miRNAs in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis

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The relationship between non-alcoholic fatty liver disease and hypothyroidism: A systematic review and meta-analysis

Background:Whether hypothyroidism is related to non-alcoholic fatty liver disease (NAFLD) is controversial. Our aim was to investigate the relationship between NAFLD and hypothyroidism that may predict the NAFLD potential of these lesions and new prevention strategies in hypothyroidism patients.Methods:Totally 51,407 hypothyroidism patients with average 28.23% NAFLD were analyzed by Revman 5.3 and Stata 15.1 softwares in the present study. The PubMed and Embase databases were systematically searched for works published through May 9, 2020.Results:The blow variables were associated with an increased risk of NAFLD in hypothyroidism patients as following: increased of thyroid stimulating hormone (TSH) levels (odds ratio [OR] = 1.23, 1.07–1.39, P = .0001); old age (mean difference [MD] = 3.18, 1.57–4.78, P = .0001); increased of body mass index (BMI) (MD = 3.39, 2.79–3.99, P < .000001); decreased of free thyroxine 4 (FT4) levels (MD = –0.28, –0.53 to –0.03, P = .03). In addition, FT3 (MD = 0.11, –0.09–0.3, P = .29) had no association with the risk of NAFLD in hypothyroidism patients.Conclusion:Our systematic review identified results are as following: hypothyroidism was positively associated with the risk of NAFLD. The increased concentration of TSH levels maybe a risk factor that increased incidence of NAFLD. The BMI of NAFLD patients was significantly higher than that of non-NAFLD patients. Old age was significantly associated with the incidence of NAFLD. FT4 was significantly associated with the risk of NAFLD due to its negatively effect while FT3 was not significantly related to the risk of NAFLD. Taken together, the present meta-analysis provides strong evidence that hypothyroidism may play a vital role in the progression and the development of NAFLD.     

Association of non-alcoholic fatty liver disease with thyroid function: A systematic review and meta-analysis

BackgroundNonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. The relationship of NAFLD with thyroid function parameters and hypothyroidism remains controversial.AimTo clarify the effect of thyroid function parameters and hypothyroidism on the development of NAFLD and progression to nonalcoholic steatohepatitis (NASH).MethodsPubMed, EMBASE, and Cochrane library databases were searched. Study quality was assessed. Weighted mean difference (WMD) and odds ratio (OR) with 95% confidence interval (CI) were calculated.ResultsTwenty six studies involving 61,548 participants were eligible, most of which were of high quality. NAFLD/NASH patients had significantly higher TSH levels than controls in adults (NAFLD versus health: WMD = 0.105, 95%CI = 0.012–0.197; NAFLD versus euthyroidism: WMD = 0.100, 95%CI = 0.005–0.194; NASH versus NAFLD: WMD = 0.540, 95%CI = 0.136–0.944) and children/adolescents (NAFLD versus lean controls: WMD = 1.039, 95%CI = 0.104–1.973; NAFLD versus overweight/obese controls: WMD = 0.485, 95%CI = 0.267–.703). Unclassified hypothyroidism was positively associated with the risk of NAFLD/NASH in adults (NAFLD versus health: OR = 1.605, 95%CI = 1.180–2.183; NASH versus NAFLD: OR = 2.317, 95%CI = 1.425–3.768) and children/adolescents (NAFLD versus overweight/obese controls: OR = 2.015, 95%CI = 1.246–3.258). However, the statistical results were inconsistent among the subgroup meta-analyses of subclinical and overt hypothyroidism. Association of NAFLD with FT3 and FT4 levels was heterogeneous among population.ConclusionTSH level may be an important risk factor for the development and progression of NAFLD, independent of thyroid hormones.     

Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta-analysis

Non-alcoholic fatty liver disease (NAFLD) is a frequent accompaniment of obesity and insulin resistance. With the prevalence approaching 85% in obese populations, new therapeutic approaches to manage NAFLD are warranted. A systematic search of the literature was conducted for studies pertaining to the effect of omega-3 polyunsaturated fatty acid (PUFA) supplementation on NAFLD in humans. Primary outcome measures were liver fat and liver function tests: alanine aminotransferase (ALT) and aspartate aminotransferase [1]. Data were pooled and meta-analyses conducted using a random effects model. Nine eligible studies, involving 355 individuals given either omega-3 PUFA or control treatment were included. Beneficial changes in liver fat favoured PUFA treatment (effect size=-0.97, 95% CI: -0.58 to -1.35, p<0.001). A benefit of PUFA vs. control was also observed for AST (effect size=-0.97, 95% CI: -0.13 to -1.82, p=0.02). There was a trend towards favouring PUFA treatment on ALT but this was not significant (effect size=-0.56, 95% CI: -1.16 to 0.03, p=0.06). Sub-analyses of only randomised control trials (RCTs) showed a significant benefit for PUFA vs. control on liver fat (effect size=-0.96, 95% CI: -0.43 to -1.48, p<0.001), but not for ALT (p=0.74) or AST (p=0.28). There was significant heterogeneity between studies. The pooled data suggest that omega-3 PUFA supplementation may decrease liver fat, however, the optimal dose is currently not known. Well designed RCTs which quantify the magnitude of effect of omega-3 PUFA supplementation on liver fat are needed.     

Clinical guidelines of non-alcoholic fatty liver disease: A systematic review

AIM To perform a systematic review to grade guidelines and present recommendations for clinical management of non-alcoholic fatty liver disease(NAFLD).METHODS A database search was conducted on Pub Med for guidelines published before May 2016, supplemented by reviewing relevant websites. The Appraisal of Guidelines for Research and Evaluation(ARGEE) instrument Ⅱ was a tool designed to appraise the methodological rigor and transparency in which a clinical guideline is developed and it is used internationally. it was used to appraise the quality of guidelines in this study. The inclusion criteria include: clinical NAFLD guidelines for adults, published in English, and released by governmental agencies or key organizations.RESULTS Eleven guidelines were included in this study. Since 2007, guidelines have been released in Asia(3 in China, 1 in South Korea, and 1 in Japan), Europe(1 in italy),America(1 in United States and 1 in Chile) and three international agencies [European associations joint, Asia-Pacific Working Party and World Gastroenterology Organization(WGO)]. Using the ARGEE Ⅱ instrument, we found US 2012 and Europe 2016 had the highest scores, especially in the areas of rigor of development and applicability. Additionally, italy 2010 and Korea 2013 also presented comprehensive content, rigorous procedures and good applicability. And WGO 2014 offered various algorithms for clinical practice. Lastly, a practical algorithm for the clinical management was developed, based on the recommended guidelines.CONCLUSION This is the first systematic review of NAFLD guidelines. it may yield insights for physicians and policy-makers in the development and application of guidelines.     

Effect of novel glucose lowering agents on non-alcoholic fatty liver disease: A systematic review and meta-analysis

