Search

This article summarizes the epidemiological characteristics and clinical manifestations of nonalcoholic fatty liver disease (NAFLD). The incidence of NAFLD has been increased dramatically and become the leading cause of chronic liver disease worldwide. In addition to its adverse outcomes of liver fibrosis, cirrhosis, and hepatocellular carcinoma, and related complications, NAFLD has recently been found to be associated with the high-risk extrahepatic carcinomas, such as various types of lung cancer ( i.e ., lung adenocarcinoma, squamous cell carcinoma, and small cell lung cancer). The presence of hepatic steatosis also predisposes lung cancer to liver metastasis, but has better response to immune checkpoint inhibitors. Whether other factors ( i.e ., gender, smoking, etc .) are associated with NAFLD and lung cancer remains controversial. We also comment on the reciprocal relationships between NAFLD and components of metabolic syndrome. Most metabolic syndrome components are suggested to facilitate lung cancer development via activating insulin/insulin-like growth factor axis. In addition, suppressed anti-tumor immunity and accelerated tumor progression could be attributed to the cell-specific metabolic reprogramming in condition of high-fat diet and related obesity. These findings may reveal the role of NAFLD in pulmonary carcinoma and help develop new treatment strategies for this disease., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.)

Endoscopic bariatric and metabolic therapies (EBMTs) are minimally invasive endoscopic procedures that have shown to demonstrate significant weight loss in people with obesity. While abundant data support their positive effect on weight loss, there remains a notable dearth of information regarding their effects on metabolic dysfunction-associated steatotic liver disease (MASLD). As rates of type 2 diabetes and obesity have grown worldwide, so has the rate of MASLD. Therefore, addressing these knowledge gaps is crucial in improving liver health worldwide. In this review, we aim to provide the existing evidence delineating the effects of primary and secondary endoscopic bariatric therapies on MASLD and determine knowledge gaps requiring future study. Utilizing PubMed search with relevant keywords such as "endoscopic bariatric therapies," "NAFLD" (nonalcoholic fatty liver disease), "MAFLD" (metabolic dysfunction-associated fatty liver disease), "MASLD" (metabolic dysfunction-associated steatotic liver disease), we gathered case reports, reviews, and retrospective analyses, evaluating their data and limitations. In our manuscript, we detail many primary and secondary endoscopic therapies and the literature available exploring their impact on liver health. This review demonstrates that primary EBMTs improve noninvasive liver markers, weight loss, and overall metabolic syndrome suggesting significant benefit in MASLD. There is, however, a significant lack of literature studying how primary endoscopic therapies compare amongst each other and how revisional therapies affect MASLD. We additionally offer suggestions for future research to deepen our understanding of EBMTs and their effects on MASLD., Competing Interests: Disclosures The authors have no commercial associations that might be a conflict of interest in relation to this article., (Copyright © 2025 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: The HEPAKID index, a novel diagnostic tool with a sensitivity of 82% and specificity of 62% for detecting nonalcoholic fatty liver disease in obese adolescents. Our study aimed to explore the potential relationship between the HEPAKID index and risk factors contributing to the development of cardiovascular disease in obese adolescents with metabolic syndrome. Methods: This prospective cross-sectional study, conducted at two medical centers from December 2023 to March 2024, included 208 obese adolescents, with a median age of 14.5 years and an average body mass index (BMI) of 30.57 kg/m 2 . Results: Elevated HEPAKID index values were found in obese adolescents with metabolic syndrome, showing positive associations with BMI, waist and hip circumferences, alanine aminotransferase level, fasting insulin, and homeostasis model assessment for insulin resistance. In those with metabolic syndrome, waist circumference (WC) and homeostasis model assessment for insulin resistance were significant independent variables linked to the HEPAKID index, while WC was the sole influencer in the nonmetabolic syndrome group. Multivariate logistic regression highlighted systolic and diastolic blood pressures, triglycerides, high-density lipoprotein cholesterol, and the HEPAKID index as reliable predictors of metabolic syndrome. A predictive cutoff value of 60.84 for the HEPAKID index showed 61.7% sensitivity and 59.1% specificity in identifying metabolic syndrome. Conclusions: Our study highlighted the potential value of the HEPAKID index in combination with other clinical parameters for predicting metabolic syndrome in obese adolescents, underscoring its role as a valuable screening tool. Furthermore, our findings revealed a correlation between the HEPAKID index and insulin sensitivity in this high-risk population.

Nonalcoholic fatty liver disease (NAFLD) is a multisystemic clinical condition that presents with a wide spectrum of extrahepatic manifestations, such as obesity, type 2 diabetes mellitus, metabolic syndrome, cardiovascular diseases, chronic kidney disease, extrahepatic malignancies, cognitive disorders, and polycystic ovarian syndrome. Among NAFLD patients, the most common mortality etiology is cardiovascular disorders, followed by extrahepatic malignancies, diabetes mellitus, and liver-related complications. Furthermore, the severity of extrahepatic diseases is parallel to the severity of NAFLD. In clinical practice, aware-ness of the associations of concomitant diseases is of major importance for initiating prompt and timely screening and multidisciplinary management of the disease spectrum. In 2020, a consensus from 22 countries redefined the disease as metabolic (dysfunction)-associated fatty liver disease (MAFLD), which resulted in the redefinition of the corresponding population. Although the patients diagnosed with MAFLD and NAFLD mostly overlap, the MAFLD and NAFLD populations are not identical. In this review, we compared the associations of key extrahepatic diseases between NAFLD and MAFLD.

We investigated the risk of cardiovascular events, all-cause mortality, and liver-related mortality according to the presence of metabolic syndrome (MetS) and fatty liver index (FLI). In this retrospective longitudinal population-based cohort study, we used Korean National Health Insurance Service data from 2009 to 2012. Nonalcoholic fatty liver disease (NAFLD) was defined as FLI ≥ 60. Risk of all-cause mortality, liver-related mortality, and major adverse cardiovascular events (MACE) including myocardial infarction (MI), stroke, heart failure (HF), and cardiovascular disease (CVD)-related mortality was assessed according to the presence of MetS and FLI among adults (aged 40 to 80 years) who underwent health examinations (n = 769,422). During a median 8.59 years of follow up, 44,356 (5.8%) cases of MACE, 24,429 (3.2%) cases of all-cause mortality, and 1114 (0.1%) cases of liver-related mortality were detected in the entire cohort. When the FLI < 30 without MetS group was set as a reference, the FLI ≥ 60 with MetS group had the highest risk of MACE (adjusted hazard ratio [aHR] 2.05, 95% confidence interval [CI] 1.98-2.13) and all-cause mortality (aHR 1.96, 95% CI 1.86-2.07). The risk of liver-related mortality (aHR 10.71, 95% CI 8.05-14.25) was highest in the FLI ≥ 60 without MetS group. The FLI ≥ 60 with MetS group had a higher risk of MACE (aHR 1.39, 95%CI 1.28-1.51), a lower risk of liver-related mortality (aHR 0.44, 95%CI 0.33-0.59), and no significant difference in all-cause mortality compared with the FLI ≥ 60 without MetS group. The FLI ≥ 60 with MetS group was associated with the highest risk of MACE and the FLI ≥ 60 without MetS group had the highest risk liver-related mortality, but there was no significant difference in all-cause mortality between two groups. In conclusion, as FLI levels increase, the risk of MACE increases, and the risk increases additively in the presence of MetS. The risk of liver-related mortality increases with higher FLI levels, the effect of high FLI on increased risk is more significant in groups without MetS compared to those with MetS., Competing Interests: Declarations. Competing interests: The authors have no competing interests. Ethics approval and consent to participate: The study was approved by the Institutional Review Board of Samsung Medical Center (approval no. SMC 2019–11-051), Seoul, Republic of Korea. The researchers cannot identify any participant in order to obtain informed consent. Consent for publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Rising global pediatric obesity rates, increase non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) prevalence, with MetS being a NAFLD risk factor. NAFLD can be asymptomatic, with liver function tests insensitive to mild disease, and liver biopsy, risking complications. Thus, we investigated multiparametric MRI (mpMRI) metrics of liver fat (proton density fat fraction, PDFF) and disease activity (fibro-inflammation; iron-corrected T1, cT1), in a Hispanic pre-pubertal pediatric cohort, with increased risk of NAFLD. Pre-pubertal boys (n = 81) of varying Body-Mass Index (BMI) were recruited in Mexico City. Most children (81%) had normal liver transaminase levels, 38% had high BMI, and 14% had ≥ 3 MetS risk factors. Applying mpMRI thresholds, 12%, 7% and 4% of the cohort had NAFLD, NASH and high-risk NASH respectively. Participants with ≥ 3 MetS risk factors had higher cT1 (834 ms vs. 737 ms, p = 0.004) and PDFF (8.7% vs. 2.2%, p < 0.001) compared to those without risk factors. Those with elevated cT1 tended to have high BMI and high insulin (p = 0.005), HOMA-IR (p = 0.005) and leptin (p < 0.001). The significant association of increased risk of MetS with abnormal mpMRI, particularly cT1, proposes the potential of using mpMRI for routine pediatric NAFLD screening of high-risk (high BMI, high MetS risk score) populations., (© 2024. The Author(s).)

