In 2023, nonalcoholic fatty liver disease was renamed metabolic dysfunction-associated steatotic liver disease by the American and European liver associations. This new nomenclature recognizes metabolic dysfunction as the central driver of the disease, and the diagnostic criteria now require the presence of hepatic steatosis plus at least one of five cardiometabolic risk factors. B-mode ultrasonography remains the most common and practical method for detecting hepatic steatosis, although newer ultrasound techniques based on attenuation, backscatter, and speed of sound have gained traction as tools to diagnose and quantify hepatic steatosis. Additionally, ultrasound elastography is increasingly used in routine clinical practice to assess liver fibrosis, diagnose cirrhosis, and identify clinically significant portal hypertension.

Background/Objectives: Recently, the term metabolic dysfunction-associated steatotic liver disease (MASLD) has replaced non-alcoholic fatty liver disease (NAFLD). Through analysis of the trends and disparities regarding cardiovascular disease (CVD) among individuals with MASLD, identifying the leading cause of death in this population is crucial. Methods: We conducted a cross-sectional analysis of National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and NHANES 2017-2020 data. MASLD was identified by using clinical profiles and liver ultrasonography to exclude other liver diseases. We estimated the prevalence of CVD among individuals with MASLD and calculated the prevalence ratios for those with and without MASLD. Results: In 2017-2020, MASLD affected 31.2% or 61.9 million US adults, and 17.0% (95% confidence interval: 13.7-20.3%) of these individuals had CVD. The absolute CVD prevalence in individuals with MASLD doubled from that in the NHANES III cohort, which was 8.7% (6.4%, 10.9%). These increases were especially notable among older adults, non-Hispanic whites, and those with higher education and income. Individuals with MASLD had a higher prevalence of total CVD than those without MASLD, even after adjusting for socioeconomic and metabolic factors. These differences were more pronounced in younger age groups. Conclusions: This study revealed a doubled 30-year trend in CVD prevalence among adults with MASLD in the US. Sociodemographic disparities emphasize the need for tailored screening, prevention, and policy measures to address gaps and promote cardiovascular health in this population.

Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a contributor to chronic kidney disease (CKD), yet its impact remains underappreciated in clinical practice. Recent studies reveal a strong association between NAFLD and CKD progression, with evidence linking hepatic dysfunction to renal impairment through metabolic and inflammatory pathways. NAFLD not only increases the risk of CKD but also accelerates its progression, leading to worse cardiovascular outcomes and higher mortality, particularly in patients with advanced fibrosis. Despite this growing evidence, NAFLD often goes undiagnosed in CKD patients and routine hepatic evaluation is rarely integrated into nephrology care. Emerging diagnostic tools, including noninvasive biomarkers and imaging techniques, offer potential for earlier detection, yet their clinical implementation remains inconsistent. Although lifestyle modifications remain the foundation of treatment, pharmacotherapeutic strategies, including SGLT2 inhibitors and GLP-1 receptor agonists, have demonstrated potential in mitigating both hepatic and renal impairment. Recognizing the interplay between NAFLD and CKD is essential for improving patient outcomes. A multidisciplinary approach, integrating hepatology and nephrology expertise, is crucial to refining screening strategies, optimizing treatment, and reducing the long-term burden of these coexisting conditions.

The association between menopause, changes in body composition, and nonalcoholic fatty liver disease is not clear, and there is a lack of weight management strategies for perimenopausal women from the perspective of preventing nonalcoholic fatty liver disease.

A total of 1316 postmenopausal and 3049 premenopausal women in the Kailuan cohort in China between 2006 and 2017 were enrolled and followed up till 2021. Cox regression models, including the causal mediation analyses, were used to estimate the association between menopause and nonalcoholic fatty liver disease and the potential mediation effect of changes in body composition. We also explored the impact of weight changes on the correlation between menopause and nonalcoholic fatty liver disease.