BackgroundThe efficacy of novel glucose-lowering drugs in treating non-alcoholic fatty liver disease (NAFLD) in patients with and without type-2 diabetic patients (T2DM) remains unclear.AimTo conduct a meta-analysis to evaluate the efficacy of 3 novel glucose-lowering drug classes, namely glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter 2 (SGLT2) inhibitors, and dipeptidyl-peptidase-4 (DPP4) inhibitors on hepatic parameters: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-Glutamyl Transferase (GGT), Bilirubin, and FIB-4 (Fibrosis).MethodsMEDLINE was searched from inception through October 2021 for randomized placebo or active glucose-lowering drug-controlled trials. A random-effects model was used to pool the results. A p-value of less than or equal to 0.05 was considered significant. Results were presented as weighted mean differences (WMD) and corresponding 95% confidence intervals (CIs).ResultsOur pooled analysis consisted of 40 studies. A significant reduction was seen in AST with SGLT2 inhibitors (WMD = -2.31 IU/L, 95%CI: -3.16 to -1.47 IU/L, P < 0.00001) and GLP-1RA (WMD = -3.29 IU/L, 95%CI: -5.98 to -0.61 IU/L, P = 0.02). Similarly, significant reduction was seen in ALT with SGLT2 inhibitors (WMD = -5.93 IU/L, 95%CI: -7.70 to -4.16 IU/L, P < 0.00001) and GLP-1RAs (WMD = -9.92 IU/L, 95%CI: -19.89 to 0.05 IU/L, P = 0.05). In contrast, DPP-4 inhibitors showed no significant reduction in AST (WMD = -3.20 IU/L, 95%CI: -11.13 to 4.73 IU/L, P = 0.43) or ALT (WMD = -4.81 IU/L, 95%CI: -15.83 to 6.21 IU/L, P = 0.39). A significant reduction in GGT was seen with SGLT2 inhibitors (WMD = -6.49 IU/L, 95%CI: -11.09 to -1.89 IU/L, P = 0.006) and GLP-1RAs (WMD = -12.38 IU/L, 95%CI: -15.69 to -9.07 IU/L, P < 0.00001). However, significant results were not observed with DPP-4 inhibitors (WMD = -0.92 IU/L, 95%CI: -5.80 to 3.96 IU/L, P = 0.71). There was a statistically significant reduction in FIB-4 index with SGLT2 inhibitors (WMD = -0.21, 95%CI: -0.40 to -0.03, P = 0.02) and GLP-1 RA (WMD = -0.15, 95%CI: -0.29 to 0.00, P = 0.05). Lastly, SGLT2 inhibitors led to a significant change in bilirubin levels (WMD = 2.03, 95%CI: 0.76 to 3.30, P = 0.002) while the change in bilirubin was not significant with GLP-1 agonists (WMD = -0.21, 95%CI: -1.09 to 0.66, P = 0.63) and DPP-4 inhibitors (WMD = 0.14, 95%CI: -1.55 to 1.83, P = 0.87).ConclusionSGLT2 inhibitors and GLP-1 agonists have a beneficial effect on hepatic parameters in patients with NAFLD. However, further research is needed to evaluate the effect of DPP-4 inhibitors on hepatic function properly.     

Prognostic non-invasive biomarkers for all-cause mortality in non-alcoholic fatty liver disease: A systematic review and meta-analysis

BACKGROUNDNon-alcoholic fatty liver disease (NAFLD) represents a growing public health concern, with patients having higher risk of morbidity and mortality. It has a considerably high prevalence in the general population, estimated 20%-40% in Europe, and is asymptomatic until late in the disease course. It is therefore important to identify and validate tools that predict hard outcomes such as mortality for use in clinical practice in risk-stratifying NAFLD patients.AIMTo evaluate available evidence on the use of non-invasive test(s) as prognostic factors for mortality in NAFLD. METHODSWe performed electronic searches of Medline and EMBASE (Ovid) until 7^th January 2021 of studies in NAFLD populations. Prognostic markers included serum biomarkers, non-invasive scoring systems, and non-invasive imaging. The population included all spectrums of disease severity, including NAFLD and non-alcoholic steatohepatitis (NASH). Outcomes included all-cause, and cardiovascular mortality. All non-invasive tests were synthesised in a narrative systematic review. Finally, we conducted a meta-analysis of non-invasive scoring systems for predicting all-cause and cardiovascular mortality, calculating pooled hazard ratios and 95% confidence (STATA 16.1).RESULTSDatabase searches identified 2850 studies – 24 were included. 16 studies reported non-invasive scoring systems, 10 studies reported individual biomarkers, and 1 study reported imaging modalities. 4 studies on non-invasive scoring systems (6324 participants) had data available for inclusion in the meta-analysis. The non-invasive scoring system that performed best at predicting all-cause mortality was NAFLD fibrosis score (NFS) [pHR 3.07 (1.62-5.83)], followed by fibrosis-4 index [pHR 3.06 (1.54-6.07)], BARD [pHR 2.87 (1.27-6.46)], and AST to platelet ratio index [pHR 1.90 (1.32-2.73)]. NFS was also prognostic of cardiovascular-related mortality [pHR 3.09 (1.78-5.34)].CONCLUSIONThis study reaffirms that non-invasive scoring systems, especially NFS, are reliable prognostic markers of all-cause mortality and cardiovascular mortality in NAFLD patients. These findings can inform clinical practice in risk stratifying NAFLD patients.     

