The liver is vulnerable to damage from environmental pollutants, but evidence on the effects of non-essential metal/metalloid (NEM) mixture on liver function and their mechanisms remains limited. The study aimed to explore the correlations between individual NEMs and their combinations with liver function, and the mediating roles of lipid profiles. The research involved 2642 individuals aged 60 and older in China. Urine concentrations of arsenic (As), cesium (Cs), barium (Ba), thallium (Tl), and cadmium (Cd) were analyzed using ICP-MS. Liver function was assessed based on the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB). To evaluate the individual and combined effects of these NEMs on liver function, linear regression, restricted cubic splines (RCS), weighted quantile sum (WQS), quantile g-computation (QGC), and Bayesian kernel machine regression (BKMR) models were utilized. Mediation analyses were conducted to explore the potential role of lipid profiles in NEM-liver function relations. Adjusted linear regression revealed positive associations of Tl with ALT (β = 0.044, 95 % CI: 0.022 to 0.066) and AST (β = 0.019, 95 % CI: 0.004 to 0.035), and negative associations of Cs (β = -0.015, 95 % CI: -0.020 to -0.010), Tl (β = -0.010, 95 % CI: -0.015 to -0.005), and Cd (β = -0.019, 95 % CI: -0.024 to -0.014) with ALB. The RCS model confirmed these linear relationships. Mixture models consistently demonstrated a positive association between the NEM mixture and ALT/AST, primarily driven by Tl, and a negative association with ALB, predominantly influenced by Cd. Mediation analyses suggested triglycerides and total cholesterol partially mediated the associations between Tl, the NEM mixture, and liver function. In conclusion, the NEM mixture, mainly driven by Tl and Cd, is linked to liver function impairment, with lipid profiles potentially mediating these effects. More research is needed to confirm these findings and clarify the mechanisms.

Metabolic dysfunction-associated fatty liver disease (MAFLD) affects over one-fourth of the global adult population and is the leading cause of liver disease worldwide. To address this, the Asian Pacific Association for the Study of the Liver (APASL) has created clinical practice guidelines focused on MAFLD. The guidelines cover various aspects of the disease, such as its epidemiology, diagnosis, screening, assessment, and treatment. The guidelines aim to advance clinical practice, knowledge, and research on MAFLD, particularly in special groups. The guidelines are designed to advance clinical practice, to provide evidence-based recommendations to assist healthcare stakeholders in decision-making and to improve patient care and disease awareness. The guidelines take into account the burden of clinical management for the healthcare sector.

This study investigates the influence of metabolic dysfunction-associated fatty liver disease (MAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) on the incidence of hepatocellular carcinoma (HCC) among general population and patients with chronic hepatitis B (CHB). It also explores its implications for the long-term prognosis of HCC patients following hepatic resection.

Relevant studies were selected based on predefined inclusion and exclusion criteria, including adherence to diagnostic criteria for MAFLD/MASLD and reporting hazard ratios (HRs) using Cox proportional hazards models. The meta-analysis utilized R statistical software (version 4.3.0) with random-effects models to calculate pooled HRs. Sensitivity analyses were performed to ensure the robustness of results.

Our analysis included 19 studies, among which 12 studies focused on the cumulative incidence of HCC in the general population (979,213 individuals; 294,984 with MAFLD/MASLD and 684,229 without). MAFLD/MASLD significantly increased the cumulative incidence of HCC in the general population (HR = 1.82; 95% CI, 1.34-2.48). In CHB patients (316,445 participants; 108,183 with MAFLD/MASLD and 208,262 without), the cumulative incidence of HCC was also higher in the MAFLD/MASLD group (HR = 1.36; 95% CI, 1.32-1.40). For 7383 postoperative HCC patients (2192 with MAFLD/MASLD and 5191 without), MAFLD/MASLD did not significantly affect overall survival (OS) (HR = 0.93; 95% CI, 0.69-1.26) or recurrence-free survival (RFS) (HR = 0.98; 95% CI, 0.86-1.13).

