Nonalcoholic Fatty Liver Disease Fibrosis Research Articles

Associations of perfluoroalkyl substances with metabolic-associated fatty liver disease and non-alcoholic fatty liver disease: NHANES 2017-2018.

This study investigated the potential effects of perfluoroalkyl substance (PFAS) in serum on MAFLD, NAFLD, and liver fibrosis. Our sample included 696 participants (≥ 18years) from the 2017-2018 NHANES study with available serum PFASs, covariates, and outcomes. Using the first quartile of PFAS as the reference group, we used weighted binary logistic regression and multiple ordered logistic regression used to analyze the relationship between PFAS and MAFLD, NAFLD, and liver fibrosis and multiple ordinal logistic regression to investigate the relationship between PFAS and MAFLD, NAFLD, and liver fibrosis and calculated the odds ratio (OR) and 95% confidence interval for each chemical. Finally, stratified analysis and sensitivity analysis were performed according to gender, age, BMI, and serum cotinine concentration. A total of 696 study subjects were included, including 212 NAFLD patients (weighted 27.03%) and 253 MAFLD patients (weighted 32.65%). The quartile 2 of serum PFOA was positively correlated with MAFLD and NAFLD (MAFLD, OR 2.29, 95% CI 1.05-4.98; NAFLD, OR 2.37, 95% CI 1.03-5.47). PFAS were not significantly associated with liver fibrosis after adjusting for potential confounders in MAFLD and NAFLD. Stratified analysis showed that PFOA was strongly associated with MAFLD, NAFLD, and liver fibrosis in males and obese subjects. In women over 60years old, PFHxS was also correlated with MAFLD, NAFLD, and liver fibrosis. The serum PFOA was positively associated with MAFLD and NAFLD in US adults. After stratified analysis, the serum PFHxS was correlated with MFALD, NAFLD, and liver fibrosis.

Non-invasive biomarkers prognostic of decompensation events in NASH cirrhosis: a systematic literature review.

Liver cirrhosis due to nonalcoholic steatohepatitis (NASH) is a life-threatening condition with increasing incidence world-wide. Although its symptoms are unspecific, it can lead to decompensation events such as ascites, hepatic encephalopathy, variceal hemorrhage, and hepatocellular carcinoma (HCC). In addition, an increased risk for cardiovascular events has been demonstrated in patients with NASH. Pharmacological treatments for NASH cirrhosis are not yet available, one of the reasons being the lack in surrogate endpoints available in clinical trials of NASH cirrhosis. The feasibility of non-invasive prognostic biomarkers makes them interesting candidates as possible surrogate endpoints if their change following treatment would result in better outcomes for patients in future clinical trials of NASH cirrhosis. In this systematic literature review, a summary of the available literature on the prognostic performance of non-invasive biomarkers in terms of cardiovascular events, liver-related events, and mortality is outlined. Due to the scarcity of data specific for NASH cirrhosis, this review includes studies on NAFLD whose evaluation focuses on cirrhosis. Our search strategy identified the following non-invasive biomarkers with prognostic value in studies of NASH patients: NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4), aspartate aminotransferase (AST) to platelet ratio index (APRI), enhanced liver fibrosis (ELF™), BARD (BMI, AST/ALT (alanine aminotransferase) ratio, diabetes), Hepamet Fibrosis Score (HFS), liver enzymes (AST + ALT), alpha-fetoprotein, platelet count, neutrophil to lymphocyte ratio (NLR), Lysyl oxidase-like (LOXL) 2, miR-122, liver stiffness, MEFIB (liver stiffness measured with magnetic resonance elastography (MRE) + FIB-4), and PNPLA3 GG genotype. The aim of the present systematic literature review is to provide the reader with a summary of the non-invasive biomarkers with prognostic value in NASH cirrhosis and give an evaluation of their utility as treatment monitoring biomarkers in future clinical trials.

