Non-Alcoholic Fatty Liver Disease (NAFLD) refers to a range of conditions marked by the buildup of triglycerides in liver cells, accompanied by inflammation, which contributes to liver damage, clinical symptoms, and histopathological alterations. Multiple molecular pathways contribute to NAFLD pathogenesis, including immune dysregulation, endoplasmic reticulum stress, and tissue injury. Both the innate and adaptive immune systems play crucial roles in disease progression, with intricate crosstalk between liver and immune cells driving NAFLD development. Among emerging therapeutic strategies, cell and gene-based therapies have shown promise. This study reviews the pathophysiological mechanisms of NAFLD and explores the therapeutic potential of cell-based interventions, highlighting their immunomodulatory effects, inhibition of hepatic stellate cells, promotion of hepatocyte regeneration, and potential for hepatocyte differentiation. Additionally, we examine gene delivery vectors designed to target NAFLD, focusing on their role in engineering hepatocytes through gene addition or editing to enhance therapeutic efficacy.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent among people with HIV (PWH) and increasingly recognized as a major contributor to morbidity and mortality. The field of MASLD is rapidly evolving with adoption of a new nomenclature and approval of the first FDA-approved therapy within the past year. These developments underscore the need to consider the current state of the science specifically in the context of HIV.

MASLD in PWH (MASLD-HIV) follows a more aggressive clinical course compared to HIV-negative individuals. While MASLD-HIV shares common pathogenic mechanisms with MASLD in the general population, HIV-specific factors - including altered body composition, chronic immune activation, enhanced gut permeability, and antiretroviral therapy - exacerbate disease progression. Despite an expanding pipeline of MASLD therapies, a critical gap remains in evaluating these interventions specifically among PWH. Nonetheless, dedicated studies of glucagon-like peptide-1 receptor agonists and the growth hormone-releasing hormone analog tesamorelin have shown promise in MASLD-HIV.

MASLD is a key contributor to liver-related and cardiovascular-morbidity in PWH. While there have been exciting advances to improve diagnosis and management of MASLD in the general population, differences in MASLD pathophysiology demonstrate the need to tailor our approach specifically for PWH.

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

With its increasing prevalence, metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a major global public health concern over the past few decades. Growing evidence has proposed the microbiota-derived metabolites short-chain fatty acids (SCFAs) as a potential factor in the pathophysiology of MASLD and related metabolic conditions, such as obesity and type 2 diabetes mellitus (T2DM). By influencing key pathways involved in energy homeostasis, insulin sensitivity, and inflammation, SCFAs play an important role in gut microbiota composition, intestinal barrier function, immune modulation, and direct metabolic signaling. Furthermore, recent animal and human studies on therapeutic strategies targeting SCFAs demonstrate their potential for treating these metabolic disorders.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common cause of liver disease worldwide. In patients with MASLD, liver fibrosis stage is the most significant predictor of mortality; therefore, early identification of patients at the greatest risk of advanced fibrosis is essential. Noninvasive tests predict advanced fibrosis and are recommended for use in primary care settings to determine which patients would benefit most from specialty care. The adoption of these tools is not widespread, and several studies have reported underrecognition of cirrhosis in patients with MASLD and diabetes. The finding of hepatic steatosis on imaging performed for evaluation of nonliver conditions may present an avenue for opportunistic screening to identify more patients with MASLD. This article will review recommendations for when hepatic steatosis is found on imaging and noninvasive tests that can be used to help predict fibrosis staging. This is a significant area of research because a new treatment for MASLD has been approved, and other treatments may follow.

Background and objectives: To investigate the effect of carbohydrate intake before laparoscopic Roux-en-Y gastric bypass (LRYGB) on body weight, body composition and glycaemic status after surgery. Methods: In a tertiary centre cohort study, dietary habits, body composition and glycaemic status were evaluated before and 3, 6 and 12 months after LRYGB. Detailed dietary food records were processed by specialized dietitians on the basis of a standard protocol. The study population was subdivided according to relative carbohydrate intake before surgery. Results: Before surgery, 30 patients had a moderate relative carbohydrate intake (26%-45%, M-CHO), a mean body mass index (BMI) of 40.4 ± 3.9 kg/m² and a mean glycated haemoglobin A1c (A1C) of 6.5 ± 1.2% compared to 20 patients with a high relative carbohydrate intake (> 45%, H-CHO), mean BMI of 40.9 ± 3.7 kg/m² (non-significant, NS) and a mean A1C of 6.2% (NS). One year after surgery, body weight, body composition and glycaemic status were similar in the M-CHO (n = 25) and H-CHO groups (n = 16), despite less caloric intake in the H-CHO group (1317 ± 285 g vs. 1646 ± 345 g in M-CHO, p < 0.01). Their relative carbohydrate intake converged to 46% in both groups, but the H-CHO group reduced the absolute total carbohydrate consumption more than the M-CHO group (190 ± 50 g in M-CHO vs. 153 ± 39 g in H-CHO, p < 0.05), and this was especially pronounced for the mono- and disaccharides (86 ± 30 g in M-CHO vs. 65 ± 27 g in H-CHO, p < 0.05). Conclusion: A high relative carbohydrate intake before LRYGB, did not influence the change in body composition or diabetes status after surgery, despite a significantly lower total energy intake and less mono- and disaccharide consumption after surgery.

