-nodular type. In view of the similarity of values for p1 in chronic hepatitis and portal cirrhosis, the former is considered to give rise to the latter by continuous change in structure or through "piecemeal" progression of the periportal lesion. Development of posthepatitic cirrhosis from chronic hepatitis is possible only through a substantial reduction in p1, which is brought about by parenchymal necrosis sufficient in extent to cause multiple disconnection of the network.

Actin-like contractile protein in carbon tetrachloride-induced cirrhosis in the rat

Cryostat sections of livers from rats treated with carbon tetrachloride (CCl4) for 12 weeks were examined by indirect immunofluorescence for reactivity with human serum containing smooth muscle antibody (SMA). Increased binding of SMA serum to hepatocytes was observed as early as the first week of CCl4 treatment and remained enhanced during the 12 weeks of study. No difference in staining intensity was observed between pre-cirrhotic liver parenchymal cells and hepatocytes in regenerative nodules of frankly cirrhotic livers. In addition, granulation tissue fibroblasts in cirrhotic livers showed strong reactivity with SMA serum. The specificity of the staining reaction for actin was established by its prevention on neutralization absorptions of the serum with homogenates of smooth muscle or extracts containing actin derived from smooth muscle. Circulating SMA was not demonstrated in the serum of rats at any phase of the study. The observations show that there is an increased expression of actin-like protein in regenerating hepatocytes and granulation tissue fibroblasts in cirrhotic livers.

Enzymic studies in small amounts of human tissue with the help of microanalytical methods: III. Energetic metabolism of cirrhotic and precirrhotic liver tissue removed by needle biopsy

1. 1. Using micro analytical methods that allowed work on tissue aliquots of 10 mg, the oxidative ATP-resynthesis, oxygen consumption, and the activity of seven liver enzymes have been measured in total homogenates of human liver samples removed by needle biopsy. 2. 2. A significant decrease of oxidative ATP-resynthesis and oxygen consumption has been found in cirrhotic and precirrhotic patients showing gross histological liver changes, as well as in precirrhotic states with no evident microscopical involvement. This result provides new evidence of an impaired energetic liver metabolism in cirrhotic diseases. 3. 3. The activities of lactic dehydrogenase, malic dehydrogenase, isocitric dehydrogenase, succinic dehydrogenase, aldolase, DPN-cytochrome c reductase, and glutamic-oxalacetic transaminase were found to be significantly reduced with reference to a tissue wet weight basis. When calculated in terms of parenchymal protein content this reduction remained significant for aldolase and isocitric dehydrogenase. Thus 2 steps of the glycolytic chain and tricarboxylic cycle appear to be impaired in the remaining parenchyma of cirrhotic and precirrhotic livers. 4. 4. The reduction of oxidative ATP-resynthesis, oxygen uptake and aldolase activity does not seem to be specific for cirrhotic and precirrhotic states. In a group of 40 patients including noncirrhotic diseases, a significant correlation was found between the results of these in vitro determinations and the clinical evaluation of liver function. 5. 5. It is assumed that the direct in vitro measurement of an overall cellular process like oxidative ATP-resynthesis in human liver samples could provide a more accurate and more representative evaluation of the liver function than most of the usual clinical tests.