The long-term association between total energy intake and clinical outcomes in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. The present study aimed to explore the associations between total energy intake and mortality in MASLD patients and to evaluate whether the associations differ by sex. A total of 2,466 MASLD patients from the Third National Health and Nutrition Examination Survey was included. Total energy intake was assessed using 24-hour dietary recall. Mortality was ascertained by linkage to National Death Index records through 31 December 2019. Multivariable Cox proportional hazards model was used to estimate the association between total energy intake and mortality. In MASLD patients, both low and high total energy intake were significantly associated with elevated risk of all-cause mortality. Compared with moderate total energy intake (2,000-3,000 kcal/day for males and 1,600-2,400 kcal/day for females), the HRs (95% CIs) for low and high total energy intake were 1.27 (1.05-1.53; P = 0.01) and 1.40 (1.03-1.92; P = 0.03), respectively. A significant interaction was demonstrated between sex and total energy intake for all-cause mortality (P value for interaction = 0.03). In males, both low and high total energy intake were significantly associated with elevated risk of all-cause mortality. The HRs (95% CIs) for low and high total energy intake were 1.35 (1.02-1.80; P = 0.04) and 1.54 (1.05-2.28; P = 0.03), respectively. However, no significant association was observed in females. The HRs (95% CIs) for low and high total energy intake were 1.14 (0.86-1.52; P = 0.34) and 1.14 (0.81-1.61; P = 0.46), respectively. These findings provide novel evidence supporting sex-specific dietary guidelines for MASLD, with particular emphasis on maintaining moderate energy intake to mitigate mortality risk in male patients.

The prognostic value of the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. This study aimed to evaluate the associations between the NHHR and all-cause and cause-specific mortality in patients with MASLD.

Data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES III and the National Death Index (NDI). The NHHR was calculated according to the formula. The results of mortality associated with the NDI were recorded as of December 31, 2019. We used a multivariate Cox proportional hazard model and restricted cubic spline (RCS) regression to assess the associations between the NHHR and all-cause and cause-specific mortality. In addition, subgroup analyses were performed to explore the relationships between the NHHR and all-cause and cause-specific mortality.

This study included 3155 patients with a definite diagnosis of MASLD. A total of 1,381 (43.8%) patients with MASLD died, and 1,774 (56.2%) survived. Multivariate Cox proportional hazards model analysis showed that NHHR was not significantly associated with all-cause mortality in MASLD patients. The RCS curve showed a significant nonlinear trend between the NHHR and all-cause mortality in patients with MASLD. Subgroup analysis revealed that the NHHR was better suited to predict cardiovascular mortality in patients without advanced fibrosis.

Our study revealed the clinical value of the NHHR in the prediction of mortality in the MASLD population. The NHHR can be used as a biomarker for follow-up in people without advanced fibrosis.

Estimated remnant cholesterol (Rem-C) level, a risk factor for cardiovascular disease, is associated with metabolic dysfunction-associated steatotic liver disease (MASLD) diagnosed via ultrasonography. However, the relationship between accurate serum Rem-C level measurements and histological findings of MASLD remains unclear.

We aimed to elucidate the relationship between accurately measured serum Rem-C levels and histological findings of MASLD.

Cross-sectional single-center observational study.

We assessed 222 patients (94 men and 128 women; age 20-80) who were diagnosed with MASLD via liver biopsy with available medical history, physical examination, and biochemical measurement data. Serum ester-type cholesterol and free cholesterol contents in the remnant lipoproteins were measured using an enzymatic method.

Serum Rem-C levels were significantly higher in patients with NAFLD activity score (NAS) 5 to 8, >66% steatosis grade, lobular inflammation with ≥5 foci, and many cells/prominent ballooning cells (a contiguous patch of hepatocytes showing prominent ballooning injury) than in patients with NAS 1 to 4, < 33% steatosis grade, lobular inflammation with <2 foci, and few ballooning cells (several scattered balloon cells), respectively. While univariate analysis revealed no significant association between Rem-C levels and advanced fibrosis, a significant association between Rem-C levels and NAS was evident. This relationship remained significant in multivariate analysis adjusted for confounders. Furthermore, in the analysis by sex, these relationships were significant for men but not for women.

High serum Rem-C levels were associated with high NAS but not with fibrosis stage, particularly in men. Controlling serum Rem-C level may improve MASLD activity.

Metabolic hepatic steatosis (MetHS) is a clinically heterogeneous, multisystemic, dynamic, and complex disease, whose progression is one of the main causes of cirrhosis and hepatocarcinoma. This clinical practice guideline aims to respond to its main challenges, both in terms of disease burden and complexity. To this end, recommendations have been proposed to experts through the Delphi method. The consensus was optimal in recommendations regarding type 2 diabetes as a risk factor (1.5.1, 4.5.1), in which cases early detection of MetHS should be carried out (4.5.2). Its results also emphasize the importance of the use of non-invasive tests (FIB-4, NFS, HFS) for the exclusion of significant fibrosis in patients with suspected MetHS (2.3.1, 2.3.3). Diagnosis should be carried out through the sequential combination of non-invasive indices and transient elastography by FibroScan® for its risk stratification (2.3.3). A nearly unanimous consensus was reached regarding the role of early prevention in the impact on the quality of life and survival of patients (5.1.2), as well as on the effectiveness of the Mediterranean diet and physical exercise in relation to the improvement of steatosis, steatohepatitis and fibrosis in MetHS patients (5.2.2) and on the positive results offered by resmiterom and semaglutide in promoting fibrosis regression (5.4.1). Finally, a great consensus has been reached regarding the importance of multidisciplinary management in MetHS, for which it is essential to agree on multidisciplinary protocols for referral between levels in each health area (6.2.1), as well as ensuring that referrals to Hepatology/Digestive and Endocrinology or Internal Medicine services are effective and beneficial to prevent the risk of disease progression (6.2.3, 6.3.1).

The purpose of this systematic review and meta-analysis is to investigate the association of metabolic dysfunction-associated steatotic liver disease (MASLD) with arterial stiffness and enlighten on potential cardiometabolic co-factors.

A literature search in PubMed/Medline, Embase, Scopus, and Web of Science databases was conducted. All the observational studies comparing arterial stiffness indices between adults with Non-alcoholic Fatty Liver Disease (NAFLD), Metabolic Dysfunction Associated-Fatty Liver Disease (MAFLD), or MASLD and apparently healthy individuals with normal liver function were included. Pulse wave velocity (PWV) and augmentation index (AIx) were mainly used as arterial stiffness indices.

