Visceral adipose tissue area is an independent risk factor for hepatic steatosis

Background and Aim:  Recent data indicate that hepatic steatosis is associated with insulin resistance, dyslipidemia and obesity (especially central body fat distribution). There have been few studies on the correlation between biopsy-proven hepatic steatosis and the above factors in a disease-free population. The aim of the present study was to evaluate the relation between hepatic steatosis assessed by biopsy and clinical characteristics including regional fat distribution measured by computed tomography (CT) in living liver donors.
Methods:  Laboratory data, liver/spleen Hounsfield ratio (L/S ratio), regional fat distribution by CT and liver status by biopsy were evaluated retrospectively in a total of 177 living liver donors without a history of alcohol intake.
Results:  The unpaired t -test showed that age, triglycerides (TG), high density lipoprotein, total cholesterol, alanine aminotransferase, body mass index, L/S ratio, visceral adipose tissue area (VAT) and subcutaneous adipose tissue area (SAT) were associated with hepatic steatosis. In the multiple logistic regression analysis, VAT (odds ratio 1.031, 95% CI 1.013–1.048, P  < 0.01) and TG (odds ratio 1.012, 95% CI 1.004–1.020, P  < 0.01) were independent risk factors of hepatic steatosis. Subgroup analysis also showed that VAT was an independent risk factor in men (odds ratio 1.022, 95% CI 1.003–1.041, P  < 0.05) and women (odds ratio 1.086, 95% CI 1.010–1.168, P  < 0.05).
Conclusion:  Our results suggest that visceral abdominal adiposity is correlated with hepatic steatosis in healthy living liver donors.     

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.     

Xiaochaihu decoction for nonalcoholic fatty liver disease: A protocol for a systematic review and meta-analysis

Background:Nonalcoholic fatty liver disease (NAFLD) is a clinicopathologic syndrome characterized by excessive deposition of fat in hepatocytes except for alcohol and other specific hepatic factors. Xiaochaihu decoction (XD) has been widely used to treat NAFLD in China. However, there is no systematic review found. In order to evaluate the efficacy and safety of XD in the treatment of NAFLS, we need to conduct a meta-analysis and systematic evaluation.Methods:There are enrolled randomized controlled trials (RCTs) evaluating the effectiveness and safety of XD in the treatment of NAFLD. Data come mainly from 4 Chinese databases (CNKI, CBM, Wanfang, and VIP Database) and 4 English databases (Pubmed, Embase, Cochrane Library, and Web of science). The enrollment of RCTs is from the starting date of database establishment till September 30, 2021. The work such as selection of literature, data collection, quality evaluation of included literature, and assessment of publication bias will be conducted by 2 independent researchers. Meta-analysis will be performed by RevMan 5.0 software.Results:This study will provide high-quality evidence for the effectiveness and safety of XD in the treatment of NAFLD.Conclusion:The results of the study will help us determine whether XD can effectively treat NAFLD.Ethics and dissemination:This study does not require ethical approval. We will disseminate our findings by publishing results in a peer-reviewed journal.OSF registration number:DOI 10.17605/OSF.IO/A5XEM     

Cardiovascular and mortality outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: A meta-analysis with the FREEDOM cardiovascular outcomes trial

Background and aimsFREEDOM, a cardiovascular outcome trial with a GLP-1 receptor agonist, testing a continuous subcutaneous infusion of exenatide (ITCA 650), recently reported its findings.MethodsWe meta-analysed its results with eight prior GLP-1 receptor agonists trials.ResultsGLP-1 receptor agonists reduced MACE by 13% (HR 0.87 [95% CI 0.81–0.94]; p = 0.00065) and all-cause mortality by 11% (HR 0.89 [0.83–0.95]; p = 0.00084). However, FREEDOM results appear dissimilar to prior GLP-1 receptor agonist trials.ConclusionFREEDOM results should not influence current considerations about the benefits or harms of approved formulations of GLP-1 receptor agonists. There is also an ongoing debate about the safety of ITCA 650.     