Serum bile acid and unsaturated fatty acid profiles of non-alcoholic fatty liver disease in type 2 diabetic patients.

The understanding of bile acid (BA) and unsaturated fatty acid (UFA) profiles, as well as their dysregulation, remains elusive in individuals with type 2 diabetes mellitus (T2DM) coexisting with non-alcoholic fatty liver disease (NAFLD). Investigating these metabolites could offer valuable insights into the pathophy-siology of NAFLD in T2DM. To identify potential metabolite biomarkers capable of distinguishing between NAFLD and T2DM. A training model was developed involving 399 participants, comprising 113 healthy controls (HCs), 134 individuals with T2DM without NAFLD, and 152 individuals with T2DM and NAFLD. External validation encompassed 172 participants. NAFLD patients were divided based on liver fibrosis scores. The analytical approach employed univariate testing, orthogonal partial least squares-discriminant analysis, logistic regression, receiver operating characteristic curve analysis, and decision curve analysis to pinpoint and assess the diagnostic value of serum biomarkers. Compared to HCs, both T2DM and NAFLD groups exhibited diminished levels of specific BAs. In UFAs, particular acids exhibited a positive correlation with NAFLD risk in T2DM, while the ω-6:ω-3 UFA ratio demonstrated a negative correlation. Levels of α-linolenic acid and γ-linolenic acid were linked to significant liver fibrosis in NAFLD. The validation cohort substantiated the predictive efficacy of these biomarkers for assessing NAFLD risk in T2DM patients. This study underscores the connection between altered BA and UFA profiles and the presence of NAFLD in individuals with T2DM, proposing their potential as biomarkers in the pathogenesis of NAFLD.

Muscle Quality as a Potential Diagnostic Marker of Advanced Liver Fibrosis in Patients with Non-alcoholic Fatty Liver Disease.

Muscle-liver crosstalk plays an important role in the development and progression of non-alcoholic fatty liver disease (NAFLD). The measurement of muscle echo-intensity during ultrasonography is a real-time, non-invasive method of assessing muscle quality. In this retrospective study, we investigated the significance of poor muscle quality (namely, a greater mass of non-contractile tissue, including intramuscular fat) as a risk factor for advanced liver fibrosis and considered whether it may represent a useful tool for the diagnosis of advanced liver fibrosis. We analyzed data from 307 patients with NAFLD (143 men and 164 women) who visited the University of Tsukuba Hospital between 2017 and 2022. The patients were stratified into the following tertiles of muscle quality according to their muscle echo-intensity on ultrasonography: modest (84.1 A.U.), intermediate (97.4 A.U.), and poor (113.6 A.U.). We then investigated the relationships between muscle quality and risk factors for advanced liver fibrosis and calculated appropriate cutoff values. Patients with poor muscle quality showed a significant, 7.6-fold greater risk of liver fibrosis compared to those with modest muscle quality. Receiver operating characteristic curve analysis showed that muscle quality assessment was as accurate as the Fibrosis-4 index and NAFLD fibrosis score in screening for liver fibrosis and superior to the assessment of muscle quantity and strength, respectively. Importantly, a muscle echo-intensity of ≥92.4 A.U. may represent a useful marker of advanced liver fibrosis. Muscle quality may represent a useful means of identifying advanced liver fibrosis, and its assessment may become a useful screening tool in daily practice.

Socioeconomic status and health disparities drive differences in accelerometer-derived physical activity in fatty liver disease and significant fibrosis

