Prognosticher Wert von Leberfunktionstests--Klinik, laborchemische Parameter und quantitative Funktionstests

In view of increasing therapeutic possibilities interest focuses on prognosis of liver cirrhosis. Until nowadays studies on prognosis revealed significant importance only for some parameters: Ascites, encephalopathy and portal hypertension as signs of decompensation, bilirubin, albumin and prothrombin time as laboratory indices of decreasing liver function. The commonly used Child-Pugh-score is based on these parameters and allows a reasonable classification of diseased patients. Cholestasis and inflammation seem to be of minor prognostic importance. Assessment of liver function by quantitative tests is desirable (e.g. aminopyrine breath test, bile acids). The prognostic value, however, has not yet been proven in large studies. Use of these tests should therefore be restricted to studies (prognosis, therapy, indication to liver transplantation

Prognostic value of the intravenous 14C-aminopyrine breath test compared to the Child-Pugh score and serum bile acids in 84 cirrhotic patients

The prognostic value of the intravenous 14C-aminopyrine breath test (ABT) in liver cirrhosis was compared to that of the well-established multiparametric Child-Pugh classification and that of serum bile acids, an endogenous parameter of liver function for which a prognostic value in patients with liver cirrhosis has been demonstrated previously. 84 patients with liver cirrhosis were studied. 32 of the patients died during the observation period. Survival was analyzed for periods of 3, 6 and 12 months after examination. For all chosen observation periods, the Child-Pugh score was of prognostic value. ABT gave prognostic information for periods of 6 and 12 months of survival, but was by far inferior to the Child-Pugh score. Serum bile acids in our population did not yield prognostic information at any time interval studied. We conclude that in our group of cirrhotic patients, the prognostic value of the Child-Pugh classification was by far superior to quantitative liver function tests in predicting surviva

Twin Res Hum Genet

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder caused by heterozygotic inactivation of the NF1 tumor suppressor gene at 17q11.2. The associated phenotypes are highly variable, and modifying genes have been proposed to explain at least in part the intriguing expressivity. Given that haploinsufficiency of the NF1 gene product neurofibromin is responsible for some of the clinical manifestations, variations in expression of the wildtype NF1 allele might modify the phenotype. We therefore investigated epigenetic molecular modifications that could result in variable expression of the normal NF1 allele. To exclude confounding by DNA sequence variations, we analyzed monozygotic twin pairs with NF1 who presented with several discordant features. We fine-mapped the methylation pattern of a nearly 1 kb NF1 promoter region in lymphocytes of 8 twin pairs. All twin pairs showed significant intra-pair differences in methylation, especially of specific promoter subregions such as 5'UTR, exon 1 and intron 1 (+7 to +622), transcription factor binding sites and promoter elements like NF1HCS. Furthermore, we detected significant intra-pair differences in cytosine methylation for the region from -249 to -234 with regard to discordance for optic glioma with a higher grade of methylation in glioma cases. In conclusion, our findings of epigenetic differences of the NF1 promoter in leukocytes within mono zygotic twin pairs may serve as a proof of principle for other tissues. The results point towards a role of methylation patterns of the normal NF1 allele for expression differences and for modification of the NF1 phenotype