Fourty one unique studies were included in the systematic review, with 27 deemed eligible for meta-analysis. Patients with MASLD had increased carotid-femoral PWV (14 studies, Mean difference (MD): 0.96 m/s, 95% confidence interval (CI) 0.65-1.27, p < 0.001) compared with healthy individuals. This finding was independent from body mass index, triglycerides, high-density lipoprotein, systolic blood pressure, and fasting plasma glucose. Moreover, patients with MASLD had higher brachial-ankle PWV (13 studies, MD: 78.14 cm/s, 95% CI 60.37-95.90, p < 0.001) and AIx (7 studies, MD: 3.85%, 95% CI 0.87-6.82, p = 0.0195) compared with controls.

MASLD is correlated with increased arterial stiffness. This relation is unaffected by common cardiometabolic risk factors.

PROSPERO (ID: CRD42023468258).

Controversy remains whether the mortality risk in people with fatty liver disease (FLD) including metabolic-(dysfunction) associated steatotic liver disease (MASLD) and metabolic-(dysfunction) associated fatty liver disease (MAFLD) is higher than observed in those without FLD. We aimed to determine the mortality rate and mortality rate ratio (MRR) for these FLDs.

The study population was a randomly selected cohort of community-dwelling adults in regional Victoria, Australia between 2001 and 2003 with sufficient data evaluable for Fatty Liver Index and determination on alcohol consumption. MASLD and MAFLD were diagnosed by established criteria. The primary outcome was overall mortality and main secondary outcome was major adverse liver outcomes (MALO) (i.e., decompensated liver disease, primary liver cancer and liver-related death). Non-fatal and fatal outcomes were captured via data linkage to hospital admission, cancer registry, and death registries. MRR was calculated with non-FLD participants as the comparator.

1444 (99.3%) and 1324 (91.1%) individuals from a total of 1454 were included in the final MAFLD and MASLD analyses. The median follow-up was 19.7 years (IQR 19.1-20.1) and there were 298 deaths. The MRR for MAFLD and MASLD was 1.39 (95% CI 1.10-1.76) and 1.25 (95% CI 0.96-1.61), respectively. MAFLD persisted as a risk factor for all-cause death on multivariable models correcting for lifestyle and socioeconomic variables, but not when adjusted for metabolic risk factors. MALOs were increased in MAFLD [incidence rate ratio (IRR) 3.03, 95% CI 1.22-8.18] and MASLD (IRR 2.80, 95% CI 1.05-7.90). Metabolic risk factors increased the risk of overall mortality and MALO, and cancer (34.3-34.6%) and cardiovascular disease (30.1-33.7%) were the most common cause of death in FLD.

In this population-based longitudinal study, MAFLD but not MASLD increases the risk of overall mortality, with metabolic syndrome components key risk factors increasing risk of death.

The validity of non-invasive tests (NITs) of liver fibrosis for the prediction of liver and mortality outcomes in an Australian cohort is unknown. We aimed to verify the utility of available NITs to predict overall and cause-specific mortality and major adverse liver outcome (MALO).

This was an analysis from the Crossroads 1 clinic sub-study of a randomly sampled adult cohort from regional Australia between 2001 and 2003. Baseline variables included demographic details, anthropometry, health and lifestyle data, and laboratory tests. Non-alcoholic fatty liver disease (NAFLD) and metabolic-(dysfunction) associated fatty liver disease (MAFLD) were defined by fatty liver index ≥ 60 and other accepted criteria. Outcomes were defined by the International Statistical Classification of Diseases and Related Health Problems 10th Revision codes for linked hospitalization and death registry data. Available serum-based NITs were analyzed as predictors of overall, cardiovascular disease-related, and cancer-related mortality and MALO in those with fatty liver disease (FLD).

In total, 1324 and 1444 participants were included for NAFLD and MAFLD analysis (prevalence 35.4% and 40.7%, respectively). There were 298 deaths (89 cardiovascular disease-related and 98 cancer-related) and 24 MALO over a median 19.7 years of follow-up time. In both forms of FLD, fibrosis-4 index, Steatosis-Associated Fibrosis Estimator score, and Forns fibrosis score consistently had the highest area under the receiver operating characteristic curve (AUROC) for overall and cause-specific mortality, with AUROC > 0.70 for each outcome. However, all had poor discriminatory ability for determining MALO in each FLD.

Several liver fibrosis NITs perform similarly reasonably well in predicting the risk of mortality outcomes in those with FLD but are poorly discriminatory for MALO prediction.

A new term, metabolic dysfunction-associated steatotic liver disease (MASLD), has been proposed by a multi-society expert panel. However, it remains unclear whether hepatic steatosis per se in MASLD contributes to an increased risk of mortality in individuals with any cardio-metabolic risk factor (CMRF), which is also a significant risk factor for increased mortality. This study aimed to compare all-cause and cause-specific mortality between the "MASLD/MetALD" and "no steatotic liver disease (SLD)" groups in individuals with any CMRF.

A population-based cohort study was conducted using 10,750 participants of the Third National Health and Nutrition Examination Survey. All-cause and cause-specific (cardiovascular, cancer, diabetes, and liver) mortality risks were compared between the "MASLD," "MetALD," and "no SLD" groups using the Cox proportional hazards model with complex survey design weights, adjusted for confounders. Over 26 years, the "MASLD" group did not show significantly increased all-cause (adjusted HR 1.04[95% CI: 0.95-1.14], p = 0.413), cardiovascular (0.88 [0.75-1.04], p = 0.139), or cancer (1.06[0.84-1.33], p = 0.635) mortality risk compared to the "no SLD" group in individuals with any CMRF. The MetALD group was associated with increased all-cause (1.41 [1.05-1.89], p = 0.022), cancer (2.35 [1.33-4.16], p = 0.004), and liver (15.04 [2.96-76.35], p = 0.002) mortality risk compared with the no SLD group. This trend was more pronounced in the MetALD group with advanced fibrosis assessed by Fibrosis-4 (FIB-4).

In individuals with CMRF, the presence of steatotic liver disease (MASLD) alone did not increase the risk of mortality, except in cases with more alcohol consumption (MetALD). Therefore controlling metabolic risk factors and reducing alcohol consumption in people with MASLD or MetALD will be crucial steps to improve long-term health outcomes.

Serum folate and vitamin B12 levels correlate with the prevalence of fatty liver disease, but it is not clear how they affect mortality. Therefore, this study aimed to investigate the association of serum folate and vitamin B12 concentrations with all-cause mortality in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD).

MASLD subjects were from the Third National Health and Nutrition Examination Survey (NHANES III) in the United States, and mortality follow-up data were obtained by linkage to death records from the National Death Index. Multivariable Cox proportional regression models and restricted cubic spline (RCS) models were used to evaluate the association of serum folate/vitamin B12 with all-cause mortality in the MASLD population.

