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Cureus Aug 2023Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide, especially in people with obesity, dyslipidemia, type 2 diabetes mellitus (T2DM),... (Review)
Review
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.
PubMed: 37719477
DOI: 10.7759/cureus.43635 -
International Journal of Medical... 2023The members of the transmembrane emp24 domain-containing protein (TMED) family are summarized in human as four subfamilies, α (TMED 4, 9), β (TMED 2), γ (TMED1, 3, 5,... (Review)
Review
The members of the transmembrane emp24 domain-containing protein (TMED) family are summarized in human as four subfamilies, α (TMED 4, 9), β (TMED 2), γ (TMED1, 3, 5, 6, 7) and δ (TMED 10), with a total of nine members, which are important regulators of intracellular protein transport and are involved in normal embryonic development, as well as in the pathogenic processes of many human diseases. Here we systematically review the composition, structure and function of TMED family members, and describe the progress of TMED family in human diseases, including malignancies (head and neck tumors, lung cancer, breast cancer, ovarian cancer, endometrial cancer, gastrointestinal tumors, urological tumors, osteosarcomas, etc.), immune responses, diabetes, neurodegenerative diseases, and nonalcoholic fatty liver disease, dilated cardiomyopathy, mucin 1 nephropathy (MKD), and desiccation syndrome (SS). Finally, we discuss and prospect the potential of TMED for disease prognosis prediction and therapeutic targeting, with a view to laying the foundation for therapeutic research based on TMED family causative genes.
Topics: Pregnancy; Female; Humans; Membrane Proteins; Protein Transport; Non-alcoholic Fatty Liver Disease; Vesicular Transport Proteins
PubMed: 37928880
DOI: 10.7150/ijms.87272 -
Biomedicine & Pharmacotherapy =... Dec 2023This systematic review and meta-analysis aimed to evaluate the overall effect of caper fruit on the modulation of glycemic, lipid profile, liver enzymes, and body mass.... (Meta-Analysis)
Meta-Analysis Review
Effect of caper fruit (Capparis spinosa L.) consumption on liver enzymes, lipid profile, fasting plasma glucose, and weight loss. A systematic review and a preliminary meta-analysis of randomized controlled trials.
This systematic review and meta-analysis aimed to evaluate the overall effect of caper fruit on the modulation of glycemic, lipid profile, liver enzymes, and body mass. Google Scholar, PubMed, and Scopus were explored to collect relevant studies in the last 10 years. RCTs with caper fruit supplementation or consumption in different cohorts of subjects with non-alcoholic fatty liver disease (NAFLD), Type-2-Diabetes (T2D), metabolic syndrome, and hyperlipidemia were included in this systematic review with a mean intervention duration from 2 to 12 weeks. The outcomes measured in this meta-analysis were liver enzymes such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT), the lipid profile represented by triglycerides, total cholesterol (TC) with LDL and HDL and also, weight, and fasting blood glucose. Five randomized controlled trials, which involved a total of 178 adults, were included. According to the results, caper fruit seems to decrease liver enzymes ALT -12.29 U/L [-24.47, -0.11], AST -2.20 U/L [-4.70, 0.31]. Furthermore, the lipid profile seems to improve with a decrease in triglycerides. -11.89 mg/dL [-33.73, 9.95], LDL -4.80 mg/dL [-16.34, 6.74], HDL 0.72 mg/dL [0.10, 1.34], total cholesterol -7.83 mg/dL [-20.04, 4.38], FPG -17.93 [-42.66, 6.79], weight -1.00 kg [-1.44, -0.56]. Significant modulations were found only for ALT, HDL, and weight. In conclusion, this systematic review and meta-analysis showed the paucity of data available on the topic while showing the potential role of caper fruit as a promising food for improving the liver-lipid profile axis in patients with metabolic syndrome and diabetes. Further studies are required to confirm these results.