In conclusion, MAFLD/MASLD can significantly increase the incidence of HCC in both the general population and CHB patients. However, it does not significantly influence long-term prognosis after hepatic resection, suggesting that other factors may have a greater role in determining postoperative outcomes. This highlights the need for tailored management strategies for MAFLD/MASLD patients undergoing HCC resection.

Rhubarb has the effect of breaking blood stasis and abnormal mass, and was often used to treat various tumor diseases including liver cancer in ancient China. Recipes containing rhubarb have anti-liver cancer properties and are still used today. However, the main components and mechanism of action of rhubarb against liver cancer are still unclear.

To conduct a review of the anti-liver cancer effects and toxicity of rhubarb anthraquinones (AQs).

This article reviewed the effects of rhubarb AQs in the treatment of liver cancer and the signaling pathways involved, and discussed the toxicity and pharmacokinetics of rhubarb AQs by searching the Web of Science, PubMed and CNKI databases.

Rhubarb (Rhei Radix et Rhizoma) is a traditional Chinese medicine that has been existed for thousands of years and is used as an anti-cancer drug. Modern pharmacological research shows that rhubarb AQs, as the main component of rhubarb, contains emodin, rhein, chrysophanol, physcione and aloe-emodin, which has anti-liver cancer effects and can be considered as a potential therapeutic drug for liver cancer. However, many modern studies have shown that rhubarb AQs have certain toxicity, which hinders in-depth research on rhubarb AQs.

Rhubarb AQs can be used as a potential anti-liver cancer drug, but its research still has many limitations. Strengthening research on related experiments and finding a balance between toxicity and efficacy are all directions worth studying in the future.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are the leading causes of liver disease and are emerging as the main risk factors for primary liver cancer (PLC). However, updated global data on MASH remain scarce.

This study analyzed data from the Global Burden of Disease study between 2000 and 2021 to assess the age-standardized incidence, mortality, and disability-adjusted life years (DALYs) from MASH-associated PLC, stratified by geographical region, sociodemographic index, age, and sex.

There were 42,290 incident cases, 40,920 deaths, and 995,470 DALYs from PLC globally. Global incidence (+98%), death (+93%), and DALYs (+76%) from MASH-associated PLC increased steeply over the study period. Among different etiologies, only MASH-associated PLC had increased mortality rates (annual percent change [APC], +0.46; 95% confidence interval [CI], 0.33%-0.59%). Africa and low sociodemographic index countries exhibited the highest age-standardized incidence, death, and DALYs from MASH-associated PLC. DALYs increased in females (APC, 0.24%; 95% CI, 0.06%-0.42%), whereas they remained stable in males. Americas experienced the highest percentage increase in age-standardized incidence rate (APC, 2.09%; 95% CI, 2.02%-2.16%), age-standardized death rate (APC, 1.96%; 95% CI, 1.69%-2.23%), and age-standardized DALYs (APC, 1.96%; 95% CI, 1.63%-2.30%) from MASH-associated PLC.

Over the past 2 decades, the burden of MASH-associated PLC has risen, though there are sociodemographic and geographic disparities. This necessitates urgent strategies across the globe to mitigate the epidemic of MASH-associated PLC as well as its metabolic drivers.