3,636 and 2,125 MASLD individuals were included in the analyses related to serum folate and vitamin B12, respectively. During a follow-up period of more than 20 years, the RCS models demonstrated significant nonlinear associations of both serum folate (P <0.001) and vitamin B12 (P =0.016) with all-cause mortality in MASLD. When their serum concentrations were below the median level, the risk of all-cause mortality decreased with increasing concentration, reaching a lowest risk around the median level, and then leveled off. In the multivariable cox regression model, for vitamin B12, the risk of all-cause mortality was reduced by 42% and 28% in the third and fourth quartile groups, respectively, compared with the lowest quartile group (hazard ratio [HR]=0.58, 95% CI: 0.39-0.86, P =0.008; HR =0.72, 95% CI: 0.54-0.96, P=0.026, respectively). For folate, the risk of all-cause mortality was reduced by 28% in the third quartile compared with the lowest quartile (HR =0.72, 95% CI: 0.57-0.91, P =0.005).

This longitudinal cohort study suggests that low serum folate and vitamin B12 levels in patients with MASLD are significantly associated with an elevated risk of all-cause mortality.

This study aims to assess the prognostic value of the fatty liver index (FLI), a noninvasive tool for hepatic steatosis assessment, in predicting all-cause and disease-specific mortality.

We linked data from the National Health and Nutrition Examination Survey III (1988-1994) with Public-Use Mortality Files, forming a cohort of 11 297 participants with a median follow-up period of 26.25 years. Cox proportional hazards models were used to evaluate the association between FLI and all-cause mortality, while Fine and Gray's models assessed the relationship between FLI and disease-specific mortality.

The FLI ≥ 60 was independently associated with an increased risk of all-cause mortality (hazard ratio = 1.24, P  < 0.001), as well as mortality from malignant neoplasms (hazard ratio = 1.18, P  = 0.048), diabetes (hazard ratio = 2.62, P  = 0.001), and cardiovascular diseases (CVDs) (hazard ratio = 1.18, P  = 0.018), compared to FLI < 30. No significant associations were found with Alzheimer's disease, influenza and pneumonia, chronic lower respiratory diseases, or renal disorders. Subgroup analyses indicated that individuals who were females aged 40-60 (hazard ratio = 1.67, P  = 0.003), non-overweight (hazard ratio = 1.75, P  = 0.007), or without abdominal obesity (hazard ratio = 1.75, P  = 0.007) exhibited a stronger association between FLI ≥ 60 and all-cause mortality.

These findings support the prognostic value of the FLI for predicting mortality from all causes, malignant neoplasms, diabetes, and CVDs. Targeted attention is needed in postmenopausal women, non-overweight, and non-abdominally obese populations.

The choroid, a highly vascular structure within the eye, is significantly influenced by various systemic conditions. The advent of enhanced depth optical coherence tomography has improved our ability to evaluate choroidal pathophysiology. The choroidal vascularity index (CVI), a noninvasive and reliable tool, serves as an effective means of assessing the choroidal vascular structure. Recent studies have increasingly focused on exploring CVI alterations under different systemic conditions. This study aims to provide a comprehensive summary of the latest research findings in this area.

A systematic literature review was conducted on October 1, 2023, using two databases, MEDLINE (via PubMed) and Scopus. Search terms were tailored specifically for each database to ensure a thorough exploration of relevant literature. The studies identified were qualitatively assessed, with particular emphasis on outcomes related to CVI and choroidal thickness.

A total of 48 studies were included in the review, encompassing a diverse range of systemic conditions such as diabetes, central nervous system disorders, cardiovascular diseases, autoimmune disorders, and infectious diseases. Notable reductions in CVI were observed in diabetic retinopathy, autoimmune diseases, and neurodegenerative disorders. Additionally, the review highlighted variations in CVI values related to the severity of systemic diseases, indicating its potential use as a biomarker for disease progression.

This review highlights the significant correlation between variations in the choroidal vascularity index and diverse systemic conditions affecting hemodynamics. An enhanced understanding of CVI provides deeper insights into the pathophysiological mechanisms underlying these disorders and positions CVI as a promising biomarker for early detection and monitoring. Nevertheless, its clinical utility warrants careful assessment. Future research should address the potential limitations of CVI to fully capitalize on its diagnostic and prognostic potential.

The global burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is growing, but its subsequent health consequences have not been thoroughly examined.

A phenome-wide association study was conducted to map the associations of MASLD with 948 unique clinical outcomes among 361,021 Europeans in the UK Biobank. Disease trajectory and comorbidity analyses were applied to visualize the sequential patterns of multiple comorbidities related to the occurrence of MASLD. The associations jointly verified by observational and polygenic phenome-wide analyses were further replicated by two-sample Mendelian randomization analysis using data from the FinnGen study and international consortia.

The observational and polygenic phenome-wide association study revealed the associations of MASLD with 96 intrahepatic and extrahepatic diseases, including circulatory, metabolic, genitourinary, neurological, gastrointestinal, and hematologic diseases. Sequential patterns of MASLD-related extrahepatic comorbidities were primarily found in circulatory, metabolic, and inflammatory diseases. Mendelian randomization analyses supported the causal associations between MASLD and the risk of several intrahepatic disorders, metabolic diseases, cardio-cerebrovascular disease, and ascites but found no associations with neurological diseases.

This study elucidated multisystem comorbidities and health consequences of MASLD, contributing to the development of combination interventions targeting distinct pathways for health promotion among patients with MASLD.

X.L. was funded by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001) and the National Nature Science Foundation of China (82204019) and Y.D. was funded by the Key Project of Traditional Chinese Medicine Science and Technology Plan of Zhejiang Province (GZY-ZJ-KJ-24077) and the National Natural Science Foundation of China (82001673 and 82272860).

Non-alcoholic fatty liver disease (NAFLD) is estimated to affect approximately 25% of the global population. Both, coronary artery disease and NAFLD are linked to underlying insulin resistance and inflammation as drivers of the disease. Coronary flow reserve parameters, including coronary flow reserve velocity (CFRV), baseline diastolic peak flow velocity (DPFV), and hyperemic DPFV, are noninvasive markers of coronary microvascular circulation. The existing literature contains conflicting findings regarding these parameters in NAFLD patients.

A comprehensive systematic search was conducted on major electronic databases from inception until May 8, 2024, to identify relevant studies. We pooled the standardized mean differences (SMD) with 95% confidence intervals (CI) using the inverse-variance random-effects model. Statistical significance was set at P < .05.