Association between non-alcoholic fatty liver disease and decreased lung function in adults: A systematic review and meta-analysis

AimRecent observational studies assessed the association between non-alcoholic fatty liver disease (NAFLD) and lung function in adults, but the magnitude of this association remains uncertain. We estimated the magnitude of the association between NAFLD and lung function on spirometry (predicted forced expiratory volume in 1 s [FEV₁] and forced vital capacity [FVC]).MethodsWe searched publication databases using predefined keywords to identify studies (published up to October 4, 2018), in which NAFLD was diagnosed by imaging or biochemistry (no studies with biopsy-proven NAFLD were available). Data from selected studies were extracted, and meta-analysis was performed using random-effects modelling.ResultsSix observational studies (5 cross-sectional and 1 longitudinal) with aggregate data on 133,707 individuals (27.8% with NAFLD) of predominantly Asian ethnicity (74.6%) were included in the final analysis. There were significant differences in predicted FEV₁ (n = 5 studies; pooled weighted mean difference [WMD]: −2.43%, 95% CI: −3.28 to −1.58; I² = 69.7%) and predicted FVC (pooled WMD: −2.96%, 95% CI: −4.75 to −1.17; I² = 91.7%) between individuals with and without NAFLD. Decreased FEV₁ and FVC at baseline were also independently associated with a ∼ 15% increased risk of incident NAFLD (n = 1 study in Korean individuals). Subgroup analyses did not materially modify these findings.ConclusionsNAFLD is associated with significant reductions of both FEV₁ and FVC in Asian and United States adults, and such small, but significant, reductions of lung volumes at baseline may be also associated with increased NAFLD incidence in Asian individuals. Further research is needed to better elucidate the link between NAFLD and impaired lung volumes.     

Association between obstructive sleep apnea and non-alcoholic fatty liver disease: a systematic review and meta-analysis

Sleep and Breathing - The relationship between obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) has been an issue of great concern. The primary purpose of this study was...     

非酒精性脂肪性肝病男性人群患结直肠息肉风险增高

【据Journal of Gastroenterology and Hepatology 2020年6月报道】题:非酒精性脂肪性肝病男性人群患结直肠息肉风险增高:一项系统回顾和荟萃分析(作者Chen W等)该荟萃分析旨在探讨非酒精性脂肪性肝病(NAFLD)患者发生结直肠息肉的风险。来自汕头大学医学院第一附属医院的Chen等根据预设的关键词检索了PubMed、EMBASE和Cochrane图书馆数据库,以全面检索、确定符合条件的研究(截至2019年11月7日)。通过标准化的信息收集表格从合格的研究中提取相应数据,并使用随机效应模型进行荟萃分析,同时进行了异质性评估(I 2)、亚组分析、Meta回归分析和发表偏倚分析。     

The relationship between obesity and the severity of non-alcoholic fatty liver disease: systematic review and meta-analysis

Introduction: A number of researches have explored the association between obesity and nonalcoholic fatty liver disease (NAFLD) liver function, histopathology, complications, genetic factors and prognosis, but the results were conflicting and inconclusive.

Areas covered: In this meta-analysis, the liver function, histopathology, metabolic complications, patatin-like phospholipase domain-containing protein 3 (PNPLA3) genetic polymorphism and prognosis were compared between non-obese and obese NAFLD. Pubmed, EMBASE, Cochrane databases were searched to identify eligible studies. The odds ratio (OR) or standardized mean difference (SMD) with 95% confidence intervals (CI) were pooled using fixed- or random-effects models.