Topics: Adult; Humans; Blood Glucose; Capparis; Metabolic Syndrome; Fruit; Randomized Controlled Trials as Topic; Liver; Non-alcoholic Fatty Liver Disease; Weight Loss; Triglycerides; Diabetes Mellitus, Type 2; Cholesterol; Fasting
PubMed: 37806093
DOI: 10.1016/j.biopha.2023.115638 -
Addiction (Abingdon, England) Jul 2024Increasing levels of alcohol use are associated with a risk of developing an alcohol use disorder (AUD), which, in turn, is associated with considerable burden. Our aim... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Increasing levels of alcohol use are associated with a risk of developing an alcohol use disorder (AUD), which, in turn, is associated with considerable burden. Our aim was to estimate the risk relationships between alcohol consumption and AUD incidence and mortality.
METHOD
A systematic literature search was conducted, using Medline, Embase, PsycINFO and Web of Science for case-control or cohort studies published between 1 January 2000 and 8 July 2022. These were required to report alcohol consumption, AUD incidence and/or AUD mortality (including 100% alcohol-attributable deaths). The protocol was registered with PROSPERO (CRD42022343201). Dose-response and random-effects meta-analyses were used to determine the risk relationships between alcohol consumption and AUD incidence and mortality and mortality rates in AUD patients, respectively.
RESULTS
Of the 5904 reports identified, seven and three studies from high-income countries and Brazil met the inclusion criteria for quantitative and qualitative syntheses, respectively. In addition, two primary US data sources were analyzed. Higher levels of alcohol consumption increased the risk of developing or dying from an AUD exponentially. At an average consumption of four standard drinks (assuming 10 g of pure alcohol/standard drink) per day, the risk of developing an AUD was increased sevenfold [relative risk (RR) = 7.14, 95% confidence interval (CI) = 5.13-9.93] and the risk of dying fourfold (RR = 3.94, 95% CI = 3.53-4.40) compared with current non-drinkers. The mortality rate in AUD patients was 3.13 (95% CI = 1.07-9.13) per 1000 person-years.
CONCLUSIONS
There are exponential positive risk relationships between alcohol use and both alcohol use disorder incidence and mortality. Even at an average consumption of 20 g/day (about one large beer), the risk of developing an alcohol use disorder (AUD) is nearly threefold that of current non-drinkers and the risk of dying from an AUD is approximately double that of current non-drinkers.
Topics: Humans; Alcohol Drinking; Alcoholism; Incidence; Risk Factors; Alcohol-Related Disorders
PubMed: 38450868
DOI: 10.1111/add.16456 -
Journal of Education and Health... 2023Non-alcoholic fatty liver disease (NAFLD) is a systemic disorder with a complex multifactorial and heterogeneous pathogenesis and has become the most common cause of... (Review)
Review
Non-alcoholic fatty liver disease (NAFLD) is a systemic disorder with a complex multifactorial and heterogeneous pathogenesis and has become the most common cause of chronic liver disease in many countries around the world. Numerous studies in Iran have presented different results on the prevalence and risk factors of NAFLD, in this study, which has been done in a systematic review and meta-analysis, provides a good estimate of the prevalence and risk factors of the disease in Iran. Following the peer review of electronic search strategies (PRESS and the preferred reporting items for systematic reviews and meta-analyses [PRISMA] statement, we searched Web of Science, PubMed, Embase, Scopus, and Persian scientific searcher (Elmnet) from inception to September 19, 2022. In the present study, 71 articles were reviewed for qualitative and meta-analysis. The overall mean prevalence of NAFLD in children studies was 22.4% (95% confidence interval [CI]: 10.9% to 33.9%). The prevalence was notably higher in adult studies 40.5% (95% CI: 35.1% to 46%). In 24 studies, the association between NAFLD and sex was reported, 10 of which showed significant relationships. Out of 46 studies observed that NAFLD prevalence increased significantly with body mass index (BMI). Eight out of 14 studies reported significant associations between FBS and NAFLD in children's studies. Though Iran has a high NAFLD prevalence compared to most areas, and due to the unfavorable situation of risk factors contributing to the NAFLD, it is necessary to take the necessary interventions to control these risk factors and prevent NAFLD.
