An open-label randomized control study to compare the efficacy of vitamin e versus ursodeoxycholic acid in nondiabetic and noncirrhotic Indian NAFLD patients

Abstract

Background/Aim:The study was carried out to compare the efficacy of Vitamin E versus Ursodeoxycholic acid (UDCA) in nondiabetic nonalcoholic fatty liver disease (NAFLD) patients.Patients and Methods:We randomized 250 non cirrhotic and non diabetic NAFLD patients diagnosed on ultrasound, with raised alanine aminotransferase (ALT) level. (>40 IU/L), to receive Vitamin E 400 mg twice a day (Group A) or UDCA 300 mg twice a day (Group B) for 52 weeks. Lifestyle modification to achieve at least 5% weight reduction and subsequent weight control and regular exercise was advised to both groups. The primary study endpoint was normalization of ALT. Secondary endpoints were the proportion of patients with reduction in ALT, relative reduction in the NAFLD Fibrosis score (NFS), symptomatic improvement and tolerability.Results:One hundred and fifty patients received UDCA as compared to 100 patients receiving Vitamin E. The treatment groups were comparable at entry with regard to age (44.1 vs 42.4 years), gender (67% vs 63% female), risk factors for nonalcoholic steatohepatitis, hypochondriac pain, serum liver biochemistries, and NAFLD Fibrosis score. The primary endpoint was achieved in 21 (14%) and 19 (19%) of patients in Group A and Group B, respectively (P = 0.2). The proportion of patients with reduction in ALT (56% vs 63%, P = 0.2), symptomatic improvement (78% vs 67%, P= 0.058), reduction in the NFS (44% vs 47%, P= 0.69), and tolerability (98% vs 95%, P= 0.2) were similar between Group A and Group B, respectively.Conclusion:UDCA is an effective and safe alternative to Vitamin E in nondiabetic–noncirrhotic Indian NAFLD patients.

Relationship between three commonly used non‐invasive fibrosis biomarkers and improvement in fibrosis stage in patients with non‐alcoholic steatohepatitis

“…Several previous studies evaluated longitudinal changes in non‐invasive measures of fibrosis and associations with histologic or clinical outcomes; however, limited reports have paired these assessments with liver biopsy evaluations . Among the serum markers currently available for non‐invasive evaluation of fibrosis, APRI, FIB‐4 index and NFS have been used and validated most extensively .…”

“…In addition, the limited sampling frequency in the FLINT trial for both laboratory biomarkers (ie, once every 24 weeks) and histologic evaluations (ie, at baseline and 72 weeks) precluded the ability to assess the time to effect of OCA on these outcomes and the predictive value of APRI, FIB-4 index, and NFS at time points earlier than 24 weeks. Moreover, the relatively wide CIs for the AUROC findings in this analysis may suggest the need to investigate the predictive value of additional biomarkers.Several previous studies evaluated longitudinal changes in non-invasive measures of fibrosis and associations with histologic or clinical outcomes[24][25][26][27][28][29][30] ; however, limited reports have paired these assessments with liver biopsy evaluations 25,27,28,30. Among the serum markers currently available for non-invasive evaluation of fibrosis, APRI, FIB-4 index and NFS have been used and validated most extensively 9,31.…”

The role of bile acids in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

“…However, multiple trials have shown a lack of improvement in NAFLD or NASH and it is not currently recommended for use in patients with NAFLD or NASH (Dufour et al, 2006; Haedrich and Dufour, 2011; Leuschner et al, 2010; Lindor et al, 2004; Parikh et al, 2016). C57BL/6 mice fed a HFD given UDCA in conjunction with omega-3 had decreased liver fibrosis and inflammation compared with a group of mice given only omega-3 (Kim et al, 2014).…”

“…In a randomized controlled trial conducted by Parikh et al, patients with NAFLD were given either vitamin E or UDCA (Parikh et al, 2016). UDCA was not superior to vitamin E when comparing improvements in ALT and NAFLD fibrosis score.…”

An Open-label Randomized Clinical Study to Compare the Effects of a Nutritional Supplement versus Vitamin E on Fibroscan Score in Nonalcoholic Steatohepatitis (NASH) Patients

“…These include pentoxifylline, orlistat, Vitamin E, ursodeoxycholic acid, omega -3 fatty acids, and insulin sensitizers and lipid-lowering agents [6]. However, the American Association for the Study of Liver Diseases (AASLD) recommends the use of Vitamin E administered at daily doses of 800 IU/day in non-diabetic adults with biopsy-proven NASH and is considered as a first line pharmacotherapy for this patient population [7].…”