bims-fatlid Biomed News
on Fatty liver disease
Issue of 2024–11–17
thirty papers selected by
Saqib Mahmood



  1. Curr Diab Rep. 2024 Nov 13. 25(1): 5
       PURPOSE OF REVIEW: Provide a concise update on metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), as well as a practical approach to screening and initial evaluation.
    RECENT FINDINGS: Nomenclature changes have placed a greater focus on cardiometabolic risk factors in the definition of MASLD. Screening for MASLD is by stepwise noninvasive serum and imaging tests which can identify patients at risk for advanced fibrosis and liver-related complications. MASLD has been increasing in prevalence and disease burden but is underrecognized in primary care and endocrinology clinics. Multiple society guidelines, synthesized here, provide a framework for the initial approach in the diagnosis and evaluation of MASLD. Recent advances in pharmacologic treatment underline the importance of screening for patients who are at risk for advanced fibrosis as they are most likely to benefit from new drug classes, such as the liver-directed thyroid receptor agonist resmiterom.
    Keywords:  Metabolic dysfunction-associated steatotic liver disease; Non-invasive testing; Screening; Steatohepatitis; Steatosis; Type 2 diabetes
    DOI:  https://doi.org/10.1007/s11892-024-01558-y
  2. touchREV Endocrinol. 2024 Oct;20(2): 5-9
      Type 2 diabetes (T2D) and metabolic dysfunction-associated steatotic liver disease (MASLD) are both facets of the metabolic syndrome, associated with obesity and insulin resistance. MASLD, a term that replaces non-alcoholic fatty liver disease (NAFLD), occurs in up to 70% of people with T2D. Not only do T2D and MASLD commonly co-occur, but there is a synergistic, bidirectional relationship between these conditions, meaning that each affects the natural disease course of the other. As such, it is important for those caring for people with T2D to recognize the importance of this co-diagnosis. In this summary, we detail the synergistic relationship between T2D and MASLD, explain the current challenges in recognizing this common co-diagnosis and suggest practical approaches for those caring for people with T2D to improve the diagnosis and treatment of MASLD.
    Keywords:  Alcohol-related liver disease; cardiometabolic risk factors; liver cirrhosis; metabolic and alcoholic-related steatotic liver disease; metabolic dysfunction-associated steatohepatitis; metabolic dysfunction-associated steatotic liver disease; non-alcoholic fatty liver disease; non-alcoholic steatohepatitis; steatotic liver disease; type 2 diabetes
    DOI:  https://doi.org/10.17925/EE.2024.20.2.2
  3. J Clin Transl Hepatol. 2024 Nov 28. 12(11): 955-974
    Chinese Society of Hepatology, Chinese Medical Association
      With the rising epidemic of obesity, metabolic syndrome, and type 2 diabetes mellitus in China, metabolic dysfunction-associated non-alcoholic fatty liver disease has become the most prevalent chronic liver disease. This condition frequently occurs in Chinese patients with alcoholic liver disease and chronic hepatitis B. To address the impending public health crisis of non-alcoholic fatty liver disease and its underlying metabolic issues, the Chinese Society of Hepatology and the Chinese Medical Association convened a panel of clinical experts to revise and update the "Guideline of prevention and treatment of non-alcoholic fatty liver disease (2018, China)". The new edition, titled "Guideline for the prevention and treatment of metabolic dysfunction-associated fatty liver disease (Version 2024)", offers comprehensive recommendations on key clinical issues, including screening and monitoring, diagnosis and evaluation, treatment, and follow-up for metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatotic liver disease. Metabolic dysfunction-associated fatty liver disease is now the preferred English term and is used interchangeably with metabolic dysfunction-associated steatotic liver disease. Additionally, the guideline emphasizes the importance of multidisciplinary collaboration among hepatologists and other specialists to manage cardiometabolic disorders and liver disease effectively.
    Keywords:  Cardiovascular disease; Guideline; Management; Metabolic dysfunction-associated fatty liver disease; Metabolic dysfunction-associated steatotic liver disease; Non-alcoholic fatty liver disease; Type 2 diabetes mellitus
    DOI:  https://doi.org/10.14218/JCTH.2024.00311
  4. Front Public Health. 2024 ;12 1437432
       Background: Currently, there is a lack of global or even country/regional level data on adolescent non-alcoholic fatty liver disease (NAFLD) prevalence. However, an evidenced dose-dependent relationship exists between body mass index (BMI) and the risk of NAFLD. We aim to estimate the global and regional prevalence of adolescent NAFLD and related non-alcoholic steatohepatitis (NASH) based on BMI.
    Methods: Sigmoidal fitting curves were generated between BMI and the risk of NAFLD/NASH using the data extracted from the NHANES database. With global and regional BMI data from the NCD-RisC database, adolescent NAFLD/NASH prevalence was estimated at the international, regional, and country levels from 1975 to 2016. The prevalence of adolescent NAFLD/NASH from 2017 to 2030 was also forecasted.
    Results: The mean NAFLD prevalence was 15.31, and 12.68%, while the mean NASH prevalence was 2.50, and 2.47%, in boys, and girls aged 12-18, respectively. For both boys and girls, NAFLD/NASH prevalence increased with increasing BMI, and age. The global prevalence of adolescent NAFLD/NASH has gradually increased in the period from 1975 to 2016 and will maintain a similar trend between 2017 and 2030. High-income Western Countries had higher adolescent NAFLD/NASH whereas South Asia and Sub-Saharan Africa exhibited relatively lower adolescent NAFLD/NASH prevalence. The estimated annual percentage change (EAPC) of NAFLD prevalence in boys ranged from 0.72% (age 18) to 1.16% (age 12) while that in girls ranged from 0.69% (age 18) to 0.92% (age 12). EAPC of NASH prevalence in boys ranged from 1.65% (age 18) to 1.77% (age 12), and in girls from 1.48% (age 18) to 1.68% (age 12).