Background and aims The cornerstone of clinical management of patients with nonalcoholic fatty liver disease (NAFLD) are lifestyle changes such as increasing physical activity (PA) aimed at improving cardiometabolic risk. To inform NAFLD prevention and treatment guidelines we aimed to: (i) quantify the role of PA on lowering the risk for NAFLD and fibrosis; (ii) characterize NAFLD and fibrosis association with PA in the context of socioeconomic environment. Methods A sample of 2648 participants from the NHANES 2003–2006 was selected to develop survey weighted multivariable logistic regression models for predicting NAFLD and significant fibrosis, diagnosed non-invasively via fatty liver index (FLI) and fibrosis-4 (FIB-4) index. The PA measures were obtained from a hip-worn accelerometer. Results The predictive model for NAFLD showed AUC of 0.687 and a decrease of 43% in NAFLD risk with moderate vigorous PA (MVPA) (OR = 0.569, p < 0.001). The predictive model for fibrosis had AUC of 0.755 and there was a 48% and a 70% decrease in significant fibrosis risk with MVPA (OR = 0.518, p = 0.022) and total log activity count (TLAC) (OR = 0.296, p = 0.017), respectively. Participants with NAFLD and NAFLD with fibrosis engage in declining PA. Despite having jobs with higher level of PA and participating in more moderate-to-vigorous PA, a larger proportion of Hispanics participants had NAFLD and significant fibrosis. Conclusions These findings demonstrate the role of PA as a protective factor against the presence of NAFLD and significant fibrosis. Protective levels of PA in NAFLD differ by races.

Impact of GLP-1 Receptor Agonist Use in Patients With Steatotic Liver Disease and Type 2 Diabetes: A Retrospective Cohort Study.

Background: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) help manage type 2 diabetes (T2DM) and may have efficacy in steatotic liver disease. Objective: To determine the prevalence and clinical impact of GLP-1 RA use in patients with T2DM and liver disease. Methods: This was a retrospective study of adult patients with T2DM and nonalcoholic fatty liver disease (NAFLD), nonalcoholic fatty liver (NAFL), or nonalcoholic steatohepatitis (NASH) between 1/1/21-12/31/21. Patients with hepatitis B or C, or on pioglitazone were excluded. Eligible patients treated with a GLP-1 RA were compared to controls. The primary outcome was change in Fibrosis-4 (FIB-4) score, with NAFLD Fibrosis Score (NFS) as a secondary outcome. Follow-up scores were calculated from labs within 3 to 15 months after baseline. Results: Of 242 eligible patients, 79 patients (32.6%) were treated with a GLP-1 RA. At baseline, FIB-4 score was lower and NFS was higher in the GLP-1 RA group vs controls (1.80 vs 2.33; P = .101, .36 vs -.47, P < .001; respectively). At follow up, FIB-4 score decreased to 1.77 in the GLP-1 RA group and increased to 2.71 in controls (P = .045). Follow up NFS was stable in the GLP-1 RA group and increased in the control group (.36 vs -.43; P = .308). Conclusion: Patients treated with GLP-1 RAs had less evidence of liver fibrosis progression compared to no treatment, although the differences were small. These results suggest that treatment with GLP-1 RAs may have clinical impact on slowing liver fibrosis, however results should be confirmed in a larger, more diverse sample.

Diagnostic performances of Fibrosis-4 index and nonalcoholic fatty liver disease fibrosis score in metabolic dysfunction-associated steatotic liver disease in Asian primary care clinics.

We aimed to explore the extent to which individuals previously diagnosed with nonalcoholic fatty liver disease (NAFLD) meet the criteria fulfilled with the new nomenclature, metabolic dysfunction-associated steatotic liver disease (MASLD), within an Asian primary clinic cohort. Additionally, we assessed the reliability of the diagnostic performance of FIB-4 and NAFLD fibrosis score (NFS) for MASLD within the primary clinic cohort. This retrospective cross-sectional study included participants who underwent magnetic resonance elastography and abdominal ultrasonography during their health checkups at nationwide health promotion centers (n=6740). The prevalence rates of NAFLD and MASLD diagnosed based on ultrasonography results were 36.7% and 38.0%, respectively. Notably, 96.8% of patients in the NAFLD cohort fulfilled the new criteria for MASLD. A small proportion of patients with NAFLD (n=80, 3.2%) did not meet the MASLD criteria. Additionally, 168 patients (6.6%) were newly added to the MASLD group. The areas under the receiver operating characteristic curves for diagnosing advanced hepatic fibrosis for FIB-4 (0.824 in NAFLD vs. 0.818 in MASLD, p=0.891) and NFS (0.803 in NAFLD vs. 0.781 in MASLD, p=0.618) were comparable between the MASLD and NAFLD groups. Furthermore, the sensitivity, specificity, positive predictive value, and negative predictive value of FIB-4 and NFS for advanced fibrosis in MASLD were also comparable to those in NAFLD. Most patients (96.8%) previously diagnosed with NAFLD fulfilled the new criteria for MASLD in an Asian primary clinic cohort. Diagnostic performance of FIB-4 in the MASLD cohort demonstrated satisfactory results.