Women who experienced menopause had a higher risk of nonalcoholic fatty liver disease than premenopausal women (9-year cumulative incidence: 56.87 % vs. 48.80 %, adjusted hazard ratio = 1.219, 95 % confidence interval: 1.088-1.365). The nine-year cumulative incidence of nonalcoholic fatty liver disease was higher among overweight/obese postmenopausal women (67.24 % vs. 45.74 %, P < 0.001) and those with abdominal obesity (63.36 % vs. 49.69 %, P < 0.001); however, the hazard ratio of menopause for nonalcoholic fatty liver disease was more evident in women with a body mass index under 23.0 kg/m2 (hazard ratio = 1.434, 95 % confidence interval: 1.168-1.759) and those with normal waist circumference (hazard ratio = 1.362, 95 % confidence interval: 1.129-1.643), which could partially be explained by the visceral fat index (7.09 % and 7.35 % mediation, respectively). Weight loss of 3 % or more or reduction in waist circumference by 5 % or more was associated with a 31.1 % reduction (95 % confidence interval, 20.8 %-40.0 %) or a 14.2 % reduction (95 % confidence interval, 1.1 %-25.6 %) in the risk of nonalcoholic fatty liver disease among the premenopausal women. For postmenopausal women, weight gain of 3 % or more was associated with an increased risk of nonalcoholic fatty liver disease, especially in individuals with a body mass index under 23.0 kg/m2.

Menopause was associated with a higher risk of nonalcoholic fatty liver disease, partially by increasing visceral fat. Controlling weight in perimenopausal women may reduce the risk.

It is not clear if conventional liver fat cutoff of 5.56% weight which has been used for identifying fatty liver in western populations is also applicable for Asians. In Asian women of reproductive age, we evaluate the optimum metabolic syndrome (MetS)-linked liver fat cutoff, the specific metabolomic alterations apparent at this cutoff, as well as prospective associations of preconception liver fat levels with gestational dysglycemia.

Liver fat (measured by magnetic resonance spectroscopy), MetS, and nuclear magnetic resonance (NMR)-based plasma metabolomic profiles were assessed in 382 Asian women, who were planning to conceive. Ninety-eight women went on to become pregnant and received an oral glucose tolerance test at week 26 of gestation.

The optimum liver fat cutoff for diagnosing MetS was 2.07%weight. Preconception liver fat was categorized into Low (liver fat < 2.07%), Moderate (2.07% ≤ liver fat < 5.56%), and High (liver fat ≥ 5.56%) groups. Individual MetS traits showed worsening trends, going from Low to Moderate to High groups. Multiple plasma metabolomic alterations, previously linked to incident type 2 diabetes (T2D), were already evident in the Moderate group (adjusted for ethnicity, age, parity, educational attainment, and BMI). Both a cross-sectional multi-metabolite score for incident T2D and mid-gestational glucose area under the curve showed increasing trends, going from Low to Moderate to High groups (p < 0.001 for both). Gestational diabetes incidence was 2-fold (p = 0.23) and 7-fold (p < 0.001) higher in the Moderate and High groups relative to the Low group.

In Asian women of reproductive age, moderate liver fat accumulation below the conventional fatty liver cutoff was not metabolically benign and was linked to gestational dysglycemia. The newly derived cutoff can aid in screening individuals before adverse metabolic phenotypes have consolidated, which provides a longer window for preventive strategies.

The Weight-Adjusted Waist Index (WWI) is a novel indicator of obesity that accurately reflects body composition. However, the association between WWI and depression in patients with non-alcoholic fatty liver disease (NAFLD) remains unclear. This study aims to explore this relationship through a nationally representative cross-sectional analysis.

This study included adult participants diagnosed with NAFLD from NHANES 2017-2020. WWI was calculated as the waist circumference (cm) divided by the square root of body weight (kg). NAFLD diagnosis relied on vibration-controlled transient elastography (VCTE) with a controlled attenuation parameter (CAP) exceeding 248 dB/m to indicate hepatic steatosis. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), with scores ≥ 10 indicating the presence of major depression.

After adjusting for all covariates, a significant positive association was found between WWI and depression in NAFLD (OR = 1.725, 95% CI: 1.442-2.063, p < 0.00001), with a dose-response relationship indicated by restricted cubic spline analysis. The association was stronger in men and lean/normal weight NAFLD patients. Adjusting further for BMI did not alter these findings (OR = 1.643, 95% CI: 1.357-1.989, p < 0.00001). BMI's association with depression was negated after adjusting for WWI.

WWI had a positive association with depression in NAFLD, independent of BMI. This association was more pronounced in men and lean/normal weight NAFLD. These findings suggest that WWI may be a novel indicator of depression in NAFLD and potentially valuable in depression prevention.