    Conclusion: The adolescent NAFLD/NASH prevalence increases year by year, and its burden varies significantly among different countries and regions. BMI is a precise predictor of NAFLD/NASH prevalence.
    Keywords:  body mass index; epidemiology; model simulation; non-alcoholic steatohepatitis; nonalcoholic fatty liver disease
    DOI:  https://doi.org/10.3389/fpubh.2024.1437432
  5. Heliyon. 2024 Nov 15. 10(21): e38848
       Background: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of liver-related morbidity and mortality. The diagnosis of non-alcoholic steatohepatitis (NASH) plays a crucial role in the management of NAFLD patients.
    Objective: The aim of our observational study was to build a machine learning model to identify NASH in NAFLD patients.
    Methods: The clinical characteristics of 259 NAFLD patients and their initial laboratory data (Cohort 1) were collected to train the model and carry out internal validation. We compared the models built by five machine learning algorithms and screened out the best models. Receiver operating characteristic (ROC) curves, sensitivity, specificity, and accuracy were used to evaluate the performance of the model. In addition, the NAFLD patients in Cohort 2 (n = 181) were externally verified.
    Results: We finally identified six independent risk factors for predicting NASH, including neutrophil percentage (NEU%), aspartate aminotransferase/alanine aminotransferase (AST/ALT), hematocrit (HCT), creatinine (CREA), uric acid (UA), and prealbumin (PA). The NASH-XGB6 model built using the XGBoost algorithm showed sufficient prediction accuracy, with ROC values of 0.95 (95 % CI, 0.91-0.98) and 0.90 (95 % CI, 0.88-0.93) in Cohort 1 and Cohort 2, respectively.
    Conclusions: NASH-XGB6 can serve as an effective tool for distinguishing NASH patients from NAFLD patients.
    Keywords:  Machine learning; NAFLD; NASH; Non-invasive tests (NITs)
    DOI:  https://doi.org/10.1016/j.heliyon.2024.e38848
  6. Sci Total Environ. 2024 Nov 13. pii: S0048-9697(24)07686-1. [Epub ahead of print] 177529
      Air pollution has been linked with non-alcoholic fatty liver disease (NAFLD), but the underlying mechanisms characterized by perturbations in the circulating proteome profile are largely unknown. Therefore, we included 51,357 participants from the UK Biobank with 2941 plasma proteins measured in blood samples collected between 2006 and 2010, measurements of annual fine particular matter <2.5 μm in diameter (PM2.5) and nitrogen dioxide (NO2), and follow-up data on NAFLD (743 incident cases occurred over a median follow-up of 13.6 years). Multiple linear regression was used to identify proteins associated with PM2.5 and NO2. Cox proportional hazards models were applied to assess associations of PM2.5 and NO2 and identified proteins with incident NAFLD. Mediation analyses were conducted to explore the mediation role of proteins in the associations between air pollution and incident NAFLD. After adjusting for selected covariates, PM2.5 (hazard ratio [HR] = 2.57, 95%CI:1.27, 5.21, per ln increase) and NO2 (HR = 1.43, 95%CI: 1.10, 1.84, per ln increase) were positively associated with incident NAFLD. We identified 138 proteins associated with PM2.5 (92 positively, 46 inversely, FDR <0.05) and 143 with NO2 (100 positively, 43 inversely). Of the proteins that were significantly associated with both PM2.5 and NO2, 93 (79 positively, 14 inversely) and 79 (69 positively, 10 inversely) were significantly associated with incident NAFLD. Furthermore, 84 PM2.5-associated proteins and 66 NO2-associated proteins significantly mediated the corresponding association between air pollutants and incident NAFLD, with the proportion of mediation effects ranging from 3.2 % to 27.3 % for PM2.5 and 2.6 % to 20.8 % for NO2, respectively. Of note, the majority of significant mediating proteins were enriched in pathways of cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptor. Our findings suggested that long-term exposure to PM2.5 and NO2 was associated with an increased risk of NAFLD partially by perturbating circulating proteins involved in pathways of inflammation and immunity responses.
    Keywords:  Air pollution; Mediation analysis; Non-alcoholic fatty liver disease (NAFLD); Protein biomarkers
    DOI:  https://doi.org/10.1016/j.scitotenv.2024.177529
  7. Int Breastfeed J. 2024 Nov 12. 19(1): 75
       BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), characterized by excess liver fat, is common in women with a history of gestational diabetes mellitus (GDM). While breastfeeding improves postpartum lipid levels, its impact on NAFLD in these women is not well studied. We aimed to investigate the relationship between the duration and intensity of breastfeeding and the amount of liver fat and prevalence of NAFLD in women with previous GDM at approximately 1 year postpartum.
    METHODS: This prospective cohort study was conducted at a university hospital in Bangkok, Thailand between November 2021 and February 2024. Overall, 130 women who had experienced GDM in their most recent pregnancy were followed up for 1 year postpartum. We collected data on breastfeeding practices and quantified liver fat using controlled attenuation parameters (CAPs) during transient elastography. NAFLD was defined as a CAP of ≥ 302 dB/m. Women were divided into three groups according to the duration and intensity of breastfeeding: group 1 (breastfeeding for < 6 months), group 2 (breastfeeding for ≥ 6 months and exclusive breastfeeding [EBF] for < 6 months), and group 3 (breastfeeding for ≥ 6 months and EBF for 6 months).
