Lysosomal Acid Lipase Activity Is Reduced Both in Cryptogenic Cirrhosis and in Cirrhosis of Known EtiologyReportar como inadecuado

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Lysosomal acid lipase deficiency LAL-d is a rare autosomal recessive disease in which LAL activity is almost absent, with consequent massive microvesicular steatosis evolving to cirrhosis and liver failure. We aimed to determine LAL-activity, and to investigate the most common single nucleotide polymorphism SNP affecting the LIPA gene and responsible for 50–70% of LAL-d cases rs116928232 c.894G>A, in patients with cryptogenic cirrhosis. Sixty-three patients with cryptogenic cirrhosis, 88 cirrhotics of known etiology, and 97 healthy subjects were enrolled. LAL-activity was determined in dried-blood-spot DBS. The c.894G>A mutation was analyzed by pyrosequencing method in SNP mode. LAL-activity was severely reduced in patients with cryptogenic cirrhosis with respect to healthy subjects 0.62 0.44–0.86 Vs 0.96 0.75–1.25 nmol-spot-h, p<0.001, but it was also reduced in known-etiology cirrhotics 0.54 0.42–0.79 nmol-spot-h, p<0.001 Vs healthy subjects; p = 0.5 Vs cryptogenic cirrhotics. Fourteen percent of cryptogenic cirrhotics and 20% of known-etiology cirrhotics showed a LAL-activity in the range of heterozygous carriers of LIPA gene mutations 0.15–0.40 nmol-spot-h. However, none of the subjects with reduced LAL-activity carried the c.894G>A SNP except for one patient with HCV cirrhosis. By multivariate analysis, LAL-activity was not associated with age, sex, liver enzymes, liver function or lipid parameters, while it was independently associated with white blood cell β = 0.2; p<0.01 and platelet β = 0.4; p<0.001 counts and with the condition of cirrhosis β = -0.2; p = 0.04.


Liver cirrhosis is characterized by a severe acquired reduction of LAL-activity, the precise causes and consequences of which need to be further addressed. DBS-determined lysosomal enzyme activities seem to be affected by white blood cell and platelet counts, and the specificity of these tests can be reduced when applied to determined populations, such as cirrhotics.

Autor: Umberto Vespasiani-Gentilucci , Paolo Gallo, Fiorella Piemonte, Elisabetta Riva, Aldostefano Porcari, Ferruccio Vorini, Giulia To



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