Four studies with 1139 participants (226 with NAFLD and 913 as controls) were included. NAFLD was associated with a significantly lower CFRV (SMD: -0.77; 95% CI: -1.19, -0.36; P < .0002) and hyperemic DPFV (SMD: -0.73; 95% CI: -1.03, -0.44; P < .00001) than the controls. NAFLD demonstrated a statistically insignificant trend toward a reduction in baseline DPFV (SMD: -0.09; 95% CI: -0.38, 0.19; P = .52) compared to healthy controls.

Patients with NAFLD are at a higher risk of coronary microvascular dysfunction, as demonstrated by reduced CFRV and hyperemic DPFV. The presence of abnormal coronary flow reserve in patients with NAFLD provides insights into the higher rates of cardiovascular disease in these patients. Early aggressive targeted interventions for impaired coronary flow reserve in subjects with NAFLD may lead to improvement in clinical outcomes.

Primary liver cancer is the third leading cause of cancer deaths worldwide and has one of the worst 5-year survival rates. This study examines US primary liver cancer incidence and incidence-based mortality trends over four decades.

The SEER-9 registry was used to study primary liver cancer cases from 1978 to 2018. The incidence and mortality rates were calculated based on gender, age, race, and stage of diagnosis. Joinpoint regression software was used to calculate the annual percent change.

The overall incidence rate of primary liver cancer from 1978 to 2018 increased by 2.71%/year (p<0.001). Rates in patients <50 years old began to fall in 2002 at a rate of -3.62%/year (p<0.001). Similarly, the incidence-based mortality rates for primary liver cancer increased by 2.15%/year (p<0.001). Whereas Whites incidence-based mortality rates began to plateau in 2012 (0.18%/year; p = 0.84), Blacks rates have declined since 2010 (-2.93%/year; p = 0.03), and Asian rates have declined since 1999 (-1.30%/year; p<0.001).

While the overall primary liver cancer incidence and incidence-based mortality have been increasing over the last four decades, there was an observed decline in incidence and incidence-based mortality in recent years, especially among at-risk subgroups.

The association between fatty liver disease (FLD) and cardiovascular disease (CVD) in an Australian context has yet to be defined. The primary aim of this study was to investigate the association between FLD and 3-point major adverse cardiovascular events (MACE).

This was a longitudinal follow-up study of a randomly sampled adult cohort from regional Australia between 2001 and 2003. Baseline covariates included demographic details, anthropometry, health and lifestyle data, and laboratory tests. Non-alcoholic fatty liver disease (NAFLD) and metabolic-(dysfunction) associated fatty liver disease (MAFLD) were diagnosed in participants with fatty liver index (FLI) ≥ 60 and meeting other standard criteria. ICD-10 codes were used to define clinical outcomes linked to hospitalisations. Three-point MACE defined as non-fatal myocardial infarction (MI) and cerebrovascular accident (CVA) and CVD death.

In total, 1324 and 1444 participants met inclusion criteria for NAFLD and MAFLD analysis, respectively. Over 23,577 and 25,469 person-years follow-up, NAFLD and MAFLD were independent predictors for 3-point MACE, adjusting for demographic covariates and known cardiometabolic risk factors, whilst considering non-CVD death as a competing event (NAFLD: sub-hazard ratio [sHR] 1.56, 95% confidence interval [CI 1.12-2.19]; MAFLD: sHR 1.51, 95% CI 1.11-2.06). The results held true on several sensitivity analyses.

Both forms of FLD increase the risk for CVD independent of traditional cardiometabolic risk factors.

The prognostic value of triglyceride-glucose (TyG) related indices in non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is still unclear. This study aimed to determine the associations between TyG-related indices and long-term mortality in this population.

The data came from the National Health and Nutrition Examination Survey (NHANES III) and National Death Index (NDI). Baseline TyG, TyG combining with body mass index (TyG-BMI), and TyG combining with waist circumference (TyG-WC) indices were calculated, and mortality status was determined through 31 December 2019. Multivariate Cox and restricted cubic spline (RCS) regression models were performed to evaluate the relationship between TyG-related indices and long-term mortality among participants with NAFLD/MASLD. In addition, we examined the association between TyG-related indices and all-cause mortality within subgroups defined by age, sex, race/ethnicity, and fibrosis-4 index (FIB-4).

There were 10,390 participants with completed ultrasonography and laboratory data included in this study. NAFLD was diagnosed in 3672/10,390 (35.3%) participants, while MASLD in 3556/10,390 (34.2%) amongst the overall population. The multivariate Cox regression analyses showed high levels of TyG-related indices, particularly in TyG-BMI and TyG-WC indices were significantly associated with the all-cause mortality, cardiovascular mortality, and diabetes mortality in either NAFLD or MASLD. The RCS curves showed a nonlinear trend between three TyG-related indices with all-cause mortality in either NAFLD or MASLD. Subgroup analyses showed that TyG-BMI and TyG-WC indices were more suitable for predicting all-cause mortality in patients without advanced fibrosis.

Our study highlights the clinical value of TyG-related indices in predicting the survival of the NAFLD/MASLD population. TyG-BMI and TyG-WC indices would be the surrogate biomarkers for the follow-up of the population without advanced fibrosis.

Many systematic reviews explore the association of non-alcoholic fatty liver disease (NAFLD) with mortality, but none of them explores sex-based differences in detail. We aimed to assess whether NAFLD is associated with cause-specific mortality, all-cause mortality, and cancer incidence in both men and women.

The PubMed, Embase, and Medline databases were searched from inception through April 2023 for eligible studies. We separately pooled relative risks (RRs) for men and women using a random effects model. Subsequently, the RRs and 95% CIs (confidence intervals) in each study were used to calculate the women-to-men ratio of RRs (RRR). Furthermore, subgroup analyses were performed to explore the robustness of outcomes. The random-effects model was employed to conduct sensitivity analyses to determine the impact of specific studies on the overall findings.

The meta-analysis included nine cohort studies comprising 557 614 patients with NAFLD were chosen. Women were 44% more likely than men to get cancer among those with NAFLD (RRR: 1.44; 95% CI: 1.02-2.04; p = .039). However, no sex-related differences were observed between NAFLD and all-cause mortality (RRR: 1.06; 95% CI: 0.56-2.01; p = .861), liver-related mortality (RRR: 1.06; 95% CI: 0.02-69.82; p = .977), cardiovascular mortality (RRR: 1; 95% CI: 0.65-1.53; p = .987) and liver cancer (RRR: 0.76; 95% CI: 0.43-1.36; p = .36).

There may be sex variations between NAFLD and the risk of cancer, with the connection being stronger in females than in males.

