Severe liver impairment in a cystic fibrosis-affected child homozygous for the G542X mutation.

The clinical and laboratory findings of a cystic fibrosis (CF) patient homozygous for the G542X mutation are described. This is the first case, among the 7 G542X homozygous CF subjects described so far who shows severe liver involvement, associated pancreatic insufficiency, and moderate pulmonary expression of the disease, as demonstrated by laboratory and imaging data. This case adds to the conclusion that genotype/phenotype correlation in cystic fibrosis is more complex than formerly suspected.

Quantitative analysis of aldolase A mRNA in liver discriminates between hepatocellular carcinoma and cirrhosis.

BACKGROUND: Chronic liver diseases can progress to cirrhosis and to hepatocellular carcinoma. Timely and unequivocal recognition of the neoplastic evolution of cirrhosis is critical. To this aim, we used a noncompetitive reverse transcription-PCR procedure to analyze aldolase A mRNA in liver tissue from patients with chronic liver diseases at different stages. METHODS: We studied 12 patients with hepatocellular carcinoma, 19 patients affected by chronic hepatitis C or cirrhosis, and 7 healthy controls. Aldolase A mRNA was reverse-transcribed to cDNA, which was then amplified by PCR. The amplified segments were "read" with a novel dot-blot procedure. A calibrator with the same sequence, synthesized in vitro using a T7 phage promoter, was processed at scalar dilutions in parallel to the target samples to generate a calibration curve and so quantify the target mRNA (detection limit, 0.03 amol; linearity spanning five orders of magnitude). RESULTS: Aldolase A mRNA was approximately 10-fold higher in liver biopsies from patients with hepatocellular carcinoma vs patients with chronic hepatitis C or cirrhosis, and healthy individuals. Furthermore, aldolase A mRNA concentrations were 1.2- to 21.3-fold higher in 12 liver biopsies compared with the paired surrounding cirrhotic tissue. CONCLUSIONS: The quantitative analysis of liver tissue aldolase A mRNA differentiates between nonneoplastic chronic liver diseases and hepatocellular carcinoma, which suggests that it has diagnostic potential.