Polycystic ovary syndrome (PCOS) is a disease affecting as many as about 10% of women of reproductive age, also 3-11% of teenage patients, and can lead to numerous complications and coexists with many diseases. Research is ongoing to establish an appropriate diagnostic and therapeutic path for adolescent girls with PCOS. It is also important to implement appropriate check-ups among teenagers with PCOS in order to prevent PCOS complications and initiate appropriate treatment as soon as possible and prevent the long-term consequences of these complications. The relationship between the co-occurrence of PCOS and diseases such as metabolic syndrome, hypertension, obesity, insulin resistance, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) is increasingly being investigated. A great attention is also being paid to the problem of mental health in this group of patients. In our study, we will review the latest reports on the treatment of PCOS and look at the complications that this syndrome can cause., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jakubowska-Kowal, Skrzyńska and Gawlik-Starzyk.)

Introduction: Metabolic dysfunction associated fatty liver disease (MAFLD) is a prevalent condition in patients with type 2 diabetes mellitus (T2DM). Isthmin-1 (ISM1) is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis. Although ISM1 has been shown to be associated with T2DM, its role in patients with MAFLD and metabolic syndrome (MetS) remains insufficiently examined. This study aimed to investigate the relationship between serum ISM1 and MAFLD in patients with T2DM and the potential involvement of MetS in this association., Research Design and Methods: A total of 250 participants were divided into four groups: 60 patients with T2DM and MAFLD, 60 with newly diagnosed T2DM, 60 with MAFLD, and 70 healthy controls. Serum ISM1 levels were measured using ELISA. The distribution of ISM1 concentration in the combined data was divided into quartiles, and the Cochran-Armitage trend test was performed to estimate the significant trends across increasing quartiles., Results: Compared with the controls, patients with coexisting MAFLD, MetS, and T2DM exhibited significantly elevated serum ISM1 concentrations. Serum ISM1 levels in the overweight/obese group were also higher than those in the lean group. Serum ISM1 levels were positively correlated with body mass index (BMI), uric acid, alanine aminotransferase, aspartate aminotransferase, total cholesterol (TC), low-density lipoprotein cholesterol, fasting insulin, and homeostasis model assessment of insulin resistance and negatively associated with age and high-density lipoprotein cholesterol (HDL-C). BMI, TC, and HDL-C were independently associated with serum ISM1 concentration. The relative risks for MAFLD, T2DM, and T2DM with MAFLD increased significantly with higher ISM1 quartiles. Furthermore, a positive correlation was observed between serum ISM1 levels and the number of MetS components, with the elevated plasma levels of ISM1 escalating the risk of developing MetS to some extent., Conclusions: The combination of ISM1 with TG and UA was identified as the best predictive factor for diagnosing MAFLD and MetS, potentially due to their contribution to aggravating the metabolic state., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Nonalcoholic fatty liver disease (NAFLD) is a major health problem with a paucity of available information about its impact on female sexual dysfunction (FSD)., Aim: We aimed to study the association between NAFLD and FSD in Egyptian premenopausal women., Methods: Sexually active married premenopausal women who visited our NAFLD outpatient screening clinic (2019 to 2022) were divided into NAFLD and non-NAFLD (control) groups based on liver ultrasound and fatty liver index data. All participants completed the Arabic Female Sexual Function Index (ArFSFI) questionnaire. The resulting data were used to calculate the domains and total scores. FSD is then graded as follows: no FSD (≥28.2), minimal (21.7-28.1), mild (14.5-21.6), moderate (7.3-14.4), and severe (≤7.2)., Outcomes: We determined the proportions of patients and controls for whom ArFSFI scores indicated dissatisfaction with their sexual lives., Results: Of 995 women participants whose FSFI scores were available, NAFLD was detected in 487 (48.9%) and absent in 508 (51.1%). The two groups were comparable in age, socioeconomic level, residence, and history of female genital cutting. The NAFLD patients had significantly much lower mean scores for the sexual arousal, lubrication, orgasm, satisfaction, and pain domains of the FSFI (P < .001 for all), while no statistical difference was noticed in the desire domain for NAFLD patients compared with the controls. NAFLD women had significantly lower mean total FSFI scores than the controls (mean [SD] 16.7 [6.8] vs 21.7 [5.1], respectively; P < .001) with higher rates of FSD (98.5% vs 82.1%; P < .001, respectively). Most NAFLD women had higher FSD grades than controls (%): no FSD (1.5, 17.9), minimal (20.6, 51.8), mild (42.5, 38.8), moderate (26.2, 9.4), and severe (10.7, none), respectively., Clinical Implications: Given the high prevalence of FSD in patients with NAFLD, greater attention to FSF could improve the quality of life in patients with NAFLD., Strengths and Limitations: This study was limited by the lack of testing of sex hormones and some other important factors that were not tested (eg, age, socioeconomic level, residence, and female genital cutting), as these characteristics were previously matched. Strengths of the study include the large study size, to our knowledge the largest to date to investigate the possible link between FSD and NAFLD in premenopausal women, together with the inclusion of the detailed version of the validated ArFSFI., Conclusions: In Egyptian premenopausal women, NAFLD could harm their sexual function., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The aim of this study was to evaluate the prevalence and risk factors related to metabolic dysfunction-associated steatotic liver disease in inflammatory bowel disease patients., Methods: This is a cross-sectional study conducted on adults with inflammatory bowel disease from 2019 to 2021. Metabolic dysfunction-associated steatotic liver disease encompasses patients with steatosis and at least one cardiometabolic risk factor. Patients with alcohol consumption ≥20 g/day, chronic liver diseases, or methotrexate use were excluded., Results: Almost 140 patients were included: 67.1% were female, with a mean age of 49.7±13.7 years, and 63.6% had Crohn's disease. The mean duration of inflammatory bowel disease was 9.7±7.9 years. Metabolic dysfunction-associated steatotic liver disease was observed in 44.3% and advanced liver fibrosis was excluded in 63.5% by Fibrosis-4. Patients with metabolic dysfunction-associated steatotic liver disease were older (p = 0.003) and had a higher number of metabolic syndrome components (2.9±1.1 versus 1.6±1.0; p<0.001), greater abdominal circumference (p<0.001), and body mass index (p<0.001). The only factor related to inflammatory bowel disease associated with metabolic dysfunction-associated steatotic liver disease was disease duration (11.6±9.5 versus 8.3±6.2; p = 0.017). A higher number of metabolic syndrome components and obesity increase by 2.2 times and an altered waist circumference by 2.6 times the occurrence of metabolic dysfunction-associated steatotic liver disease., Conclusion: A high prevalence of metabolic dysfunction-associated steatotic liver disease was observed in patients with inflammatory bowel disease, with the main risk factors being associated with metabolic syndrome predicting it, but not with inflammatory bowel disease features and/or its treatment.

The metabolic syndrome, characterized by type 2 diabetes mellitus (T2DM), hypertension, hyperlipidemia, and obesity, collectively increases the risk of cardiovascular diseases. Nonalcoholic fatty liver disease (NAFLD) is a prominent manifestation, affecting over a third of the global population with a concerning annual increase in prevalence. Nearly 70 % of overweight individuals have NAFLD, and NAFLD-related deaths are predicted to rise, especially among young adults. The association of T2DM and NAFLD has led to the proposal of "metabolic dysfunction-associated steatotic liver disease" (MASLD) terminology, encompassing individuals with T2DM, overweight/obesity, hypertension, hypertriglyceridemia, or low HDL-cholesterol. Patients with MASLD will likely have double the risk of developing T2DM, and the combination of insulin resistance, overweight/obesity, and MASLD significantly elevates the risk of T2DM. Cardiovascular diseases remain the leading cause of mortality in the MASLD and T2DM population, with MASLD directly associated with coronary artery disease, compounded by coexisting insulin resistance and T2DM. Urgency lies in early detection of subclinical cardiovascular diseases among patients with T2DM and MASLD. Novel strategies targeting multiple pathways offer hope for effectively improving cardiometabolic health. Understanding and addressing the intertwined factors contributing to these disorders can pave the way towards better management and prevention of cardiometabolic complications., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [C.S.P.L. is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore; has received research support from Bayer and Roche Diagnostics; has served as consultant or on the Advisory Board/Steering Committee/Executive Committee for Abbott, Actelion, Alleviant Medical, Allysta Pharma, Amgen, AnaCardio AB, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma Inc, EchoNous Inc, Impulse Dynamics, Ionis Pharmaceutical, Janssen Research & Development LLC, Medscape/WebMD Global LLC, Merck, Novartis, Novo Nordisk, Prosciento Inc, Radcliffe Group Ltd, Roche Diagnostics, Sanofi, Siemens Healthcare Diagnostics, and Us2.ai; and serves as cofounder and nonexecutive director of Us2.ai. N.W.S.C. has received research grant support from NUHS Seed Fund and National Medical Research Council Research Training Fellowship.]., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background/aims: Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events., Methods: We performed a systematic review and meta-analysis of cohort studies of adults with NAFLD to evaluate the pooled incidence of adverse events., Results: 19,406 articles were screened, 409 full-text articles reviewed, and 79 eligible studies (1,377,466 persons) were included. Mean age was 51.47 years and body mass index 28.90 kg/m2. Baseline comorbidities included metabolic syndrome (41.73%), cardiovascular disease (CVD) (16.83%), cirrhosis (21.97%), and nonalcoholic steatohepatitis (NASH) (58.85%). Incidence rate per 1,000 person-years for mortality included: all-cause (14.6), CVD-related (4.53), non-liver cancer-related (4.53), and liver-related (3.10). Incidence for liver-related events included overall (24.3), fibrosis progression (49.0), cirrhosis (10.9), liver transplant (12.0), and hepatocellular carcinoma (HCC) (3.39). Incidence for non-liver events included metabolic syndrome (25.4), hypertension (25.8), dyslipidemia (26.4), diabetes (19.0), CVD (24.77), renal impairment (30.3), depression/anxiety (29.1), and non-liver cancer (10.5). Biopsy-proven NASH had higher incidence of HCC (P=0.043) compared to non-NASH. Higher rates of CVD and mortality were observed in North America and Europe, hypertension and non-liver cancer in North America, and HCC in Western Pacific/Southeast Asia (P<0.05). No significant differences were observed by sex. Time-period analyses showed decreasing rates of cardiovascular and non-liver cancer mortality and increasing rates of decompensated cirrhosis (P<0.05)., Conclusion: People with NAFLD have high incidence of liver and non-liver adverse clinical events, varying by NASH, geographic region, and time-period, but not sex.