Expert commentary: This meta-analysis indicated that for NAFLD patients, obesity (according to ethnic-specific BMI cut-off points to define obesity) could predict a worse long-term prognosis. However, obesity may not be an independent factor for the development of NASH or advanced fibrosis in NAFLD patients and NAFLD should be considered as potential population for pharmacologic treatment regardless of obesity. In addition, PNPLA3 rs738409 may be more relevant to the progression of non-obese NAFLD when compared to obese NAFLD. Importantly, large-sample, long-term follow-up cohort studies based on liver biopsy are highly needed due to limited liver pathology and long-term follow-up data at present.     

Dairy product consumption and risk of non-alcoholic fatty liver disease: A systematic review and meta-analysis of observational studies

Background and aimsIt is unclear whether regular consumption of dairy products is associated with the risk of developing non-alcoholic fatty liver disease (NAFLD). Thus, we conducted a systematic review followed by a meta-analysis of studies reporting on the association of dairy consumption with NAFLD risk.Methods and resultsWe comprehensively searched PubMed, Web of Science, and Scopus for observational studies that evaluated the association between dairy intake and NAFLD likelihood that were published before September 1, 2022. The reported odds ratios (ORs) of fully adjusted models and their 95% confidence intervals (CIs) were pooled using a random-effects model for the meta-analysis. Out of 1206 articles retrieved, 11 observational studies, including 43,649 participants and 11,020 cases, were included. Pooled OR indicated a significant association between dairy intake and NAFLD (OR = 0.90; 95% CI: 0.83, 0.98; I² = 67.8%, n = 11). Pooled ORs revealed that milk (OR: 0.86; 95% CI: 0.78, 0.95; I² = 65.7%, n = 6), yogurt (OR: 0.88; 95% CI: 0.82; I² = 0.0%, n = 4), and high-fat dairy (OR: 0.38; 95% CI: 0.19, 0.75; I² = 0.0%, n = 5) consumption was inversely associated with NAFLD while cheese was not linked to NAFLD risk.ConclusionWe observed that consumption of dairy products is linked to a reduced risk of developing NAFLD. Overall, the data in the source articles is of low to moderate quality; therefore, further observational studies are required to support the current findings (PROSPERO Reg. number: CRD42022319028).     

Acupuncture combined with Chinese herbal medicine on non-alcoholic fatty liver disease: A protocol for systematic review and meta-analysis

Background:Non-alcoholic fatty liver disease (NAFLD) is a global health burden. However, there are no approved drugs for NAFLD. A number of studies have shown that acupuncture combined with Chinese herbal medicine (CHM) can be beneficial for NAFLD. However, high-quality trials are still lacking. Therefore, we aimed to conduct a systematic review and meta-analysis to assess the effectiveness and safety of acupuncture combined with CHM for NAFLD.Methods:Eight electronic databases including PubMed, the Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure, Chinese Scientific and Technical Journals Database, and Wan-fang Database from inception to November 2021 will be searched. We will also search for Clinical Trials Registry Platforms as a supplement. Randomized controlled trials on acupuncture combined with CHM for NAFLD will be included. Literature screening, data extraction, and risk of bias assessment were independently conducted by 2 reviewers. All differences between the 2 reviewers will be discussed and resolved by a third reviewer. Revman5.3 software will be used for meta-analysis.Result:This study aimed to evaluate the effectiveness and safety of acupuncture combined with CHM for NAFLD.Conclusion:The findings of this study will provide more evidence to determine whether acupuncture combined with CHM for NAFLD is an effective and safe intervention for NAFLD.     