In this prospective cohort study, 1197 patients with type 2 diabetes (T2D) were divided into two groups (360 patients with NAFLD and 847 without NAFLD) and were followed for a median of 5 years for the incidence of CVD. Cox regression analysis was used to assess the association between NAFLD, liver enzyme level, aspartate aminotransferase to platelet ratio index (APRI), and the incidence risk of CVD and its subgroups (i.e., myocardial infarction, chronic heart disease, coronary artery bypass grafting, and percutaneous coronary intervention). There was a significant positive association between CVD incidence and NAFLD (HR = 1.488, 95% CI = 1.041-2.124, p value = 0.029). Although patients with NAFLD had higher levels of ALT and AST levels (p value = <0.001), there was no significant association between liver enzymes and the incidence risk of CVD when adjusted for different variables. Furthermore, NAFLD was associated with NAFLD APRI Q (2), APRI Q (3), and APRIQ (4) (1.365 (1.046-1.781), 1.623 (1.234-2.135), and 3.373 (2.509-4.536)), respectively.

NAFLD increased the incidence risk of CVD in T2D. However, there was no association between liver enzymes (ALT, AST, ALK-P, and GGT) and a higher incidence risk of CVD in T2D when adjusted for confounding variables.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to increased cardiovascular (CV) risks, notably congestive heart failure (CHF). We evaluated the influence of MASLD on CHF and mortality among hospitalized cirrhotic patients.

We analyzed the National Inpatient Sample from 2016 to 2020, identifying adult cirrhosis patients. We focused on CHF and in-hospital mortality, plus hospital stay length, costs, and discharge status. Propensity score matching created balanced cohorts for comparison. Poisson and logistic regression provided adjusted CHF risks and mortality odds ratios (ORs) for MASLD patients.

Before matching, 4.1% of 672,625 cirrhotic patients had MASLD. Post-matching, each group had 23,161 patients. Patients with MASLD showed higher CHF risk (OR 1.14, 95% CI 1.10-1.21, p<0.001) but lower in-hospital mortality (OR 0.57, 95% CI 0.52-0.63, p<0.01) and decreased costs (median $24,447 vs. $28,630, OR 0.86, 95% CI 0.85-0.87, p<0.001).

In this nationwide study of patients with cirrhosis, MASLD was associated with a higher prevalence of CHF and lower in-patient mortality. These findings mirror the "adiposity paradox" phenomenon, where obese/overweight individuals with cardiometabolic dysfunction may experience less severe or beneficial health outcomes than those with a normal weight. Further investigation is warranted to decode the intricate interplay between MASLD, cirrhosis, CHF, and in-hospital mortality and its clinical practice implications.

Clinical observation revealed an increase in metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence among adults and adolescents and young adults (AYA). However, its prevalence trend in specific subgroups and its characteristics are unclear.

This cross-sectional study included adults and AYA aged 20-79 and 12-19 years, respectively, from the National Health and Nutrition Examination Survey from 1999 to 2018. MASLD was defined as US Fatty Liver Index ≥30 in adults and alanine amino transaminase elevation and obesity in AYA. Joinpoint and logistic regression were used to evaluate the MASLD prevalence trend and its associated characteristics. MASLD was diagnosed in 17 156 892 of 51 109 914 (33.6%) adults and 1 705 586 of 29 278 666 AYA (5.8%). During the study period, MASLD prevalence significantly increased from 30.8% to 37.7% ( P  < 0.01) in adults and in subgroups of female participants, individuals aged 20-45 and 61-79 years, and non-Hispanic white individuals. Conversely, MASLD prevalence did not significantly change in AYA (from 5.1% to 5.2%, P  = 0.139), except in the subgroup of Mexican Americans (from 8.2% to 10.8%, P  = 0.01). Among adults, high MASLD prevalence was associated with male sex, Mexican American ethnicity, age >50 years, being unmarried, poverty income ratio <130, poor or fair health condition, obesity or overweight, and chronic conditions. Among AYA, high MASLD prevalence was associated with male sex, poverty income ratio <130, and education.

Accordingly, we concluded that health care providers should prevent and treat conditions associated with MASLD by raising awareness of the increasing trend of MASLD.

Pericoronary adipose tissue (PCAT) CT attenuation of right coronary artery (RCA) and non-alcoholic fatty liver disease (NAFLD) have prognostic value for major adverse cardiovascular events (MACE) in patients with coronary artery disease. However, the superior prognostic value between RCA PCAT CT attenuation and NAFLD remains unclear in patients with acute chest pain. This study is to evaluate the prognostic value of NAFLD for MACE, and further assess the incremental prognostic value of NAFLD over PCAT CT attenuation.

Between January 2011 and December 2021, all consecutive emergency patients with acute chest pain referred for coronary CT angiography (CCTA) were retrospectively enrolled. MACE included unstable angina requiring hospitalization, coronary revascularization, non-fatal myocardial infarction, and all-cause death. Patients' baseline and CCTA characteristics, RCA PCAT CT attenuation, and the presence of NAFLD were used to evaluate risk factors of MACE using multivariable Cox regression analysis. The prognostic value of NAFLD compared to RCA PCAT CT attenuation was analyzed.

A total of 514 patients were enrolled (mean age, 58.36 ± 13.05 years; 310 men). During a median follow-up of 31 months, 60 patients (11.67%) experienced MACE. NAFLD (HR = 2.599, 95% CI: 1.207, 5.598, P = 0.015) and RCA PCAT CT attenuation (HR = 1.026, 95% CI: 1.001, 1.051, P = 0.038) were independent predictors of MACE. The global Chi-square analysis showed that NAFLD improved the risk of MACE more than that using clinical risk factors and CCTA metrics (59.51 vs 54.44, P = 0.024) or combined with RCA PCAT CT attenuation (63.75 vs 59.51, P = 0.040).

NAFLD and RCA PCAT CT attenuation were predictors of MACE. NAFLD had an incremental prognostic value beyond RCA PCAT CT attenuation for MACE in patients with acute chest pain. Adding CT-FFR into the risk prediction of patients with acute chest pain is worth considering.