Obesity, especially central obesity is associated with increased risk of metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus. The study aimed to investigate the associations of the changes of abdominal fat thicknesses with changes of anthropometric indexes and improvements of metabolic phenotypes in patients with obesity and T2DM before and after bariatric surgery. Between April 2016 and January 2017, 34 adult patients with concurrent obesity and T2DM scheduled for different bariatric surgeries were prospectively evaluated by ultrasound before and 1-year after bariatric surgery to determine abdominal fat thicknesses (mesenteric fat, preperitoneal fat and subcutaneous fat) and NAFLD. At 1 year, of the 25 patients that finished the study, significant decrease in mesenteric-fat-thickness was associated with significant reduction of obesity, that is, BMI (-24%, p < .001), remission of metabolic syndrome (32%, p = .008), NAFLD (60%, p < .001) and T2DM (44%, p < .001). Lower baseline mesenteric fat thickness was associated with remission of metabolic syndrome. Lower baseline mesenteric-fat-thickness may have the potential to predict metabolic syndrome remission after bariatric surgery., (© 2023 The Authors. Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Aim: Metabolic syndrome (MetS) is associated with higher cardiovascular and metabolic risks, as well as with psychosocial disorders. Data regarding quality of life (QoL) in patients with MetS, point towards a significative association between MetS and a worse QoL. It remains unclear whether MetS components and non-alcoholic fatty liver disease (NAFLD) are associated with QoL in these individuals. We aimed to evaluate the association between QoL of patients with MetS and prespecified metabolic parameters (anthropometric, lipidic and glucose profiles), the risk of hepatic steatosis and fibrosis, and hepatic elastography parameters., Methods: Cross-sectional study including patients from microDHNA cohort. This cohort includes patients diagnosed with MetS, 18 to 75 years old, followed in our tertiary center. The evaluation included anamnesis, physical examination, a QoL questionnaire (Short-Form Health Survey, SF-36), blood sampling and hepatic elastography. We used ordered logistic regression models adjusted to sex, age and body mass index to evaluate the associations between the QoL domains evaluated by SF-36 and the prespecified parameters., Results: We included a total of 65 participants with MetS, with 54% being female and the mean age 61.9 ± 9.6 years old. A worse metabolic profile, specifically higher waist circumference, lower HDL, higher triglycerides, and more severe hepatic steatosis, were associated with worse QoL scores in several domains. We found no significant association of hepatic fibrosis with QoL., Conclusion: Our data suggests that there is a link between a worse metabolic profile (specifically poorer lipidic profile and presence of hepatic steatosis) and a worse QoL in patients with MetS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Metabolic dysfunction-associated fatty liver disease (MAFLD), the hepatic component of the metabolic syndrome caused by insulin resistance, is a major public health problem, affecting about the 25 % of the general population in Western countries. Morbidity and mortality of MAFLD patients is increased primarily due to cardiovascular disease (CVD). Liver fibrosis, the byproduct of hepatic repair, is the main determinant of MAFLD progression and the strongest predictor for overall mortality. Since the mechanistic relationship between MAFLD, fibrosis, insulin resistance and the cardiometabolic risk is far to be clear, deciphering the functional link of hepatic fibrogenesis with genetic factors and hypercoagulability in MAFLD-associated CVD may hold translational potential for risk profiling and innovative therapeutic targeting., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) have been steadily increasing worldwide, with a huge societal and economic burden. Recently, NAFLD and non-alcoholic steatohepatitis have been renamed and redefined as metabolic dysfunction associated steatotic liver disease (MASLD) and steatohepatitis (Metabolic Dysfunction Associated Steatohepatitis (MASH)), which result from an imbalance between metabolic and inflammatory stress (mainly as a consequence of adipose tissue dysfunction and insulin resistance) and the defence and repair mechanisms of the steatotic liver. Once MASLD progresses to end-stage of liver disease, treatment efficacy becomes limited and may require liver transplantation. Early detection and intervention are crucial. Lifestyle modification is consequently the cornerstone of its management. Timely consideration of bariatric surgeries should be given to patients meeting specific criteria. A multidisciplinary approach is warranted, starting from the concept that MASLD/MASH is at the centre of the cardiovascular-liver-metabolic syndrome. In some cases, pharmacological treatment can complement lifestyle modification. Several drugs used to treat the cardiometabolic co-morbidities have some potential efficacy in slowing Down disease progression, and some have demonstrated efficacy on histological endpoints that are likely to translate into long-term clinical benefits. Optimising the use of these drugs within their licenced indications is thus paramount for patients with MASLD. Several MASH-specific drugs are on the horizon and are likely to enrich our therapeutic armamentarium in the near future, particularly in non-cirrhotic stages of the disease. Much work still needs to be done to understand the specific features of MASH cirrhosis and develop efficacious treatments for this disease stage., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Metabolic dysfunction-associated steatotic (fatty) liver disease (MASLD), previously termed non-alcoholic fatty liver disease, is a worldwide epidemic that can lead to hepatic inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The disease is typically a component of the metabolic syndrome that accompanies obesity, and is often overlooked because the liver manifestations are clinically silent until late-stage disease is present (i.e., cirrhosis). Moreover, Asian populations, including Koreans, have a higher fraction of patients who are lean, yet their illness has the same prognosis or worse than those who are obese. Nonetheless, ongoing injury can lead to hepatic inflammation and ballooning of hepatocytes as classic features. Over time, fibrosis develops following activation of hepatic stellate cells, the liver's main fibrogenic cell type. The disease is usually more advanced in patients with type 2 diabetes mellitus, indicating that all diabetic patients should be screened for liver disease. Although there has been substantial progress in clarifying pathways of injury and fibrosis, there no approved therapies yet, but current research seeks to uncover the pathways driving hepatic inflammation and fibrosis, in hopes of identifying new therapeutic targets. Emerging molecular methods, especially single cell sequencing technologies, are revolutionizing our ability to clarify mechanisms underlying MASLD-associated fibrosis and HCC.

Introduction: Nonalcoholic fatty liver disease is the leading cause of pediatric chronic liver disease. Although nonalcoholic fatty liver disease is closely associated with obesity, its relationship with metabolic syndrome in children is not fully understood. The main aim of this study was to evaluate the association between nonalcoholic fatty liver disease and a combination of cardiometabolic risk factors in adolescents with overweight/obesity, using a pediatric metabolic syndrome score (PsiMS) to predict metabolic syndrome., Methods: A retrospective cohort study was conducted. Subjects with overweight/obesity aged 10 to 17 followed at two clinical centers in Portugal (2018 - 2021) were enrolled. The independent association of nonalcoholic fatty liver disease with PsiMS, and of other potential predictors, was tested through multiple regression analyses. Receiver operator characteristic curve analysis was performed to estimate the optimal cutoff of PsiMS to discriminate metabolic syndrome., Results: Eighty-four subjects were included (median age at baseline 11.5 years). The prevalence rate of nonalcoholic fatty liver disease was 51% and the prevalence rate of metabolic syndrome was 7%. The mean PsiMS was 2.05 ± 0.48 at the first evaluation, and 2.11 ± 0.52 at the last evaluation (mean follow-up time was 15 months). The nonalcoholic fatty liver disease group had significantly (p < 0.05) higher weight and body mass index z-scores, higher rate of severe obesity and higher waist circumference percentile. PsiMS was highly accurate in predicting metabolic syndrome (area under the curve = 0.96), with an optimal cutoff of 2.46 (sensitivity 100%, specificity 89%). In the univariate analysis, no statistically significant association was observed between nonalcoholic fatty liver disease and PsiMS. In the multiple regression analysis, female sex had a negative association with PsiMS (first and last evaluation). Independent predictors of a higher PsiMS at first evaluation were: ≥ 2 metabolic syndrome criteria, body mass index z-score, insulin resistance and dyslipidemia. At the last evaluation, independent predictors of a higher PsiMS were: nonalcoholic fatty liver disease, baseline PsiMS and body mass index increase from baseline., Conclusion: The results suggest a good performance of the PsiMS to assess metabolic syndrome and that nonalcoholic fatty liver disease is associated with PsiMS at follow-up.