    RESULTS: Overall, 57 (43.8%), 26 (20.0%), and 47 (36.2%) participants were categorized into groups 1, 2, and 3, respectively. Group 3 had the lowest CAPs, followed by groups 2 and 1. The median values (interquartile ranges) of the CAPs were 219.0 (189.0-271.0) dB/m, 257.5 (205.3-317.3) dB/m, and 279.0 (191.5-324.0) dB/m for groups 3, 2, and 1, respectively (p = 0.034). NAFLD prevalence was significantly lower in group 3 compared to groups 2 and 1 (19.1% vs. 38.5% vs. 43.9%, respectively; p = 0.026). Multivariate analysis showed that breastfeeding for ≥ 6 months and EBF for 6 months reduced the risk of NAFLD, with an adjusted odds ratio of 0.34 (95% confidence interval 0.14, 0.95).
    CONCLUSIONS: Breastfeeding for ≥ 6 months, particularly EBF for the first 6 months, may offer a practical strategy to reduce the risk of NAFLD in women with prior GDM.
    TRIAL REGISTRATION: Thai Clinical Trials Registry: Registration no. TCTR20211027008. Date of registration: October 27, 2021. Date of initial participant enrollment: November 1, 2021.
    Keywords:  Breastfeeding; Fatty liver; Gestational diabetes mellitus; Hepatic steatosis; Lactation; Non-alcoholic fatty liver disease
    DOI:  https://doi.org/10.1186/s13006-024-00684-3
  8. Medicine (Baltimore). 2024 Nov 08. 103(45): e40378
      Alcoholic liver disease (ALD) is a spectrum of liver damage caused by chronic alcohol consumption. The disease progresses in stages, starting with simple fatty liver, progressing to alcoholic hepatitis and potentially leading to fibrosis and cirrhosis. The pathophysiology of ALD is complex and involves several cellular and molecular mechanisms. Recent research has highlighted the role of long non-coding RNAs (LncRNAs) as critical regulators in the development and progression of ALD. This article reviews the current understanding of LncRNAs in ALD, focusing on their functions in key pathological processes and their potential as diagnostic markers and therapeutic targets.
    DOI:  https://doi.org/10.1097/MD.0000000000040378
  9. Liver Int. 2024 Nov 14.
       BACKGROUND: Although metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with obesity, around 20% of individuals with hepatic steatosis may nonetheless have normal body mass index, a condition often referred to as lean nonalcoholic fatty liver disease (NAFLD). Under the new nomenclature and definition of MASLD, lean NAFLD can be further divided into lean MASLD (when there is one or more cardiometabolic risk factors) and cryptogenic steatotic liver disease (when there is no cardiometabolic risk factor).
    RESULTS: Current studies suggest that the at-risk PNPLA3 rs738409 variant is more common among individuals with lean NAFLD than their overweight and obese counterparts. However, even in this group, cardiometabolic risk factors are often required for the development of hepatic steatosis and liver injury. In the general population, PNPLA3 gene polymorphism is associated with an increased risk of MASLD, more severe liver histology (i.e., the presence of steatohepatitis and fibrosis) and future development of hepatocellular carcinoma and cirrhotic complications. Emerging data also suggest that individuals carrying the PNPLA3 GG genotype might have a greater reduction in hepatic steatosis and liver enzymes with lifestyle intervention and metabolic treatments, such as glucagon-like peptide-1 receptor agonists.
    CONCLUSION: Studies have not specifically examined the impact of PNPLA3 in lean individuals.
    Keywords:  MASLD; NAFLD; PNPLA3; obese
    DOI:  https://doi.org/10.1111/liv.16164
  10. Nutrients. 2024 Oct 29. pii: 3686. [Epub ahead of print]16(21):
       BACKGROUND/OBJECTIVES: Fatty acids are involved in some hepatic disorders. The proprotein convertase subtilisin kexin 9 (PCSK9) inhibits the uptake of low-density lipoproteins (LDLs), which contain lipids, into the liver and may thus be associated with nonalcoholic fatty liver disease (NAFLD), a cardiovascular disorder (CVD) risk. Statins reduce blood LDL-cholesterol (LDL-C) levels and CVD risk and can attenuate the development of NAFLD while increasing blood PCSK9 levels.
    METHODS: We investigated the correlation between PCSK9 and liver conditions in patients with familial hypercholesterolemia (FH), a CVD risk population with elevated blood LDL-C levels, under statin treatment. Blood tests for lipids, PCSK9, and liver function (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) were performed in patients with FH taking statins (n = 25, mean age = 57 years, 12% of males). The ALT:AST ratio was used as a marker of NAFLD risk.
    RESULTS: The mean LDL-C level was 3.38 mmol/L, and the median PCSK9 level was 312 ng/mL. The median ALT:AST ratio was 0.88. A significant negative correlation was observed between the PCSK9 and ALT:AST ratio (β = -0.67, p < 0.05).
    CONCLUSIONS: Their negative correlation might give a hypothetical insight into the effect of statin treatment on the development of NAFLD, in relation to PCSK9 behavior, in patients with FH.
    Keywords:  HMG-CoA reductase inhibitor; fatty acids; fatty liver disease; lipid-lowering therapy
    DOI:  https://doi.org/10.3390/nu16213686
  11. J Ultrasound. 2024 Nov 13.
       INTRODUCTION: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is the most prevalent chronic liver condition worldwide, affecting over 25% of the population. Fatty infiltration in MASLD leads to hemodynamic changes in hepatic circulation, which can be quantitatively assessed using Color Doppler Ultrasonography (US). In this study, we aimed to investigate the correlation of Color Doppler US findings of the portal, hepatic, and splenic venous system within various degrees of MASLD.
    METHODS AND MATERIALS: Between 2021 and 2024, 104 patients referred to Mousavi Hospital at Zanjan University of Medical Sciences were enrolled. Participants were divided into four groups based on the degree of hepatic fatty infiltration on biopsy results: normal, grade 1, grade 2, and grade 3, with 26 subjects in each group (13 men and 13 women). All patients were biopsy proved. Gray-scale and Color Doppler US were used to assess portal and splenic vein peak systolic velocity (PSV), portal and splenic vein diameter, hepatic vein waveform, and spleen size. The Spearman rank correlation was employed to evaluate the relationship between these variables under non-parametric conditions.