It is currently unclear whether there is a connection between Life's Essential 8 (LE8) and cardiovascular disease (CVD), as well as mortality in people with nonalcoholic fatty liver disease (NAFLD). Our goal was to explore these relationships by examining data collected in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. We identified eligible participants with NAFLD based on NHANES 2005-2018 data. CVD status was acquired through self-reported information, and using the National Death Index, mortality data were prospectively matched. The diagnosis of NAFLD relied on noninvasive biomarkers. The research involved 9094 individuals who were identified as having NAFLD, with a mean age of 52.05 years. Each incremental LE8 score exhibited a significant association, leading to a 3%, 3%, 4%, 3%, 3%, 4%, and 4% reduction in the odds of experiencing CVD, ischemic heart disease, congestive heart failure, coronary heart disease, heart attack, angina, and stroke in individuals with NAFLD. A strong correlation was found between maintaining a superior level of Cardiovascular Health (CVH), as shown by a LE8 score ranging from 80 to 100, and a reduced occurrence of CVD and its various forms in NAFLD (all p for trend < 0.0001). Likewise, LE8 demonstrated protective benefits on mortality in NAFLD, showing that following a high CVH (in contrast to low CVH) was linked to reductions of 64%, 71%, and 74% in all-cause, CVD, and cancer mortality, respectively. Restricted cubic spline analyses suggested noteworthy dose-response relationships between LE8 and CVD, specifically its types in NAFLD, and a nonlinear correlation with CVD mortality. Interaction analyses highlighted age and race as significant effect modifiers. CVH, as evaluated by LE8, demonstrated an independent association with decreased odds of CVD and mortality risk in individuals with NAFLD. Our findings substantiate that adhering to LE8 may alleviate the excessive burden of CVD and mortality in the context of NAFLD.

The impact of sleep on metabolic dysfunction-associated steatotic liver disease (MASLD) in American adults remains unclear. This study aimed to address the relationship of sleep patterns and disorders with MASLD and liver fibrosis comprehensively.

This cross-sectional study included adult participants from the National Health and Nutrition Examination Survey 2017-2020. Multivariate adjusted regression analysis were used to examine the association of sleep with MASLD and liver fibrosis. We further addressed these associations using restricted cubic splines, mediation analysis, stratified analysis and multiple sensitivity analysis.

We enrolled 5368 participants. Certain sleep disorders, sleep duration, high sleep debt and specific sleep-wake time were associated with MASLD. Late workday sleep was a shared risk factor for MASLD and liver fibrosis. Short sleep on workdays and free days favored MASLD, whereas average weekly long sleep protected against MASLD. Workday, free day and average weekly optimal sleep duration was 7.5 h, 8 h and 7.78 h, respectively. Mediation analysis suggested that fasting glucose and high-density lipoprotein cholesterol indirectly mediated the relationship between sleep duration and MASLD, whereas stratified analysis showed that sex influenced the relationship, and that the correlation was only observed in women and specific age groups.

Sleep duration independently affected MASLD but only in women and specific age groups. Moreover, late sleep on workdays was a shared risk factor for MASLD and liver fibrosis. These results suggest targeting sleep behaviors for MASLD prevention and developing age- and sex-specific strategies.

Non-alcoholic fatty liver disease (NAFLD) is a common long-lasting liver disease that affects millions of people around the world. It is best identified with a hepatic fat build-up that ultimately leads to inflammation and damage. The classification and nomenclature of NAFLD have long been a controversial topic, until 2020 when a group of international experts recommended substituting NAFLD with MAFLD (metabolic dysfunction-associated FLD). MAFLD was then terminologically complemented in 2023 by altering it to MASLD, i.e., metabolic dysfunction-associated steatotic liver disease (MASLD). Both the MAFLD and the MASLD terminologies comprise the metabolic element of the disorder, as they offer diagnostic benchmarks that are embedded in the metabolic risk factors that underlie the disease. MASLD (as a multisystemic disease) provides a comprehensive definition that includes a larger population of patients who are at risk of liver morbidity and mortality, as well as adverse cardiovascular and diabetes outcomes. MASLD highlights metabolic risks in lean or normal weight individuals, a factor that has not been accentuated or discussed in previous guidelines. Novel antihyperglycemic agents, anti-hyperlipidemic drugs, lifestyle modifications, nutritional interventions, and exercise therapies have not been extensively studied in MAFLD and MASLD. Nutrition plays a vital role in managing both conditions, where centralizing on a diet rich in whole vegetables, fruits, foods, healthy fats, lean proteins, and specific nutrients (e.g., omega-3 fatty acids and fibers) can improve insulin resistance and reduce inflammation. Thus, it is essential to understand the role of nutrition in managing these conditions and to work with patients to develop an individualized plan for optimal health. This review discusses prevention strategies for NAFLD/MAFLD/MASLD management, with particular attention to nutrition and lifestyle correction.

