Nonalcoholic fatty liver disease (NAFLD) is a disorder in which excess fat accumulates in hepatocytes and can lead to serious complications. Oxidative stress is one of the leading causes of NAFLD. Pomegranates are considered antioxidant-rich fruit. This systematic review study was aimed to investigate the impact of pomegranate on NAFLD. PubMed, Scopus, and Google Scholar databases/search engines (from inception up to July 2023) were searched for interventional studies (human and animal) that examined the effects of supplementation with different parts of pomegranate including fruits, peels, seeds, or flower on NAFLD outcomes. A total of 222 articles were retrieved following the initial search. After excluding duplicates, the title and abstract of 114 articles were screened. Afterward, irrelevant articles were removed and the full texts of the remaining 27 articles were reviewed. Eventually, 19 articles (16 animal and three human interventional studies) that met the inclusion criteria, published between 2009 and 2023, were included in this systematic review. Our study indicates the potential beneficial effects of different parts of pomegranate on the improvement of NAFLD. However, given that the majority of the included articles were animal studies, further investigations in the form of human clinical trials are warranted to suggest a clinical indication of such interventions.

Hepatocellular carcinoma (HCC) represents a significant burden on global healthcare systems due to its considerable incidence and mortality rates. Recent trends indicate an increase in the worldwide incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) and a shift in the etiology of HCC, with MASLD replacing the hepatitis B virus as the primary contributor to new cases of HCC. MASLD-related HCC exhibits distinct characteristics compared to viral HCC, including unique immune cell profiles resulting in an overall more immunosuppressive or exhausted tumor microenvironment. Furthermore, MASLD-related HCC is frequently identified in older age groups and among individuals with cardiometabolic comorbidities. Additionally, a greater percentage of MASLD-related HCC cases occur in noncirrhotic patients compared to those with viral etiologies, hindering early detection. However, the current clinical practice guidelines lack specific recommendations for the screening of HCC in MASLD patients. The evolving landscape of HCC management offers a spectrum of therapeutic options, ranging from surgical interventions and locoregional therapies to systemic treatments, for patients across various stages of the disease. Despite ongoing debates, the current evidence does not support differences in optimal treatment modalities based on etiology. In this study, we aimed to provide a comprehensive overview of the current literature on the trends, characteristics, clinical implications, and treatment modalities for MASLD-related HCC.

Objective: Nonalcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant contributor to chronic liver disease worldwide. Orlistat blocks intestinal fat absorption, leading to decreased liver fat content. Therefore, it is a viable option for NAFLD management. Methods: We performed a systematic review and metaanalysis using randomized controlled trials (RCTs). We used mean difference (MD) to pool continuous outcomes presented with the corresponding confidence interval (CI). Results: We included four RCTs with a total of 379 patients. Orlistat was effective in reducing liver fat content (MD: -5.02, 95% CI [-7.23, -2.82], P = 0.00001), alanine transferase (MD: -10.03, 95% CI [-17.80, -2.26], P = 0.01), aspartate transferase (MD: -4.29, 95% CI [-7.59, -0.99], P = 0.01), waist circumference (MD: -3.18, 95% CI [-4.25, -2.10], P = 0.00001), body mass index (MD: -1.03, 95% CI [-1.34, -0.73], P = 0.00001), total cholesterol (MD: -3.75, 95% CI [-4.02, -3.49], P = 0.00001), and low-density lipoprotein (MD: -3.83, 95% CI [-4.05, -3.61], P = 0.00001). However, orlistat was associated with increased serum triglycerides (MD: 7.46, 95% CI [6.48, 8.44], P = 0. 00001). Conclusion: Orlistat is a viable option for NAFLD management; however, it increases triglyceride levels. Larger RCTs are required.

BACKGROUND: Recently, significant associations between non-alcoholic fatty liver disease (NAFLD) and extra-hepatic cancer have been reported.
OBJECTIVE: To carry out a comprehensive review of the current evidence in the literature on the association between NAFLD and extra-hepatic cancer.
METHODS: A narrative literature review was performed through an online search for the MeSH terms \"fatty liver\" and \"cancer\" in MEDLINE (via PubMed) and LILACS (via BVS). Original studies that described the impact of NAFLD on different types of extra-hepatic malignancies were included.
RESULTS: After careful analysis, nine prospective cohort studies, one retrospective cohort study, three case-control studies, and three cross-sectional studies were selected.
CONCLUSIONS: There is consistent evidence on the association between NAFLD and extra-hepatic carcinogenesis, especially in relation to colorectal, gastric, pancreatic, breast, prostate, and bladder cancers.