    RESULTS: A significant negative correlation was found between portal vein PSV and MASLD grade (r = - 0.499, p = 0.000). A significant difference was also observed in hepatic venous waveform abnormality between different grades of MASLD (p = 0.043). Accordingly, portal vein PSV and splenic vein PSV had a significantly positive correlation (r = 0.209, p = 0.033). We also observed a positive correlation between the portal vein and splenic diameter (r = 0.210, p = 0.032).
    CONCLUSION: Increasing MASLD severity is associated with reduced portal vein PSV and more pronounced abnormalities in hepatic vein flow. Routine assessment of portal and hepatic vein flow using Color Doppler US is recommended to accurately diagnose and monitor the effects of MASLD on hepatic circulation, potentially improving disease management and patient outcomes.
    Keywords:  Color Doppler ultrasonography; Hepatic vein; Metabolic dysfunction-associated steatotic liver disease (MASLD); Non-alcoholic fatty liver (NAFLD); Portal vein; Splenic vein
    DOI:  https://doi.org/10.1007/s40477-024-00965-x
  12. Saudi J Med Med Sci. 2024 Oct-Dec;12(4):12(4): 284-291
      Non-alcoholic fatty pancreatic disease (NAFPD), also known as pancreatic steatosis, is a benign condition characterized by deposition of lipids in the pancreas and is associated with insulin resistance, malnutrition, obesity, metabolic syndrome, aging, and absence of heavy alcohol intake or infection. Similar to nonalcoholic fatty liver disease, NAFPD is a phenotypic entity that includes fat buildup in the pancreas, pancreatic inflammation, and subsequent fibrosis. The extent to which pancreatic fat infiltration is clinically important remains unclear. Despite these clinical associations, most of the clinical effects of NAFPD are not known. NAFPD may be identified by transabdominal and elastography ultrasound, computed tomography scan, or magnetic resonance imaging modalities, but a confirmatory diagnosis can only be made through tissue histology. In addition to complications such as acute and chronic pancreatitis, NAFPD may progress to pancreatic ductal adenocarcinoma. However, further research is required to fully understand the associations, pathophysiology, and effects of NAFPD. This review provides a narrative synthesis of the current literature on the epidemiology, pathophysiology, complications, diagnostic and imaging tools, and management of NAFPD.
    Keywords:  Diagnosis; metabolic syndrome; nonalcoholic fatty pancreatic disease; obesity; pancreatic steatosis; pathophysiology
    DOI:  https://doi.org/10.4103/sjmms.sjmms_526_23
  13. Cancers (Basel). 2024 Nov 01. pii: 3703. [Epub ahead of print]16(21):
      Background: Humans cannot avoid plastic exposure due to its ubiquitous presence in the natural environment. The waste generated is poorly biodegradable and exists in the form of MPs, which can enter the human body primarily through the digestive tract, respiratory tract, or damaged skin and accumulate in various tissues by crossing biological membrane barriers. There is an increasing amount of research on the health effects of MPs. Most literature reports focus on the impact of plastics on the respiratory, digestive, reproductive, hormonal, nervous, and immune systems, as well as the metabolic effects of MPs accumulation leading to epidemics of obesity, diabetes, hypertension, and non-alcoholic fatty liver disease. MPs, as xenobiotics, undergo ADMET processes in the body, i.e., absorption, distribution, metabolism, and excretion, which are not fully understood. Of particular concern are the carcinogenic chemicals added to plastics during manufacturing or adsorbed from the environment, such as chlorinated paraffins, phthalates, phenols, and bisphenols, which can be released when absorbed by the body. The continuous increase in NMP exposure has accelerated during the SARS-CoV-2 pandemic when there was a need to use single-use plastic products in daily life. Therefore, there is an urgent need to diagnose problems related to the health effects of MP exposure and detection. Methods: We collected eligible publications mainly from PubMed published between 2017 and 2024. Results: In this review, we summarize the current knowledge on potential sources and routes of exposure, translocation pathways, identification methods, and carcinogenic potential confirmed by in vitro and in vivo studies. Additionally, we discuss the limitations of studies such as contamination during sample preparation and instrumental limitations constraints affecting imaging quality and MPs detection sensitivity. Conclusions: The assessment of MP content in samples should be performed according to the appropriate procedure and analytical technique to ensure Quality and Control (QA/QC). It was confirmed that MPs can be absorbed and accumulated in distant tissues, leading to an inflammatory response and initiation of signaling pathways responsible for malignant transformation.
    Keywords:  carcinogenesis; micro/nanoplastics; microplastic detection; microplastic exposure; microplastic pollution; microplastic toxicity
    DOI:  https://doi.org/10.3390/cancers16213703
  14. Am J Manag Care. 2024 Nov;30(9 Suppl): S159-S174
      Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by hepatic steatosis that is confirmed by imaging or histology in the setting of at least 1 metabolic risk factor in the absence of significant alcohol consumption. Nonalcoholic steatohepatitis, or NASH, was recently renamed metabolic dysfunction-associated steatohepatitis (MASH); it represents the progressive form of MASLD. MASH is defined by hepatic steatosis, lobular inflammation, and ballooning degeneration (hepatocellular injury) in a characteristic histologic pattern. Multiple pathophysiologic mechanisms underlie the development of MASLD, and multiple factors (eg, metabolic, hormonal, genetic, nutritional, and epigenetic components) are related to liver injury. MASH has a prevalence in the United States of 1% to 6%, and it is expected to rise in the next decade. Individuals living with MASH frequently suffer from comorbidities such as type 2 diabetes and cardiovascular disease. Several guidelines have been published to support the timely diagnosis of MASH that incorporate noninvasive tests that obviate the need for liver biopsy. Multiple MASH treatment options are in various stages of development. The THR-β agonist resmetirom, approved by FDA in March 2024, offers a liver-directed treatment for those patients living with moderate to severe fibrosis without cirrhosis. Considering the progressive nature of the disease and the availability of a treatment that can be initiated early to halt MASH progression, patients who have risk factors for MASH should urgently be encouraged to visit their health care providers for MASH screening.