Effect of glucagon-like peptide-1 (GLP-1) analogues on epicardial adipose tissue: A meta-analysis

Background and aimsGlucagon-like peptide-1 (GLP-1) analogues reduce body fat and cardiovascular events in patients with type 2 diabetes. Accumulation of epicardial adipose tissue (EAT) is associated with increased cardio-metabolic risks and coronary events in type 2 diabetes.MethodsA systematic review and meta-analysis were performed from Glucagon-like peptide-1 analogues therapy on type 2 diabetes patients, reporting data from changes in EAT, after searching the PubMed/MEDLINE, Embase, Science Direct, Scopus, Google Scholar, and Cochrane databases.ResultsIt has been found a limited number of studies, a total of 4 studies (n = 160 patients with GLP-1 analogues therapy) were included in the final analysis. Pooled analysis revealed that GLP-1 analogues reduce EAT (MD: 1.83 mm [-2.50; ?1.10]; P < 0.01). Compared with the patients before the treatment, the patients after the treatment had a smaller HbA1c (MD -1.10%[-1.80; ?0.30]; p = 0.0143) and body mass index was reduced (MD -2.20 kg/m²[-3.70; ?0.60]; p = 0.0058), GLP-1 therapy reduced low-density lipoprotein levels (MD-13.53 mg/dL [-21.74; ?5.31]; p = 0.001) and reduced triglycerides levels significantly (MD -18.32 -28.20 mg/dL; ?8.50); p = 0.0003).ConclusionsThis meta-analysis suggests that the amount of EAT is significantly reduced in T2D patients with Glucagon-like peptide-1 analogues.     

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.     

胰高血糖素样肽1受体激动剂对代谢相关脂肪性肝病作用机制的研究进展

非酒精性脂肪性肝病(NAFLD)(现已更名为代谢相关脂肪性肝病)是一种以肝实质内脂质过度沉积为特征,常与中心性肥胖、2型糖尿病、胰岛素抵抗、代谢综合征等疾病合并存在,被认为是代谢综合征的肝脏表现.非酒精性脂肪性肝炎(NASH)是一种可能导致肝硬化、肝细胞癌的进行性肝病.目前尚无批准用于治疗NAFLD/NASH的药物.近...     

PNPLA3 I148M and response to treatment for hepatic steatosis: A systematic review

Background

It is unclear whether the patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 C-to-G single nucleotide polymorphism, resulting in the substitution of isoleucine to methionine at position 148 (I148M), impedes regression of hepatic steatosis when treating non-alcoholic fatty liver disease (NAFLD).

Objectives

Investigate if carriage of the PNPLA3 148M allele affects the anti-steatotic efficacy of all possible anti-NAFLD interventions, identify gaps in current knowledge and provide guidance for individual treatment.

Methods

Research available in public databases was searched up to 13 November 2022. Studies were included if a treatment in NAFLD patients decreased hepatic steatosis in the pooled patient group or a PNPLA3 I148M polymorphism subgroup (II/IM/MM). The risk of bias was assessed using the Cochrane Risk-Of-Bias 2 Tool and the Newcastle–Ottawa Scale.

Results

Moderate evidence indicates that NAFLD patients homozygous for the PNPLA3 148M allele benefit less or not at all from omega-3 carboxylic acids to decrease liver fat, while the PNPLA3 148I allele shows moderate benefit. Low evidence suggests that interventions employing lifestyle changes are more effective to reduce liver fat in NAFLD patients homozygous for the PNPLA3 148M allele compared to patients with wild-type PNPLA3.

Conclusions

NAFLD patients homozygous for the PNPLA3 148M allele might not benefit from omega-3 carboxylic acids to reduce hepatic steatosis in contrast to patients with wild-type PNPLA3. Instead, patients with two PNPLA3 148M alleles should be especially advised to adopt lifestyle changes. Genotyping for PNPLA3 I148M should be encouraged in therapeutic studies for NAFLD.