Cholangiocarcinoma (CCA) is a hepatic malignancy that has a rapidly increasing incidence. CCA is anatomically classified into intrahepatic (iCCA) and extrahepatic (eCCA), which is further divided into perihilar (pCCA) and distal (dCCA) subtypes, with higher incidence rates in Asia. Despite its rarity, CCA has a low 5-year survival rate and remains the leading cause of primary liver tumor-related death over the past 10-20 years. The systemic therapy section discusses gemcitabine-based regimens as primary treatments, along with oxaliplatin-based options. Second-line therapy is limited but may include short-term infusional fluorouracil (FU) plus leucovorin (LV) and oxaliplatin. The adjuvant therapy section discusses approaches to improve overall survival (OS) post-surgery. However, only a minority of CCA patients qualify for surgical resection. In comparison to adjuvant therapies, neoadjuvant therapy for unresectable cases shows promise. Gemcitabine and cisplatin indicate potential benefits for patients awaiting liver transplantation. The addition of immunotherapies to chemotherapy in combination is discussed. Nivolumab and innovative approaches like CAR-T cells, TRBAs, and oncolytic viruses are explored. We aim in this review to provide a comprehensive report on the systemic and locoregional therapies for CCA.

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.

A multi-stakeholder consensus has proposed MASLD (metabolic dysfunction-associated steatotic liver disease). We aimed to investigate the pathological findings related to the mid-term mortality of patients with biopsy-proven MASLD in Japan.

We enrolled 1349 patients with biopsy-proven MASLD. The observational period was 8010 person years. We evaluated independent factors associated with mortality in patients with MASLD by Cox regression analysis. We also investigated pathological profiles related to mortality in patients with MASLD using data-mining analysis.

The prevalence of MASH and stage 3/4 fibrosis was observed in 65.6% and 17.4%, respectively. Forty-five patients with MASLD died. Of these, liver-related events were the most common cause at 40% (n = 18), followed by extrahepatic malignancies at 26.7% (n = 12). Grade 2/3 lobular inflammation and stage 3/4 fibrosis had a 1.9-fold and 1.8-fold risk of mortality, respectively. In the decision-tree analysis, the profiles with the worst prognosis were characterised by Grade 2/3 hepatic inflammation, along with advanced ballooning (grade 1/2) and fibrosis (stage 3/4). This profile showed a mortality at 8.3%. Furthermore, the random forest analysis identified that hepatic fibrosis and inflammation were the first and second responsible factors for the mid-term prognosis of patients with MASLD.

In patients with biopsy-proven MASLD, the prevalence of MASH and advanced fibrosis was approximately 65% and 20%, respectively. The leading cause of mortality was liver-related events. Hepatic inflammation and fibrosis were significant factors influencing mid-term mortality. These findings highlight the importance of targeting inflammation and fibrosis in the management of patients with MASLD.

Metabolic dysfunction associated steatotic liver disease (MASLD) increases the risk of incident chronic kidney disease (CKD). However, the relative risk of CKD associated with increasing hepatic fibrosis, and consequent mortality risk, remains underexplored in real-world cohorts. In this study, we sought to establish whether hepatic fibrosis is associated with increased CKD risk and explore differences in mortality risk in a cohort of people living with MASLD, contingent on liver fibrosis and CKD status.

This was an observational study of people who underwent routine liver function testing in Tayside, Scotland. MASLD was defined as: elevated ALT (>30 U/L) or GGT (>73 U/L); presence of diabetes, and/or hypertension, and/or obesity; weekly alcohol consumption <14 units (112g (+/-8g) alcohol); and negative screen for other aetiologies. Data was collected from digital health records. We used log-binomial models to quantify the risk of CKD among those with and without fibrosis, and Cox regression models to estimate differences in mortality risk dependent on fibrosis and CKD.