ZNFX1 Antisense RNA 1 (ZFAS1) act as an oncogenic long noncoding RNA in multiple types of cancer. Ferroptosis is an iron-dependent cell death characterized by excessive iron accumulation and lipid peroxidation. However, to date, the functional role and mechanism of ZFAS1 in ferroptosis in hepatocellular carcinoma (HCC) remains largely unknown. The present study revealed that ZFAS1 was upregulated in HCC and upregulation of ZFAS1 indicated poor clinical outcome of HCC patients. Loss- and gain-of-function experiments demonstrated that knockdown of ZFAS1 inhibited HCC cell proliferation and induced ferroptosis, while overexpression of ZFAS1 exerted opposite effects. ZFAS1 enhanced cell proliferation via suppression of ferroptotic death. Mechanistically, ZFAS1 interacted with miR-150 and decreased its expression. AIFM2, the critical ferroptosis protector, was a direct target of ZFAS1/miR-150. ZFAS1 accelerated HCC proliferation and inhibited ferroptosis by the regulation of the miR-150/AIFM2 axis. These discoveries intimate an essential part of ZFAS1/miR-150/AIFM2 in governing HCC ferroptosis, which may provide a promising therapeutic strategy for HCC patients.

Liver oncogenesis is accompanied by discernible protein changes in the bloodstream. By employing plasma proteomic profiling, we can delve into the molecular mechanisms of liver cancer and pinpoint potential biomarkers. In this nested case-control study, we applied liquid chromatography-tandem mass spectrometry for proteome profiling in baseline plasma samples. Differential protein expression was determined and was subjected to functional enrichment, network, and Mendelian randomization (MR) analyses. We identified 193 proteins with notable differential levels between the groups. Of these proteins, MR analysis offered a compelling negative association between apolipoprotein B (APOB) and liver cancer. This association was further corroborated in the UK Biobank cohort: genetically predicted APOB levels were associated with a 31% (95% CI 19-42%) decreased risk of liver cancer; and phenotypic analysis indicated an 11% (95% CI 8-14%) decreased liver cancer risk for every 0.1 g/L increase of circulating APOB levels. Multivariable MR analysis suggested that the hepatic fat content might fully mediate the APOB-liver cancer connection. In summary, we identified some plasma proteins, particularly APOB, as potential biomarkers of liver cancer. Our findings underscore the intricate link between lipid metabolism and liver cancer, offering hints for targeted prophylactic strategies and early detection.

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.

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.

In recent years, there has been a significant increase in the incidence of metabolic-associated fatty liver disease (MAFLD), which has been attributed to the increasing prevalence of type 2 diabetes mellitus (T2DM) and obesity. MAFLD affects more than one-third of adults worldwide, making it the most prevalent liver disease globally. Moreover, MAFLD is considered a significant risk factor for hepatocellular carcinoma (HCC), with MAFLD-related HCC cases increasing. Approximately 1 in 6 HCC patients are believed to have MAFLD, and nearly 40 % of these HCC patients do not progress to cirrhosis, indicating direct transformation from MAFLD to HCC. N6-methyladenosine (m6A) is commonly distributed in eukaryotic mRNA and plays a crucial role in normal development and disease progression, particularly in tumors. Numerous studies have highlighted the close association between abnormal m6A modification and cellular metabolic alterations, underscoring its importance in the onset and progression of MAFLD. However, the specific impact of m6A modification on the progression of MAFLD to HCC remains unclear. Can targeting m6A effectively halt the progression of MAFLD-related HCC? In this review, we investigated the pivotal role of abnormal m6A modification in the transition from MAFLD to HCC, explored the potential of m6A modification as a therapeutic target for MAFLD-related HCC, and proposed possible directions for future investigations.

The progression of metabolic dysfunction-associated steatotic liver disease (MASLD) has been found to manifest in a series of hepatic and extrahepatic complications. A comprehensive meta-analysis of the longitudinal outcomes associated with MASLD has yet to be conducted.

To investigate the longitudinal outcomes associated with MASLD, Medline and Embase databases were searched to identify original studies that evaluated the longitudinal risks of incident clinical outcomes among MASLD patients compared with non-MASLD individuals. DerSimonian Laird random-effects meta-analysis was performed. Pooled effect estimates were calculated, and heterogeneity among studies was evaluated.