Ectopic fat is reduced by effective weight management, but difficult to assess clinically.

We evaluated paired data on 42 participants in the intervention group of the Diabetes Remission Clinical Trial (DiRECT) at baseline, 12 and 24 months after weight loss as indicators of liver fat content measured by 3-point Dixon MRI.

Baseline liver fat was elevated at 13.0 [7.8-23.3]% with fasting plasma glucose 7.9 [7.1-10.1] mmol/L. Prevalence of baseline MASLD was 86.4%. After weight loss of 11.9 ± 1.2 kg (0-37 kg) at 12 months, remission of MASLD occurred in 74% and liver fat normalised for many (1.8 [1.2-5.2]%; p < 0.0001) as did fasting glucose (5.9 [5.5-7.2] mmol/L; p < 0.0001). Alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) decreased at 12 months by 38 [19-60]% (p < 0·0001) and 38 [16-53]% (p < 0.0001) respectively. The positive predictive value for decrease in liver fat, with baseline values of >40 IU/L, was 100% for ALT and 87.5% for GGT. As expected, change in liver fat correlated with change in ALT (r = 0.64; p < 0.0001), GGT (r = 0.38; p = 0.013), AST (r = 0.36; p = 0.018), fatty liver index (r = 0.50; p < 0.0001) and hepatic steatosis index (r = 0.44; p < 0.0001).

Metabolic dysfunction-associated steatotic liver disease, an important marker of ill-health is improved by intentional weight loss. If enzyme levels are raised at baseline, following weight loss, changes in ALT and GGT usefully reflect change in liver fat content, with high positive predictive value. Monitoring liver enzymes can provide a simple way to assess change in liver fat following weight loss in day-to-day clinical practice.

This review highlights the impact of weight loss on metabolic dysfunction associated steatotic liver disease (MASLD), formally known as nonalcoholic fatty liver disease (NAFLD), and its progressive form of metabolic dysfunction associated steatohepatitis (MASH), formally known as nonalcoholic steatohepatitis (NASH). The effects of weight loss, as achieved through lifestyle modification, pharmacotherapy, bariatric surgery or endobariatric procedures on MASLD/MASH and hepatic fibrosis are discussed.

Although foundational in the treatment of MASLD/MASH, weight loss through life-style modification is challenging for most patients to achieve and sustain long-term. In patients with MASLD/MASH, a multidisciplinary approach may facilitate success with lifestyle modification, individualized consideration of pharmacotherapies and/or surgical approaches that have potential to lend an improvement in MASLD/MASH. Effective and sustained weight loss improves hepatic steatosis, steatohepatitis and potentially hepatic fibrosis. Improvement in hepatic fibrosis can improve patient-related outcomes associated with complications of advanced hepatic fibrosis or cirrhosis in patients with MASLD/MASH. Identifying risk factors that influence MASLD/MASH and early implementation of therapeutic weight loss strategies may improve chronic liver injury and decrease risk for adverse clinical outcomes related to progressive hepatic fibrosis attributable to MASLD/MASH.

Obesity-associated nonalcoholic fatty liver disease (NAFLD) is a significant cause of chronic liver disease. Our study sought to investigate preoperative NAFLD and the effect at 6 months and 2 years after surgery of one anastomosis gastric bypass (OAGB) and its development 6 months after surgery regarding weight loss outcomes.

A retrospective cohort study was conducted on patients with severe obesity who underwent primary OAGB at Hazrat-e-Rasool Hospital between March 2020 and June 2021. Preoperative assessments included abdominal ultrasound (US) for NAFLD grading, weight, and biochemical blood tests. Follow-up examinations were performed at 10 days and 1, 3, 6, 9, 12, and 24 months postsurgery, with subsequent US examinations at the 6-month follow-up.