    DOI:  https://doi.org/10.37765/ajmc.2024.89635
  15. Radiol Clin North Am. 2025 Jan;pii: S0033-8389(24)00100-3. [Epub ahead of print]63(1): 13-28
      Diffuse liver disease is a substantial world-wide problem. With the combination of conventional ultrasound of the abdomen, fat quantification and elastography, appropriate staging of the patient can be assessed. This information allows for the diagnosis of steatosis and detection of fibrosis as well as prognosis, surveillance, and prioritization for treatment. With the potential for reversibility with appropriate treatment accurate assessment for the stage of chronic liver disease is critical.
    Keywords:  Chronic liver disease; Fat quantification; Focal liver lesions; Liver; Liver steatosis; MASLD; NAFLD; Quantitative ultrasound
    DOI:  https://doi.org/10.1016/j.rcl.2024.07.003
  16. J Clin Transl Hepatol. 2024 Nov 28. 12(11): 939-948
      Bilirubin, the primary breakdown product of hemoproteins, particularly hemoglobin, plays a key role in the diagnosis, prognosis, and monitoring of liver diseases. In acute liver diseases, such as acute liver failure, drug-induced liver injury, and viral hepatitis, bilirubin serves as a biomarker reflecting the extent of hepatocyte loss and liver damage. Chronic liver diseases, including alcohol-related liver disease, chronic hepatitis C virus infection, metabolic dysfunction-associated fatty liver disease, and autoimmune liver diseases, are marked by persistent liver injury and inflammation. Bilirubin levels in chronic liver diseases provide insight into liver function, disease severity, and prognosis. As a versatile biomarker, bilirubin offers valuable information on the pathophysiology of liver diseases and aids in guiding clinical decision-making regarding the treatment of liver diseases and their complications. This review aimed to explore the multifunctional role of bilirubin in liver diseases by analyzing its biological functions beyond its role as a biomarker of liver damage.
    Keywords:  Acute-on-chronic liver failure; Bilirubin; Chronic liver failure; Hepatitis; Liver failure; Metabolic dysfunction-associated fatty liver disease
    DOI:  https://doi.org/10.14218/JCTH.2024.00156
  17. FASEB Bioadv. 2024 Nov;6(11): 477-502
      Behavioral and environmental risk factors are critical in the development and progression of cardiovascular disease (CVD). Understanding the molecular mechanisms underlying these risk factors will offer valuable insights for targeted preventive and therapeutic strategies. Epigenetic modifications, including DNA methylation, histone modifications, chromatin remodeling, noncoding RNA (ncRNA) expression, and epitranscriptomic modifications, have emerged as key mediators connecting behavioral and environmental risk factors to CVD risk and progression. These epigenetic alterations can profoundly impact on cardiovascular health and susceptibility to CVD by influencing cellular processes, development, and disease risk over an individual's lifetime and potentially across generations. This review examines how behavioral and environmental risk factors affect CVD risk and health outcomes through epigenetic regulation. We review the epigenetic effects of major behavioral risk factors (such as smoking, alcohol consumption, physical inactivity, unhealthy diet, and obesity) and environmental risk factors (including air and noise pollution) in the context of CVD pathogenesis. Additionally, we explore epigenetic biomarkers, considering their role as causal or surrogate indicators, and discuss epigenetic therapeutics targeting the mechanisms through which these risk factors contribute to CVD. We also address future research directions and challenges in leveraging epigenetic insights to reduce the burden of CVD related to behavioral and environmental factors and improve public health outcomes. This review aims to provide a comprehensive understanding of behavioral and environmental epigenetics in CVD and offer valuable strategies for therapeutic intervention.
    Keywords:  behavioral and environmental factors; biomarkers; cardiovascular disease; epigenetics; therapeutics
    DOI:  https://doi.org/10.1096/fba.2024-00080
  18. BJC Rep. 2024 May 03. 2(1): 39
       BACKGROUND: Current opinion holds that hepatocellular carcinoma (HCC) arises as a stepwise progression from chronic liver disease (CLD) to cirrhosis and then to HCC. However, some HCCs may develop in a non-cirrhotic liver, raising uncertainty about their origin.
    METHODS: We analysed a prospectively accrued cohort of 2592 CLD patients (median follow-up = 13 years) with no prior evidence of liver cirrhosis. To track the progression of liver fibrosis prior to HCC diagnosis, we examined serial measurements of Fib-4 (an index of liver fibrosis). We also evaluated fibrosis progression in response to antiviral treatment in patients with hepatitis C (HCV) and hepatitis B (HBV). Recognising the limitations of serologic fibrosis assessment, we correlated Fib-4 and fibrosis histology within this cohort.
    RESULTS: Among HCC patients, 28% had no indication of cirrhosis prior to HCC diagnosis. Only 31% of HBV-related HCC cases followed the cirrhotic pathway. HCV patients who achieved sustained virological response (SVR) developed cirrhosis approximately 7 years before HCC diagnosis.
    CONCLUSIONS: Our analysis challenges the notion of cirrhosis as an obligatory stage of HCC development in CLD patients. We affirm HBV's direct oncogenic potential and find that achieving SVR does not universally prevent HCC development. Our findings have major implications for HCC surveillance.