BACKGROUND: Bariatric surgery is one of the effective therapeutic options for people with obesity and obesity-related co-morbidities. In addition to weight-related co-morbid diseases, including diabetes, hypertension, and hypercholesterolemia, non-alcoholic fatty liver disease (NAFLD) is common in patients with morbid obesity. Bariatric surgery is one of the therapeutic options in the management of NAFLD. Hence, this review focused on the potential role of bariatric surgery on hepatic elasticity measured through shear wave elastography.
METHODS: A systematic literature search was performed, and the studies regarding heterogeneity were evaluated using the random-effects model.
RESULTS: The meta-analysis on 6 trials (3-12 months follow-up) including 350 participants showed a significant reduction of liver elasticity after surgery (WMD: -1.149, 95% CI: -1.767, -0.532, p < 0.001; I2:81.55%).
CONCLUSIONS: Bariatric surgery is associated with decreased liver elasticity. This improvement could be related to weight loss or other mechanisms of bariatric surgery.

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent causes of chronic liver disease worldwide which is often seen in patients with metabolic abnormalities such as those with obesity and insulin resistance. On the other hand, sarcopenia is a generalized and progressive skeletal muscle disorder characterized by low muscle strength, low muscle quality, low physical performance, or a combination of the three. Both disease entities share several underlying risk factors and pathophysiologic mechanisms. These include: (1) cardiometabolic overlaps such as insulin resistance, chronic systemic inflammation, decreased vitamin D levels, sex hormone modifications; (2) muscle-related factors such as those mitigated by myostatin signaling, and myokines (i.e., irisin); and (3) liver-dysfunction related factors such as those associated with growth hormone/insulin-like growth factor 1 Axis, hepatokines (i.e., selenoprotein P and leukocyte cell-derived chemotaxin-2), fibroblast growth factors 21 and 19 (FGF21 and FGF19), and hyperammonemia. This narrative review will examine the pathophysiologic overlaps that can explain the links between NAFLD and sarcopenia. Furthermore, this review will explore the emerging roles of nonpharmacologic (e.g., weight reduction, diet, alcohol, and smoking cessation, and physical activity) and pharmacologic management (e.g., roles of β-hydroxy-β-methylbutyrate, branched-chain amino acid supplements, and testosterone therapy) to improve care, intervention sustainability, and acceptability for patients with sarcopenia-associated NAFLD.

Nonalcoholic fatty liver disease (NAFLD) is one of the leading causes of chronic liver disease worldwide. Epidemiological studies have reported that exposure of the population to environmental endocrine-disrupting chemicals (EDCs) is associated with NAFLD. However, EDCs are of different types, and there are inconsistencies in the relevant evidence and descriptions, which have not been systematically summarized so far. Therefore, this study aimed to determine the association between population exposure to EDCs and NAFLD. Three databases, including PubMed, Web of science, and Embase were searched, and 27 articles were included in this study. Methodological quality, heterogeneity, and publication bias of the included studies were assessed using the Newcastle-Ottawa scale, I2 statistics, Begg\'s test, and Egger\'s test. The estimated effect sizes of the included studies were pooled and evaluated using the random-effects model (I2 > 50 %) and the fixed-effects model ( I2 < 50 %). The pooled-estimate effect sizes showed that population exposure to Phthalates (PAEs) (OR = 1.18, 95 % CI:1.03-1.34), cadmium (Cd) (OR = 1.37, 95 % CI:1.09-1.72), and bisphenol A (OR = 1.43, 95 % CI:1.24-1.65) were positively correlated with the risk of NAFLD. Exposure to mercury (OR =1.46, 95 % CI:1.17-1.84) and Cd increased the risk of \"elevated alanine aminotransferase\". On the contrary, no significant association was identified between perfluoroalkyl substances (OR =0.99, 95 % CI:0.93-1.06) and NAFLD. However, female exposure to perfluorooctanoic acid (OR =1.82, 95 % CI:1.01-3.26) led to a higher risk of NAFLD than male exposure. In conclusion, this study revealed that EDCs were risk factors for NAFLD. Nonetheless, the sensitivity analysis results of some of the meta-analyses were not stable and demonstrated high heterogeneity. The evidence for these associations is limited, and more large-scale population-based studies are required to confirm these findings.