Two hundred thirty-one patients were included, with an average age of 40.3±10.5 years and a percentage of 78.4 women. Their mean weight and BMI were 131.2±26.8 and 48.8±8.5, respectively. Six-month grades of NAFLD showed that patients with grade 3 NAFLD had significantly lower TWL% compared with the lower grades. NAFLD grades improved in 72.3% of our patients, remained the same at 21.2%, and worsened at 6.5%. The 6-month TWL% was 28.4±4.3 in the no-change group, 28.4±5.3 for the improved group, and 25.2±14.6 in the worse group.

The severity and progression of NAFLD can significantly impact weight loss outcomes post-OAGB, highlighting the importance of monitoring and managing NAFLD in patients undergoing bariatric surgery.

There is a new awareness of the widespread nature of metabolic dysfunction-associated steatotic liver disease (MASLD) and its connection to cardiovascular disease (CVD). This has catalyzed collaboration between cardiologists, hepatologists, endocrinologists, and the wider multidisciplinary team to address the need for earlier identification of those with MASLD who are at increased risk for CVD. The overlap in the pathophysiologic processes and parallel prevalence of CVD, metabolic syndrome, and MASLD highlight the multisystem consequences of poor cardiovascular-liver-metabolic health. Metabolic dysfunction and associated insulin resistance, together with the predilection for ectopic fat deposition in the liver and surrounding tissues, are associated with elevated risk of endothelial dysfunction, systemic inflammatory response, and ectopic fat deposition in the epicardium. This complex pathophysiology can accelerate atherogenic dyslipidemia, atherogenesis, diastolic dysfunction, valvular calcification, and cardiac arrhythmias. Despite the mounting evidence of mechanistic pathways underpinning MASLD and CVD, current recommendations have not clearly focused upon MASLD as a risk factor or target for intervention in CVD. We have brought together a diverse range of international experts committed to promoting cardiovascular-liver-metabolic health and related outcomes across the globe. The overarching goal of this document is to offer a construct for clinicians in the cardiovascular field with regards to (1) diagnosis and screening of MASLD through the use of noninvasive serum and imaging tests; (2) screening for CVD in all individuals with MASLD regardless of established atherosclerotic risk factors; and (3) the approach to management of MASLD with respect to prevention of CVD through lifestyle, as well as pharmacologic and surgical strategies. To achieve this, the modified Delphi method was applied and a series of evidence-based quality standard recommendations have been identified.

With the obesity pandemic, metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease and a leading cause of end-stage liver disease and liver-related deaths in the USA. Therefore, we aimed to compare the long-term outcomes of patients with MASLD and cirrhosis with and without bariatric surgery.

Patients were retrospectively identified from the California Department of Healthcare Access and Information database, 2005 to 2019, for a population-based cohort study. Propensity score matching (PSM) was used to balance background risks between patients with cirrhosis who underwent bariatric surgery and those who did not. Overall, liver-related and non-liver-related mortality were analyzed.

Of 91,708 eligible patients with MASLD and cirrhosis, PSM yielded 2,107 patients who underwent bariatric surgery and 8,428 non-bariatric controls. Compared to matched controls, patients who underwent bariatric surgery had lower 5-year overall (24.9% vs. 37.1%; p<0.0001), liver-related (3.3% vs. 14%; p<0.0001), and non-liver-related mortality (22.3% vs. 26.9%; p=0.046). In multivariable analysis, bariatric surgery was associated with decreased overall mortality (adjusted hazard ratio [aHR]=0.63; p<0.0001), liver-related (aHR=0.24; p<0.0001), and non-liverrelated (aHR=0.81; p=0.0026) mortality. However, only laparoscopic surgeries were associated with lower overall mortality (aHR=0.39; p<0.0001) whereas open surgeries were associated with higher overall mortality (aHR=1.24; p=0.022).

Patients with MASLD and cirrhosis who underwent bariatric surgery, specifically laparoscopic approaches, had significantly lower mortality risk than non-surgical counterparts.

Morbid obesity requires active intervention, with treatment options including lifestyle modification, pharmacotherapy, and surgery. As the prevalence of obesity continues to rise in Korea, it is crucial for specialists and general practitioners to have a comprehensive understanding of obesity and its management. Bariatric surgery is the most effective treatment modality for obesity, leading to significant weight loss and metabolic benefits. It involves surgical alterations of normal anatomical structures to improve overall health. Therefore, selecting the appropriate procedure based on the individual characteristics of patients is crucial. This review highlights the two most commonly performed bariatric procedures worldwide, including in Korea: sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). Furthermore, it provides a comprehensive overview of the surgical techniques involved in SG and RYGB, addresses potential complications, and presents findings from key studies on the weight loss and metabolic outcomes of these surgeries. Additionally, to support clinical application, the review provides outcome data for these procedures based on studies conducted in Korean populations. In addition to SG and RYGB, this review briefly introduces other surgical and endoscopic options, as well as pharmacological treatments that are currently available or may become viable options in the near future.