Background Of liver-related disorders, cirrhosis is currently the leading cause of death and has become a significant global public health concern. Aspartate aminotransferase to platelet ratio index (APRI), a newer prognostic modality, is a very effective noninvasive diagnostic for identifying advanced liver fibrosis. Methods A prospective observational study was conducted among individuals with liver disease, 100 cases and 100 controls for two years. All the sociodemographic details, clinical features of the patients, and clinical findings such as prothrombin time (PT), liver function tests, kidney function tests, and total blood count were recorded using a pretested semi-structured questionnaire. Results According to our survey results, 48% of the participants were between the ages of 40 and 60. Regarding aPTT (activated partial thromboplastin time) and liver function test characteristics (serum glutamic-oxaloacetic transaminase(SGOT), serum glutamic pyruvic transaminase (SGPT)), we showed a substantial difference between the patients and controls. Regarding the APRI distribution, we also found a statistically significant variation between the research groups. When we compared the validity of APRI scores in diagnosing cirrhosis, we discovered that the ideal cutoff value of APRI was determined to be 3.99, with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 33%, 86%, 70%, and 56%, respectively. The area under the receiver operating characteristic (ROC) curve for APRI in detecting cirrhosis was also 0.693. Conclusion Thus, our study results conclude that APRI is a crucial noninvasive prognostic tool that can be utilized to prognostize liver cirrhosis.

Following the classification of metabolic dysfunction-associated fatty liver disease (MAFLD), non-alcoholic fatty liver disease (NAFLD) has recently been redefined again as metabolic dysfunction-associated steatotic liver disease (MASLD). However, the distinctions in characteristics and mortality outcomes between NAFLD, MAFLD and MASLD remain unclear.

We analysed data from 7519 participants in the third National Health and Nutrition Examination Surveys of United States (US) and their linked mortality until 2019. Survey weight-adjusted multivariable Cox proportional model was used to study the mortality over three terms.

The prevalence of NAFLD, MAFLD and MASLD was 18.5%, 19.3% and 20.8%, respectively. Most individuals with NAFLD (94.5%) or MAFLD (100%) can be classified as MASLD, while a relatively low percentage of those with MASLD were also diagnosed with either NAFLD (84.1%) or MAFLD (92.7%). During a median follow-up of 26.9 years, both MAFLD and MASLD were associated with increased risk of all-cause mortality (adjusted hazard ratio [aHR] 1.18, 95% CI 1.04-1.33 and 1.19, 1.06-1.34, respectively), this association was mainly observed in NAFLD-/MASLD+ subgroups. NAFLD was not associated with all-cause mortality. However, all three terms were associated with an increased risk of all-cause mortality in individuals with advanced fibrosis (aHR: 1.71-1.81). Subgroup analyses showed that higher risk of all-cause mortality for both MAFLD and MASLD were observed among older adults (≥65 year), non-Hispanic whites and those without diabetes.

Both MASLD and MALFD were linked to higher all-cause mortality risk, but MASLD identified a greater number of individuals compared to MAFLD.

The systematic review aimed to assess the risks of metabolic dysfunction-associated steatotic liver disease (MASLD) on all-cause and cause-specific mortality in patients with type 2 diabetes (T2DM). EMBASE and MEDLINE were searched from inception to June 2022 for observational studies examining the relationship between MASLD and the risk of mortality among T2DM patients. Meta-analysis was conducted using random-effects models with hazard ratios (HRs) to quantify the risk of mortality. A total of 5877 articles were screened, and ultimately, 12 eligible studies encompassing 368 528 T2DM patients, with a median follow-up of 8.9 years (interquartile range, 4.7-14.5), were included. Our analysis revealed a significant association between MASLD and an increased risk of all-cause mortality in T2DM patients [HR 1.28; 95% confidence interval (CI), 1.05-1.58; I 2  = 90%]. Meta-regression analyses did not show significant effects of mean age, mean BMI, and percentage of smokers, hypertension, and hyperlipidemia on the association between MASLD and the risk of all-cause mortality. However, we found that MASLD was not significantly associated with mortality related to cardiovascular diseases (HR 1.05; 95% CI, 0.82-1.35; I2  = 0%) or cancer (HR 1.21; 95% CI, 0.41-3.51; I 2  = 79%) among patients with T2DM. No publication bias was observed. This comprehensive meta-analysis provides substantial evidence supporting a significant association between MASLD and an increased risk of all-cause mortality among the T2DM population. These findings underscore the potential benefits of screening for MASLD in T2DM patients, aiding in the early identification of high-risk individuals and enabling risk modification strategies to improve survival.

Hepatocellular carcinoma (HCC) is a major contributor to the world's cancer burden. Understanding the HCC incidence rate in Taiwan is thus an interesting avenue of research.

From an NHI database, those patients who had been newly diagnosed with HCC and who had been listed on a registry in a catastrophic illness dataset during the years 2013-2021 were enrolled in this study. Antineoplastic agent usage and comorbidities were also studied.

The incidence rate of HCC decreased from 57.77 to 44.95 in 100,000 from 2013 to 2021. The average age of patients with HCC increased from 65.54 years old with a CCI score of 4.98 in 2013 to 67.92 years old with a CCI score of 5.49 in 2021. Among these HCC patients, the patients under antineoplastic agent treatment decreased from 53.47% to 31.41% from 2013 to 2021. The presence of comorbidities in HCC patients was about 55.77-83.01% with mild liver disease and 29.93-37.30% with diabetes (without complications) in the period 2013-2021.

The incidence rate of HCC slightly decreased in Taiwan. Due to antineoplastic agent usage decreasing over time, these results may indicate that more early-stage HCC patients detected in recent years were mainly treated with surgeries.

Policosanol is a mixture of long chain alcohols refined from sugar cane. Significant reductions in liver enzymes have been observed in some studies. However, the impact of policosanol on liver enzymes remained controversial. The current meta-analysis aims to evaluate the effect of policosanol supplementation on the levels of alanine transaminase (ALT) and aspartate transaminase (AST).

The literature was systematically searched for studies published up to November 2023 in PubMed/Medline, Google Scholar, EMBASE, and Scopus. Randomized controlled trial (RCT) studies were included to evaluate the intervention effect of policosanol compared to placebo on ALT and AST. DerSimonian and Laird models were used to calculate effect sizes.

Twenty-three trials including 2535 participants were included in the study. The combination of effect sizes, regarding the random-effects model, demonstrated significant changes in ALT serum levels after intervention (WMD: -1.48 U/L; 95% CI: -2.33 to -0.64; P = 0.001), and AST (WMD: -1.10 U/L; 95% CI: -1.70 to -0.51; P < 0.001). Subgroup analysis of AST and ALT showed that this reduction effect was most often observed at the dose of 20 mg/d. The dose-response analysis represented a non-significant non-linear connection between the dosage and duration of policosanol intervention in ALT and AST serum reduction.

Policosanol supplementation exerts a beneficial effect on liver enzymes as well as ALT and AST concentrations in adults. However, further long-term and well-designed RCTs with better quality are needed to further assess and confirm these results.

We conducted a systematic review and meta-analysis to study the association between non-alcoholic fatty liver disease (NAFLD) and incident cardiovascular disease (CVD).