One hundred twenty-nine studies were included in the meta-analysis. Meta-analysis revealed a significant increase in the risk of cardiovascular outcomes (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.27-1.60; P < .01), various metabolic outcomes such as incident hypertension (HR, 1.75; 95% CI, 1.46-2.08; P < .01), diabetes (HR, 2.56; 95% CI, 2.10-3.13; P < .01), pre-diabetes (HR, 1.69; 95% CI, 1.22-2.35; P < .01), metabolic syndrome (HR, 2.57; 95% CI, 1.13-5.85; P = .02), chronic kidney disease (HR, 1.38; 95% CI, 1.27-1.50; P < .01), as well as all cancers (HR, 1.54; 95% CI, 1.35-1.76; P < .01) among MASLD patients compared with non-MASLD individuals. By subgroup analysis, MASLD patients with advanced liver disease (HR, 3.60; 95% CI, 2.10-6.18; P < .01) were also found to be associated with a significantly greater risk (P = .02) of incident diabetes than those with less severe MASLD (HR, 1.63; 95% CI, 1.0-2.45; P = .02) when compared with non-MASLD.

The present study emphasizes the association between MASLD and its clinical outcomes including cardiovascular, metabolic, oncologic, and other outcomes. The multisystemic nature of MASLD found in this analysis requires treatment targets to reduce systemic events and end organ complications.

Experimental studies have shown that disinfection byproducts (DBPs) including haloacetic acids (HAAs) can cause liver toxicity, but evidence linking this association in humans is sparse.

We aimed to explore the associations between HAA exposures and liver injury.

We included 922 women between December 2018 and January 2020 from the Tongji Reproductive and Environmental (TREE) cohort study in Wuhan, China. Urinary HAA concentrations including trichloroacetic acid (TCAA) and dichloroacetic acid (DCAA) and serum indicators of liver function, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) were measured. Liver injury was defined as if any of serum indicator levels were above the 90th percentile. Multivariate logistic and linear regression models were fitted to assess the associations of urinary HAA concentrations with the risk of liver injury and liver function indicators. Stratified analyses by age, body mass index (BMI), alcohol use, and passive smoking were also applied to evaluate the potential effect modifiers.

There is little evidence of associations of urinary TCAA concentrations with liver injury risk and liver function indicators. However, urinary DCAA concentrations were associated with a higher risk of liver injury [odds ratios (OR) for 1-interquartile range (IQR) increase in natural log (ln) transformed DCAA concentrations: 1.45; 95% confidence interval (CI): 1.07, 1.98]. This association was observed only among nondrinkers (p interaction = 0.058 ). We also found that a 1-IQR increase in ln-transformed DCAA concentrations was positively associated with ALT levels (percentage change = 6.06 % ; 95% CI: 0.48%, 11.95%) and negatively associated with AST/ALT (percentage change = - 4.48 % ; 95% CI: - 7.80 % , - 1.04 % ). In addition, urinary DCAA concentrations in relation to higher GGT levels was observed only among passive smokers (p interaction = 0.040 ).

Our findings suggest that exposure to DCAA but not TCAA is associated with liver injury among women undergoing assisted reproductive technology. https://doi.org/10.1289/EHP13386.

This study builds upon the groundbreaking mRNA vaccine Nobel Prize win in 2023 for COVID-19 prevention, paving the way for next-generation mRNA cancer vaccines to revolutionize immunotherapy. Despite the existing challenges, such as the presence of a suppressive tumor microenvironment and the identification of cancer-associated antigens, recent results from the KEYNOTE-942 trial have successfully demonstrated the effectiveness of mRNA-based cancer treatments, providing clinical evidence for the first time. This trial aimed to evaluate the efficacy and safety of combining immune checkpoint inhibitors with mRNA-based therapies in treating cancer. This advancement undeniably represents new hope for hepatocellular carcinoma (HCC) patients. However, progress in this field remains limited. In this article, we summarized the current state of applying immune checkpoint inhibitors (ICIs) combined with neoantigen mRNA vaccines. Additionally, we discussed potential targets for designing novel mRNA vaccines and potential mRNA vaccine delivery vehicles. The objective of this article is to inspire enthusiasm for the exploration of innovative therapeutic strategies that combine ICIs with neoantigen mRNA vaccines for HCC treatment and HCC prevention.