Obesity is associated with a higher incidence of fatty liver disease, intrahepatic triglyceride content, and hepatic fibrosis. These abnormalities could progress to severe liver disease.

To evaluate the effects of bariatric surgery (BaS)-induced weight loss on liver volume, hepatic function tests, and lipid profile.

Academic Hospital, United States.

We conducted a retrospective review of an institutional review board (IRB)-approved database on patients who underwent BaS from 2006 to 2018. To determine changes in liver volume, we reviewed abdominal computed tomography scans before BaS (Group 1) and up to 18 months after (Group 2). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lipid profiles were collected before and after BaS.

Seventy-three patients met the inclusion criteria. Patients were predominantly females 78.1% (57), with an average age of 51.29+12.54 years. The liver volume was 1870.73 + 638.5 mm3 before and 1555.15 + 464.8 after BaS (P = .004). ALT was 36.9 + 25.3 before versus 23.8 + 19.3 after BaS (P = .024).Triglyceride levels changed from 135.62 + 69.98 before to 97.50 + 47.33 after BaS (P = .009). Low-density lipoprotein decreased from 107.9 + 38.1 to 89.6 + 32.8 (P = .048).

BaS-induced weight loss determines significant liver shrinkage by reducing liver volume, and coincides with improvements in hepatic function tests and lipid profile. Our results suggest that BaS might contribute to reduction of the progression of fatty liver disease to fibrosis.

The aim of this study was to investigate the consequences of the histological progression of metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis on long-term survival after bariatric surgery.

From 1994 to 2021, 3028 patients at the University Hospital of Lille were prospectively included. Baseline liver biopsies were systematically performed with proposed follow-up biopsies 1 year after surgery, mainly in patients with MASH. We evaluated the association of the baseline and 1-year histologic progression of MASH and fibrosis status and long-term survival using Cox regression models.

At baseline, 2641 patients (89%) had a biopsy, including 232 with MASH (8.7%) and 266 (10.8%) with significant fibrosis (grade F2-F4). The median follow-up was 10.1 years. At 1 year, 594 patients had qualitative paired biopsies. Survival was shorter at the 15-year follow-up in patients with baseline MASH, than in those without (hazard ratio [HR], 2.21; 95% confidence interval [CI], 1.38-3.53) and in F2 to F4 than in F0 to F1 (HR, 3.38; 95% CI, 2.24-5.10). At the 1-year landmark analysis, compared with patients without baseline MASH, mortality increased in those with persistent MASH and/or if fibrosis worsened (adjusted HR, 2.54; 95% CI, 1.06-6.10), but not if MASH resolved without the worsening of fibrosis (adjusted HR, 0.73; 95% CI, 0.28-1.87). Similarly, compared with patients without significant fibrosis at baseline, patients with persistent significant fibrosis had increased mortality (adjusted HR, 4.03; 95% CI, 1.86-8.72) but not if fibrosis improved from F2 to F4 to F0 to F1 (adjusted HR; 1.49; 95% CI, 0.52-4.24).

Histologic remission of MASH or significant fibrosis improves survival after bariatric surgery.

Metabolic dysfunction-associated steatotic liver disease (MASLD) exhibits considerable variability in clinical outcomes. Identifying specific phenotypic profiles within MASLD is essential for developing targeted therapeutic strategies. Here we investigated the heterogeneity of MASLD using partitioning around medoids clustering based on six simple clinical variables in a cohort of 1,389 individuals living with obesity. The identified clusters were applied across three independent MASLD cohorts with liver biopsy (totaling 1,099 participants), and in the UK Biobank to assess the incidence of chronic liver disease, cardiovascular disease and type 2 diabetes. Results unveiled two distinct types of MASLD associated with steatohepatitis on histology and liver imaging. The first cluster, liver-specific, was genetically linked and showed rapid progression of chronic liver disease but limited risk of cardiovascular disease. The second cluster, cardiometabolic, was primarily associated with dysglycemia and high levels of triglycerides, leading to a similar incidence of chronic liver disease but a higher risk of cardiovascular disease and type 2 diabetes. Analyses of samples from 831 individuals with available liver transcriptomics and 1,322 with available plasma metabolomics highlighted that these two types of MASLD exhibited distinct liver transcriptomic profiles and plasma metabolomic signatures, respectively. In conclusion, these data provide preliminary evidence of the existence of two distinct types of clinically relevant MASLD with similar liver phenotypes at baseline, but each with specific underlying biological profiles and different clinical trajectories, suggesting the need for tailored therapeutic strategies.