Nonalcoholic fatty liver disease (NAFLD), which can manifest as nonalcoholic steatohepatitis (NASH) or severe fibrosis, is the most prevalent chronic liver disease in children and adolescents. However, there is no proven cure for it so far. This study was conducted to determine whether adolescents with NAFLD would improve with treatment intervention with orlistat. This study is a randomized controlled trial (RCT). Fifty-three adolescents with overweight/obese as well as with NAFLD randomly allocated to receive orlistat (n = 27) or placebo as control (n = 26) for 12 weeks. In addition, NAFLD activity score, anthropometric factors, biochemical parameters including serum levels of lipid profiles, liver enzyme, and glucose metabolism taken from subjects at baseline and end of the study were investigated. The findings of our article indicated that orlistat improves liver enzymes (alanine transaminase and aspartate transaminase) (P =  < 0.001), steatosis score (P = 0.001), NAFLD activity score (P =  < 0.001), weight (P =  < 0.001), body mass index (BMI) (P =  < 0.001), waist circumferences (WC) (P =  < 0.001), BMI-Z score (P =  < 0.001), glucose metabolism (P = 0.001), total cholesterol (TC) (P = 0.009), low density lipoprotein-cholesterol (LDL) (P =  < 0.001), and high density lipoprotein-cholesterol HDL levels (P = 0.014) compared to the control group after adjusting for possible confounders for 12 weeks. However, no significant changes were observed on triglyceride (TG) following intake of orlistat compared to placebo after adjusting for confounders., Conclusion: The findings of our study reported that orlistat improved NAFLD-related factors and metabolic syndrome-related factors compared to placebo for 12 weeks., Trial Registration: (Clinical trial registry number: IRCT20220409054467N2, with a registration date of 2022-05-13)., What Is Known: • Among the interventions of interest for the management of pediatric NAFLD, we can mention lifestyle and pharmaceutical measures., What Is New: • This study was conducted to determine whether adolescents with NAFLD would improve with treatment intervention with orlistat. • The findings of our study reported that orlistat improved NAFLD-related factors and metabolic syndrome-related factors compared to placebo for 12 weeks., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The aim was to evaluate the effect different types of abdominal fat have on NAFLD development and the effects of abdominal fat has on the association between Metabolic Syndrome (MetS) and NALFD., Methods: Data was collected from the cross-sectional NHANES dataset (2017-2018 cycle). Using the controlled attenuation parameter (USG CAP, dB/m), which measures the level of steatosis, the cohort was stratified into two groups: NAFLD(+) (≥274 dB/m) and NAFLD(-). Using complex samples analyses, associations between liver steatosis or NAFLD and types of abdominal fat area [Total abdominal (TAFA), subcutaneous (SAT), and visceral (VAT)] were determined. Pearson's correlation coefficient (r) was calculated to evaluate the associations between adipose tissues and NAFLD. Logistic regression was used to determine the risk [odds ratio (OR) and 95% confidence interval (95%CI)]. Participants were also classified by MetS, using the Harmonizing Definition criteria., Results: Using 1,980 participants (96,282,896 weighted), there was a significant (p<0.001) correlation between USG CAP and TAFA (r = 0.569), VAT (r = 0.645), and SAT (r = 0.479). Additionally, the risk of developing NAFLD was observed for total abdominal obesity (OR = 19.9, 95%CI: 5.1-77.8, p<0.001), visceral obesity (OR = 9.1, 95%CI: 6.2-13.5, p<0.001) and subcutaneous obesity (OR = 4.8, 95%CI: 3.2-6.9, p<0.001). Using 866 participants (44,399,696 weighted), for visceral obesity, participants with MetS and visceral obesity (OR = 18.1, 95%CI: 8.0-41.3, p<0.001) were shown to have a greater risk than participants with MetS only (OR = 6.3, 95%CI: 2.6-15.2, p<0.001). For subcutaneous obesity, again, participants with MetS and subcutaneous obesity (OR = 18.3, 95%CI: 8.0-41.9, p<0.001) were shown to have a greater risk than the MetS-only group (OR = 10.3, 95%CI: 4.8-22.4, p<0.001)., Conclusion: TAFA, VAT, and SAT were positively associated with USG CAP values and increased the risk of developing NAFLD. Also, the type of abdominal fat depots did affect the association between MetS and NAFLD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Elguezabal Rodelo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Context: Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Obesity and metabolic syndrome are known risk factors for thyroid cancer., Objective: We investigated the association between NAFLD and thyroid cancer risk in young adults., Methods: This nationwide cohort study included 1 135 967 participants aged 20 to 39 years who underwent 4 consecutive health screenings in South Korea. NAFLD was categorized using the fatty liver index (FLI), as follows: ≥60, 30 to 60, and <30. The cumulative FLI points were defined as the number of times participants had a FLI of ≥30 (0-4)., Results: During a median follow-up of 5.2 years, 4126 participants (0.36%) were newly diagnosed with thyroid cancer. Compared with the participants with an FLI of <30, those with an FLI of 30 to 60 (men: hazard ratio [HR] 1.36 [95% CI, 1.22-1.51] and women: HR 1.44 [1.21-1.70]) and those with an FLI of ≥60 (men: HR 1.71 [1.53-1.92] and women: HR 1.81 [1.46-2.25]) had a significantly higher risk of thyroid cancer. Participants with higher cumulative FLI points had a higher risk of thyroid cancer compared to those with a cumulative FLI point of 0 (P < .001). During the follow-up period, the participants with an increased FLI exhibited an increased risk of thyroid cancer., Conclusion: NAFLD was associated with an increased risk of thyroid cancer in young adults. Repeatedly elevated FLI and progression of NAFLD were associated with an increased risk of thyroid cancer in this study., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The concept of metabolically obese, normal weight (MONW) has emerged to describe individuals with a normal body mass index (BMI) who are at a relatively high risk of chronic diseases. However, BMI itself is a suboptimal index for the assessment of the health risks associated with visceral fat. The triglyceride-glucose (TyG) index is considered to be a reliable and cost-effective marker of insulin resistance. Therefore, in the present study, we aimed to determine the TyG index cut-off values that could be used to define MONW in older people and to determine the usefulness of these values for the prediction of chronic diseases., Methods: A total of 4,721 participants in the Korea National Health and Nutritional Examination Survey who were ≥ 60 years of age and did not have underweight or obesity were included. MONW was defined using the criteria for metabolic syndrome (MS), and the TyG index was calculated on the basis of the fasting plasma triglyceride and glucose concentrations. Chronic diseases, including T2DM, hypertension, and non-alcoholic fatty liver disease (NAFLD), were diagnosed., Results: The prevalence of MS increased from the lowest to the highest TyG index tertile. The cut-off values of the TyG index for MONW were calculated as 8.88 and 8.80 for males and females, respectively. MONW, defined using these cut-off values, was associated with high odds ratios for NAFLD, T2DM, and hypertension in both males and females., Conclusions: The TyG index cut-off values calculated in the present study can be used to discriminate individuals with MONW from other older individuals without obesity and to predict the risk of chronic diseases. These findings show that the TyG index is an effective and cost-efficient method of assessing the risk of chronic diseases in people with MONW., (© 2024. The Author(s).)