Recent cross-sectional studies found that exposure to ambient air pollution (AP) was associated with an increased risk of metabolic dysfunction-associated fatty liver disease (MAFLD). The alternation of blood lipids may explain the association, but epidemiological evidence is lacking. We aimed to examine whether and to what extent the association between long-term exposure to AP and incident MAFLD is mediated by blood lipids and dyslipidemia in a prospective cohort.

We included 6350 participants from the China Multi-Ethnic Cohort (CMEC, baseline 2018-2019, follow-up 2020-2021). Three-year average (2016-2018) of AP (PM1, PM2.5, PM10, NO2), blood lipids (TC, LDL-C, HDL-C, TG with their combinations) and incident MAFLD for each individual were assessed chronologically. Linear and logistic regression was used to assess the associations among AP, blood lipids, and MAFLD, and the potential mediation effects of blood lipids were evaluated using causal mediation analysis.

A total of 744 participants were newly diagnosed with MAFLD at follow-up. The odds ratios of MAFLD associated with a 10 μm increase in PM1, PM2.5, and NO2 were 1.35 (95 % CI: 1.14, 1.58), 1.34 (1.10, 1.65) and 1.28 (1.14, 1.44), respectively. Blood lipids are important mediators between AP and incident MAFLD. LDL-C (Proportion Mediated: 6.9 %), non-HDL (13.4 %), HDL-C (20.7 %), LDL/HDL (30.1 %), and dyslipidemia (6.5 %) significantly mediated the association between PM2.5 and MAFLD. For PM1, the indirect effects were similar to those for PM2.5, with a larger value for the direct effect, and the mediation proportion by blood lipids was less for NO2.

Blood lipids are important mediators between AP and MAFLD, and can explain 5 %-30 % of the association between AP and incident MAFLD, particularly cholesterol-related variables, indicating that AP could lead to MAFLD through the alternation of blood lipids. These findings provided mechanical evidence of AP leading to MAFLD in epidemiological studies.

Uterine endometrial cancer (EC) is the most common gynecological malignancy in Taiwan. This study aimed to investigate the association between human papillomavirus (HPV) infection and the development of uterine EC among Taiwanese women. A nationwide population cohort research approach was employed, leveraging longitudinal health insurance databases (LHID 2007 and 2015) from the National Health Insurance Research Database alongside data from the Taiwan Cancer Registry datasets. A comparative analysis examined 472,420 female patients with HPV infection and 944,840 without HPV infection. The results demonstrated that the HPV cohort exhibited a significantly elevated risk of uterine EC, as evidenced by an adjusted hazard ratio (aHR) of 1.588 (95% CI: 1.335-1.888). Furthermore, this elevated risk extended to type 1 EC with an aHR of 1.671 (95% CI: 1.376-2.029), specifically the endometrioid adenocarcinoma subtype with an aHR 1.686 (95% CI: 1.377-2.065). Importantly, these findings were statistically significant (p < 0.001). In conclusion, this research unveils a potential association between HPV infection and an increased risk of uterine EC, particularly the type 1 endometrial cancer subtype, within the Taiwanese female population. These findings have implications for preventive measures and screening programs targeting HPV infection to reduce the risk of this prevalent gynecological malignancy in Taiwan.

The association between the age at onset of metabolic syndrome and cancer risk remains unknown. This study explored the association between age at metabolic syndrome onset and the risk of overall and site-specific cancer incidence.