Registration Number (Prospero)

CRD42022375028.     

Gender difference in cardiovascular outcomes with SGLT-2 inhibitors and GLP-1 receptor agonist in type 2 diabetes: A systematic review and meta-analysis of cardio-vascular outcome trials

Background and aimsType 2 diabetes confers a differential risk of cardiovascular (CV) disease according to the gender. Whether newly approved anti-diabetic drugs like sodium-glucose co-transport-2 inhibitors (SGLT-2Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) that have shown a significant reduction in the CV end-points in CV outcome trials (CVOTs) also have a differential impact gender-wise, is still not clearly known.MethodsWe systematically searched the medical database up to December 31, 2019 and retrieved all the dedicated CVOTs conducted with SGLT-2Is and GLP-1RAs that explicitly reported the outcome of major adverse cardiac events (MACE). Subsequently, we pooled the hazard ratio (HR) of MACE in both sexes separately and meta-analyzed the result gender-wise.ResultsThe meta-analysis of three CVOTs conducted with SGLT-2Is (N = 34,322), demonstrated a significant reduction in MACE in men but not in women (Men - HR, 0.90; 95% CI, 0.83 to 0.97; P = 0.006; Women - HR, 0.88; 95% CI, 0.77 to 1.00; P = 0.06) compared to placebo. The meta-analysis of seven CVOTs conducted with GLP-1RAs (N = 56,004) demonstrated a significant reduction in MACE in both sex (Men - HR, 0.88; 95% CI, 0.82 to 0.93; P < 0.0001; Women - HR, 0.88; 95% CI, 0.79 to 0.99; P = 0.03), against the placebo.ConclusionsThe reduction in MACE with SGLT-2Is appears to be significantly less in women with diabetes vs men, while GLP-1RAs confers a similar reduction in MACE, irrespective of the gender. Whether these results are related to inadequate statistical power (underrepresentation of women) in CVOT, or it reflects a true gender difference, still remains to be established.     

Cardiovascular outcomes with SGLT-2 inhibitors and GLP-1 receptor agonist in Asians with type 2 diabetes: A systematic review and meta-analysis of cardiovascular outcome trials

Background and aimsBoth type 2 diabetes and cardiovascular (CV) disease develops at a younger age in Asians and often have a higher risk of mortality. Both sodium-glucose co-transport-2 inhibitors (SGLT-2Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown a significant reduction in CV end-points in CV outcome trials (CVOTs). Whether similar CV benefit exists in Asians, is not yet clearly known.MethodsWe systematically searched relevant medical database up to January 31, 2020 and retrieved all the dedicated CVOTs conducted with SGLT-2Is and GLP-1RAs. Subsequently, we meta-analyzed the pooled data of hazard ratio (HR) of major adverse cardiac events (MACE) in Asians. We additionally analyzed the data of heart failure hospitalization (HHF) or CV-death with SGLT-2Is in Asians.ResultsThe meta-analysis of three CVOTs conducted with SGLT-2Is (N = 4987), did not find any significant reduction in MACE (HR, 0.88; 95% CI, 0.67 to 1.15; P = 0.35) and HHF or CV-death (HR, 0.86; 95% CI, 0.55 to 1.36; P = 0.53) in Asians, compared to the placebo. In contrast, the meta-analysis of seven CVOTs conducted with GLP-1RAs (N = 4298) demonstrated a significant reduction in MACE, compared to the placebo (HR, 0.71; 95% CI, 0.59 to 0.86; P < 0.0001).ConclusionsThis meta-analysis found a significant reduction in MACE with GLP-1RAs but not with SGLT-2Is in Asians. No significant reduction in HHF or CV-death demonstrated either with SGLT-2Is in Asians. Whether these results are related to an inadequate statistical power, or due to underrepresentation of Asians, or a true ethnic difference, remains to be established.     