Efficacy of statins in treatment and development of non-alcoholic fatty liver disease and steatohepatitis: A systematic review and meta-analysis

BackgroundNon-Alcoholic Fatty Liver Disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. There is no universally accepted effective treatment for NAFLD. Although various studies propose statins effective in lowering liver enzymes and in improving liver histology, their potency in the treatment and development of NAFLD remains unknown.PurposeWe conducted this meta-analysis to evaluate the efficacy of statins in the treatment and the development of NAFLD.MethodsElectronic databases (MEDLINE and Cochrane CENTRAL) were searched from their inception until May 2021 for observational studies and randomized controlled trials (RCTs) that assessed the efficacy of statins for the treatment of NAFLD and its development. Studies were included irrespective of the dosage or duration, and their risk of bias was assessed. The outcomes of interest for our study were the effect of statins on liver histology (steatosis, fibrosis and necroinflammation, NAFLD activity score [NAS]) and liver enzymes (Alanine transaminase [ALT], Aspartate transaminase [AST], and Gamma-glutamyl transferase [GGT] levels). To pool continuous outcomes, a random-effects model was used to derive weighted mean difference (WMD) or standardized mean difference (SMD) and their corresponding 95% confidence intervals (CIs). Generic inverse variance was then used for different measurement units reported by the studies. For studies investigating the effects of statins on the development of NAFLD, generic inverse variance along with random effects model was used to derive odds ratio (ORs) and its corresponding 95% confidence interval (CI).ResultsA total of 14 studies including 1,247,503 participants were short-listed for our analysis. All the studies included in our analysis had a low to moderate risk of bias. The results of our analysis suggest that statins may significantly reduce the risk of developing NAFLD (OR:0.69, 95% CI [0.57,0.84]; p = 0.0002; I² =36%). Statin use significantly reduced ALT levels (WMD: -27.28, 95% CI [-43.06, -11.51]; p = 0.0007; I² =90%), AST levels (WMD: -10.99, 95% CI [-18.17, -3.81]; p = 0.003; I² =79%) and GGT levels (WMD: -23.40, 95% CI [-31.82, -14.98]; p < 0.00001; I² = 21%) in patients presenting with NAFLD at baseline. In liver histology outcomes, steatosis grade (SMD: -2.59, 95% CI [-4.61, -0.56]; p = 0.01; I² = 95%), NAS (WMD: -1.03, 95% CI [-1.33, -0.74]; p < 0.00001; I² = 33%), necro-inflammatory stage (WMD: -0.19, 95% CI [-0.26, -0.13]; p < 0.00001; I² = 0%) and significant fibrosis (OR:0.20, 95% CI [0.04, 0.95]; p = 0.04; I² = 97%) underwent notable reduction. However, fibrosis stage outcome (WMD: 0.07, 95% CI [-0.05, 0.20]; p = 0.27; I² = 0%) was non-significant.ConclusionThere was a significant decrease in transaminase and transferase levels. Marked improvement in liver histology of NAFLD patients was observed. Statin use also remarkably reduced the risk of developing NAFLD. Future large-scale trials can further aid in identifying the positive impact of statins in treatment for NAFLD and those at risk of developing it.     

Physical activity as a treatment of non-alcoholic fatty liver disease: A systematic review

AIM: To review the effectiveness of exercise as a therapy for nonalcoholic fatty liver disease (NAFLD) and potential benefits in treating insulin resistance and atherosclerosis.METHODS: Medline (EBSCOhost) and PubMed were searched for English-language randomized controlled trials and prospective cohort studies in human adults aged ≥ 18 which investigated the various effects of exercise alone, a combination of exercise and diet, or exercise and diet coupled with behavioral modification on NAFLD from 2010 to Feburary 2015.RESULTS: Eighteen of 2298 available studies were chosen for critical review, which included 6925 patients. Nine (50%) studies were randomized controlled trials. Five (27.8%) studies utilized biopsy to examine the effects of physical activity on hepatic histology. The most commonly employed imaging modality to determine change in hepatic steatosis was hydrogen-magnetic resonance spectroscopy. Only two studies examined the effects of low impact physical activity for patients with significant mobility limitations and one compared the efficacy of aerobic and resistance exercise. No studies examined the exact duration of exercise required for hepatic and metabolic improvement in NAFLD.CONCLUSION: While exercise improved hepatic steatosis and underlying metabolic abnormalities in NAFLD, more studies are needed to define the most beneficial form and duration of exercise treatment.