Thy-1 restricts steatosis and liver fibrosis in steatotic liver disease.

Steatotic liver disease (SLD) is generally considered to represent a hepatic manifestation of metabolic syndrome and includes a disease spectrum comprising isolated steatosis, metabolic dysfunction-associated steatohepatitis, liver fibrosis and ultimately cirrhosis. A better understanding of the detailed underlying pathogenic mechanisms of this transition is crucial for the design of new and efficient therapeutic interventions. Thymocyte differentiation antigen (Thy-1, also known as CD90) expression on fibroblasts controls central functions relevant to fibrogenesis, including proliferation, apoptosis, cytokine responsiveness, and myofibroblast differentiation. The impact of Thy-1 on the development of SLD and progression to fibrosis was investigated in high-fat diet (HFD)-induced SLD wild-type and Thy-1-deficient mice. In addition, the serum soluble Thy-1 (sThy-1) concentration was analysed in patients with metabolic dysfunction-associated SLD stratified according to steatosis, inflammation, or liver fibrosis using noninvasive markers. We demonstrated that Thy-1 attenuates the development of fatty liver and the expression of profibrogenic genes in the livers of HFD-induced SLD mice. Mechanistically, Thy-1 directly inhibits the profibrotic activation of nonparenchymal liver cells. In addition, Thy-1 prevents palmitic acid-mediated amplification of the inflammatory response of myeloid cells, which might indirectly contribute to the pronounced development of liver fibrosis in Thy-1-deficient mice. Serum analysis of patients with metabolically associated steatotic liver disease syndrome revealed that sThy-1 expression is correlated with liver fibrosis status, as assessed by liver stiffness, the Fib4 score, and the NAFLD fibrosis score. Our data strongly suggest that Thy-1 may function as a fibrosis-protective factor in mouse and human SLD.

Potential utility of l-carnitine for preventing liver tumors derived from metabolic dysfunction-associated steatohepatitis.

Recent reports have unveiled the potential utility of l-carnitine to alleviate metabolic dysfunction-associated steatohepatitis (MASH) by enhancing mitochondrial metabolic function. However, its efficacy at preventing the development of HCC has not been assessed fully. l-carnitine (2g/d) was administered to 11 patients with MASH for 10 weeks, and blood liver function tests were performed. Five patients received a serial liver biopsy, and liver histology and hepatic gene expression were evaluated using this tissue. An atherogenic plus high-fat diet MASH mouse model received long-term l-carnitine administration, and liver histology and liver tumor development were evaluated. Ten-week l-carnitine administration significantly improved serum alanine transaminase and aspartate transaminase levels along with a histological improvement in the NAFLD activity score, while steatosis and fibrosis were not improved. Gene expression profiling revealed a significant improvement in the inflammation and profibrotic gene signature as well as the recovery of lipid metabolism. Long-term l-carnitine administration to atherogenic plus high-fat diet MASH mice substantially improved liver histology (inflammation, steatosis, and fibrosis) and significantly reduced the incidence of liver tumors. l-carnitine directly reduced the expression of the MASH-associated and stress-induced transcriptional factor early growth response 1. Early growth response 1 activated the promoter activity of neural precursor cell expressed, developmentally downregulated protein 9 (NEDD9), an oncogenic protein. Thus, l-carnitine reduced the activation of the NEDD9, focal adhesion kinase 1, and AKT oncogenic signaling pathway. Short-term l-carnitine administration ameliorated MASH through its anti-inflammatory effects. Long-term l-carnitine administration potentially improved the steatosis and fibrosis of MASH and may eventually reduce the risk of HCC.