    DOI:  https://doi.org/10.1038/s44276-024-00050-0
  19. PLoS One. 2024 ;19(11): e0313185
      Metabolic associated fatty liver disease (MAFLD) is considered an indicator of metabolic syndrome, which affects millions of people around the world and no effective treatment is currently available. MAFLD involves a wide spectrum of liver damage, that initiates from steatosis (fatty live) and may progress to more complex pathophysiology. Then, details in lipid metabolism controlling should be explored aiming to control the fatty liver. In this context, the miR-1914-5p can be considered a potential biotechnology tool to control lipid metabolism in hepatic cells. This miRNA finds potential mRNA binding sequences in more than 100 molecules correlated with energy production and lipid metabolism pointed in bioinformatic platforms. The present study addressed the miR-1914-5p effects in hepatic HepG2/LX-2 co-cultured cells in a in vitro steatotic environment stablished by the addition of 400 μM of a mixture of oleic and palmitic acids. The analyses demonstrated that the inhibition of the miRNA reduced energetic metabolites such as total lipids, triglycerides, cholesterol and even glucose. In addition, the miR-inhibitor-transfected cells did not present any deleterious effect in cellular environment by controlling reactive oxygen species production (ROS), mitochondrial membrane potential (ΔΨm) and even the pro-inflammatory environment. Moreover, the functional effect of the investigated miR, suggested its close connection to the modulation of Sirt-1-PGC1-α pathway, a master switch metabolic route that controlls cellular energetic metabolism. Our assays also suggested a synergistic effect of this miR-1914-5p in cell metabolism, which should be considered as a strong candidate to control steatotic environment in future clinical trials.
    DOI:  https://doi.org/10.1371/journal.pone.0313185
  20. Methods Mol Biol. 2025 ;2866 265-286
      Massively parallel sequencing technologies have been a boon to many fields of biological science, including oncology. Cancer is an umbrella term for many diseases featuring abnormal cellular growth due to genetic and epigenetic aberrations. Advances in sequencing technology allow for interrogation of the DNA and RNA of cancer cells and other cells in the tumor microenvironment down to a single-base resolution. However, these strides come after a rich history of ground-breaking biological assays, like the discovery of the Philadelphia chromosome in the context of leukemia. Many specific genetic and epigenetic modifications have been implicated in oncogenesis, cancer progression, and response to treatment. Sequencing technologies have also helped to associate populations of bacteria in the microbiome to cancer development and prognosis. However, all this new information, especially when procured via high-throughput methods, comes at the cost of being more computationally and staff-resource intensive. There is also more risk to the privacy of the individuals with sequenced genomes. Notwithstanding, the overall benefit of sequencing technologies can greatly outweigh the risks with careful advancements and continued focus on the goal: helping those affected by cancer via precision medicine. Cancer biology has been and will continue to be elucidated by sequencing innovations in ways unimaginable without it.
    Keywords:  Cancer; Modern history; Next-generation sequencing; Oncogenesis; Technology
    DOI:  https://doi.org/10.1007/978-1-0716-4192-7_15
  21. Cureus. 2024 Oct;16(10): e71451
      Lean metabolic dysfunction-associated steatotic liver disease (MASLD) defies traditional views of fatty liver diseases by manifesting in nonobese individuals. The renaming from nonalcoholic fatty liver disease to MASLD underscores a broader understanding of its pathophysiology, highlighting the complex interplay of metabolic factors beyond obesity. Despite its clinical importance, diagnosing and managing lean MASLD remains challenging due to its historical ties to obesity and a general lack of awareness about its unique characteristics. On December 4, 2023, a systematic literature search was conducted across six databases, focusing on peer-reviewed studies in English related to the diagnosis and management of lean MASLD. This study was registered with the International Prospective Register of Systematic Reviews (CRD42023489308). Out of 95 studies following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 43 addressed diagnosis and surveillance, whereas 52 explored management strategies. The results revealed the difficulties in diagnosing lean MASLD, pointing out the limitations of traditional markers and the potential of advanced imaging techniques. Management strategies discussed included lifestyle changes and possible pharmacological treatments tailored to the specific metabolic features of this patient group. The study highlights the necessity for increased clinical awareness, regular monitoring, and personalized therapeutic approaches for lean MASLD. It calls for further research to refine diagnostic criteria and develop targeted treatments, aiming to enhance care for individuals with lean MASLD.
    Keywords:  diagnosis; lean masld; lean phenotype management; metabolic dysfunction-associated steatotic liver disease; nonobese fatty liver disease
    DOI:  https://doi.org/10.7759/cureus.71451
  22. BMC Nephrol. 2024 Nov 07. 25(1): 400
      Chronic kidney disease (CKD) is a complex disease that affects the global population's health, with dyslipidemia being one of its major complications. High density lipoprotein (HDL) is regarded as the "hero" in the bloodstream due to its role in reverse cholesterol transport, which lowers cholesterol levels in the blood and prevents atherosclerosis. However, in the complex internal environment of CKD, even this "hero" may struggle to perform its beneficial functions and could potentially become harmful. This article reviews HDL heterogeneity, HDL subclasses, functional changes in HDL during the progression of CKD, and the application of HDL in CKD treatment. This review aims to deepen understanding of lipid metabolism abnormalities in CKD patients and provide a basis for new therapeutic strategies.
