A randomized double-blind study of the short-time treatment of obese patients with nonalcoholic fatty liver disease with ursodeoxycholic acid

Abstract

In order to determine the effect of ursodeoxycholic acid on nonalcoholic fatty liver disease, 30 patients with body mass indices higher than 25, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) or γ-glutamyltransferase (γ-GT) at least more than 1.5 times the upper limit of normality, and hepatic steatosis demonstrated by ultrasonography were randomized into two groups of 15 patients to receive placebo or 10 mg kg -1 day -1 ursodeoxycholic acid for three months. Abdominal computed tomography was performed to quantify hepatic fat content, which was significantly correlated with histological grading of steatosis (r s = -0.83, P < 0.01). Patient body mass index remained stable for both groups throughout the study, but a significant reduction in mean (± SEM) serum levels of ALT, AST and γ-GT was observed only in the treated group (ALT = 81.2 ± 9.7, 44.8 ± 7.7, 48.1 ± 7.7 and 52.2 ± 6.3 IU/l at the beginning and after the first, second and third months, respectively, N = 14, P < 0.05). For the placebo group ALT values were 66.4 ± 9.8, 54.5 ± 7, 60 ± 7.6 and 43.7 ± 5 IU/l, respectively. No alterations in hepatic lipid content were observed in these patients by computed tomography examination (50.2 ± 4.2 Hounsfield units (HU) at the beginning versus 51.1 ± 4.1 HU at the third month). These results show that ursodeoxycholic acid is able to reduce serum levels of hepatic enzymes in patients with nonalcoholic fatty liver disease, but this effect is not related to modifications in liver fat content.

Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials

“…Seven RCTs (639 participants, 21% diabetic; three RCTs with post-treatment histology, five RCTs with a low risk of bias) evaluated UDCA in NAFLD (ESM Table 5) [82][83][84][85][86][87][88].…”

A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease

“…5). [45][46][47] Two of these RCTs assessed post-treatment-histology, finding no benefit over placebo, but the effect of high-dose UDCA on liver histology is unknown ( Figs. 2-4; Table 1).…”

“…In three RCTs (113 participants, 1 RCT with quality score !7), UDCA for 1.5 to 6 months did not significantly improve ALT levels or radiological steatosis [47][48][49] (Fig. 5, Table 1).…”

Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis

“…So far, four randomized trials with 279 patients have been performed to evaluate the efficacy of ursodeoxycholic acid in the treatment of NAFLD (Santos et al, 2003;Lindor et al, 2004;Méndez-Sá nchez et al, 2004;Ersöz et al, 2005). Although improvement in liver function parameters was reported in individual trials, a metaanalysis showed that ursodeoxycholic acid treatment was not associated with significant differences in mortality or liver function tests (Orlando et al, 2007).…”