PubMed: 38144003
DOI: 10.4103/jehp.jehp_1056_22 -
Cureus Oct 2023Silymarin, extracted from milk thistle (), is esteemed for its antioxidative, anti-inflammatory, and antifibrotic properties, notably within liver-related contexts.... (Review)
Review
Silymarin, extracted from milk thistle (), is esteemed for its antioxidative, anti-inflammatory, and antifibrotic properties, notably within liver-related contexts. Nevertheless, a comprehensive grasp of its effects on liver enzymes remains elusive. This systematic review aims to scrutinize the influence of silymarin supplements on liver enzyme levels, elucidating its potential for hepatoprotection. Following PRISMA 2020 guidelines, we systematically reviewed pertinent studies in PubMed/MEDLINE (Medical Literature Analysis and Retrieval System Online). Our inclusion criteria comprised randomized clinical trials (RCTs) published between 1992 and 2023, accessible in English, with a primary focus on liver enzyme levels. Non-original research, ambiguously defined studies, and those lacking essential data were excluded. Of the 1,707 initially identified articles, 29 RCTs met the inclusion criteria, encompassing 3,846 participants with diverse underlying conditions. Silymarin dosages ranged from 140 mg to 420 mg, administered for various durations. Results revealed that 65.5% of the studies reported reduced liver enzyme levels, 20.7% exhibited no significant change, and 13.8% observed elevated liver enzymes. The systematic review implies a potential advantageous influence of silymarin on liver enzyme levels, indicating its hepatoprotective potential. Nevertheless, outcome disparities may stem from comorbidities, suboptimal doses, and underlying diseases. Notably, silymarin's impact on liver enzymes could be context-dependent, with varying responses among different conditions, with the decrease of liver enzyme levels in patients with non-alcoholic fatty liver disease. Silymarin supplements exhibit potential for hepatoprotection by ameliorating liver enzyme levels across diverse conditions. Further research should ascertain optimal dosages and contexts, accounting for individual patient characteristics and underlying diseases.
PubMed: 38021897
DOI: 10.7759/cureus.47608 -
Hepatology International Oct 2023For the first time in nearly half a century, fatty liver disease has undergone a change in name and definition, from the exclusive term, non-alcoholic fatty liver... (Review)
Review
INTRODUCTION
For the first time in nearly half a century, fatty liver disease has undergone a change in name and definition, from the exclusive term, non-alcoholic fatty liver disease (NAFLD), to the inclusion-based, metabolic-associated fatty liver disease (MAFLD). This has led investigators across the globe to evaluate the impact the nomenclature change has had on the epidemiology and natural history of the disease.
METHODS
This systematic review provides a comprehensive overview on how the shift in name and diagnostic criteria has influenced point prevalence in different geographic regions, as well as morbidity and mortality risk, whilst highlighting gaps in the literature that need to be addressed.
CONCLUSIONS
MAFLD prevalence is higher than NAFLD prevalence, carries a higher risk of overall mortality, with greater granularity in risk-stratification amongst MAFLD subtypes.
Topics: Humans; Non-alcoholic Fatty Liver Disease
PubMed: 37556065
DOI: 10.1007/s12072-023-10568-z -
International Journal of Molecular... Feb 2024Cannabidiol (CBD), a non-psychoactive phytocannabinoid abundant in , has gained considerable attention for its anti-inflammatory, antioxidant, analgesic, and... (Review)
Review
Cannabidiol (CBD), a non-psychoactive phytocannabinoid abundant in , has gained considerable attention for its anti-inflammatory, antioxidant, analgesic, and neuroprotective properties. It exhibits the potential to prevent or slow the progression of various diseases, ranging from malignant tumors and viral infections to neurodegenerative disorders and ischemic diseases. Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, and viral hepatitis stand as prominent causes of morbidity and mortality in chronic liver diseases globally. The literature has substantiated CBD's potential therapeutic effects across diverse liver diseases in in vivo and in vitro models. However, the precise mechanism of action remains elusive, and an absence of evidence hinders its translation into clinical practice. This comprehensive review emphasizes the wealth of data linking CBD to liver diseases. Importantly, we delve into a detailed discussion of the receptors through which CBD might exert its effects, including cannabinoid receptors, CB1 and CB2, peroxisome proliferator-activated receptors (PPARs), G protein-coupled receptor 55 (GPR55), transient receptor potential channels (TRPs), and their intricate connections with liver diseases. In conclusion, we address new questions that warrant further investigation in this evolving field.