In our cohort (n = 2,046), 1,448 (70.8%) people had MASLD without fibrosis and 598 (29.2%) with fibrosis; 161 (11.1%) and 117 (19.6%) respectively also had CKD. After excluding individuals with structural, autoimmune, or malignant CKD (n = 22), liver fibrosis (n = 593; 18.9% with CKD) was associated with increased CKD risk (aRR = 1.31, 1.04-1.64, p = 0.021). Increased mortality risk was observed for those with liver fibrosis (aHR = 2.30, 1.49-3.56, p = <0.001) and was higher again among people with both fibrosis and CKD (aHR = 5.07, 3.07-8.39, p = <0.014).

Liver fibrosis was an independent risk factor for CKD in this cohort of people living with MASLD. Furthermore, those with MASLD with liver fibrosis had higher risk for mortality and this risk was further elevated among those with co-morbid CKD. Given the increased risk of CKD, and consequent mortality risk, among people living with MASLD fibrosis, renal function screening should be considered within liver health surveillance programmes and guidelines.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Much of the recognised health-care burden occurs in the minority of people with NAFLD who progress towards cirrhosis and require specialist follow-up, including risk stratification and hepatocellular carcinoma surveillance. NAFLD is projected to become the leading global cause of cirrhosis and hepatocellular carcinoma, but the frequency of non-cirrhotic hepatocellular carcinoma provides a challenge to existing surveillance strategies. Deaths from extrahepatic cancers far exceed those from hepatocellular carcinoma in NAFLD. Unlike hepatocellular carcinoma, the increased extrahepatic cancer risk in NAFLD is not dependent on liver fibrosis stage. Given that almost 30% of the world's adult population has NAFLD, extrahepatic cancer could represent a substantial health and economic issue. In this Review, we discuss current knowledge and controversies regarding hepatocellular carcinoma risk stratification and surveillance practices in people with NAFLD. We also assess the associations of extrahepatic cancers with NAFLD and their relevance both in the clinic and the wider community.

Aims: To evaluate and compare lipid accumulation product (LAP) with alanine aminotransferase (ALT), aspartate aminotransferase (AST), visceral adiposity index (VAI) and triglyceride-glucose index (TyG) as biomarkers for hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). Methods: LAP, ALT, AST, VAI and TyG were measured in 52 biopsy-proven NAFLD patients and 21 control subjects. Additionally, LAP was also measured in 448 ultrasound-proven NAFLD patients and 1009 control subjects. Results: LAP was positively associated with hepatic steatosis and inflammation in biopsy-proven NAFLD. The risk of NAFLD was positively related to LAP and TyG, but LAP showed a better area under the receiver operating characteristic curve for hepatic steatosis and NAFLD. LAP also performed well in recognizing ultrasound-proven NAFLD. Conclusion: LAP is an ideal biomarker of hepatic steatosis and NAFLD.

Non-alcoholic fatty liver disease (NAFLD) has been linked to an increased risk of kidney stones in prior observational studies, However, the results are inconsistent, and the causality remains to be established. We aimed to investigate the potential causal relationship between NAFLD and kidney stones using two-sample Mendelian randomization (MR).

Genetic instruments were used as proxies for NAFLD. Summary-level data for the associations of exposure-associated SNPs with kidney stones were obtained from the UK Biobank study (6536 cases and 388,508 controls) and the FinnGen consortium (9713 cases and 366,693 non-cases). MR methods were conducted, including inverse variance weighted method (IVW), MR-Egger, weighted median, and MR-PRESSO. MR-Egger Regression Intercept and Cochran's Q test were used to assess the directional pleiotropy and heterogeneity.

cALT-associated NAFLD did not exhibit an association with kidney stones in the Inverse variance weighted (IVW) methods, in both the FinnGen consortium (OR: 1.02, 95%CI: 0.94-1.11, p = 0.632) and the UKBB study (OR: 1.000, 95%CI: 0.998-1.002, p = 0.852). The results were consistent in European ancestry (FinnGen OR: 1.05, 95%CI: 0.98-1.14, p = 0.144, UKBB OR: 1.000, 95%CI: 0.998-1.002, p = 0.859). IVW MR analysis also did not reveal a significant causal relationship between NAFLD and the risk of kidney stone for the other three NAFLD-related traits, including imaging-based, biopsy-confirmed NAFLD, and more stringent biopsy-confirmed NAFLD. The results remained consistent and robust in the sensitivity analysis.