Liver fibrosis assessed via non-invasive tests is associated with incident heart failure in a general population cohort

To determine whether liver fibrosis is associated with heart failure in a general population cohort, and if genetic polymorphisms (PNPLA3 rs738409; TM6SF2 rs58542926), linked to increased risk of liver fibrosis and decreased risk of coronary artery disease, modify this association. Using UK Biobank data, we prospectively examined the relationship between non-invasive fibrosis markers [NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4) and AST to platelet ratio index (APRI)] and incident hospitalization/death from heart failure (n=413,860). Cox-regression estimated hazard ratios (HR) for incident heart failure. Effects of PNPLA3 and TM6SF2 on the association between liver fibrosis and heart failure were estimated by stratifying for genotype, and testing for an interaction between genotype and liver fibrosis using a likelihood ratio test. 12,527 incident cases of heart failure occurred over a median of 10.7 years. Liver fibrosis was associated with an increased risk of hospitalization or death from heart failure (multivariable adjusted high risk NFS score HR 1.59 [1.47-1.76], p<0.0001; FIB-4 HR 1.69 [1.55-1.84], p<0.0001; APRI HR 1.85 [1.56-2.19], p<0.0001; combined fibrosis scores HR 1.90 [1.44-2.49], p<0.0001). These associations persisted for people with metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with alcohol consumption (Met-ALD) and harmful alcohol consumption. PNPLA3 rs738409 GG and TM6SF2 rs58542926 TT did not attenuate the positive association between fibrosis markers and heart failure. For PNPLA3 a statistically significant interaction was found between PNPLA3 rs738409, FIB-4, APRI score and heart failure. In the general population, serum markers of liver fibrosis are associated with increased hospitalization/death from heart failure. Genetic polymorphisms associated with liver fibrosis were not positively associated with elevated heart failure risk.

Benchmarking clinical risk prediction algorithms with ensemble machine learning for the non-invasive diagnosis of liver fibrosis in NAFLD.

Ensemble machine learning methods, like the superlearner, combine multiple models into a single one to enhance predictive accuracy. Here we explore the potential of the superlearner as a benchmarking tool for clinical risk prediction, illustrating the approach in identifying significant liver fibrosis among patients with non-alcoholic fatty liver disease (NAFLD). We used 23 demographic/clinical variables to train superlearner(s) on data from the NASH-CRN observational study (n=648) and validated models with data from the FLINT trial (n=270) and NHANES participants with NAFLD (n=1244). Comparing the superlearner's performance to existing models (FIB-4, NFS, Forns, APRI, BARD, and SAFE), it exhibited strong discriminative ability in the FLINT and NHANES validation sets, with AUCs of 0.79 (95% CI: 0.73-0.84) and 0.74 (95% CI: 0.68-0.79) respectively. Notably, the SAFE score performed similarly to the superlearner, both of which outperformed FIB-4, APRI, Forns, and BARD scores in the validation datasets. Surprisingly, the superlearner derived from 12 base models matched the performance of one with 90 base models. Overall, the superlearner, being the "best-in-class" ML predictor, excelled in detecting fibrotic NASH, and this approach can be used to benchmark the performance of conventional clinical risk prediction models.