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.     

Association between epicardial adipose tissue and blood pressure: A systematic review and meta-analysis

AimsEpicardial adipose tissue has been reported to be associated with the development of cardiometabolic disease. Whether this is true for hypertension and non-dipper blood pressure remains controversial. Here, we conducted a systemic review and meta-analysis to evaluate the association between EAT and blood pressure.Data synthesisPubmed, Embase, and Web of Science were searched for relevant papers. Studies reported on the difference of EAT thickness between hypertensive and normotensive patients, or those recorded odds ratio (OR) between EAT and hypertension were included. The standard mean difference (SMD) and ORs were extracted and pooled using a random-effects model respectively. We further assessed the effect of EAT on circadian rhythm of blood pressure by combining multiple-adjusted ORs for non-dipper blood pressure. Seven studies with an overall sample of 1089 patients reported the mean difference of EAT thickness between hypertensive and normotensive patients, and the hypertensive patients had higher EAT (SMD = 1.07; 95% CI: 0.66–1.48; I2 = 89.2%) compared with controls. However, the pooled association between EAT and hypertension from two studies was not significant (OR = 1.65, 95%CI 0.62–4.68; I2 = 87.5%). The summary risk effect of EAT on non-dipper blood pressure from six studies comprising1208 patients showed that each 1 mm increment of EAT was associated with a 2.55-fold risk of non-dipper blood pressure.ConclusionHypertensive patients tend to present higher EAT thickness near the right ventricular wall and increased EAT thickness might be associated with high risk of non-dipper blood pressure. Future researches are warranted to determine the causal link between EAT and hypertension and the underlying mechanism.     

Metformin in the treatment of non-alcoholic fatty liver disease: safety,efficacy and mechanism

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease etiology worldwide. It encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis. Although the physiopathology of NAFLD is partly known. Insulin-resistance plays a central role in the development and progression of NAFLD. Several studies have indicated that metformin, as an insulin sensitizer, effectively improves NAFLD and its related metabolic status. Metformin was effective in reducing enzyme levels in the short period, but very limited and controversial information are available on liver histology. Larger randomized controlled trials of sufficient duration using clearly defined histological endpoints are needed to fully assess the efficacy of this drug in modifying the natural history of NAFLD.     

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

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What are the mechanisms of action of anti-inflammatory agents in adipose tissue?: A protocol for systematic review and meta-analysis

Background:Obesity is a disease characterized by the abnormal accumulation of adipose tissue in the body, triggering a chronic subclinical state of inflammation. Bioactive compounds, given their anti-inflammatory properties, are a safe and promising alternative in controlling the inflammatory condition of obesity. This study describes a systematic review protocol aiming to analyze the anti-inflammatory molecules mechanisms and compounds action on adipocytes.Methods:Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) will outline the protocol and PRISMA to the systematic review. The databases used for research will be PubMed, Science Direct, Scopus, Web of Science, BVS, and EMBASE. Experimental studies performed on rats and mice with a control group that describes treatment with anti-inflammatory agents (drugs, nutraceuticals, bio active compounds, among others) at any frequency, time, and dose will be included. Three independent reviewers will select studies and extract data. The evaluation of the methodological quality of each research will be performed using the SYRCLE tool. If at least 2 studies show clinical and/or methodological and/or statistical homogeneity, a meta-analysis will be performed, using the RevMan Analyzes statistical package in Review Manager v.5.3.Results:In this study, we hope to find a considerable number of articles presenting mechanisms involved in the action of anti-inflammatory molecules and compounds on adipocytes.Conclusion:The systematic review produced from this protocol will present evidence on the mechanisms involved in the action of anti-inflammatory molecules and compounds in adipocytes. It will also contribute to developing new research and new insights about anti-inflammatory therapies with a future application view.Record of systematic review:This review was registered with the International Register of Prospective Systematic Reviews on May 18, 2020 (registration: CRD42020182897). Available at: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020182897.