We searched Medline, Embase, Cochrane database and TRIP database. Random-effects model meta-analyses were used to obtain pooled effect sizes and 95% confidence intervals. The certainty in evidence was rated using the GRADE tool.

Altogether 36 studies including a total of 7,068,007 participants were included in the systematic review and meta-analysis. Pooled data from 19 cohort studies demonstrated a significant increase in the risk of non-fatal CVD events in patients with NAFLD (HR 1.57, 95% CI 1.33-1.85, I2 = 95%). Pooled data from eight studies showed a significant increase in fatal CVD (HR 1.40, 95% CI 1.24-1.57, I2 =27%), and eight cohort studies suggested a significant increase in combined non-fatal and fatal CVD (HR 1.41, 95% CI 1.13-1.76, I2 =80%). Meta-analysis of studies reporting adjusted estimates in NAFLD patients with fibrosis revealed a significant increase in CVD events with acceptable level of heterogeneity (HR 1.64, 95% CI 1.25-2.16, I2 = 31%). The anticipated absolute increase in the risk of combined fatal and non-fatal CVD was estimated to be 29 more per thousand with NAFLD; that of fatal CVD events 16 more per thousand and that of non-fatal CVD events 19 more per thousand with NAFLD. The GRADE rating ranged from very low to low for overall and subgroup analyses.

The present systematic review suggests that NAFLD increases the risk of incident CVD. Cohort studies with the ability to analyze subgroup effects based on severity, along with randomized controlled trials that provide experimental evidence demonstrating a decrease in cardiovascular disease events through the treatment of non-alcoholic fatty liver disease, are necessary to validate and reinforce these findings.

To summarize the key factors contributing to the onset and progress of nonalcoholic fatty liver disease (NAFLD) and put them in a system genetics context. We particularly focus on how genetic regulation of hepatic lipids contributes to NAFLD.

NAFLD is characterized by excessive accumulation of fat in the liver. This can progress to steatohepatitis (inflammation and hepatocyte injury) and eventually, cirrhosis. The severity of NAFLD is determined by a combination of factors including obesity, insulin resistance, and lipotoxic lipids, along with genetic susceptibility. Numerous studies have been conducted on large human cohorts and mouse panels, to identify key determinants in the genome, transcriptome, proteome, lipidome, microbiome and different environmental conditions contributing to NAFLD. We review common factors contributing to NAFLD and put them in a systems genetics context. In particular, we describe how genetic regulation of liver lipids contributes to NAFLD. The combination of an unhealthy lifestyle and genetic predisposition increases the likelihood of accumulating lipotoxic specie lipids that may be one of the driving forces behind developing severe forms of NAFLD.

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.

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.

MAFLD prevalence is higher than NAFLD prevalence, carries a higher risk of overall mortality, with greater granularity in risk-stratification amongst MAFLD subtypes.

The impact of non-alcoholic fatty liver disease (NAFLD) on morbidity and mortality has yet to be documented at the general population level. This study aimed to assess whether NAFLD was associated with morbidities and mortality and to estimate its impact on health status and mortality.

The study population consisted of 137 206 participants from Constances cohort. Non-invasive diagnosis of NAFLD and advanced fibrosis was performed using the fatty liver index and Forns index, respectively. Constances data were linked to health care and hospitalization data to identify liver-related events, cardiovascular diseases (CVD), extrahepatic cancers (EHC), chronic kidney disease (CKD) and all-cause mortality.

The prevalence of NAFLD was 18.3% in subjects without other chronic liver diseases, among whom 2.7% had fibrosis. NAFLD after IPTW-weighted remained associated with an increased risk of death (HR 1.26, 95% CI 1.01-1.57), hepatic-related complications (HR 2.48, 95% CI 1.99-3.29), CVD (HR 1.42, 95% CI 1.30-1.55), EHC (HR 1.11, 95% CI 1.01-1.28) and CKD (HR 1.81, 95% CI 1.53-2.07) compared to those without chronic liver diseases risk factors (Non-NAFLD). In the trend analysis over the study period of inclusion and compared to Non-NAFLD, NAFLD has shown a fastest growing cause of hepatic events (HR 1.38, 95% CI 1.07-1.76 per year), CVD (HR 1.08, 95% CI 1.03-1.12), CKD (HR 1.16, 95% CI 1.07-1.25), and death (HR 1.39, 95% CI 1.39-1.50).

This large community-based cohort showed that NAFLD was associated with excess morbidity and mortality and demonstrated a fastest-growing trend.

In recent years, the diagnosis and understanding of nonalcoholic fatty liver disease (NAFLD), recently redefined as metabolic dysfunction-associated steatotic liver disease (MASLD), and its relationship with cardiovascular diseases (CVD) are gaining better understanding. As MASLD shares common risk factors with CVD, including obesity, insulin resistance, hypertension, and dyslipidemia, research increasingly identifies it as a potential independent risk factor for CVD. The exact mechanisms linking MASLD to CVD remain complex and multifaceted, involving metabolic, inflammatory, and vascular pathways. Current cardiology guidelines recognize the significant association between MASLD and CVD, advocating its integration into cardiovascular risk assessment and management. Despite the progress, gaps persist in understanding underlying molecular and cellular mechanisms and the representation of diverse populations in epidemiological studies. The review illuminates the clinical implications of the MASLD-CVD link and identifies directions for future research.

We aimed to examine the impact of non-alcoholic fatty liver disease (NAFLD) on the clinical outcomes in patients with type 2 diabetes (T2D).

Between 2013 and 2014, 1,734 patients with T2D underwent transient elastography (TE) to assess liver status indicated by controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). Liver steatosis was defined by CAP ≥ 248 dB/m and advanced liver fibrosis by LSM ≥ 10 kPa. In 2019, we assessed their clinical outcomes including hospitalizations and mortality.

In this prospective cohort [56% men, mean (±standard deviation) age:60.8±11.5 years; glycated hemoglobin (HbA1c)7.8±1.6 %], 798 patients had liver steatosis, 296 patients had advanced liver fibrosis and 640 patients had normal liver at baseline. T2D with advanced liver fibrosis had higher body mass index, waist circumference, waist-hip ratio, fasting plasma glucose, HbA1c, blood pressure and lipid profiles than their counterparts with NAFLD or normal liver (all p < 0.05). After a median follow-up of 6.07 (interquartile range:5.84 to 6.30) years, there were 4,403 incident hospitalizations, 32,119 days of hospital stay, and 171 deaths. Using Cox regression analysis, advanced liver fibrosis was associated with increased risk of heart failure (hazard ratio [95% confidence interval] HR:3.07[1.08-8.68], p=0.035) and hospitalizations (HR:1.39[1.14-1.70], p=0.001) while liver steatosis was associated with reduced mortality (HR:0.60[0.41-0.87], p=0.007) compared to their counterparts with normal liver after adjustment for potential confounders.