This study included 31,688 participants with new-onset metabolic syndrome and 31,688 participants matched according to sex, age (±1 y), and examination year among the 179,328 participants who underwent Kailuan health examinations from 2006 to 2017 in Tangshan, China. Weighted Cox regression was used to calculate the hazard ratios and 95% confidence intervals of new-onset metabolic syndrome for overall and site-specific cancer incidence across age groups. Population-attributable risk proportions were used to estimate the number of cases that could be prevented by eliminating the risk factors from the population.

During an average follow-up period of 10.22 y, we identified 2,710 cases of cancer and 4,218 deaths that occurred before the diagnosis of cancer. With an increase in metabolic syndrome onset age, the hazards of overall cancer incidence were gradually attenuated. The average hazard ratios (95% confidence intervals) of overall cancer were 1.94 (1.25-2.99) for metabolic syndrome onset age <45 year old, 1.41 (1.15-1.71) for age 45-54 years old, 1.38 (1.11-1.73) for age 55-64 years old, and 1.07 (0.89-1.28) for age ≥65 years old, respectively (p for interaction = 0.005). Similar results were obtained for colorectal, liver, and breast cancers in the site-specific analysis.

New-onset metabolic syndrome was associated with a higher risk of overall cancer and incidence of several types of cancer, and the associations were stronger with a younger age of onset.

Kailuan Study, ChiCTR2000029767 (Registered February 12, 2020, https://www.chictr.org.cn/showprojEN.html?proj=48316).

Hepatocellular carcinoma has a substantial global mortality burden which is rising despite advancements in tackling the traditional viral risk factors. Metabolic (dysfunction) associated fatty liver disease (MAFLD) is the most prevalent liver disease, increasing in parallel with the epidemics of obesity, diabetes and systemic metabolic dysregulation. MAFLD is a major factor behind this sustained rise in HCC incidence, both as a single disease entity and often via synergistic interactions with other liver diseases. Mechanisms behind MAFLD-related HCC are complex but is crucially underpinned by systemic metabolic dysregulation with variable contributions from interacting disease modifiers related to environment, genetics, dysbiosis and immune dysregulation. MAFLD-related HCC has a distinct clinical presentation, most notably its common occurrence in non-cirrhotic liver disease. This is just one of several major challenges to effective surveillance programmes. The response of MAFLD-related HCC to immune-checkpoint therapy is currently controversial, and is further complicated by the high prevalence of MAFLD in individuals with HCC from viral aetiologies. In this review, we highlight the current data on epidemiology, clinical characteristics, outcomes and screening controversies. In addition, concepts that have arisen because of the MAFLD paradigm such as HCC in MAFLD/NAFLD non-overlapping groups, dual aetiology tumours and MAFLD sub-phenotypes is reviewed.

As the clinical course of metabolic-associated fatty liver disease (MAFLD) is unclear, we compared the clinical courses of MAFLD and non-alcoholic FLD (NAFLD).

Asian FLD patients (n = 987) from 1991 to 2021 (biopsy-proven in 939) were enrolled. The patients were divided into NAFLD (N-alone, n = 92), both MAFLD and N (M&N, n = 785), and M-alone (n = 90) groups. Clinical features, complications, and survival rates were compared among the three groups. Risk factors of mortality were subjected to Cox regression analysis.

The N-alone group patients were significantly younger (N alone, M&N, and M alone: 50, 53, and 57 years, respectively), more frequently male (54.3%, 52.6%, and 37.8%), and had a low body mass index (BMI, 23.1, 27.1, and 26.7 kg/m²) and FIB-4 index (1.20, 1.46, and 2.10). Hypopituitarism (5.4%) and hypothyroidism (7.6%) were significantly observed in the N-alone group. Hepatocellular carcinoma (HCC) developed in 0.0%, 4.2%, and 3.5% of the cases, and extrahepatic malignancies in 6.8%, 8.4%, and 4.7% of the cases, respectively, with no significant differences. The cardiovascular event rate was significantly higher in the M-alone group (1, 37, and 11 cases, P < 0.01). Survival rates were similar among the three groups. Risk factors for mortality were age and BMI in the N-alone group; age, HCC, alanine transaminase, and FIB-4 in the M&N group; and FIB-4 in the M-alone group.

