Ursodeoxycholic acid as a means of preventing atherosclerosis, steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease

ARTICLE HIGHLIGHTS

Research background

Nonalcoholic fatty liver disease (NAFLD) is currently the leading cause of liver disease and liver transplantation in developed countries. Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality in patients with NAFLD. Weight loss is a key factor for successful NAFLD and cardiovascular disease therapy. Ursodeoxycholic acid (UDCA), which is one of the first-line therapeutic agents for treatment of NAFLD, is reported to have a beneficial effect on dyslipidemia and ASCVD risk because of antioxidant properties.

Research motivation

The main motivation was our wish to improve the treatment outcomes of patients with NAFLD. Each author of our international study had a personal positive experience of treating NAFLD with UDCA. We sincerely wanted to combine our efforts to gain a new knowledge.

Research objectives

To evaluate the effects of 6-mo administration of UDCA on liver function tests (LFT), lipid profile, hepatic steatosis and fibrosis, carotid intima-media thickness (CIMT), and ASCVD risk in total sample with NAFLD, separately in men and women, in patients with and without > 5% weight loss.

Research methods

An open international noncomparative study was carried out at primary health care settings. The study was completed by 174 patients who were included in the final analysis and received UDCA (Ursosan^®) therapy at a dose of 15 mg/kg body weight daily for 6 mo. In addition, total sample was given recommendations to modify lifestyle behaviors and diet. The body mass index, waist circumference, and LFT were compared between baseline and 3 mo as well as between 3 and 6 mo of the treatment. The lipid profile, fatty liver index (FLI), nonalcoholic fatty liver disease fibrosis score, liver fibrosis index, 10-year and lifetime ASCVD risk, and CIMT were compared between baseline and the end of the follow-up.

Research results

The magnitude of LFT decrease was greater during the first 3 mo of treatment compared to the subsequent 3 mo. At 6 mo, in the total sample, we observed a statistically significant decrease in body mass index, waist circumference, and levels of FLI (P < 0.001), total cholesterol (TC) (Р < 0.001), low-density lipoprotein (LDL) (Р < 0.001), triglyceride (TG) (Р < 0.001), and the CIMT (P = 0.013), whereas the high-density lipoprotein (HDL) (Р = 0.036) and 10-year ASCVD risk improved significantly only in women (Р = 0.003). No effect on nonalcoholic fatty liver disease fibrosis score, and liver fibrosis index was found. At the end of the study, the FLI decreased significantly in patients with and without > 5% weight loss; the changes in LFT, TC, TG, and LDL levels were similar between the subgroups.

Research conclusions

The study suggests that 6-mo UDCA therapy at a dose of 15 mg/kg/d may improve LFT, TC, LDL, and TG levels, FLI, and CIMT in total sample with NAFLD. These changes are observed independent of sex and weight loss. UDCA has also a beneficial effect on HDL and 10-year ASCVD risk in women.

Research perspectives

Further long-term studies with control groups are needed to confirm these findings. For further research, we suggest to compare lipid profile and hepatic steatosis between baseline to 3 mo and 3 to 6 mo; evaluate the effects of long-term UDCA therapy (during 1-year follow-up or more) on HDL and 10-year and lifetime risk ASCVD in men and women.