Discussion
non-alcoholic fatty liver disease, NAFLD, metabolic alterations, overdose, gallstone, inflammation, PBC, weight loss, steatohepatitis
PBC, GALLSTONE, INFLAMMATION, MINOR, NON-ALCOHOLIC FATTY LIVER DISEASE, STEATOHEPATITIS
In this study, we evaluated the effects of UDCA treatment for six months on liver enzymes, lipid profile, glucose level, and inflammatory markers in patients after bariatric surgery. We found a higher increase in mean ALP level in patients who used UDCA compared to patients receiving placebo treatment. No other significant changes in blood values were observed. Cross-sectional analysis of postoperative blood values did also reveal lower AST and ALT levels, and a slightly higher level of cholesterol in patients who were adherent to UDCA treatment. However, the observed effects of UDCA treatment on liver enzymes, metabolism, and inflammation are minor or absent, and the clinical consequences are negligible. In view of these results, it is confirmed that UDCA treatment in patients after bariatric surgery is safe, but the role in metabolic alterations after surgery seems limited.To our knowledge, only one study has previously examined the effects of UDCA treatment on clinical blood values in patients after bariatric surgery [In contrast to these previous studies, we were not able to detect clinically relevant effects of UDCA use on blood values in this study. Cross-sectional analyses did reveal slightly lower levels of ALT and AST and a marginally higher level of total cholesterol in the UDCA group. Also, the main analysis in which changes in values were compared, showed a greater decrease of AST and ALT and less decrease of total cholesterol in the UDCA group, but these differences did not reach statistical significance. This might be explained by the different populations in our study with substantial changes occurring in the body composition and metabolism after bariatric surgery, especially in the first 6 months. For instance, studies focusing on the underlying mechanisms of action of UDCA showed that a changed bile acid profile and microbiome remodeling might be involved [The strengths of this study include the randomized controlled study design (as part of the UPGRADE trial) and the relatively large sample size. Although power calculations were not performed for the endpoints of the present study, we were not able to detect any additional effects of UDCA. Even if these effects on laboratory markers could be detected in larger study populations, they are probably too small and therefore nog clinically relevant. Furthermore, adherence was assessed in a structured manner, providing the possibility to assess both clinical effects in the entire population and biological effects in patients who actually used UDCA according to prescriptions. However, several limitations should be addressed. First, laboratory measurements were not included in the UPGRADE trial design but were part of regular clinical assessment in the largest participating center, which resulted in missing values and exclusion of results on blood drawn more than 4 weeks after the last dose of trial medication. Second, patients allocated to prophylactic UDCA use were prescribed 900 mg of UDCA daily. This was independent of their body weight before or in the first 6 months after bariatric surgery, whereas UDCA in other conditions such as PBC is prescribed based on body weight. Hence, for some patients, 900 mg might be below the recommended dose at first and might have changed to an appropriate dose or overdose during weight loss. On the other hand, the recommended dose is higher for PBC than for gallstone dissolution. Third, the number of patients known with non-alcoholic fatty liver disease or steatohepatitis in our study population was limited, most probably because these conditions were not structurally recorded in patient’s records. Therefore, we cannot make any statements about the effects of UDCA treatment in this subgroup of patients. However, the analysis in the subgroup of the patient with any of the liver enzymes elevated before surgery did not result in clinically relevant changes either. This is in line with previous studies in patients with NAFLD showing ambivalent effects of UDCA treatment [In conclusion, UDCA treatment after bariatric surgery does not seem to affect liver function, lipid, glucose, and inflammatory metabolism in a clinically relevant way. Only a limited effect on ALP was noted, which could not be explained by an altered calcium metabolism either. The mechanisms leading to protection against gallstone formation have yet to be identified. Future studies in patients after bariatric surgery should focus on the underlying mechanisms of action in humans and also investigate the effects of treatment with other bile acids, for example, chenodeoxycholic acid, which might be more beneficial to human metabolism.