Dietary inflammatory impact on NAFLD development in obese vs. lean individuals: an analysis based on NHANES 2003–2018

BackgroundNon-alcoholic fatty liver disease (NAFLD), often linked with obesity, can also affect individuals with normal weight, a condition known as “lean NAFLD”, imposing comparable burdens and adverse effects. However, the impact of diet on lean NAFLD remains underexplored. The objective of this study is to investigate the correlation between the Dietary Inflammatory Index (DII) and NAFLD among Americans, stratified by waist-to-height ratio (WHtR) and body mass index (BMI).MethodsFive thousand one hundred fifty-two participants from the National Health and Nutrition Examination Survey (NHANES) 2003–2018 were comprised in the final analysis. NAFLD and advanced liver fibrosis were diagnosed by serological markers. Lean and abdominal lean individuals were identified using BMI and WHtR, separately. DII was determined by assigning scores to 28 distinct food parameters based on their inflammatory potential, obtained from the NAHNES website. Differences across DII quartiles were evaluated using the Kruskal-Wallis H Test, Chi-Square Test along with One-Way ANOVA. The correlation between DII and NAFLD was determined by multiple regression models and subgroup analyses.ResultsAmong the 5152 subjects, 2503 were diagnosed with NAFLD, including 86 cases of lean NAFLD and 8 cases of abdominal lean NAFLD. DII was positively linked with NAFLD (Odds Ratio (OR) = 1.81 [1.48–2.21], P < 0.001) and advanced liver fibrosis (OR = 1.46 [1.02–2.07], P = 0.037). Further analysis revealed that this association was primarily observed in obese or abdominal obese participants (In BMI ≥ 25.00 kg/m^2, OR = 1.56 [1.23–1.98], P < 0.001. In WHtR> 0.50, OR = 1.48 [1.23–1.79], P < 0.001.), rather than their lean counterparts. Subgroup analyses indicated that female individuals, without a diagnosis of hypertension or diabetes appeared to be more sensitive to the rise in DII.ConclusionsOur data demonstrated a significant positive correlation between DII and NAFLD in the general population. However, the impact of a pro-inflammatory diet was less prominent in lean individuals compared to obese ones.

Prevalence and outcome of sarcopenia in non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of conditions, progressing from mild steatosis to advanced fibrosis. Sarcopenia, characterized by decreased muscle strength and mass, shares common pathophysiological traits with NAFLD. An association exists between sarcopenia and increased NAFLD prevalence. However, data on the prevalence of sarcopenia in NAFLD and its impact on the outcomes of NAFLD remain inconsistent. To analyze the prevalence and outcomes of sarcopenia in patients with NAFLD. We conducted a comprehensive search for relevant studies in MEDLINE, Embase, and Scopus from their inception to June 2023. We included studies that focused on patients with NAFLD, reported the prevalence of sarcopenia as the primary outcome, and examined secondary outcomes, such as liver fibrosis and other adverse events. We also used the Newcastle-Ottawa scale for quality assessment. Of the 29 studies included, the prevalence of sarcopenia in NAFLD varied widely (1.6% to 63.0%), with 20 studies reporting a prevalence of more than 10.0%. Substantial heterogeneity was noted in the measurement modalities for sarcopenia. Sarcopenia was associated with a higher risk of advanced fibrosis (odd ratio: 1.97, 95% confidence interval: 1.44-2.70). Increased odds were consistently observed in fibrosis assessment through biopsy, NAFLD fibrosis score/body mass index, aspartate aminotransferase to alanine aminotransferase ratio, diabetes (BARD) score, and transient elastography, whereas the fibrosis-4 score showed no such association. Sarcopenia in NAFLD was associated with a higher risk of steatohepatitis, insulin resistance, cardiovascular risks, and mortality. This systematic review highlights the critical need for standardized diagnostic criteria and measurement methods for sarcopenia in NAFLD patients. The variability in study designs and assessment methods for sarcopenia and liver fibrosis may account for the inconsistent findings. This review demonstrates the multidimensional impact of sarcopenia on NAFLD, indicating its importance beyond liver-related events to include cardiovascular risks, mortality, and metabolic complications.

Impact of alcohol consumption on metabolic dysfunction-associated fatty liver disease development and remission: A longitudinal cohort study.

