Reduced lysosomal acid lipase activity – A potential role in the pathogenesis of non alcoholic fatty liver disease in pediatric patients

Selvakumar, Praveen Kumar Conjeevaram; Kabbany, Mohammad Nasser; López, Rocío; Tozzi, Giulia; Alisi, Anna; Alkhouri, Naim; Nobili, Valério

doi:10.1016/j.dld.2016.04.014

Cited by 31 publications

(23 citation statements)

References 25 publications

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“…These findings are in agreement with Shteyer et al who found that low LAL activity correlates with advanced liver disease and that LAL activity < 0.5 indicates severe liver injury in patients with fatty liver and cirrhosis. Finally, they are also in keeping with Selvakumar PK et al who reported a correlation between reduced blood LAL activity and the severity of liver fibrosis in children with NAFLD …”

Section: Discussionsupporting

confidence: 89%

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Lysosomal acid lipase activity and liver fibrosis in the clinical continuum of non‐alcoholic fatty liver disease

Baratta

Pastori

Tozzi

et al. 2019

Liver International

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Background and Aims Recent evidence showed a reduced activity of the lysosomal acid lipase (LAL) in patients with non‐alcoholic fatty liver disease (NAFLD) and cryptogenic cirrhosis (CC). However, the relationship between LAL activity and liver fibrosis has never been investigated. Methods Cross‐sectional study including 575 outpatients referred for the management of cardio‐metabolic and liver disease. The absence of liver fibrosis was defined by a FIB‐4 < 1.30 and NAFLD fibrosis score (NFS) <−1.455. LAL activity was measured with dried blood spot technique. Results Overall, 515 patients had a diagnosis of NAFLD (454 NAFL and 61 biopsy‐proven NASH) and 60 of CC. The value of LAL activity progressively decreased from healthy subjects to NAFL/NASH patients to CC (P < .001). LAL activity was reduced by 10% in patients with NAFL, by 20% in NASH and by 50% in CC. The prevalence of CC decreased across the tertiles of LAL activity: 22.2% in the lowest, 4.6% in the intermediate and 0.5% in the highest tertile. In NAFLD patients, 69.9% had a FIB4 < 1.30, and 43.1% a NFS <−1.455. Multivariate logistic regression analysis showed that Log (LAL activity) was associated with FIB‐4 < 1.30 (Odds ratio [OR] 2.19 95% confidence interval [CI] 1.33‐3.62, P = .002) and NFS < −1.455 (OR 2.43, 95% CI 1.51‐3.91, P < .001) after adjustment for confounding factors. Conclusions We found a progressive reduction of LAL activity according to liver disease severity. LAL activity was inversely associated with markers of liver fibrosis in patients with NAFLD.

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Section: Discussionsupporting

confidence: 89%

“…More recently, in patients with cryptogenic cirrhosis (CC), a further reduction in the activity of LAL has been described . These results were similar to those obtained in children with biopsy‐proven NASH …”

Section: Introductionsupporting

confidence: 77%

Lysosomal acid lipase activity and liver fibrosis in the clinical continuum of non‐alcoholic fatty liver disease

Baratta

Pastori

Tozzi

et al. 2019

Liver International

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“…Later, Shteyer et al [7] showed that a low serum LAL-activity correlated with advanced liver disease. Finally, a recent paper by Selvakumar et al [20] correlated LAL deficiency with the severity of liver fibrosis in 168 consecutive children with biopsy-proven NAFLD.…”

Section: Discussionmentioning

confidence: 99%

A Relative Deficiency of Lysosomal Acid Lypase Activity Characterizes Non-Alcoholic Fatty Liver Disease

Tovoli

Napoli

Negrini

et al. 2017

IJMS

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Lysosomal acid lipase (LAL) is a key enzyme in lipid metabolism. Initial reports have suggested a role for a relative acquired LAL deficiency in non-alcoholic fatty liver disease (NAFLD)—however, it is still unclear whether this mechanism is specific for NAFLD. We aimed to determine LAL activity in a cohort of NAFLD subjects and in a control group of hepatitis C virus (HCV)-infected patients, investigating the role of liver cirrhosis. A total of 81 patients with a diagnosis of NAFLD, and 78 matched controls with HCV-related liver disease were enrolled. For each patient, LAL activity was determined on peripheral dried blood spots (DBS) and correlated with clinical and laboratory data. A subgroup analysis among cirrhotic patients was also performed. LAL activity is significantly reduced in NAFLD, compared to that in HCV patients. This finding is particularly evident in the pre-cirrhotic stage of disease. LAL activity is also correlated with platelet and white blood cell count, suggesting an analytic interference of portal-hypertension-induced pancytopenia on DBS-determined LAL activity. NAFLD is characterized by a specific deficit in LAL activity, suggesting a pathogenetic role of LAL. We propose that future studies on this topic should rely on tissue specific analyses, as peripheral blood tests are also influenced by confounding factors.

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“…Diagnosis is theoretically important because of the potential for treatment with sebelipase alfa. 88 However, despite the possibility of misdiagnosis of LAL-D as NAFLD, or a role of LAL in NAFLD, 89 to date there are no reports of identification of LAL-D in cohorts of children with fatty liver; therefore, its relevance to routine clinical practice remains to be established. It is not clear how best to monitor pediatric NAFLD, but it is well established that aminotransferases are a poor marker of disease activity.…”

Section: Dangerous Liaisonsmentioning

confidence: 99%

Nonalcoholic Fatty Liver Disease in Children

et al. 2018

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Nonalcoholic steatohepatitis, a progressive form of nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in children who present with particular risk factors including obesity, sedentary lifestyle, and/or a predisposing genetic background. The worldwide prevalence of NAFLD in children is a worrying phenomenon because this disease is closely associated with the development of both cirrhosis and cardiometabolic syndrome in adulthood. To date, the etiopathogenesis of primary NAFLD in children is unknown. Understanding the pathogenetic mechanisms provides the basis to characterize early predictors of the disease and noninvasive diagnostic tools and to design novel specific treatments and possible management strategies. Despite a few clinical trials on the use of antioxidants combined with lifestyle intervention for NAFLD, no treatment exists for children with NAFLD. In this review, the authors provide an overview of current concepts in epidemiology, histological features, etiopathogenesis, diagnosis, and treatment of NAFLD in pediatric population.

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Reduced lysosomal acid lipase activity – A potential role in the pathogenesis of non alcoholic fatty liver disease in pediatric patients

Cited by 31 publications

References 25 publications

Lysosomal acid lipase activity and liver fibrosis in the clinical continuum of non‐alcoholic fatty liver disease

Lysosomal acid lipase activity and liver fibrosis in the clinical continuum of non‐alcoholic fatty liver disease

A Relative Deficiency of Lysosomal Acid Lypase Activity Characterizes Non-Alcoholic Fatty Liver Disease

Nonalcoholic Fatty Liver Disease in Children

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