Different risk factors for mortality may exist among the FLD groups.

Metabolic syndrome (MetS) is a cluster of risk factors including hypertension, hyperglycemia, dyslipidemia, and abdominal obesity. Metabolism-related risk factors include diabetes and heart disease. MetS is also linked to numerous cancers and chronic kidney disease. All of these variables raise medical costs. Developing a prediction model that can quickly identify persons at high risk of MetS and offer them a treatment plan is crucial. Early prediction of metabolic syndrome will highly impact the quality of life of patients as it gives them a chance for making a change to the bad habit and preventing a serious illness in the future. In this paper, we aimed to assess the performance of various algorithms of machine learning in order to decrease the cost of predictive diagnoses of metabolic syndrome. We employed ten machine learning algorithms along with different metaheuristics for feature selection. Moreover, we examined the effects of data augmentation in the prediction accuracy. The statistics show that the augmentation of data after applying feature selection on the data highly improves the performance of the classifiers.

Obesity has been labeled as the global pandemic of the 21st century, resulting from a sedentary lifestyle and caloric excess. Nonalcoholic fatty liver disease (NAFLD), characterized by excessive hepatic steatosis, is strongly associated with obesity and metabolic syndrome and is estimated to be present in one-quarter of the world population, making it the most common cause of the chronic liver disease (CLD). NAFLD spectrum varies from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. The burden of NAFLD has been predicted to increase in the coming decades resulting in increased rates of decompensated cirrhosis, hepatocellular carcinoma (HCC), and liver-related deaths. In the current review, we describe the pathophysiology of NAFLD and NASH, risk factors associated with disease progression, related complications, and mortality. Later, we have discussed the changing epidemiology of HCC, with NAFLD emerging as the most common cause of CLD and HCC. We have also addressed the risk factors of HCC development in the NAFLD population (including demographic, metabolic, genetic, dietary, and lifestyle factors), presentation of NAFLD-associated HCC, its prognosis, and the issue of HCC development in non-cirrhotic NAFLD. Lastly, the problems related to HCC screening in the NAFLD population, the remaining challenges, and future directions, especially the need to identify the high-risk individuals, will be discussed. We will conclude the review by summarizing the clinical evidence for treating fibrosis and preventing HCC in those at risk with NAFLD-associated HCC.

Obesity, oxidative stress, and inflammation are risk factors for hepatocellular carcinoma (HCC). We examined, in mice, the effects of Krüppel-like factor 9 (KLF9) knockout on: adiposity, hepatic and systemic oxidative stress, and hepatic expression of pro-inflammatory and NOX/DUOX family genes, in a high-fat diet (HFD) context. Male and female Klf9^+/+ (wild type, WT) and Klf9^-/- (knockout, KO) mice were fed HFD (beginning at age 35 days) for 12 weeks, after which liver and adipose tissues were obtained, and serum adiponectin and leptin levels, liver fat content, and markers of oxidative stress evaluated. Klf9^-/- mice of either sex did not exhibit significant alterations in weight gain, adipocyte size, adipokine levels, or liver fat content when compared to WT counterparts. However, Klf9^-/- mice of both sexes had increased liver weight/size (hepatomegaly). This was accompanied by increased hepatic oxidative stress as indicated by decreased GSH/GSSG ratio and increased homocysteine, 3-nitrotyrosine, 3-chlorotyrosine, and 4HNE content. Decreased GSH to GSSG ratio and a trend toward increased homocysteine levels were observed in the corresponding Klf9^-/- mouse serum. Gene expression analysis showed a heightened pro-inflammatory state in livers from Klf9^-/- mice. KLF9 suppresses hepatic oxidative stress and inflammation, thus identifying potential mechanisms for KLF9 suppression of HCC and perhaps cancers of other tissues.