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Effects of Canagliflozin on Fatty Liver Indexes in Patients with Type 2 Diabetes: A Meta-analysis of Randomized Controlled Trials.
Li, B, Wang, Y, Ye, Z, Yang, H, Cui, X, Wang, Z, Liu, L
Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques. 2018;(1):222-235
Abstract
PURPOSE Non-alcoholic fatty liver disease (NAFLD) affects about 75% of patients with type 2 diabetes mellitus (T2DM). We conducted a meta-analysis to determine the effect of canagliflozin on fatty liver indexes in T2DM patients. METHODS A literature search of PubMed, Embase and Cochrane was conducted up to March 30, 2017. The liver function test and lipid profile were extracted from randomized controlled trials (RCTs) to evaluate the effect of canagliflozin on fatty liver. Weighted mean differences (WMDs) or relative risks and 95% confidence intervals (CIs) were computed by using either fixed or random-effects models. Sensitivity analysis and publication bias were evaluated. RESULTS Our results showed that canagliflozin decreased serum concentrations of alanine amino transferase (WMD: -11.68 [95% CI: -18.95, -10.95]; P<0.001), aspartate amino transferase (WMD: -7.50 [95% CI: -10.61, -4.38]; P<0.001), gamma-glutamyl transferase (WMD: -15.17 [95% CI: -17.73, -12.61]; P<0.001), triglycerides (WMD: -0.10 [95% CI: -0.15, -0.05]; P<0.001) but increased low-density lipoprotein cholesterol (WMD: 0.1 [95% CI: 0.06, 0.13]; P<0.001), high-density lipoprotein cholesterol (WMD: 0.06 [95% CI: 0.05, 0.07]; P<0.001) at week 26 or 52. CONCLUSIONS Our results indicated that canagliflozin may have a protective effect on fatty liver in T2DM patients. The limitation was that the liver biopsy was hard to obtain in published studies. More RCTs specified on NAFLD are needed to get further information. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
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Noninvasive Tests Do Not Accurately Differentiate Nonalcoholic Steatohepatitis From Simple Steatosis: A Systematic Review and Meta-analysis.
Verhaegh, P, Bavalia, R, Winkens, B, Masclee, A, Jonkers, D, Koek, G
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2018;(6):837-861
Abstract
BACKGROUND & AIMS Nonalcoholic fatty liver disease is a rapidly increasing health problem. Liver biopsy analysis is the most sensitive test to differentiate between nonalcoholic steatohepatitis (NASH) and simple steatosis (SS), but noninvasive methods are needed. We performed a systematic review and meta-analysis of noninvasive tests for differentiating NASH from SS, focusing on blood markers. METHODS We performed a systematic search of the PubMed, Medline and Embase (1990-2016) databases using defined keywords, limited to full-text papers in English and human adults, and identified 2608 articles. Two independent reviewers screened the articles and identified 122 eligible articles that used liver biopsy as reference standard. If at least 2 studies were available, pooled sensitivity (sensp) and specificity (specp) values were determined using the Meta-Analysis Package for R (metafor). RESULTS In the 122 studies analyzed, 219 different blood markers (107 single markers and 112 scoring systems) were identified to differentiate NASH from simple steatosis, and 22 other diagnostic tests were studied. Markers identified related to several pathophysiological mechanisms. The markers analyzed in the largest proportions of studies were alanine aminotransferase (sensp, 63.5% and specp, 74.4%) within routine biochemical tests, adiponectin (sensp, 72.0% and specp, 75.7%) within inflammatory markers, CK18-M30 (sensp, 68.4% and specp, 74.2%) within markers of cell death or proliferation and homeostatic model assessment of insulin resistance (sensp, 69.0% and specp, 72.7%) within the metabolic markers. Two scoring systems could also be pooled: the NASH test (differentiated NASH from borderline NASH plus simple steatosis with 22.9% sensp and 95.3% specp) and the GlycoNASH test (67.1% sensp and 63.8% specp). CONCLUSION In the meta-analysis, we found no test to differentiate NASH from SS with a high level of pooled sensitivity and specificity (≥80%). However, some blood markers, when included in scoring systems in single studies, identified patients with NASH with ≥80% sensitivity and specificity. Replication studies and more standardized study designs are urgently needed. At present, no marker or scoring system can be recommended for use in clinical practice to differentiate NASH from simple steatosis.
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Systematic review with meta-analysis: non-alcoholic steatohepatitis - a case for personalised treatment based on pathogenic targets.