Metabolic dysfunction-associated steatohepatitis (MASH) represents a critical stage in the progression of metabolic dysfunction-associated steatotic liver disease (MASLD), significantly increasing the risk of cirrhosis, hepatocellular carcinoma (HCC), and liver-related mortality. Despite the rising global prevalence of MASLD, gaps in understanding the pathophysiological mechanisms driving MASH to cirrhosis persist, leading to challenges in early diagnosis, prevention, and treatment. This review explores the current knowledge on MASH, focusing on its pathophysiology, clinical management, and treatment strategies in the advanced stages. The role of metabolic dysfunction, portal hypertension, decompensation, and HCC occurrence is highlighted, alongside an evaluation of therapeutic options including lifestyle intervention, bariatric surgery, pharmacological therapies and liver transplantation. Furthermore, we emphasize the need for a multidisciplinary care approach to improve patient outcomes and address the complex metabolic and hepatic interplay in MASLD. Bridging these gaps will require an integrated effort combining advanced diagnostic tools, novel treatments, and comprehensive care strategies.

The associations between obesity and liver diseases are complex and diverse. To explore the causal relationships between obesity and liver diseases, we applied two-sample Mendelian randomisation (MR) and multivariable MR analysis. The data of exposures (BMI and WHRadjBMI) and outcomes (liver diseases and liver function biomarker) were obtained from the open genome-wide association study database. A two-sample MR study revealed that the genetically predicted BMI and WHRadjBMI were associated with non-alcoholic fatty liver disease, liver fibrosis and autoimmune hepatitis. Obesity was not associated with primary biliary cholangitis, liver failure, liver cell carcinoma, viral hepatitis and secondary malignant neoplasm of liver. A higher WHRadjBMI was associated with higher levels of biomarkers of lipid accumulation and metabolic disorders. These findings indicated independent causal roles of obesity in non-alcoholic fatty liver disease, liver fibrosis and impaired liver metabolic function rather than in viral or autoimmune liver disease.

Bariatric surgery has been shown to improve the histopathological findings in patients with obesity and metabolic dysfunction-associated steatohepatitis, but there are also reports about non-responders or progressive disease after bariatric interventions. Therefore, it is of utmost importance to understand the pathophysiological processes in the liver after bariatric surgery.

In the present study, 4 weeks old male C57/Bl6 mice were fed a Western Diet to induce metabolic dysfunction-associated steatohepatitis and sleeve-gastrectomy (SG), or sham operation in the pair-fed and ad libitum control group were performed. Mice were observed for two or eight weeks after surgery and metabolic assessment was performed throughout the experiment. Histopathology, flow cytometry and proteomic analyses were conducted to evaluate hepatic inflammation, liver metabolism and affected signaling pathways.

Weight loss was higher, and metabolism significantly improved after SG. Two weeks after SG major inflammatory and regulatory disturbances in the liver were observed. The proportion of hepatic CD3+NK1.1+ cells were decreased, and proteins involved in apoptosis like Fas, Casp1 and Casp9 or in the acute phase response were upregulated in SG mice. These disturbances decreased in the long-term and we observed an increase of many proteins involved in lipid metabolism eight weeks following SG.

The rapid weight loss and decrease of hepatic fat after SG lead to a proinflammatory response in the liver in the early phase after surgery, which changes to a more moderate immune response in the long-term. We suggest a preoperative risk stratification and postoperative surveillance depending on the histopathological findings.

The role of metabolic dysfunction-associated steatotic liver disease (MASLD) in sleeve gastrectomy (SG)-related outcomes remains uncertain. In this study, we aimed to assess the influence of preoperative biopsy-proven MASLD and its stages on weight loss after SG.

One hundred sixty-three patients with obesity undergoing SG with concomitant intraoperative liver biopsy were followed up for 1 year. Fifty-eight participants were categorized as no MASLD, thirty-eight as metabolic dysfunction-associated steatotic liver (MASL), and sixty-seven as metabolic dysfunction-associated steatohepatitis (MASH). Percentage total weight loss (%TWL) and percentage excess weight loss (%EWL) 1 year after SG were calculated for the different groups. We also evaluated the association between preoperative MASLD (and its stages) and weight loss, after adjusting for potential confounders.

Significant differences among groups were detected in %EWL (p = 0.004, ANOVA test), but not in %TWL (p = 0.079). However, significant differences in %TWL were found when MASH and no MASH (i.e., participants with MASL and participants without MASLD) groups were compared (27.3 ± 9.9 vs. 30.7 ± 9, respectively, p = 0.025). In the linear regression model for predicting %EWL 1 year after SG, the presence of MASH was independently associated with a lower %EWL, after adjusting for age, sex, baseline body mass index (BMI), and baseline glycated hemoglobin (HbA1c) (Beta -7.1; 95% CI -13.6, -0.5; p = 0.035). The presence of MASLD, liver fibrosis, or advanced liver fibrosis (≥F2) was also associated with lower %EWL after SG in crude models, although they did not remain significant after adjusting for these confounders. The presence of MASH was inversely related to %TWL, although the association did not remain significant after adjustment (Beta -2.7; 95% CI -5.7, 0.2; p = 0.069).