Topics: Humans; Cannabidiol; Receptors, Cannabinoid; Cannabis; Digestive System Diseases; Liver Diseases, Alcoholic; Receptor, Cannabinoid, CB1
PubMed: 38397045
DOI: 10.3390/ijms25042370 -
World Journal of Hepatology Aug 2023Non-alcoholic fatty liver disease (NAFLD) has become a prevalent cause of chronic liver disease and ranks third among the causes of transplantation. In the United States...
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) has become a prevalent cause of chronic liver disease and ranks third among the causes of transplantation. In the United States alone, annual medical costs are approximately 100 billion dollars. Unfortunately, there is no Federal Drug Administration (FDA)-approved medication for its treatment. However, various clinical trials are investigating several therapeutic classes that could potentially treat NAFLD. It is valuable to have a compilation of the data available on their efficacy.
AIM
To assess the efficacy of cyclophilin inhibitors, fibroblast growth factor 21 analogs (FGF21), and dual and pan peroxisome proliferator-activated receptor (PPAR) agonists for treating NAFLD.
METHODS
A comprehensive literature search using keywords including cyclophilin inhibitor, FGF agonist, pan-PPAR agonists, dual-PPAR agonist, NAFLD, non-alcoholic steatohepatitis, and fatty liver was conducted on October 29, 2022, in PubMed, EMBASE, Cochrane Library, Scopus and Web of Science. Animal and human research, case reports, and published articles in English from all countries with patients aged 18 and above were included. Only articles with a National Institutes of Health (NIH) Quality Assessment score of five or higher out of eight points were included. Articles that were narrative or systematic reviews, abstracts, not in English, focused on patients under 18 years old, did not measure outcomes of interest, were inaccessible, or had a low NIH Quality Assessment score were excluded. Each article was screened by two independent researchers evaluating relevance and quality. Resources were scored based on the NIH Quality Assessment Score; then, pertinent data was extracted in a spreadsheet and descriptively analyzed.
RESULTS
Of the 681 records screened, 29 met the necessary criteria and were included in this review. These records included 12 human studies and 17 animal studies. Specifically, there were four studies on cyclophilin inhibitors, four on FGF agonists/analogs, eleven on pan-PPAR agonists, and ten on dual-PPAR agonists. Different investigational products were assessed: The most common cyclophilin inhibitor was NV556; FGF agonists and analogs was Efruxifermin; pan-PPAR agonists was Lanifibranor; and dual-PPAR agonists was Saroglitazar. All classes were found to be statistically efficacious for the treatment of NAFLD, with animal studies demonstrating improvement in steatosis and/or fibrosis on biopsy and human studies evidencing improvement in different metabolic parameters and/or steatosis and fibrosis on FibroScan ( < 0.05).
CONCLUSION
The data analyzed in this review showed clinically significant improvement in individual histological features of NAFLD in both animal and human trials for all four classes, as well as good safety profiles ( < 0.05). We believe this compilation of information will have positive clinical implications in obtaining an FDA-approved therapy for NAFLD.
PubMed: 37701920
DOI: 10.4254/wjh.v15.i8.1001 -
United European Gastroenterology Journal Sep 2023Lifestyle modification comprising calorie restriction (CR) and increased physical activity enabling weight loss is the first-line of treatment for non-alcoholic fatty... (Review)
Review
Lifestyle modification comprising calorie restriction (CR) and increased physical activity enabling weight loss is the first-line of treatment for non-alcoholic fatty liver disease (NAFLD). However, CR alone is not optimal and evidence suggests that dietary pattern and composition are also critical in NAFLD management. Accordingly, high consumption of red and processed meat, saturated fat, added sugar, and sweetened beverages are associated with an increased risk of developing NAFLD and hepatocellular carcinoma, while other foods and compounds such as fish, olive oil, and polyphenols are, in contrast, beneficial for metabolic disorders. Therefore, several dietary interventions have been studied in order to determine which strategy would be the most beneficial for NAFLD. The evidence regarding the effectiveness of different dietary interventions such as low carbohydrate/low-fat diet, time-restricted eating diet, CR, and the well-studied Mediterranean diet is summarized.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Diet, Carbohydrate-Restricted; Exercise; Weight Loss; Diet, Mediterranean; Dietary Patterns
PubMed: 37491835
DOI: 10.1002/ueg2.12443