Background & Aims: If alcohol-related liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are now the two main indications for liver transplantation (LT), it has been recognized that both conditions can coexist in varying degrees and the concept of dual-aetiology fatty liver disease (DAFLD) has been proposed. This retrospective study aimed to evaluate, in a cohort of patients transplanted for ALD and NAFLD, the prevalence of DAFLD before LT and the impact on liver graft outcome., Methods: From 1990 to 2010, all patients who underwent LT for the so-called ALD or NAFLD in our centre were included. Before LT, DAFLD was defined as patients with a history of excessive alcohol consumption and obesity associated with either diabetes or hypertension. Before LT, patients were separated into three groups: DAFLD, ALD, and NAFLD. Fatty liver graft disease was classified according to the FLIP algorithm., Results: Out of 907, adult LT recipients were identified: 33 DAFLD patients, 333 ALD patients, and 24 NAFLD patients. After LT, ALD patients experienced significantly more alcohol relapse than DAFLD patients, who had twice more post-LT metabolic syndrome. Out of 926, post-LT biopsies, DAFLD patients had significantly more fatty liver graft disease due to metabolic syndrome features than ALD patients., Conclusion: Our results support that DAFLD recently emerged as an indication of LT. In the future, this particular population needs to be identified as a specific entity since post-LT outcome on the graft is different from ALD and more similar to NAFLD patients., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Context: Male hypogonadism is associated with visceral obesity and the metabolic syndrome: factors important for the development of nonalcoholic fatty liver disease (NAFLD). The Testosterone Trials (The T Trials) showed testosterone (T) treatment compared with placebo in older hypogonadal men was associated with decreases in cholesterol and insulin levels suggesting that T treatment may improve NAFLD., Objective: Compare effects of T vs placebo treatment on NAFLD scores and liver scans in elderly hypogonadal men., Methods: Secondary data analyses from 479 older hypogonadal men with total T < 275 ng/dL from The T Trials were performed. Three clinical liver fat scores-lipid accumulation product index, hepatic steatosis index, nonalcoholic fatty liver disease-metabolic syndrome score-and liver computed tomography (CT) Hounsfield units and liver to spleen ratio were evaluated at baseline and 12 months after treatment., Results: There were no statistically significant differences of change in lipid accumulation product index (P = .98), hepatic steatosis index (P = .67), and nonalcoholic fatty liver disease-metabolic syndrome (P = .52) in 246 men treated with T compared with 233 treated with placebo for 12 months. Liver CT showed no statistically significant difference of change in Hounsfield units (P = .24; n = 71 for T, n = 69 for placebo) and liver to spleen ratio (P = .74; n = 55 for T, n = 62 for placebo) between the 2 groups., Conclusions: Our study did not show improvement of NAFLD in older hypogonadal men after 12 months of T vs placebo treatment, as assessed by 3 clinical scores and liver CT for hepatic steatosis. Future studies with longer treatment duration and additional NAFLD diagnostic modalities as primary outcome are warranted., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The article analyzes the results of a set of biochemical indicators in the course of treatment with the combined use of rosuvastatin with quercetin in patients with metabolic syndrome (MS) combined with non-alcoholic fatty liver disease. Changes in blood biochemical parameters have been identified and presented with MS, essential for revealing generalbiological mechanisms development and interrelationship between the components of MS and non-alcoholic fatty liver. The effect of an increase in free cholesterol and triglycerides and activation of freeradical oxidation of lipids followed by theaccumulation of oxidative stress products was noted. In the course of long-term hypolipidemic therapy (90 days), 86 patients with non-alcoholic fatty liver disease on the background of metabolic syndrome were previously divided into 2 groups: a comparison group (45 patients), who weretreated with basic therapy - only rosuvastatin, the main group (41 patients) received quercetin together with rosuvastatin -40 mg 3 times a day, clinical and laboratory-instrumental examinations were carried out. On the 90th day of treatment, positive results in the functional state of the liver and lipid spectrum of the blood wereregistered in all patients. A more significant advantage of the therapeutic combination of rosuvastatin with quercetin was proved. The inclusion of quercetin contributed to reducing the intensity of oxidative stress and enhancing antioxidant protection activity, resultingin a decrease in apoptosis of hepatocytes (cytokeratin-18 level was 1.27 times decreased). The studies have shown the feasibility of combined use of quercetin with rosuvastatin for the prevention of the development and progression of metabolic disorders associated with non-alcoholic fatty liver disease.

Background: The aim of the present study was to evaluate: 1) the presence of liver steatosis using Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI) and Liver Fat Score (LFS) in patients suffering from metabolic syndrome (MS); and 2) the association of FLI, HSI and LFS with the cardiometabolic risks., Methods: A total of 91 patients with MS (39 men, 52 women) and 44-age matched healthy subjects (control; 23 men and 21 women) were enrolled in the study. A continuous cardiometabolic score (MetsScore) and the noninvasive tests of hepatic steatosis were calculated for comparison and association analysis., Results: Liver steatosis was detected in 86%, 84% and 80% of people diagnosed with MS using FLI, HSI and LFS respectively and MetsScore increases with FLI severity (P<0.05). Also, FLI and LFS were positively associated with MetsScore (P<0.01 and P<0.05 respectively) but not HSI. Multivariate linear regression models revealed that FLI has a stronger association with MetsScore compared with HSI and LFS (P<0.001)., Conclusions: FLI is associated with the severity of MS and represent a good indicator to assess the relation between liver steatosis and a cardiometabolic disorders in clinical routine.

Nonalcoholic fatty liver disease (NAFLD) and alcohol-related liver disease (ALD) are the leading causes of chronic liver disease worldwide. NAFLD and ALD share pathophysiological, histological and genetic features and both alcohol and metabolic dysfunction coexist as aetiological factors in many patients with hepatic steatosis. A diagnosis of NAFLD requires the exclusion of significant alcohol consumption and other causes of liver disease. However, data suggest that significant alcohol consumption is often under-reported in patients classified as having NAFLD and that alcohol and metabolic factors interact to exacerbate the progression of liver disease. In this Review, we analyse existing data on the interaction between alcohol consumption and metabolic syndrome as well as the overlapping features and differences in the pathogenesis of ALD and NAFLD. We also discuss the clinical implications of the coexistence of alcohol consumption, of any degree, in patients with evidence of metabolic derangement as well as the use of alcohol biomarkers to detect alcohol intake. Finally, we summarize the evolving nomenclature of fatty liver disease and describe a recent proposal to classify patients at the intersection of NAFLD and ALD. We propose that, regardless of the presumed aetiology, patients with fatty liver disease should be evaluated for both metabolic syndrome and alcohol consumption to enable better prognostication and a personalized medicine approach., (© 2023. Springer Nature Limited.)

Purpose of Review: The goal of this review is to summarize the recent literature linking HIV to metabolic dysfunction-associated steatotic liver disease (MASLD). This is a pressing issue due to the scale of the MASLD epidemic and the urgent need for preventive and therapeutic strategies for MASLD in PWH., Recent Findings: The prevalence of MASLD in PWH is higher than previously appreciated, approaching 50% depending on the population and definition of MASLD. MASLD in PWH is likely multifactorial due to risk factors present in the general population such as metabolic syndrome, and features unique to HIV including systemic inflammation and ART. Statin therapy results in a significant reduction in major adverse cardiovascular events in PWH. PWH are at high risk for MASLD. Screening PWH with metabolic syndrome features could enable earlier interventions to reduce morbidity and mortality associated with MASLD in PWH., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as Nonalcoholic fatty liver disease (NAFLD), is one of the most common hepatic diseases in individuals with overweight or obesity. In this context, a panel of experts from three medical societies was organized to develop an evidence-based guideline on the screening, diagnosis, treatment, and follow-up of MASLD., Material and Methods: A MEDLINE search was performed to identify randomized clinical trials, meta-analyses, cohort studies, observational studies, and other relevant studies on NAFLD. In the absence of studies on a certain topic or when the quality of the study was not adequate, the opinion of experts was adopted. Classes of Recommendation and Levels of Evidence were determined using prespecified criteria., Results: Based on the literature review, 48 specific recommendations were elaborated, including 11 on screening and diagnosis, 9 on follow-up,14 on nonpharmacologic treatment, and 14 on pharmacologic and surgical treatment., Conclusion: A literature search allowed the development of evidence-based guidelines on the screening, diagnosis, treatment, and follow-up of MASLD in individuals with overweight or obesity.

Objective: The newly proposed Metabolic Visceral Fat Score (METS-VF) is considered a more effective measure for visceral adipose tissue (VAT) than other obesity indicators. This study aimed to reveal the association between METS-VF and non-alcoholic fatty liver disease (NAFLD), and its variations across age groups within both sexes., Methods: Data from 14,251 medical examiners in the NAGALA project were employed in this study. 3D fitted surface plots were constructed based on multivariate logistic regression models to visualize the isolated and combined effects of aging and METS-VF on NAFLD. Receiver operating characteristic curve (ROC) analysis was conducted to compare the diagnostic performance of METS-VF with other VAT surrogate markers in predicting NAFLD., Results: The results of multivariate logistic regression analysis showed that each unit increase in METS-VF was independently associated with a 333% and 312% increase in the odds of NAFLD in males and females, respectively. Additionally, the 3D fitted surface plot showed that age significantly influenced the association between METS-VF and the odds of NAFLD in both sexes, as follows: (i) In males, when METS-VF was less than 6.2, the METS-VF-related odds of NAFLD increased gradually with age in the 20-45 age group, reached a plateau in the 45-65 age group, and then decreased in the group above 65 years old; however, when male METS-VF exceeded 6.2, aging and METS-VF combined to further increase the odds of NAFLD in all age groups, particularly in the 45-65 age group. (ii) In females, aging seemed to reduce METS-VF-related odds of NAFLD in the 18-40 age group, but significantly increased it in the 40-60 age group, particularly for those with higher METS-VF levels. Further ROC analysis revealed that compared to other VAT surrogate markers, METS-VF showed the highest diagnostic accuracy for NAFLD in females, especially in those under 45 years of age [area under the curve (AUC) = 0.9256]., Conclusions: This study firstly revealed a significant positive correlation between METS-VF and the odds of NAFLD, with METS-VF surpassing other VAT surrogate markers in NAFLD diagnosis. Moreover, age significantly influenced the METS-VF-related odds of NAFLD and METS-VF's diagnostic efficacy for NAFLD in both sexes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kuang, Qiu, Li, Hu, Zhang, Sheng and Zou.)