MASH may be independently associated with lower %EWL 1 year after SG in patients with obesity.

The global incidence of nonalcoholic fatty liver disease (NAFLD) is escalating considerably. NAFLD covers a range of liver conditions from simple steatosis to the more severe form known as nonalcoholic steatohepatitis, which involves chronic liver inflammation and the transformation of hepatic stellate cells into myofibroblasts that generate excess extracellular matrix, leading to fibrosis. Hepatocyte ballooning is a key catalyst for fibrosis progression, potentially advancing to cirrhosis and its decompensated state. Fibrosis is a critical prognostic factor for outcomes in patients with NAFLD; therefore, those with substantial fibrosis require timely intervention. Although liver biopsy is the most reliable method for fibrosis detection, it is associated with certain risks and limitations, particularly in routine screening. Consequently, various noninvasive diagnostic techniques have been introduced. This review examines the increasing prevalence of NAFLD, evaluates the noninvasive diagnostic techniques for fibrosis, and assesses their efficacy in staging the disease. In addition, it critically appraises current and emerging antifibrotic therapies, focusing on their mechanisms, efficacy, and potential in reversing fibrosis. This review underscores the urgent need for effective therapeutic strategies, given the dire consequences of advanced fibrosis.

Despite the slow, progressive nature of NAFLD, the number of patients with NAFLD-related cirrhosis has significantly increased. Although the management of patients with cirrhosis is constantly evolving, improving the prognosis of patients with NAFLD-related cirrhosis is a challenge because it is situated at the crossroads between the liver, the metabolic, and the cardiovascular diseases. Therefore, the therapeutic interventions should not only target the liver but also the associated cardiometabolic conditions and should be adapted accordingly. The objective of the current review is to critically discuss the particularities in the management of patients with NAFLD-related cirrhosis. We relied on the recommendations of scientific societies and discussed them in the specific context of NAFLD cirrhosis and the surrounding cardiometabolic milieu. Herein, we covered the following aspects: (1) the weight loss strategies through lifestyle interventions to avoid sarcopenia and improve portal hypertension; (2) the optimal control of metabolic comorbidities in particular type 2 diabetes aimed not only to improve cardiovascular morbidity/mortality but also to lower the incidence of cirrhosis-related complications (we discussed various aspects related to the safety of oral antidiabetic drugs in cirrhosis); (3) the challenges in performing bariatric surgery in patients with cirrhosis related to the portal hypertension and the risk of cirrhosis decompensation; (4) the particularities in the diagnosis and management of the portal hypertension and the difficulties in managing patients awaiting for liver transplantation; and (5) the difficulties in developing drugs and conducting clinical trials in patients with NAFLD-related cirrhosis. Moreover, we discussed the emerging options to overcome these obstacles.

This study investigates the effects of bariatric surgery on non-alcoholic fatty liver disease (NAFLD) by examining the interplay between gut microbiota, epigenetics, and metabolic health. A cohort of 22 patients undergoing sleeve gastrectomy (SG) was analyzed for changes in gut microbial composition and DNA methylation profiles before and six months after surgery. Correlations between gut microbial abundance and clinical markers at baseline revealed that certain genera were associated with worse metabolic health and liver markers. Following SG, significant improvements were observed in the clinical, anthropometric, and biochemical parameters of the NAFLD patients. Although alpha-diversity indices (i.e., Chao1, Simpson, Shannon) did not show significant changes, beta-diversity analysis revealed a slight shift in microbial composition (PERMANOVA, p = 0.036). Differential abundance analysis identified significant changes in specific bacterial taxa, including an increase in beneficial Lactobacillus species such as Lactobacillus crispatus and Lactobacillus iners and a decrease in harmful taxa like Erysipelotrichia. Additionally, DNA methylation analysis revealed 609 significant differentially methylated CpG sites between the baseline values and six months post-surgery, with notable enrichment in genes related to the autophagy pathway, such as IRS4 and ATG4B. The results highlight the individualized responses to bariatric surgery and underscore the potential for personalized treatment strategies. In conclusion, integrating gut microbiota and epigenetic factors into NAFLD management could enhance treatment outcomes, suggesting that future research should explore microbiome-targeted therapies and long-term follow-ups on liver health post-surgery.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most recent definition for steatotic liver disease associated with metabolic syndrome. The results of recent metabolic and observational studies suggest a potential beneficial effect of food-derived flavonoids in some chronic diseases, including MASLD. The study aims to evaluate the protective role of diet flavonoids in subjects with and without MASLD belonging to a cohort living in the South of Italy.