The MR study did not provide sufficient evidence to support the causal associations of NAFLD with kidney stones.

Non-alcoholic fatty liver disease (NAFLD) is rapidly emerging as a leading etiology of chronic liver disease (CLD) in Asia. The increasing incidence of NAFLD is projected to drive a surge in NAFLD-related hepatocellular carcinoma (HCC). A notable characteristic of NAFLD-HCC is its capacity for development in individuals without cirrhosis in more than a third of patients. Most practice guidelines recommend biannual ultrasound screening for patients with cirrhosis. In cases of severe limitations to ultrasound visualisation, cross-sectional abdominal imaging may be warranted. Improved strategies for HCC risk stratification are required for people with NAFLD but without cirrhosis. In this Review, we discuss the evolving trends of NAFLD and HCC in Asia, and implications for surveillance.

Dyslipidemia has been linked metabolic-associated fatty liver disease (MAFLD). Several genes and transcription factors involved in lipid metabolism can increase susceptibility to MAFLD. Multiple parallel 'hits' have been proposed for developing hepatic steatosis, NASH, and MAFLD, including insulin resistance and subsequent free fatty acid excess, de novo lipogenesis, and excessive hepatic triglyceride and cholesterol deposition in the liver. This lead to defective beta-oxidation in the mitochondria and VLDL export and increased inflammation. Given the significant cardiovascular risk, dyslipidemia associated with MAFLD should be managed by lifestyle changes and lipid-lowering agents such as statins, fenofibrate, and omega-3 fatty acids, with judicious use of insulin-sensitizing agents, and adequate control of dysglycemia.

Nonalcoholic fatty liver disease (NAFLD) is now the most common chronic liver disease worldwide and a leading indication for liver transplantation in the United States. NAFLD encompasses a heterogeneous clinicopathologic spectrum, ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis, and progressive fibrosis, which can lead to end-stage liver disease including cirrhosis and hepatocellular cancer. Predictive models suggest that over 100 million adults in the United States will have NAFLD by 2030, representing over a third of the population. In this manuscript, we provide an overview of NAFLD risk factors, natural history (including hepatic and extra-hepatic outcomes), diagnosis, and current management strategies.

We aimed to determine the trends in risk factor control and treatment among patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) in 2000-2020.

We conducted a territory-wide cohort study of adult patients with NAFLD and T2D diagnosed between 1 January 2000 and 31 July 2021 in Hong Kong. T2D was defined by use of any anti-diabetic agents, laboratory tests and/or diagnosis codes.

This study included 16,084 patients with NAFLD and T2D (mean age, 54.8 ± 12.0 years; 7124 male [44.3%]). The percentage of patients achieving individualised haemoglobin A1c (HbA1c ) targets increased from 44.5% (95% confidence interval [CI], 42.9-46.1) to 64.8% (95% CI, 64.1-65.5), and percentage of patients achieving individualised low-density lipoprotein-cholesterol (LDL-C) targets increased from 23.3% (95% CI, 21.9-24.7) to 54.3% (95% CI, 53.5-55.1) from 2000-2005 to 2016-2020, whereas percentage of patients achieving blood pressure control (<140/90 mm Hg) remained static at 53.1-57.2%. Combination therapy for diabetes increased, especially among those with poor glycaemic control, but there was no increase in combination therapy for hypertension. Fewer cirrhotic patients achieved blood pressure control and individualised LDL-C targets, but they were more likely to achieve individualised HbA1c targets than non-cirrhotics. Metformin and statins were underused in cirrhotic patients. Younger patients (18-44 years) were less likely to achieve individualised HbA1c targets than middle-aged (45-64 years) and older ones (≥65 years).

From 2000 to 2020, glycaemic and lipid control improved significantly, whereas blood pressure control remained static among patients with NAFLD and T2D.

