H Hartmann

To evaluate the prognostic value of quantitative liver function tests in comparison with established prognostic variables, the data of 47 patients with liver cirrhosis were analysed. A total of 16 variables, comprising the galactose elimination capacity and the indocyanine green clearance, the Child-Pugh classification, and several clinical and biochemical variables were subjected to Kaplan-Meier life-table analysis and Cox proportional hazards regression analysis. As independent variables, poor prognosis was associated significantly with increasing Child-Pugh score (p less than 0.00001), whereas the galactose elimination capacity (p = 0.03) and the indocyanine green clearance (p less than 0.001) were less sensitive indicators. The regression analysis showed prognostic value in decreasing sequence for Child-Pugh classification, age, sex, history of upper GI haemorrhage, and alkaline phosphatase activity. The quantitative liver function tests evaluated in the present work have less prognostic value than routinely accessible variables.

Hepatitis C virus (HCV) causes acute and often chronic hepatitis. On the basis of variations in nucleotide sequence, at least six genotypes and several subtypes have been identified. Histopathologically, chronic HCV infection is characterized by relatively mild hepatic inflammatory activity and a low degree of fibrosis, but hepatic lesions might be accompanied by bile duct damage, intraportal lymphoid aggregates, steatosis, or a combination of these manifestations. The histopathological lesions thus appear quite heterogeneous. To address the question of whether distinct histopathological manifestations are related to particular genotypes of HCV, 90 patients with chronic HCV infection were analyzed regarding histopathological features, biochemical liver parameters, demographic data, and virus genotype. The results revealed a significantly higher prevalence of both steatosis and bile duct lesions among patients infected by HCV type 3a compared to patients infected by types 1a or 1b. Furthermore, the data suggest interrelationships between virus genotype, patient's age, and a history of intravenous drug abuse. However, none of the histopathological manifestations were found to be related to a history of drug abuse. The data further corroborate the relationship of HCV type 1b infection to age, duration of disease, and the degree of fibrosis, respectively. Irrespective of HCV genotype, elevated serum ALT activity was shown to be associated with pronounced inflammatory activity or pronounced steatosis as well. Thus, the current data support the hypothesis that distinct genotypes of HCV appear to be associated with distinct manifestations of disease.

Chronic liver disease is characterized by numerous metabolic alterations, predominantly catabolic, resulting in the clinical picture of malnutrition and even cachexia in some patients. The following review focuses on disturbances of glucose metabolism and of hormonal interactions that could contribute to the clinical picture of malnutrition seen in chronic liver disease. Body composition is altered in a characteristic manner with an increase in fat mass and a significant loss of muscle tissue. Furthermore, defective glucose storage due to reduced insulin sensitivity predominantly of muscle tissue has been observed. The pathogenesis of insulin resistance leading to an impaired glucose tolerance or a manifest diabetes mellitus is as yet unknown. A receptor/postreceptor dysfunction probably exists in chronic liver disease that might be explained by the following factors: 1. Altered membrane lipid composition and increased levels of free fatty acids; 2. long-lasting hyperinsulinemia; 3. increased plasma levels of insulin counteracting hormones such as growth hormone, glucagon, catecholamines and possibly cytokines; 4. a lack of liver-derived humoral factors with insulin-like activity, i.e. insulin-like growth factors I and II.

Ninety analogues of suramin have been examined for their ability to inhibit the exogenous reverse transcriptase (RT) of human immunodeficiency virus type I (HIV-I). Of these compounds, 57 inhibited the poly(rC).oligo(dG)-dependent RT activity. Three classes of dose-response curves could be discriminated. Allocation of a compound to one class did not correspond with obvious structural features. Twenty-four substances were superior to suramin in our RT inhibition assay. The RT-inhibitory activity of these compounds did not correlate with their effect against filariae or trypanosomes. Preliminary antiviral evaluation in susceptible human T cells inoculated with HIV-I demonstrated in vitro therapeutic efficacy for some compounds with lower drug-related cellular toxicity than suramin. Certain structural features relevant for the RT-inhibitory effect of these compounds were recognized. Predictions are made for the design of more effective RT inhibitors. Such compounds will help to understand the molecular mechanism of reverse transcription and might be useful in the therapy of retroviral infections.