The study cohort comprised 1297 participants assessed in the NUTRIHEP cohort (2015-2018), divided into two groups, based on presence or absence of MASLD.

The results indicated statistically significant flavonoid consumption, showing a protective role against MASLD, at an optimal concentration of 165 mg/day, with an OR value of 0.63, (p = 0.001, 95% C.I.: 0.47; 0.83 t). The OR remained almost unchanged when the intake increased from 165 mg per day to 185 mg per day.

In conclusion, our study results show a protective role of flavonoids against MASLD. Consuming only 165 mg of flavonoids daily can activate this protective function, reducing the risk of MASLD.

Weight gain poses a rising concern post-liver transplantation (LT), and metabolic dysfunction-associated steatotic liver disease might impair graft health. The timing is crucial when considering bariatric surgery (BS) in a population with liver disease or transplantation. BS can be considered for post-LT weight gain, although the evidence is limited and the long-term outcome still uncertain. We conducted a national retrospective analysis in 5 Belgian transplant centers and included 25 patients with an LT followed by a bariatric procedure. A total of 187 LT patients without BS were included for comparison. Clinical, biochemical, and outcome data were retrospectively retrieved. In our nationwide cohort, 25 patients had undergone BS post-LT, at a median 3.5 years after LT. Twenty-one (84.0%) patients received a sleeve gastrectomy (SG). Patients were predominantly male (72.0%), with a lower age at time of transplantation compared with the non-BS population (54.5 vs. 60.6, p <0.001). Weight loss was significant and sustained, with a decrease in body mass index from 41.0±4.5 pre-BS to 32.6±5.8 1-3 years post-BS ( p <0.001) and 31.1±5.8 3-5 years post-BS ( p <0.001). Three pre-BS (12.0%) patients presented with recurrent and one (4.0%) de novo metabolic dysfunction-associated steatotic liver disease after LT, with 100% resolution post-BS ( p =0.016). Notable reductions were observed in alanine transaminase levels (40.5±28.5 U/L to 27.1±25.1 U/L post-BS, p =0.05) and HbA1c levels (6.9±1.6 to 6.0±1.4 post-BS, p <0.001). Three patients were re-transplanted, and eight patients died, of which five (20.0%) due to a nonhepatic malignancy and one (4.0%) due to liver failure. SG is the favored BS post-LT and has proven to be safe and feasible in a post-LT setting with favorable metabolic consequences. SG post-LT is a valid treatment for de novo and recurrent metabolic dysfunction-associated steatotic liver disease post-LT. Although we report on the largest cohort to date, there is still a need for larger cohorts to examine the effect of BS on patient and graft survival.

Nonalcoholic fatty liver disease (NAFLD) is a disease process that is gaining increasing recognition. The global prevalence of NAFLD is increasing in parallel with growing rates of risk factors for NAFLD such as hypertension, obesity, diabetes, and metabolic syndrome. NAFLD has been referred to as a risk factor for cardiovascular disease (CVD). As CVD is the leading cause of morbidity and mortality worldwide, there are constant efforts to describe and alleviate its risk factors. Although there is conflicting data supporting NAFLD as a causative or associative factor for CVD, NAFLD has been shown to be associated with structural, electrical, and atherosclerotic disease processes of the heart. Shared risk factors and pathophysiologic mechanisms between NAFLD and CVD warrant further explication. Pathologic mechanisms such as endothelial dysfunction, oxidative stress, insulin resistance, genetic underpinnings, and gut microbiota dysregulation have been described in both CVD and NAFLD. The mainstay of treatment for NAFLD is lifestyle intervention including physical exercise and hypocaloric intake in addition to bariatric surgery. Investigations into various therapeutic targets to alleviate hepatic steatosis and fibrosis by way of maintaining the balance between lipid synthesis and breakdown. A major obstacle preventing the success of many pharmacologic approaches has been the effects of these medications on CVD risk. The future of pharmacologic treatment of NAFLD is promising as effective medications with limited CVD harm are being investigated.

ZJU index, a novel calculation combining blood glucose, body mass index (BMI), lipids and liver functions, is closely related with non-alcoholic fatty liver disease (NAFLD). However, the correlation between ZJU index and hepatic steatosis and liver fibrosis has not been reported in the studies. This study aims to examine the correlation between these variables.

