Reduced lysosomal acid lipase activity: A new marker of liver disease severity across the clinical continuum of non-alcoholic fatty liver disease?

Table 2 Studies investigating the activity of lysosomal acid lipase in patients with non-alcoholic fatty liver disease and liver cirrhosis

NAFLD
Year	Paper	Study populations	Results1	Conclusions
2015	Baratta et al[27]	100 HS; 240 NAFLD patients; (35 biopsy-proven NASH)	Median LAL activity was: 1.15 (0.95-1.72) in HS; 0.78 (0.61-1.01) in NAFLD; 0.67 (0.51-0.77) in NASH	A significant reduction of LAL activity in NAFLD patients compared to HS. In particular, in the subgroup of patients with biopsy proven NASH
2016	Selvakumar et al[29]	168 children with biopsy-proven NAFLD; (80 NAFL and 88 NASH)	Mean LAL activity was: 1.3 ± 0.57 in NAFL patients; 1.2 ± 0.80 in NASH patients; 1.4 ± 0.80 in patients with F0-F1; 1.1 ± 0.45 in patients with F2-F3	No significant difference in LAL activity between children with NASH compared to those without NASH; Reduced blood LAL activity correlates with severity of liver fibrosis
2017	Polimeni et al[30]	315 NAFLD patients; with US spleen dimensions evaluation	Median LAL activity was: 0.9 (0.7-1.2) in patients with normal spleen; 0.7 (0.6-0.9) in patients with splenomegaly	Spleen enlargement and splenomegaly were significantly associated with a reduced LAL activity
2017	Tovoli et al[31]	81 NAFLD patients; (53.1% with cirrhosis)	Median LAL activity was: 0.55 (0.41-0.81) in non-cirrhotic NAFLD patients; 0.84 (0.69-1.07) in non-cirrhotic HCV patients	LAL activity is significantly reduced in non-cirrhotic NAFLD, compared to that in non-cirrhotic HCV patients.
		78 HCV patients (59.0% with cirrhosis)
Liver cirrhosis
2016	Vespasiani-Gentilucci et al[34]	63 CC patients 88 KAC patients 97 HS	Median LAL activity: 0.62 (0.44-0.86) in CC patients; 0.54 (0.42-0.79) in KAC patients; 0.96 (0.75-1.25) in HS	Liver cirrhosis is characterized by a severe acquired reduction of LAL-activity; The difference between the two groups of cirrhotics was not significant […]; LAL activity was not associated with liver function as determined with Child-Pugh class […]
2016	Shteyer et al[35]	22 patients aged 1-75 years who underwent liver biopsy; 13 at high risk for LAL-D (microvesicular steatosis or with cryptogenic cirrhosis); 9 at low risk for LAL-D; (microvesicular steatosis in metabolic/NAFLD patients)	Mean LAL activity was 0.74 ± 0.28 and was similar in both risk groups; 37.5% had LAL < 0.5	LAL < 0.5 was associated with markers of liver disease severity
2017	Tovoli et al[31]	81 NAFLD patients; (53.1% with cirrhosis)	Median LAL activity was: 0.53 (0.29-0.69) in cirrhotic NAFLD patients; 0.67 (0.50-0.89) in cirrhotic HCV patients	LAL activity is significantly reduced in NAFLD-related cirrhosis compared to HCV-cirrhosis
		78 HCV patients; (59.0% with cirrhosis)
2017	Angelico et al[33]	133 CC patients; 141 KAC patients	Median LAL activity was: 0.49 (0.38-0.75) in CC patients; 0.65 (0.46-0.94) KAC patients	A strong association between LAL activity reduction and severity of liver disease was found. A marked reduction of LAL activity in patients with cryptogenic cirrhosis compared to the other known etiologies despite a more severe liver disease in the latter

¹All lysosomal acid lipase activity values are expressed as nmol/spot per hour. HS: Healthy subjects; NAFLD: Non-alcoholic fatty liver disease; NAFL: Non-alcoholic fatty liver/simple steatosis; NASH: Non-alcoholic steatohepatitis; CC: Cryptogenic cirrhosis; KAC: Known etiology cirrhosis.