Metabolic-associated fatty liver disease (MAFLD) has become the most common cause for chronic liver disease among children and adolescents globally. Although liver biopsy remains the gold standard for diagnosis, emerging technology, like velocity controlled transient elastography, a noninvasive method, is being utilized to evaluate degree of fibrosis in these patients. The discovery of multiple gene polymorphisms has brought new hope for possible treatment targets. However, this research is still ongoing, making lifestyle changes and weight reduction the current mainstay of treatment. This review briefly reviews the most recent data regarding the epidemiology, pathophysiology, diagnostic modalities, and treatment of pediatric MAFLD.

The metabolic syndrome as a consequence of the obesity pandemic resulted in a substantial increase in the prevalence of metabolic-associated fatty live disease (MAFLD) and type 2 diabetes mellitus (T2DM). Because of the similarity in pathobiology shared between T2DM and MAFLD, both disorders coexist in many patients and may potentiate the disease-related outcomes with rapid progression and increased complications of the individual diseases. In fact, awareness about this coexistence and the risk of complications are often overlooked by both hepatologists and diabetologists. Management of these individual disorders in a patient should be addressed wholistically using an appropriate multidisciplinary team approach involving both the specialists and, when necessary, liaising with dieticians and surgeons. This comprehensive review is to compile the current evidence from a diabetologist's perspective on MAFLD and T2DM and to suggest optimal management strategies.

Chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) are closely related to immune and inflammatory pathways. This study aimed to explore the diagnostic markers for CKD patients with NAFLD.

CKD and NAFLD microarray data sets were screened from the GEO database and analyzed the differentially expressed genes (DEGs) in GSE10495 of CKD date set. Weighted Gene Co-Expression Network Analysis (WGCNA) method was used to construct gene coexpression networks and identify functional modules of NAFLD in GSE89632 date set. Then obtaining NAFLD-related share genes by intersecting DEGs of CKD and modular genes of NAFLD. Then functional enrichment analysis of NAFLD-related share genes was performed. The NAFLD-related hub genes come from intersection of cytoscape software and machine learning. ROC curves were used to examine the diagnostic value of NAFLD related hub genes in the CKD data sets and GSE89632 date set of NAFLD. CIBERSORTx was also used to explore the immune landscape in GSE104954, and the correlation between immune infiltration and hub genes expression was investigated.

A total of 45 NAFLD-related share genes were obtained, and 4 were NAFLD-related hub genes. Enrichment analysis showed that the NAFLD-related share genes were significantly enriched in immune-related pathways, programmed cell death, and inflammatory response. ROC curve confirmed 4 NAFLD-related hub genes in CKD training set GSE104954 and other validation sets. Then they were used as diagnostic markers for CKD. Interestingly, these 4 diagnostic markers of CKD also showed good diagnostic value in the NAFLD date set GSE89632, so these genes may be important targets of NAFLD in the development of CKD. The expression levels of the 4 diagnostic markers for CKD were significantly correlated with the infiltration of immune cells.

4 NAFLD-related genes (DUSP1, NR4A1, FOSB, ZFP36) were identified as diagnostic markers in CKD patients with NAFLD. Our study may provide diagnostic markers and therapeutic targets for CKD patients with NAFLD.

Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide, affecting up to ~30% of adult populations. NAFLD defines a spectrum of progressive liver conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma, which often occur in close and bidirectional associations with metabolic disorders. Chronic kidney disease (CKD) is characterized by anatomic and/or functional renal damage, ultimately resulting in a reduced glomerular filtration rate. The physiological axis linking the liver and kidneys often passes unnoticed until clinically significant portal hypertension, as a major complication of cirrhosis, becomes apparent in the form of ascites, refractory ascites, or hepatorenal syndrome. However, the extensive evidence accumulated since 2008 indicates that noncirrhotic NAFLD is associated with a higher risk of incident CKD, independent of obesity, type 2 diabetes, and other common renal risk factors. In addition, subclinical portal hypertension has been demonstrated to occur in noncirrhotic NAFLD, with a potential adverse impact on renal vasoregulation. However, the mechanisms underlying this association remain unexplored to a substantial extent. With this background, in this review we discuss the current evidence showing a strong association between NAFLD and the risk of CKD, and the putative biological mechanisms underpinning this association. We also discuss in depth the potential pathogenic role of the hepatorenal reflex, which may be triggered by subclinical portal hypertension and is a poorly investigated but promising research topic. Finally, we address emerging pharmacotherapies for NAFLD that may also beneficially affect the risk of developing CKD in individuals with NAFLD.