Data from the 2017-2020 NHANES were collected for a cross-sectional study, to explore the linear relationship between ZJU, liver stiffness measurements (LSM) and controlled attenuation parameters (CAP) with multivariate linear regression models. Restricted cubic spline (RCS) regression and threshold effect analyses were utilized to describe the nonlinear relationship. The correlation in subgroups was analyzed based on race, gender, drinking, age, BMI, diabetes and moderate activities.

In this population-based study, a total of 2,122 adults aged 18-80 years old with NAFLD were included. According to the multivariate linear regression analysis, ZJU had a significant positive correlation with liver fibrosis (LSM, β = 0.182, 95%CI = 0.154-0.211, p < 0.001) and hepatic steatosis (CAP, β = 2.35, 95%CI = 2.14-2.56, p < 0.001), which was stronger in males. According to the RCS analysis, an inverted L-shaped relationship between ZJU and CAP (inflection point at 60.56) and a J-shaped relationship between ZJU index and LSM (inflection point at 51.27) were observed.

ZJU had a positive correlation with CAP and LSM in American adults with NAFLD. The findings suggest that ZJU may be a valuable biomarker for assessing the severity of liver fibrosis and hepatic steatosis in individuals with NAFLD.

In the contemporary era of medicine, exploring the complexity of the human body and its intricate interactions has become a central concern for health researchers. The main purpose of this article is to summarize the current understanding of relevant pathophysiological factors such as chronic inflammation, dysbiosis (microbial imbalance), and metabolic disorders, as well as etiological factors including dietary habits, lifestyle choices, obesity, metabolic syndrome, and genetic predispositions, as well as to emphasize potential avenues for upcoming studies and their medical significance. Additionally, this article aims to assess the potential impact of integrated treatment approaches on patient outcomes, emphasizing the need for interdisciplinary collaboration between gastroenterologists, dentists, and other healthcare professionals to develop comprehensive care plans that address both oral and digestive health issues simultaneously. Among the branches with a significant impact on general well-being are oral cavity health and digestive diseases, which have been the subject of intensive research in recent decades. In this context, analysis of the current state of knowledge on oral cavity disorders in relation to "modern" digestive diseases such as non-alcoholic fatty liver disease (NAFLD), small intestinal bacterial overgrowth (SIBO), inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS) becomes essential for a deeper understanding of the interconnections between oral and digestive health. The temporal overlap or succession, whether preceding or following, of oral manifestations and digestive disorders should be taken seriously by both gastroenterologists and dentists to facilitate early diagnosis and explain to patients the correlation between these two body systems. In summary, this article underscores the importance of understanding the intricate relationship between oral and digestive health, advocating for interdisciplinary approaches to improve patient outcomes and guide future research.

Hepatocellular carcinoma (HCC) is an aggressive form of liver cancer that arises in a background of chronic hepatic injury. Metabolic syndrome-associated fatty liver disease (MAFLD) and its severe form, nonalcoholic steatohepatitis (NASH), are increasingly common mechanisms for new HCC cases. NASH-HCC patients are frequently obese and medically complex, posing challenges for clinical management. In this review, we discuss NASH-specific challenges and the associated implications, including benefits of minimally invasive operative approaches in obese patients; the value of y90 as a locoregional therapy; and the roles of weight loss and immunotherapy in disease management. The relevant literature was identified through queries of PubMed, Google Scholar, and clinicaltrials.gov. Provider understanding of clinical nuances specific to NASH-HCC can improve treatment strategy and patient outcomes.

Early-stage nonalcoholic fatty liver disease (NAFLD) is a silent condition, with most cases going undiagnosed, potentially progressing to liver cirrhosis and cancer. A non-invasive and cost-effective detection method for early-stage NAFLD detection is a public health priority but challenging. In this study, an adhesive, soft on-skin sensor with low electrode-skin contact impedance for early-stage NAFLD detection is fabricated. A method is developed to synthesize platinum nanoparticles and reduced graphene quantum dots onto the on-skin sensor to reduce electrode-skin contact impedance by increasing double-layer capacitance, thereby enhancing detection accuracy. Furthermore, an attention-based deep learning algorithm is introduced to differentiate impedance signals associated with early-stage NAFLD in high-fat-diet-fed low-density lipoprotein receptor knockout (Ldlr-/-) mice compared to healthy controls. The integration of an adhesive, soft on-skin sensor with low electrode-skin contact impedance and the attention-based deep learning algorithm significantly enhances the detection accuracy for early-stage NAFLD, achieving a rate above 97.5% with an area under the receiver operating characteristic curve (AUC) of 1.0. The findings present a non-invasive approach for early-stage NAFLD detection and display a strategy for improved early detection through on-skin electronics and deep learning.