Background: Hepatic steatosis, including nonalcoholic fatty liver disease (NAFLD), is common among people with HIV (PWH). We present baseline steatosis prevalence and cardiometabolic characteristics among REPRIEVE substudy participants., Methods: REPRIEVE is an international, primary cardiovascular disease prevention, randomized, controlled trial of pitavastatin calcium vs. placebo among 7769 PWH ages 40-75 years on antiretroviral therapy (ART) and with low-to-moderate cardiovascular risk. A subset of participants underwent noncontrast computed tomography, with hepatic steatosis defined as mean hepatic attenuation less than 40 HU or liver/spleen ratio less than 1.0, and NAFLD defined as steatosis in the absence of frequent alcohol use or viral hepatitis., Results: Of 687 evaluable persons, median age was 51 years, BMI 27 kg/m 2 , CD4 + T-cell count 607 cells/μl; 17% natal female sex, 36% Black, 24% Hispanic, and 98% HIV-1 RNA less than 400 copies/ml. Hepatic steatosis prevalence was 22% (149/687), and NAFLD 21% (96/466). Steatosis/NAFLD prevalence was higher in men and with older age, non-Black race, and higher BMI and waist circumference. Both were associated with BMI greater than 30 kg/m 2 , metabolic syndrome components, higher atherosclerotic cardiovascular disease (ASCVD) risk score, HOMA-IR, LpPLA-2 and hs-CRP, and lower high-density lipoprotein cholesterol. Of HIV-specific/ART-specific characteristics, only history of an AIDS-defining illness was more common among persons with steatosis/NAFLD. After adjusting for age, sex and race/ethnicity, BMI greater than 30 kg/m 2 , HOMA-IR greater than 2.0, Metabolic syndrome and each of its components were associated with NAFLD prevalence., Conclusion: In this cohort with controlled HIV and low-to-moderate cardiovascular risk, hepatic steatosis and NAFLD were common and associated with clinically relevant metabolic and inflammatory disturbances but not current HIV-related or ART-related factors., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The prevalence of nonalcoholic fatty liver disease (NASH) and cryptogenic cirrhosis (CC) is constantly increasing in adolescents and young adults (AYAs)., Methods: In a retrospective UNOS database evaluation, we analyzed postoperative outcomes of AYAs with nonalcoholic NASH/CC undergoing LT between January 1 st , 2003 and March 5 th , 2021. After exclusions, 85,970 LT recipients, 393 (47.1%) AYAs with NASH/CC and 441 (52.9%) AYAs with other metabolic conditions, were analyzed., Results: During the study period, the number of LTs performed for AYAs with NASH/CC increased from 4%-7% but decreased from 6.6%-5.3% compared to LTs performed for NASH/CC in all ages. In comparison to AYAs with other metabolic conditions, AYA LT recipients with NASH/CC had a higher prevalence of metabolic syndrome (MetS) components, including diabetes and increased body mass index (P < .0001 for both). Patient and graft survival in AYAs with NASH/CC were significantly lower in comparison to AYAs transplanted for other metabolic conditions (P < .0001) (Hazard Ratio = 1.93, P < .001). Patient survival in AYAs with NASH/CC was significantly better in comparison to older (40-65-year-old) patients with the same diagnosis (P = .01)., Conclusions: Our study found that the overall number of LTs in AYAs with NASH increased significantly, but to a lesser degree compared to the older population with the same diagnosis. Outcomes after LT in AYAs with NASH/CC were worse compared to LT for other metabolic conditions, but significantly better in comparison to older patients. The prevalence of LT for NASH/CC in AYAs is growing. MetS may contribute to worse outcomes in AYAs., Competing Interests: Declaration of Competing Interest This research was supported by a grant from the Department of Anesthesiology and Perioperative Medicine, Penn State Hershey Medical Center. Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number K23DK131290 (Dr Sine). This grant was not used for the financial support of this study but has to be mentioned by all publication related to this author., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Exposure to high maternal adiposity in utero is a significant risk factor for the later-life development of metabolic syndrome (MetS), including non-alcoholic fatty liver disease (NAFLD). We have previously shown that high pre-pregnancy adiposity programs adipose tissue dysfunction in the offspring, leading to spillover of fatty acids into the circulation, a key pathogenic event in obesity-associated MetS. Herein, we hypothesized that programming of adipose tissue dysfunction in offspring born to overweight dams increases the risk for developing NAFLD., Results: Females heterozygous for leptin receptor deficiency (Hetdb) were used as a model of high pre-pregnancy adiposity. Female wild-type (Wt) offspring born to Hetdb pregnancies gained significantly more body fat following high-fat/fructose diet (HFFD) compared with Wt offspring born to Wt dams. HFFD increased circulating free fatty acids (FFA) in male offspring of control dams, while FFA levels were similar in HFFD-fed offspring from Wt dams and CD or HFFD-fed Wt offspring from Hetdb dams. Despite female-specific protection from diet-induced FFA spillover, both male and female offspring from Hetdb dams were more susceptible to diet-induced hepatosteatosis. Lipidomic analysis revealed that CD-offspring of overweight dams had decreased hepatic polyunsaturated FA (PUFA) levels compared with control offspring. Changes to saturated FA (SFA) and the de novo lipogenic (DNL) index were diet driven; however, there was a significant effect of the intrauterine environment on FA elongation and Δ9 desaturase activity., Conclusion: High maternal adiposity during pregnancy programs a susceptibility to diet-induced hepatosteatosis., (© 2023 The Author(s).)

Obesity in adolescence is associated with significant morbidity and predisposes adolescents to the development of cardiovascular disease (CVD). Although a number of traditional CVD risk factors have been identified in youth, limited data exist regarding non-traditional CVD risk factors. In 89 adolescents with metabolic syndrome (MetS), with 60 age-, gender-, and BMI-matched controls, we determined the non-traditional CVD risk factors (hs-CRP, TG/HDL ratio, ApoB/ApoA1 ratio, NAFLD) in order to investigate whether they may be used as biomarkers for predicting future CVD, and we evaluated their response to the implementation of a multidisciplinary, personalized, lifestyle intervention program for 1 year. We demonstrated that the TG/HDL ratio, IL-2, IL-6, IL-17A, and INF-γ were significantly increased in subjects with MetS than in controls, and may be used as biomarkers to predict future CVD. Subjects with MetS had an increased mean carotid intima-media thickness (cIMT) and prevalence of NAFLD than the controls, while the prevalence of NAFLD correlated strongly with cIMT and IL-6 concentrations. Most of the non-traditional cardiovascular risk factors improved following the implementation of a lifestyle intervention program. These findings indicate that adolescents with MetS may have a greater risk for developing atherosclerosis early in life, while early lifestyle intervention is crucial for preventing the arteriosclerotic process in youth.

Purpose of Review: Acute coronary syndrome (ACS) and non-alcoholic fatty liver disease (NAFLD) are two clinically common disease entities that share numerous risk factors. This review aimed to discuss the impacts of NAFLD on ACS., Recent Findings: In an era of improved control of traditional risk factors, the substantial burden of cardiometabolic abnormalities has caused widespread concern. NAFLD is considered the hepatic component of metabolic syndrome, which can exert an impact on human health beyond the liver. Accumulating studies have demonstrated that NAFLD is closely related to cardiovascular disease, especially coronary artery disease. Interestingly, although recent data have suggested an association between NAFLD and the incidence and outcomes of ACS, the results are not consistent. In this review, we comprehensively summarized evidence and controversies regarding whether NAFLD is a contributor to either the development of ACS or worse outcomes in patients with ACS. The potential pathophysiological and molecular mechanisms involved in the impacts of NAFLD on ACS were also elucidated., (© 2023. The Author(s).)