T2D comorbid with liver steatosis and advanced liver fibrosis are distinct clinical entities with differences in outcomes. Advanced liver fibrosis is an important predictor for worse outcomes including heart failure and hospitalizations in people with T2D.

(1) Background: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease. Aims: We aimed to investigate the frequency of comorbidities and malignancies among NAFLD patients compared to the general population. (2) Methods: A retrospective study included adult patients with a NAFLD diagnosis. A control group was matched for age and gender. Demographics, comorbidities, malignancies, and mortality were collected and compared. (3) Results: 211,955 NAFLD patients were analyzed in comparison to 452,012 matched general population controls. Significantly higher rates of diabetes mellitus (23.2% vs. 13.3%), obesity (58.8% vs. 27.8%), hypertension (57.2% vs. 39.9%), chronic ischemic heart disease (24.7% vs. 17.3%), and CVA (3.2% vs. 2.8%) were found among NAFLD patients. Patients with NAFLD had significantly higher rates of the following malignancies: prostate cancer (1.6% vs. 1.2%), breast cancer (2.6% vs. 1.9%), colorectal cancer (1.8% vs. 1.4%), uterine cancer (0.4 vs. 0.2%), kidney cancer (0.8% vs. 0.5%), but a lower rate of lung cancer (0.9% vs. 1.2%) and stomach cancer (0.3% vs. 0.4%). The all-cause mortality rate among NAFLD patients was significantly lower in comparison to the general population (10.8% vs. 14.7%, p < 0.001). (4) Conclusions: Higher rates of comorbidities and malignancies among NAFLD patients were observed, but a lower rate of all-cause mortality was found.

Concerns about how non-alcoholic fatty liver disease (NAFLD) might contribute to the development of cardiovascular disease (CVD) have grown as the importance of NAFLD and its relationship to the metabolic syndrome has grown. The purpose of this cross-sectional retrospective is to investigate potential correlations between hepatic steatosis in liver segments seen when measuring calcium score and the presence of atherosclerotic CAD (coronary artery disease).

Two hundred patients (mean age, 57 years±10) who underwent coronary cardiac computed tomography (CT) scans were included. CT scans were analysed to assess the attenuation of liver parenchyma and the coronary artery calcification (CAC).

Age, gender, body mass index (BMI) and CAC score were significantly associated with hepatic steatosis. Among all patients, CAC score (r=-0.31, p<0.0001), and BMI (r=-0.40, p<0.0001) had a moderate negative correlation with the values of liver attenuation. BMI (OR: 1.109, p=0.001), CAC score (OR: 1.629, p<0.001), and age (OR: 1.050, p<0.001) were found to be independent predictors of hepatic steatosis through logistic regression.

A statistically significant correlation between CAC score and the presence of NAFLD as evaluated by non-contrast-enhanced CT was demonstrated. BMI, CAC score, and age were identified as independent predictors of hepatic steatosis.

Arsenic is a natural element with complex toxicity. Long-term exposure to arsenic can cause a variety of health damage. In recent years, there are some studies on arsenic exposure and liver injury. But few of them tried to measure the quantitative relationship between arsenic exposure and indicators of liver injury in adult. Therefore, this study aimed to elucidate the relationship between them. This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) in 2003-2018. Arsenic exposure was assessed using total urinary arsenic and dimethylarsenate acid (DMA). We selected alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total protein (TP), ALT/AST, total bilirubin (TBIL), and albumin (ALB) as markers of liver injury. Multiple linear regression was used to explore the relationship between urinary arsenic concentrations and these markers of liver function injury. In addition, six covariables (age, sex, smoker, alcohol user, BMI, diabetes) were further analyzed in subgroups. A total of 13,420 adults were included in the analysis. The multivariate linear regression analyses showed that urinary DMA was positively correlated with ALT (β 0.135, 95%CI 0.090, 0.180, p < 0.001), AST (β 0.053, 95%CI 0.014, 0.092, p < 0.01), ALT/AST (β 0.052, 95%CI 0.030, 0.074, p < 0.001), TBIL (β 0.061, 95%CI 0.034, 0.089, p < 0.001), and GGT (β 0.178, 95%CI 0.110, 0.246, p < 0.001). Similar results were observed for total urinary arsenic, suggesting a positive association with AST (β 0.048, 95%CI 0.016, 0.081, p < 0.01), ALT (β 0.090, 95%CI 0.049, 0.132, p < 0.001), and TBIL (β 0.062, 95%CI 0.037, 0.088, p < 0.001). In subgroup analysis, sex and smoker showed significant differences between subgroups. Our results demonstrate a positive association between urinary arsenic exposure and liver injury in adults. Sex and smokers may be related to arsenic pathogenicity.

Liver disease accounts for 2 million deaths and is responsible for 4% of all deaths (1 out of every 25 deaths worldwide); approximately 2/3 of all liver related deaths occur in men. Deaths are largely attributable to complications of cirrhosis and hepatocellular carcinoma, with acute hepatitis accounting for a smaller proportion of deaths. The most common causes of cirrhosis worldwide are related to viral hepatitis, alcohol, and nonalcoholic fatty liver disease (NAFLD). Hepatotropic viruses are the etiological factor in most cases of acute hepatitis, but drug-induced liver injury increasingly accounts for a significant proportion of cases. This iteration of the global burden of liver disease is an update of the 2019 version and focuses mainly on areas where significant new information is available like alcohol-associated liver disease, NAFLD, viral hepatitis, and HCC. We also devote a separate section to the burden of liver disease in Africa, an area of the world typically neglected in such documents.

Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease and is significantly associated with obesity, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. NAFLD has become the most prevalent chronic liver disease in Western countries, and the proportion of NAFLD-related cirrhosis among patients on liver transplantation waiting lists has increased. In light of the accumulated data about NAFLD, and to provide a common approach with multi-disciplines dealing with the subject, it has become necessary to create new guidance for diagnosing and treating NAFLD. This guidance was prepared following an interdisciplinary study under the leadership of the Turkish Association for the Study of the Liver (TASL), Fatty Liver Special Interest Group. This new TASL Guidance is a practical application guide on NAFLD and was prepared to standardize the clinical approach to diagnosing and treating NAFLD patients. This guidance reflects many advances in the field of NAFLD. The proposals in this guidance are meant to aid decision-making in clinical practice. The guidance is primarily intended for gastroenterology, endocrinology, metabolism diseases, cardiology, internal medicine, pediatric specialists, and family medicine specialists.