MIDTERM RESULTS OF THE OBSERVATIONAL NON-INTERVENTIONAL CLINICAL STUDY "EVALUATION OF THE EFFECTIVENESS OF THE CARNITINE OROTATE AND BIPHENYL DIMETHYL DICARBOXYLATE COMPLEX IN THE PATHOGENETIC THERAPY OF METABOLIC-ASSOCIATED FATTY LIVER DISEASE: A PROSPECTIVE COHORT STUDY»

Abstract

Introduction. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a widespread pathology requiring effective 
treatment approaches. One promising direction is the use of a complex of carnitine orotate and biphenyl dimethyl 
dicarboxylate (COC and BDD), which possess antioxidant and hepatoprotective properties. 
Materials and methods. As part of the observational, non-interventional, prospective cohort study KASVM-01 
[NCT06078722], the impact of COC and BDD on the progression of MAFLD in patients in the Republic of Kazakhstan was 
investigated. From February 2023 to July 2024, a total of 121 participants from Almaty and Almaty Region were enrolled in 
the study and received COC and BDD. The observation period lasted 12 months, with an interim analysis conducted on 78 
participants who completed a 24-week treatment course. Anthropometric parameters (BMI, waist circumference), liver 
steatosis, and fibrosis levels measured via transient elastography (FibroScan) with CAP, ALT, AST, total cholesterol,  triglycerides, and FIB-4 (a non-invasive fibrosis marker) were assessed at baseline and after completing 24 weeks of therapy 
with COC and BDD. 
Results. The interim analysis revealed a statistically significant reduction in ALT levels (from 32.4 to 20.1 U/mL, 
p<0.001), triglycerides (from 1.4 to 1.3 mmol/L, p=0.007), steatosis grade (from 304 to 283 dB/m, p<0.001), and fibrosis level 
(from 6.5 to 6.0 kPa, p=0.022). The prevalence of severe steatosis (S3) decreased from 52.7% to 45.7%, whereas mild 
steatosis (S1, S0) increased to 21.4% and 10%, respectively (p=0.001). The proportion of patients with F3 fibrosis declined 
from 8.1% to 1.4%, while F2 fibrosis decreased from 27% to 21.4% (p=0.022), indicating an improvement in fibrosis markers. 
During the observation period, BMI decreased (from 30.4 to 29.8 kg/m²), although the changes were not statistically 
significant (p=0.214). No significant changes were observed in total cholesterol and FIB-4 levels. 
Conclusion. The interim analysis confirmed the effectiveness of COC and BDD in the treatment of MAFLD, 
demonstrating improvements in biochemical parameters as well as regression of liver steatosis, and fibrosis. Further 
research and validation of these findings in later stages of observation are necessary to assess the final efficacy and long
term safety of the therapy.