UNASSIGNED: Obesity and metabolic-associated fatty liver disease (MAFLD) during pregnancy constitute significant problems for routine antenatal care, with increasing prevalence globally. Similar to obesity, MAFLD is associated with a higher risk for maternal complications (e.g. pre-eclampsia and gestational diabetes) and long-term adverse health outcomes for the offspring. However, MAFLD during pregnancy is often under-recognized, with limited management/treatment options.
UNASSIGNED: PubMed/MEDLINE, EMBASE, and Scopus were searched based on a search strategy for obesity and/or MAFLD in pregnancy to identify relevant papers up to 2024. This review summarizes the pertinent evidence on the relationship between maternal obesity and MAFLD during pregnancy. Key mechanisms implicated in the underlying pathophysiology linking obesity and MAFLD during pregnancy (e.g. insulin resistance and dysregulated adipokine secretion) are highlighted. Moreover, a diagnostic approach for MAFLD diagnosis during pregnancy and its complications are presented. Finally, promising relevant areas for future research are covered.
UNASSIGNED: Research progress regarding maternal obesity, MAFLD, and their impact on maternal and fetal/offspring health is expected to improve the relevant diagnostic methods and lead to novel treatments. Thus, routine practice could apply more personalized management strategies, incorporating individualized algorithms with genetic and/or multi-biomarker profiling to guide prevention, early diagnosis, and treatment.

BACKGROUND: Hepatic steatosis is a common finding in liver histopathology and the hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), whose global prevalence is rising.
OBJECTIVE: To review the histopathology of hepatic steatosis and its mechanisms of development and to identify common and rare disease associations.
METHODS: We reviewed literature on the basic science of lipid droplet (LD) biology and clinical research on acute and chronic liver diseases associated with hepatic steatosis using the PubMed database.
RESULTS: A variety of genetic and environmental factors contribute to the development of chronic hepatic steatosis or steatotic liver disease, which typically appears macrovesicular. Microvesicular steatosis is associated with acute mitochondrial dysfunction and liver failure. Fat metabolic processes in hepatocytes whose dysregulation leads to the development of steatosis include secretion of lipoprotein particles, uptake of remnant lipoprotein particles or free fatty acids from blood, de novo lipogenesis, oxidation of fatty acids, lipolysis and lipophagy. Hepatic insulin resistance is a key feature of MASLD. Seipin is a polyfunctional protein that facilitates LD biogenesis. Assembly of hepatitis C virus takes place on LD surfaces. LDs make important, functional contact with the endoplasmic reticulum and other organelles.
CONCLUSIONS: Diverse liver pathologies are associated with hepatic steatosis, with MASLD being the most important contributor. The biogenesis and dynamics of LDs in hepatocytes are complex and warrant further investigation. Organellar interfaces permit co-regulation of lipid metabolism to match generation of potentially toxic lipid species with their LD depot storage.

OBJECTIVE: The prevalence of non-alcoholic fatty liver disease (NAFLD) is rapidly increasing worldwide, making it the leading cause of liver related morbidity and mortality. Currently, liver biopsy is the gold standard for assessing individuals with steatohepatitis and fibrosis. However, its invasiveness, sampling variability, and impracticality for large-scale screening has driven the search for non-invasive methods for early diagnosis and staging. In this review, we comprehensively summarise the evidence on the diagnostic performance and limitations of existing non-invasive serum biomarkers and scores in the diagnosis and evaluation of steatosis, steatohepatitis, and fibrosis.
RESULTS: Several non-invasive serum biomarkers and scores have been developed over the last decade, although none has successfully been able to replace liver biopsy. The introduction of new NAFLD terminology, namely metabolic dysfunction-associated fatty liver disease (MAFLD) and more recently metabolic dysfunction-associated steatotic liver disease (MASLD), has initiated a debate on the interchangeability of these terminologies. Indeed, there is a need for more research on the variability of the performance of non-invasive serum biomarkers and scores across the diagnostic entities of NAFLD, MAFLD and MASLD. There remains a significant need for finding valid and reliable non-invasive methods for early diagnosis and assessment of steatohepatitis and fibrosis to facilitate prompt risk stratification and management to prevent disease progression and complications. Further exploration of the landscape of MASLD under the newly defined disease subtypes is warranted, with the need for more robust evidence to support the use of commonly used serum scores against the new MASLD criteria and validation of previously developed scores.