Background and Aims: Antibiotics affect the gut microbiome. Preclinical studies suggest a role of gut dysbiosis in the development of nonalcoholic fatty liver disease (NAFLD), but data from large cohorts with liver histology are lacking., Methods: In this nationwide case-control study, Swedish adults with histologically confirmed early-stage NAFLD (total n = 2584; simple steatosis n = 1435; steatohepatitis (NASH) n = 383; non-cirrhotic fibrosis n = 766) diagnosed January 2007-April 2017 were included and matched to ≤5 population controls (n = 12 646) for age, sex, calendar year and county of residence. Data for cumulative antibiotic dispensations and defined daily doses were accrued until 1 year before the matching date. Using conditional logistic regression, multivariable-adjusted odds ratios (aORs) were calculated. In a secondary analysis, NAFLD patients were compared with their full siblings (n = 2837)., Results: Previous antibiotic use was seen in 1748 (68%) NAFLD patients versus 7001 (55%) controls, corresponding to 1.35-fold increased odds of NAFLD (95% CI = 1.21-1.51) in a dose-dependent manner (p for trend  < .001). Estimates were comparable for all histologic stages (p > .05). The highest risk of NAFLD was observed after treatment with fluoroquinolones (aOR 1.38; 95% CI = 1.17-1.59). Associations remained robust when patients were compared with their full siblings (aOR 1.29; 95% CI = 1.08-1.55). Antibiotic treatment was only linked to NAFLD in patients without metabolic syndrome (aOR 1.63; 95% CI = 1.35-1.91) but not in those with metabolic syndrome (aOR 1.09; 95% CI = 0.88-1.30)., Conclusions: Antibiotic use may be a risk factor for incident NAFLD, especially in individuals without the metabolic syndrome. The risk was highest for fluoroquinolones and remained robust in sibling comparisons with whom individuals share genetic and early environmental susceptibilities., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background and Aims: Previous literature suggests an association between non-alcoholic fatty liver disease (NAFLD) and infections. We aimed to determine the rate and risk of severe infections in NAFLD compared to the general population., Methods: In this population-based cohort study, we used national registers to identify all patients with a hospital-based diagnosis of NAFLD in Sweden 1987-2020 (n = 14 869). The patients were matched with ≤10 comparators from the general population for age, sex, municipality, and calendar year (n = 137 145). Cox regression was used to estimate hazard ratios (HR) for infections in patients with NAFLD compared to comparators. Cumulative incidences were calculated while accounting for competing risks (non-infection death and liver transplantation)., Results: Severe infections leading to death or hospitalization occurred in 1990 (13.4%) patients with NAFLD and 9899 (7.2%) comparators during a median of 4.5 and 6.1 years of follow-up, respectively. The rate of severe infections per 1000 person-years was higher in patients with NAFLD (21.0) than comparators (9.1) independently of components related to the metabolic syndrome (adjusted HR 1.9, 95% CI = 1.8-2.0). Infection-related mortality was also higher in NAFLD compared to comparators (adjusted HR 1.8, 95% CI = 1.6-2.2). The 10-year cumulative incidence of severe infections was 16.6% (95% CI = 15.8-17.4) in NAFLD and 8.0% (95% CI = 7.8-8.2) in comparators., Conclusion: NAFLD was associated with severe infections and infection-related mortality, independently of components associated with the metabolic syndrome. Increased clinical vigilance of severe infections in NAFLD may diminish the risk of premature death., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Purpose of Review: The aim of this review was to provide an overview of the role of novel biomarkers in metabolic syndrome, their association with cardiovascular risk and the impact of bariatric surgery on these biomarkers., Recent Findings: Metabolic syndrome encompasses an intricate network of health problems, and its constituents extend beyond the components of its operational definition. Obesity-related dyslipidaemia not only leads to quantitative changes in lipoprotein concentration but also alteration in qualitative composition of various lipoprotein subfractions, including HDL particles, rendering them proatherogenic. This is compounded by the concurrent existence of obstructive sleep apnoea (OSA) and nonalcoholic fatty liver disease (NAFLD), which pave the common pathway to inflammation and oxidative stress culminating in heightened atherosclerotic cardiovascular disease (ASCVD) risk. Bariatric surgery is an exceptional modality to reverse both conventional and less recognised aspects of metabolic syndrome. It reduces the burden of atherosclerosis by ameliorating the impact of obesity and its related complications (OSA, NAFLD) on quantitative and qualitative composition of lipoproteins, ultimately improving endothelial function and cardiovascular morbidity and mortality., Summary: Several novel biomarkers, which are not traditionally considered as components of metabolic syndrome play a crucial role in determining ASCVD risk in metabolic syndrome. Due to their independent association with ASCVD, it is imperative that these are addressed. Bariatric surgery is a widely recognized intervention to improve the conventional risk factors associated with metabolic syndrome; however, it also serves as an effective treatment to optimize novel biomarkers., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Metabolic syndrome (MetS), prediabetes (PreDM) and Fatty Liver Disease (FLD) share pathophysiological pathways concerning type 2 diabetes mellitus (T2DM) onset. The non-invasive assessment of fatty liver combined with PreDM and MetS features screening might provide further accuracy in predicting hyperglycemic status in the clinical setting with the putative description of singular phenotypes. The objective of the study is to evaluate and describe the links of a widely available FLD surrogate -the non-invasive serological biomarker Hepatic Steatosis Index (HSI)- with previously described T2DM risk predictors, such as preDM and MetS in forecasting T2DM onset., Patients and Methods: A retrospective ancillary cohort study was performed on 2799 patients recruited in the Vascular-Metabolic CUN cohort. The main outcome was the incidence of T2DM according to ADA criteria. MetS and PreDM were defined according to ATP III and ADA criteria, respectively. Hepatic steatosis index (HSI) with standardized thresholds was used to discriminate patients with FLD, which was referred as estimated FLD (eFLD)., Results: MetS and PreDM were more common in patients with eFLD as compared to those with an HSI < 36 points (35% vs 8% and 34% vs. 18%, respectively). Interestingly, eFLD showed clinical effect modification with MetS and PreDM in the prediction of T2DM [eFLD-MetS interaction HR = 4.48 (3.37-5.97) and eFLD-PreDM interaction HR = 6.34 (4.67-8.62)]. These findings supported the description of 5 different liver status-linked phenotypes with increasing risk of T2DM: Control group (1,5% of T2DM incidence), eFLD patients (4,4% of T2DM incidence), eFLD and MetS patients (10,6% of T2DM incidence), PreDM patients (11,1% of T2DM incidence) and eFLD and PreDM patients (28,2% of T2DM incidence). These phenotypes provided independent capacity of prediction of T2DM incidence after adjustment for age, sex, tobacco and alcohol consumption, obesity and number of SMet features with a c-Harrell=0.84., Conclusion: Estimated Fatty Liver Disease using HSI criteria (eFLD) interplay with MetS features and PreDM might help to discriminate patient risk of T2DM in the clinical setting through the description of independent metabolic risk phenotypes. [Correction added on 15 June 2023, after first online publication: The abstract section was updated in this current version.]., (© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed to replace non-alcoholic fatty liver disease and focus on patients with progressive disease due to the presence of metabolic dysfunction. However, it is unclear whether the new definition actually identifies patients with hepatic steatosis at increased cardiovascular risk., Methods: A total of 4,286 asymptomatic subjects from the SAKKOPI study aged 45-80 years undergoing screening colonoscopy were analyzed. Steatosis was diagnosed by abdominal ultrasound. MASLD was diagnosed according to the recent expert consensus. Insulin resistance was assessed by homeostasis model assessment-insulin resistance score (HOMA-IR) (cutoff: ≥2.5), subclinical inflammation was estimated by ferritin/CRP/uric acid, and cardiovascular risk was assessed using SCORE2/ASCVD., Results: Mean age was 59.4 ± 8.5 years, 51.6% were male; mean BMI was 27.0 ± 4.5 kg/m², 9.2% had type 2 diabetes mellitus. In total, 1,903 (44.4%) were diagnosed with hepatic steatosis and were characterized by more severe metabolic dysfunction including insulin resistance (47.1% vs. 12.2%, p < 0.001) and central obesity (waist circumference ≥102/88 cm, 71.8% vs. 37.1%, p < 0.001). This translated into higher (subclinical) inflammation (ferritin 153 vs. 95 mg/dL, p < 0.001, uric acid 6.3 mg/dL vs. 5.2 mg/dL, p < 0.001) and 10-year cardiovascular risk (SCORE2 7.8 points vs. 5.1 points, p < 0.001, ASCVD 17.9 points vs. 10.8 points, p < 0.001). 99.0% of subjects with steatosis met the MASLD definition, 95.4% met the MAFLD definition, and 53.6% met the definition of metabolic syndrome, while 95.4% of subjects without steatosis also met the MASLD criteria for metabolic dysfunction compared to 69.0% and 17.4% who met the MAFLD and metabolic syndrome criteria, respectively. Forward stepwise regression indicated that waist circumference, HOMA-IR, and triglycerides were most relevant in explaining the presence of hepatic steatosis across all subgroups of increasing metabolic dysfunction. At the same time, hepatic steatosis was not associated with cardiovascular risk in the overall cohort (SCORE2: B = 0.060, 95% CI: -0.193-0.314, and p = 0.642) and in patients with metabolic dysfunction after adjusting for age, sex, and these three metabolic dysfunction components., Conclusion: Although hepatic steatosis is associated with increased central obesity and insulin resistance, metabolic dysfunction per se rather than hepatic steatosis explains cardiovascular risk in these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Semmler, Balcar, Wernly, Völkerer, Semmler, Hauptmann, Wernly, Aigner, Niederseer and Datz.)