Younossi, ZM, Reyes, MJ, Mishra, A, Mehta, R, Henry, L
Alimentary pharmacology & therapeutics. 2014;(1):3-14
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Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is an umbrella term, which encompasses simple steatosis and non-alcoholic steatohepatitis (NASH). The entire spectrum of NAFLD has been associated with metabolic syndrome. NASH is associated with increased mortality compared with that of the general population. Many therapeutic options for NASH have been studied. However, there is very little evidence supporting the efficacy of most regimens for the treatment of NASH. AIM: To provide a review focusing on the current therapeutic options available for patients with NASH as well as to briefly introduce possible future interventions. METHODS A MEDLINE, Pubmed and Cochrane Review database search using a combination of keywords, which included non-alcoholic fatty liver disease, non-alcoholic hepatic steatosis, NAFLD, NASH, treatment, therapeutics, vitamin E, orlistat and bariatric surgery. An overall summary of the articles was developed for each section of discussion in this review. RESULTS NASH associated with metabolic syndrome can progress advanced fibrosis and cirrhosis. Weight loss and lifestyle modification have been shown to improve NASH. Other medications used for weight loss and metabolic syndrome have been evaluated, such as orlistat, metformin and thiazolidinediones. Alternative regimens using ursodeoxycholic acid, statins and probiotics as well as bariatric surgery have been evaluated, but have not been recommended as first-line treatment for NASH. Vitamin E for NASH patients without diabetes seems to be promising. The lack of effective treatment for NASH suggests the heterogeneity of patients presenting with the NASH phenotype. The best treatment strategy for these patients may be to identify their pathogenic target and develop personalised treatment protocols. CONCLUSIONS Currently, there are few options available for the management of NASH. Future targeted treatment strategies based on the pathogenic pathways may be needed to develop effective treatment for patients with NASH.
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MTP -493G>T polymorphism and susceptibility to nonalcoholic fatty liver disease: a meta-analysis.
Zheng, W, Wang, L, Su, X, Hu, XF
DNA and cell biology. 2014;(6):361-9
Abstract
Microsomal transfer protein (MTP), a lipid transfer protein localized in the endoplasmic reticulum of hepatocytes and enterocytes, plays an important role in the development of nonalcoholic fatty liver disease (NAFLD). Many existing studies have demonstrated that a common polymorphism (-493G>T, rs1800591 G>T) in the MTP gene may be implicated in the development and progression of NAFLD, but individually published results are inconclusive. This meta-analysis aimed to investigate whether MTP -493G>T polymorphism may be a potential risk factor for NAFLD. We searched CISCOM, CINAHL, Web of Science, PubMed, Google Scholar, EBSCO, Cochrane Library, and CBM databases from inception through October 1, 2013. Meta-analysis was performed using the STATA 12.0 software. Eleven clinical case-control studies with a total of 636 NAFLD cases and 918 healthy controls met the inclusion criteria. Our meta-analysis results revealed that MTP -493G>T polymorphism was strongly correlated with an increased risk of NAFLD. Subgroup analysis by ethnicity suggested that MTP -493G>T polymorphism might increase individuals' susceptibility to NAFLD among both Caucasian and non-Caucasian populations. No publication bias was observed in this meta-analysis. In short, the present meta-analysis indicates that MTP -493G>T polymorphisms may contribute to individuals' susceptibility to NAFLD. Thus, MTP -493G>T polymorphism may be a valuable and practical biomarker for early detection of NAFLD.
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Association between the Pro12Ala polymorphism of PPAR-γ gene and the non-alcoholic fatty liver disease: a meta-analysis.
Wang, J, Guo, X, Wu, P, Song, J, Ye, C, Yu, S, Zhang, J, Dong, W
Gene. 2013;(2):328-34
Abstract
Several studies have been conducted to examine the association between PPAR-γ2 Pro12Ala polymorphism and non-alcoholic fatty liver disease (NAFLD), but the results remain inconsistent. In this study, a meta-analysis was performed to assess the association of PPAR-γ Pro12Ala polymorphism with NAFLD risk. A total of 8 case-control studies, including 1697 cases and 2427 controls, were selected. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Overall, no evidence has indicated that the Pro12Ala polymorphism was associated with the susceptibility to NAFLD. Besides, stratified analysis with ethnicity also indicated that no significant association between PPAR-γ Pro12Ala and the risk of NAFLD under all for genetic model in both Asian and Caucasian populations was observed. This meta-analysis indicated that the Pro12Ala polymorphism is not associated with NAFLD risk. Large and well-designed studies are warranted to validate our findings.