    Keywords:  Chronic kidney disease; Dyslipidemia; High density lipoproteins; Subclasses
    DOI:  https://doi.org/10.1186/s12882-024-03808-3
  23. Life Sci. 2024 Nov 07. pii: S0024-3205(24)00811-7. [Epub ahead of print] 123221
      Fatty liver syndrome is often characterized by the appearance of several tiny cysts (fluid-filled sacs) in the ovaries. It is the most significant endocrinopathy affecting 8-13 % of women during their lifetime. Within the dynamic domain of women's health, this syndrome is a widespread issue that presents with an array of signs, including insulin resistance, hirsutism, androgen development, and menstrual flaws prompted by genetic, diet/lifestyle, gut microbiota dysbiosis, and environmental toxins. Impaired folliculogenesis, aberrant cortisol metabolism, and genes associated with steroidogenesis contribute to the pathophysiology of the disease. Moreover, it combines with various concurrent metabolic and idiopathic conditions specifically type 2 diabetes, heart disease, cancer, and infertility. On persuading the reproductive framework of women from ontogeny to menopause, the complexity of the syndrome hereditates generations due to maternal inheritance of hyperandrogenism. The advancement in diagnostic norms paved the way from the Rotterdam criteria to metabolomics, 3D ultrasound, and assisted reproductive technologies. The management and treatment of this hormonal disorder can be prevailed through lifestyle modifications and prompt medications. This review entails the aforementioned benchmarks of the syndrome's complexity and its ongoing research in alleviating its intricate behavioral changes in women from in-utero to menopause.
    Keywords:  Cancer; Endocrinopathy; Hyperandrogenism; Lifestyle; Steroidogenesis; Technologies
    DOI:  https://doi.org/10.1016/j.lfs.2024.123221
  24. Int J Mol Sci. 2024 Nov 02. pii: 11801. [Epub ahead of print]25(21):
      Tuberculosis caused by the obligate intracellular pathogen, Mycobacterium tuberculosis, is one among the prime causes of death worldwide. An urgent remedy against tuberculosis is of paramount importance in the current scenario. However, the complex nature of this appalling disease contributes to the limitations of existing medications. The quest for better treatment approaches is driving the research in the field of host epigenomics forward in context with tuberculosis. The interplay between various host epigenetic factors and the pathogen is under investigation. A comprehensive understanding of how Mycobacterium tuberculosis orchestrates such epigenetic factors and favors its survival within the host is in increasing demand. The modifications beneficial to the pathogen are reversible and possess the potential to be better targets for various therapeutic approaches. The mechanisms, including histone modifications, DNA methylation, and miRNA modification, are being explored for their impact on pathogenesis. In this article, we are deciphering the role of mycobacterial epigenetic regulators on various strategies like cytokine expression, macrophage polarization, autophagy, and apoptosis, along with a glimpse of the potential of host-directed therapies.
    Keywords:  apoptosis; autophagy; epigenetics; macrophage polarization; miRNA modification; tuberculosis
    DOI:  https://doi.org/10.3390/ijms252111801
  25. Semin Liver Dis. 2024 Nov 08.
      There continues to be an ongoing need for fair and equitable organ allocation. The Model for End-stage Liver Disease (MELD) score has evolved as a calculated framework to evaluate and allocate patients for liver transplantation objectively. The original MELD score has undergone multiple modifications as it is continuously scrutinized for its accuracy in objectively representing the clinical context of patients with liver disease. Several refinements and iterations of the score have been developed, including the widely accepted MELD-Na score. In addition, the most recent updated iteration, MELD 3.0, has been created. The MELD 3.0 calculator incorporates new variables such as patient sex and serum albumin levels and assigns new weights for serum sodium, bilirubin, international normalized ratio, and creatinine levels. It is anticipated that the use of MELD 3.0 scores will reduce overall waitlist mortality and enhance access for female liver transplant candidates. However, despite the emergence of the MELD score as one of the most objective measures for fair organ allocation, various countries and healthcare systems employ alternative methods for stratification and organ allocation. This review article highlights the origins of the MELD score, its iterations, the current MELD 3.0, and future directions for managing liver transplantation organ allocation.
    DOI:  https://doi.org/10.1055/a-2464-9543
  26. Int J Mol Sci. 2024 Oct 25. pii: 11460. [Epub ahead of print]25(21):
      Dilated cardiomyopathy (DCM) is characterized by reduced systolic function and cardiac dilation. Cases without an identified secondary cause are classified as idiopathic dilated cardiomyopathy (IDC). Over the last 35 years, many cases of IDC have increasingly been recognized to be genetic in etiology with a core set of definitively causal genes in up to 40% of cases. While over 200 genes have been associated with DCM, the evidence supporting pathogenicity for most remains limited. Further, rapid advances in sequencing and bioinformatics have recently revealed a complex genetic spectrum ranging from monogenic to polygenic in DCM. These advances have also led to the discovery of causal and modifier genetic variants in secondary forms of DCM (e.g., alcohol-induced cardiomyopathy). Current guidelines recommend genetic counseling and screening, as well as endorsing a handful of genotype-specific therapies (e.g., device placement in LMNA cardiomyopathy). The future of genetics in DCM will likely involve polygenic risk scores, direct-to-consumer testing, and pharmacogenetics, requiring providers to have a thorough understanding of this rapidly developing field. Herein we outline three decades of genetics in DCM, summarize recent advances, and project possible future avenues for the field.
    Keywords:  LMNA; TTN; alcohol-induced cardiomyopathy; arrhythmogenic cardiomyopathy; dilated cardiomyopathy; genetics; heart failure; left ventricular non-compaction; peripartum cardiomyopathy; polygenic risk score
    DOI:  https://doi.org/10.3390/ijms252111460
  27. Arch Cardiovasc Dis. 2024 Oct 10. pii: S1875-2136(24)00322-X. [Epub ahead of print]
      Cardiovascular disease is the leading cause of death worldwide, and the second leading cause in France. Among the modifiable cardiovascular risk factors, metabolic diseases (hypertension, low-density lipoprotein hypercholesterolaemia, diabetes and obesity) play a major role, contributing to the development and progression of atherosclerosis. This review summarizes the latest epidemiological data available at a national level. In 2015, the prevalence among adults aged 18-74years was 17.2% for obesity, 7.4% for diabetes, 30.6% for hypertension, 23.3% for low-density lipoprotein hypercholesterolaemia and 1.5% for stage 3-5 chronic kidney disease. Awareness of these diseases among affected individuals was very poor, ranging from 23% for diabetes to 45% for hypertension. While the prevalence of obesity and hypertension remained stable between 2006 and 2015, the prevalence of diabetes increased significantly. Prevention of these risk factors, particularly through nutrition, as well as awareness and management of them, must be intensified to reduce the burden of cardiovascular diseases in France. Whereas the prevalence of metabolic factors remains higher in men, particular attention should also be paid to risk factors specific to women, such as gynaecological diseases (endometriosis, polycystic ovary syndrome) and pregnancy disorders (hypertensive disorders in pregnancy, gestational diabetes), which contribute significantly to cardiovascular risk.
