Vitamin E and Pioglitazone: A Comprehensive Systematic Review of Their Efficacy in Non-alcoholic Fatty Liver Disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide, especially in people with obesity, dyslipidemia, type 2 diabetes mellitus (T2DM), and metabolic syndrome. Weight loss and dietary modifications are established first-line treatments for NAFLD. Currently, there is no approved drug for NAFLD; however, pioglitazone and vitamin E have shown some beneficial effects. This systematic review covers the comparative efficacies of vitamin E, pioglitazone, and vitamin E plus pioglitazone. As of December 2022, the sources for prior literature review included PubMed, PubMed Central, and Medline. We included studies assessing the efficacy of pioglitazone, vitamin E, and vitamin E plus pioglitazone in improving liver histology, liver markers, and lipid profile when compared to other interventions in patients with NAFLD/non-alcoholic steatohepatitis (NASH). Review materials include randomized control trials (RCTs), traditional reviews, systematic reviews, meta-analyses, and observational studies on human participants published within the last five years in the English language. Studies on animals, pediatric populations, and with insufficient data were excluded from the review. Two authors scanned and filtered articles independently and later performed quality checks. A third reviewer resolved any conflicts. The risk of bias was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines for systematic reviews, the Cochrane Risk of Bias Tool for RCTs, and the Scale for the Assessment of Narrative Review Articles for Traditional Reviews. A total of 21 articles were shortlisted. The results showed that pioglitazone and vitamin E are effective in reducing steatosis, inflammation, and ballooning, reducing liver markers, but there seem to be conflicting data on fibrosis resolution. Pioglitazone decreases triglycerides and increases high-density lipoproteins. One study has suggested that pioglitazone has superior efficacy to vitamin E in fibrosis reduction and vitamin E plus pioglitazone has superior efficacy than pioglitazone alone for NASH resolution. However, these conclusions require further validation through extensive analysis and additional research. In conclusion, diabetic patients with NAFLD can be given pioglitazone, and non-diabetic patients with NAFLD can be given vitamin E.

MAFLD Pandemic: Updates in Pharmacotherapeutic Approach Development

“…Moreover, they appear to be involved in fibrotic processes, as agonism of the PPAR isotope gamma (γ) leads to an inhibition of the pro-fibrotic effect of hepatic stellate cells in the liver, which are activated in the course of NASH progression [86]. Generally, in MAFLD, PPARs are dysregulated, and the effect of the agonist for PPAR α/γ receptor, pioglitazone, is associated with improvement in steatosis, inflammation and hepatic biomarkers, making it a very compelling choice for MAFLD therapy [84,87,88]. This drug belongs to the drug group of thiazolidinedione commonly called "glitazone" and is indicated for T2DM due to its efficacy in lowering blood glucose levels by enhancing insulin resistance [89].…”

“…Moreover, treatment with pioglitazone is already included in several guidelines as a possible treatment option for patients with T2DM and proven MASH [90]. On the other hand, it should be pointed out that the clinical use of pioglitazone is limited due to its potential side effects including weight gain, bladder cancer, fluid retention which can cause congestive heart failure in patients having cardiomyopathy and an enhanced risk of bone loss and distal bone fractures in postmenopausal women, and therefore careful selection of patients for pioglitazone therapy is required [87,91]. The assessment of the efficacy of oral pioglitazone on hepatic steatosis and liver function tests over 24 weeks and its safety was conducted in a placebo-controlled RCT (NCT01068444) in 90 Taiwanese participants with MASH.…”