Nonalcoholic fatty liver disease (NAFLD) is closely associated with cardiometabolic abnormalities. This association could be partly influenced by weight, but not entirely. This study aimed to compare the cardiometabolic risk factors between obese and non-obese NAFLD patients, and explored the relationship between adiposity and severity of fatty liver. This cross-sectional study included 452 patients with Fibroscan-proven NAFLD. Anthropometric measurements, metabolic components and hepatic histological features were evaluated. The risk of metabolic syndrome in each body mass index (BMI) category was analyzed using logistic regression. The prevalence of metabolic syndrome was 10.2%, 27.7%, and 62.1% in normal-weight, overweight and obese participants. Regression analysis showed that the risk of metabolic syndrome in overweight and obese NAFLD patients was 3.74 and 4.85 times higher than in patients with normal weight, respectively. Waist circumference (β = 0.770, P < 0.001) and serum concentration of fasting blood glucose (β = 0.193, P = 0.002) and triglyceride (β = 0.432, P < 0.001) were the determinants of metabolic syndrome occurrence in NAFLD patients. Metabolic abnormalities were similar in obese and non-obese NAFLD patients, although, the increase in BMI was associated with an increased risk of metabolic syndrome in patients., (© 2023. Springer Nature Limited.)

Metabolic-associated fatty liver disease (MAFLD) is the hepatic manifestation of metabolic syndrome and affects about 55% of people living with diabetes. MAFLD has been shown to be an individual risk factor for cardiovascular disease and its associated mortality. Although common, MAFLD is often underdiagnosed and not given adequate attention during clinical visits. This review highlights the most recent literature available on the evaluation and management of MAFLD in the presence of diabetes. The more recently available antidiabetic agents including glucagon-like peptide-1 analogs and sodium-glucose cotransporter-2 inhibitors have been shown to effectively manage both diabetes and MAFLD., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Obesity is considered a twentieth-century epidemic and is a growing concern among health professionals. Obesity and its complications contribute to multiple chronic illnesses, such as type 2 diabetes (T2D), metabolic syndrome, obstructive sleep apnea (OSA), malignancy, and cardiovascular and liver diseases. In the last two decades, a bidirectional association between OSA and metabolic-associated fatty liver disease (MAFLD), independent of obesity, has been established. Both conditions have similar risk factors and metabolic comorbidities that may imply a common disease pathway. This review compiles the evidence and delineates the relationship between OSA and MAFLD from a clinical and diagnostic aspect., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Alcohol consumption (AC) and metabolic syndrome (MS) represent the first cause of liver disease, hepatocellular carcinoma and liver transplantation. The habit of consuming alcoholic beverages and the presence of MS and non-alcoholic fatty liver disease (NAFLD) often coexist in the same patient. The histoclinical boundaries between alcohol related liver disease (ALD) and NAFLD are often not well defined. The co-presence of AC and MS increases the risk of hepatic and extra-hepatic disease. The terminological evolution from NAFLD to metabolic associated fatty liver disease (MAFLD) is certainly a useful advance. However, it is known that the appearance of liver fibrosis increases oncologic and cardiovascular disease risk, which in the case of cirrhosis can be present even in the absence of steatosis and that the mechanisms of fibrogenesis can act independently of the presence of steatosis/steatohepatitis. For this reason, as already stated recently, a further terminological evolution can be hypothesized. This article was originally published with mistakes in the text. The new corrected citable version appears below.

Background: Nonalcoholic fatty liver disease (NAFLD) is a liver disorder commonly associated with metabolic syndrome and cardiovascular disease (CVD). Atherosclerosis, a leading cause of CVD, has been linked to liver fibrosis. However, the evidence regarding this association is conflicting., Aim: To evaluate the link between liver fibrosis and subclinical atherosclerosis in patients with NAFLD METHODS: We conducted a comprehensive search of four databases from 1950 to February 2023 to identify eligible studies investigating the association between liver fibrosis and subclinical atherosclerosis among patients with NAFLD, utilising the PICOS framework. Two independent reviewers screened the studies; quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis was performed using the DerSimonian-Liard random-effects model, and subgroup analysis was conducted based on the severity of liver fibrosis, type of subclinical atherosclerosis diagnosis and geographic region., Results: The meta-analysis included 12 studies with a total of 4725 patients. Overall pooled odds ratio (OR) for subclinical atherosclerosis was 2.18 (95% CI: 1.62-2.93), indicating a significant association with liver fibrosis in NAFLD. Subgroup analysis revealed higher ORs in patients with more severe fibrosis: 1.64 (95% CI: 1.22-2.20) in ≥F1, 2.22 (95% CI: 1.37-3.62) in ≥F2, and 3.42 (95% CI: 1.81-6.46) in ≥F3. However, there was no significant difference between the West versus East and various measurements of subclinical atherosclerosis., Conclusions: Any degree of fibrosis is significantly associated with subclinical atherosclerosis, with fibrosis severity amplifying the association., (© 2023 John Wiley & Sons Ltd.)

Non-alcoholic fatty liver disease (NAFLD)/ non-alcoholic steatohepatitis (NASH) is a rising epidemic with a potential for life threatening complications, especially in individuals with diabetes mellitus (DM) and metabolic syndrome. Though liver biopsy remains the recommended gold standard for diagnosing liver fibrosis, due to its technical feasibility and requirement of trained personnel, methods to develop non-invasive diagnostic tools for liver fibrosis have recently been underway. One such non-invasive method to diagnose liver fibrosis, point shear wave elastography using Acoustic Radiation Force Impulse (ARFI)-Imaging has gained remarkable results. This research was carried out to assess non-alcoholic steatohepatitis by acoustic radiation force impulse in individuals with diabetes and metabolic syndrome. Between March 2020 and October 2021, 140 patients with DM and metabolic syndrome, were identified. Demographic profile as well as reports of complete blood count, liver function tests, renal function tests, serum lipid profile, fasting blood sugar and postprandial blood sugar of the study participants were collected and recorded. Point shear wave liver elastography using ARFI imaging was performed for each of the study participant. NAFLD fibrosis score was determined in all of the study participants using appropriate software. Continuous and categorical variables were expressed as mean ± standard deviation and percentages respectively. Two-sided p values were considered as statistically significant at p value <0.05. Chi square test was done to see the association of clinical symptoms with fibrosis or non fibrosis. Independent t test was done to compare test variables and lab parameters between fibrosis and no fibrosis. Among the 140 study participants, 83 were males (59.29%) and 57 were (40.71%) females. On analysing the mean velocities measured by using ARFI elastography,30 participants (21.43%) had mean velocities >2.2m/s suggesting the presence of liver fibrosis and 110(78.57%) participants had mean velocities <2.2m/s did not have fibrosis. Among 83 males, 20(24.1%) had fibrosis and among 57 females, 10(17.5%) had fibrosis (p>0.05). Mean age of the 'Fibrosis' group was 54.53 (SD12.42) and that of the 'No fibrosis' group was 56.20(SD 11.76). Majority of the participants were between 56 and 65 years of age (50 participants). The mean height, weight and BMI of the 'Fibrosis' group was 152.84(±41.29), 73.33(±8.41), and 27.37(±2.73) respectively and that of the 'No fibrosis' group was 157.31(26.47), 70.89(12.46) and, 27.10(4.22) respectively (p>0.05). In the 'Fibrosis' group, majority (60%) were in the Obese 1 group and in the 'No fibrosis' group as well, majority were in the Obese 1 group (47.3%) (p=0.286). The mean (±SD) NAFLD- fibrosis Score was -1.54±1.06 in the 'No fibrosis' group and -0.61±1.81 in the 'Fibrosis' group (p value=0.012). There was no significant difference between fasting blood sugar, postprandial blood sugar, triglyceride and HbA1c levels among the 'Fibrosis' and 'No Fibrosis' groups. Among the 2 groups, there was no statistically significant difference between waist circumference, presence of hypertension, dyslipidaemia or other co-morbidities, in our study. None of the 30 individuals in the 'Fibrosis' group were on insulin (p=0.032), showing a significant difference in insulin usage among the 2 groups. There were significantly higher mean values of NAFLD-Fibrosis score in the individuals with fibrosis as compared to those with no fibrosis (p<0.05). NAFLD, diabetes mellitus and metabolic syndrome are part of the same spectrum. Individuals with diabetes mellitus and metabolic syndrome have a higher risk of developing liver fibrosis. Though in our study, parameters such as age, gender, hypertension, deranged blood sugars and lipid profile values were not significantly associated with liver fibrosis, NAFLD fibrosis score was found to have a significant association with liver fibrosis in these individuals.

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disorders ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Hepatic steatosis may result from the dysfunction of multiple pathways and thus multiple molecular triggers involved in the disease have been described. The development of NASH entails the activation of inflammatory and fibrotic processes. Furthermore, NAFLD is also strongly associated with several extra-hepatic comorbidities, i.e., metabolic syndrome, type 2 diabetes mellitus, obesity, hypertension, cardiovascular disease and chronic kidney disease. Due to the heterogeneity of NAFLD presentations and the multifactorial etiology of the disease, clinical trials for NAFLD treatment are testing a wide range of interventions and drugs, with little success. Here, we propose a narrative review of the different phenotypic characteristics of NAFLD patients, whose disease may be triggered by different agents and driven along different pathophysiological pathways. Thus, correct phenotyping of NAFLD patients and personalized treatment is an innovative therapeutic approach that may lead to better therapeutic outcomes.