Lysosomal acid lipase activity is reduced both in cryptogenic cirrhosis and in cirrhosis of known etiology

Lysosomal acid lipase deficiency (LAL-d) is a rare autosomal recessive disease in whichLAL activity is almost absent, with consequent massive microvesicular steatosis evolving tocirrhosis and liver failure. We aimed to determine LAL-activity, and to investigate the mostcommon single nucleotide polymorphism (SNP) affecting the LIPA gene and responsiblefor 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 97healthy subjects were enrolled. LAL-activity was determined in dried-blood-spot (DBS). Thec.894G>A mutation was analyzed by pyrosequencing method in SNP mode. LAL-activitywas 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 inknown-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 knownetiologycirrhotics showed a LAL-activity in the range of heterozygous carriers of LIPA genemutations (0.15–0.40 nmol/spot/h). However, none of the subjects with reduced LAL-activitycarried the c.894G>A SNP except for one patient with HCV cirrhosis. By multivariateanalysis, LAL-activity was not associated with age, sex, liver enzymes, liver function or lipidparameters, 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).ConclusionLiver cirrhosis is characterized by a severe acquired reduction of LAL-activity, the precisecauses and consequences of which need to be further addressed. DBS-determined lysosomalenzyme activities seem to be affected by white blood cell and platelet counts, and the