    Keywords:  Diabetes; Epidemiology; Hypertension; Low-density lipoprotein hypercholesterolaemia; Risk factors
    DOI:  https://doi.org/10.1016/j.acvd.2024.08.005
  28. SAGE Open Med. 2024 ;12 20503121241297000
      Alcohol-associated hepatitis is an extreme form of alcohol-related liver disease associated with high short-term mortality. Currently, there are no authorized therapies for the treatment of severe alcohol-associated hepatitis. Important diagnostic steps for alcohol-associated hepatitis include recognizing the presence of an alcohol use disorder, distinguishing alcohol-related liver disease from metabolic-dysfunction-associated steatotic liver disease, ruling out alternative causes of acute hepatitis, confirming the diagnosis with validated criteria or a liver biopsy, and using the model for end-stage liver disease score to predict clinical outcome and initiate therapy. Due to the lack of other effective therapy options, corticosteroids continue to be used as initial treatment for patients with severe alcohol-associated hepatitis. Patients who do not improve while on steroid treatment and are ideal candidates should be considered for curative liver transplantation as soon as possible. Avoiding unnecessary and ineffective pharmacological and interventional therapy can help to keep costs down. If a patient is not a good candidate for a transplant or is rapidly deteriorating in health due to a condition such as acute or chronic liver failure, a salvage/bridge to transplant should be pursued through enrolment in a clinical trial program. The role of healthy donor stool transplant and targeted bacteriophage therapy seems promising, pending prospective controlled trials.
    Keywords:  Alcoholic liver disease; cirrhosis; dysbiosis; gut microbiome; hepatitis; portal hypertension; stool transplant
    DOI:  https://doi.org/10.1177/20503121241297000
  29. Methodist Debakey Cardiovasc J. 2024 ;20(5): 47-58
      Air pollution, mostly from fossil fuel sources, is the leading environmental cause of global morbidity and mortality and is intricately linked to climate change. There is emerging evidence indicating that air pollution imposes most of its risk through proximate cardiovascular kidney and metabolic (CKM) etiologies. Indeed, there is compelling evidence linking air pollution to the genesis of insulin resistance, type 2 diabetes, hypertension, and other risk factors. Air pollution frequently coexists with factors such as noise, with levels and risks influenced substantially by additional factors such as social determinants and natural and built environment features. Persistent disparities regarding the impact and new sources of air pollution, such as wildfires attributable to climate change, have renewed the urgency to better understand root sources, characterize their health effects, and disseminate this information for personal protection and policy impacts. In this review, we summarize evidence associating air pollution with cardiovascular health, the impact of air pollution on CKM health, and how interactions with other exposures and personal characteristics may modify these associations. Finally, we discuss new integrated approaches to capture risk from air pollution in the context of an exposomic framework.
    Keywords:  air pollution; cardiovascular; environment; kidney; metabolic
    DOI:  https://doi.org/10.14797/mdcvj.1487
  30. Arch Iran Med. 2024 Nov 01. 27(11): 598-605
       BACKGROUND: Studies on the prevalence of nonalcoholic steatohepatitis (NASH) and the factors associated with its high prevalence among Iranian people are limited. This study evaluated the prevalence of NASH and its associated factors among Iranian adults using Pars Cohort Study (PCS) data.
    METHODS: This cross-sectional study was conducted based on PCS, which includes 40-75-year-old adults from the Valashahr area. NASH was defined as alanine aminotransferase (ALT) higher than 40 U/L without evidence of hepatitis B or C infections. The prevalence of NASH and its associations with basic and demographic characteristics, socioeconomic characteristics, medical history, gastrointestinal symptoms, and laboratory tests were evaluated.
    RESULTS: Overall, 8734 patients, including 3917 men (44.8%), were enrolled in this study. The mean age of participants was 52.62 years (SD=9.68), and 605 individuals had NASH (6.9%). In the regression analysis, in contrast to female gender (OR=0.31, 95% CI=0.249‒0.386, P<0.001) and age (OR=0.951, 95% CI=0.941‒0.962, P<0.001), history of heart disease (OR=1.499, 95% CI=1.146‒1.962, P=0.003), history of diabetes (OR=1.523, 95% CI=1.162‒1.995, P=0.002), hypertension (OR=1.241, 95% CI=1.023‒1.506, P=0.029), being overweight or obese (OR=2.192, 95% CI=1.755‒2.737, P<0.001), being in the richest or second richest wealth index quantiles (OR=1.315, 95% CI=1.107‒1.156, P=0.002), and increased waist circumference (OR=1.409, 95% CI=1.107‒1.793, P<0.005) were independently associated with a higher risk of having NASH.
    CONCLUSION: In this study, we determined the prevalence of NASH and found male gender, younger age, history of heart disease, history of diabetes, hypertension, socioeconomic status, and obesity as possible factors associated with a higher risk of NASH among Iranians.
    Keywords:  Epidemiology; Iran; Nonalcoholic steatohepatitis; Prevalence
    DOI:  https://doi.org/10.34172/aim.30020