Lysosomal Acid Lipase Activity in Non-alcoholic Fatty Liver Disease as a Novel Diagnostic and Therapeutic Target: A Systematic Literature Review of Current Evidence and Future Directions

Background and aim: Non-alcoholic fatty liver disease (NAFLD) presents with the accumulation of excessive intrahepatic fat without significant alcohol intake. Multifactorial pathogenesis is reported to be involved. Reduced lysosomal acid lipase (LAL) activity is suggested as one of the novel-involved pathogenic mechanisms. This review summarizes the available evidence on the role of LAL activity in NAFLD pathogenesis. Methods: Four databases namely, PubMed/Medline, Science direct, Cochrane Library, and Google scholar were searched to identify relevant observational records evaluating the role of LAL activity in the pathogenesis of NAFLD. All studies were assessed for their quality by using Newcastle-Ottawa Scale or The Joanna Briggs Institute Critical Appraisal tools for cohort and cross-sectional studies, respectively. The estimates of LAL activity and other clinical outcomes were expressed as mean (SD) and number (%) as presented in the primary studies. Results: A total of nine good quality studies with 1711 patients with NAFLD and 877 controls from different groups (healthy volunteers, alcoholics, cryptogenic cirrhosis, and HCV-positive) were included. From the NAFLD group, 59.55% were males and the overall mean age ranged between the studies from 12.6 +/- 8.5 months in pediatrics to 58.90 +/- 13.82 years in adults. In the NAFLD group, the LAL activity varied from 0.53 +/- 0.08 to 1.3 & PLUSMN; 0.70 (nmol/spot/hr) between the studies which was less than all control groups except cryptogenic cirrhosis patients (0.5 +/- 0.15 nmol/spot/hr). Of the other outcomes of interest, ALT, AST, total cholesterol, triglyceride, and LDL cholesterol were found elevated in NAFLD patients than in controls. Conclusion: The current evidence suggests a potential correlation of reduced LAL activity with NAFLD pathogenesis according to its severity. Large-scale studies are recommended, more importantly in patients with NAFLD having no metabolic or genetic involvement. Further LAL can act as a new non-invasive diagnostic biomarker to identify that specific NAFLD subgroup.