MANPOWER study: Real-world post-hoc analysis assessing essential phospholipids for non-alcoholic fatty liver disease from the Russian registry

Abstract

BACKGROUND

Since non-alcoholic fatty liver disease (NAFLD) is associated with abnormal liver function tests, treatment recommendations aim to reduce the level of known markers of liver inflammation, such as alanine transaminase (ALT), aspartate transaminase (AST) and gamma-glutamyl transferase (GGT). Essential phospholipids (EPLs) have been shown to reduce levels of these liver enzymes and improve ultrasonographic features. While non-invasive diagnostic tests have been developed to stage inflammation, these tests were not specifically designed to evaluate patients with NAFLD. This highlights the need to describe the liver enzyme profile across the different levels of NAFLD severity for improved grading and staging of NAFLD.

AIM

To describe liver enzyme profiles across NAFLD severity to inform a diagnostic staging algorithm and identify who may benefit from EPLs.

METHODS

This post-hoc analysis of the observational MANPOWER study included 2843 adult patients with newly diagnosed NAFLD. The primary endpoint was assessment of baseline liver enzyme profiles. Secondary endpoints were effectiveness of Essentiale^® (an EPL) on liver enzyme levels and ultrasonography findings across three definitions of NAFLD: (1) Statistical distribution of liver enzyme levels; (2) MANPOWER cut-offs; and (3) Presence of physician-diagnosed non-alcoholic steatohepatitis. The best performing algorithm was used to describe the risk factors and profiles associated with increased liver enzyme levels.

RESULTS

Of the 2843 patients included in this post-hoc analysis, most were female (62.2%), with a mean age of 48.4 years (SD 8.59 years). Overall, mean levels of ALT, AST and GGT increased with NAFLD severity for all three subgroups, with the rate of chronic comorbidities correlated with NAFLD severity. Across each subgroup of interest, Essentiale significantly reduced average liver enzyme levels and improved ultrasonography features, including diffuse liver hyperechogenicity and heterogeneous liver structure (P < 0.05), with greater benefit associated with increased severity. Compared with all algorithms tested, the algorithm based on the statistical distribution of liver enzymes displayed the highest accuracy, sensitivity and specificity for the grading and staging of NAFLD and could form the basis of a diagnostic algorithm.

CONCLUSION

Liver enzyme profiles may identify NAFLD severity and allow monitoring of therapeutic response. Essentiale may improve liver enzyme levels and ultrasonography features. An algorithm could aid in the diagnosis/staging of NAFLD.

Keywords: Algorithms; Essential phospholipids; Liver enzymes; Non-alcoholic fatty liver disease; Ultrasonography

Core Tip: Essentiale Forte N^®, administered as adjunctive therapy in patients with non-alcoholic fatty liver disease (NAFLD), reduced liver enzyme levels [alanine transaminase (ALT), aspartate transaminase (AST) and gamma-glutamyl transferase (GGT)] and improved ultrasonographic features of NAFLD, particularly with regard to liver hyperechogenicity and structure, with a greater reduction noted with increasing NAFLD severity. These data indicate that Essentiale, alone or in combination with other treatment, is effective for the management of NAFLD. Additionally, a non-invasive diagnostic algorithm based on the statistical distribution of three liver enzymes (ALT, AST, and GGT) could be used to increase the accuracy of diagnosis, staging, and monitoring of patients with NAFLD.