The influence of alcohol intake on metabolic dysfunction-associated fatty liver disease (MAFLD) development and remission remains unclear; thus, we aimed to investigate their longitudinal associations. This observational cohort study included 6349 patients who underwent more than two health check-ups over >2 years between April 2013 and March 2021. Generalized estimation equations were used to analyse the longitudinal associations between changes in alcohol intake and MAFLD according to repeated measures at baseline and the most recent stage. The MAFLD development and remission rates were 20.4 and 5.1 and 9.1 and 4.7% in men and women, respectively. Although alcohol consumption was not a significant factor for MAFLD development, consuming 0.1-69.9 g/week (odds ratio [OR]: 0.672, 95% confidence interval [CI]: 0.469-0.964, p < .05) and ≥280 g/week were significant factors for MAFLD development in males (OR: 1.796, 95% CI: 1.009-3.196, p < .05) and females (OR: 16.74, 95% CI: 3.877-72.24, p < .001). Regardless of quantity and frequency, alcohol consumption was not a significant factor for MAFLD remission. Several noninvasive liver fibrosis scores were significantly associated with alcohol intake quantity and frequency in males with MAFLD development and remission (p < .05). The nonalcoholic fatty liver disease fibrosis score differed significantly between males with and without reduced alcohol intake (p < .05) who showed MAFLD remission. Although the influence of alcohol intake on MAFLD development and remission differed, alcohol consumption was not beneficial for MAFLD remission in either sex. Alcohol intake reduction or cessation is recommended to prevent liver fibrosis, even in those who achieve MAFLD remission.

Association Between Liver Fibrosis Score and Diabetic Kidney Disease: A Retrospective Cross-Sectional Study of Hospitalized Patients.

To investigate the association between liver fibrosis score and diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM). A total of 897 hospitalized patients with T2DM were included in this study. Each patient completed DKD screening. Logistic regression analysis was used to assess the predictive value of non-alcoholic fatty liver disease fibrosis score (NAFLD-FS) and fibrosis-4 (FIB-4) for the occurrence of DKD and risk for DKD progression, respectively. The prevalence of DKD and risk for its progression significantly increased with increasing NAFLD-FS risk category. DKD prevalence also increased with increasing FIB-4 risk category. Multivariate logistic regression analysis showed that the "high-risk" NAFLD-FS had a significantly higher risk of DKD (odds ratio [OR]: 1.89, 95% confidence interval [CI]: 1.16-3.08) and risk for DKD progression (OR: 2.88, 95% CI: 1.23-6.78), and the "intermediate-risk" FIB-4 had a significantly higher risk of DKD (OR: 1.41, 95% CI: 1.00-1.98). Subgroup analysis showed that the association between NAFLD-FS and FIB-4 and DKD was significant in the female subgroup, whereas the association between the "high-risk" NAFLD-FS and risk for DKD progression was significant in the male subgroup. NAFLD-FS and FIB-4 are strongly associated with DKD and risk for DKD progression in patients with T2DM. Additionally, sexual dimorphism exists in this association.

Association between nonalcoholic fatty liver disease and left ventricular diastolic dysfunction: A 7-year retrospective cohort study of 3,380 adults using serial echocardiography

AimLeft ventricular diastolic dysfunction (LVDD) has been observed in people with nonalcoholic fatty liver disease (NAFLD) in cross-sectional studies but the causal relationship is unclear. This study aimed to investigate the impact of NAFLD and the fibrotic progression of the disease on the development of LVDD, assessed by serial echocardiography, in a large population over a 7-year longitudinal setting. MethodsThis retrospective cohort study included the data of 3,380 subjects from a medical health check-up program. We defined subjects having NAFLD by abdominal ultrasonography and assessed significant liver fibrosis by the aspartate transaminase (AST) to platelet ratio index (APRI), the NAFLD fibrosis score (NFS), and the fibrosis-4 (FIB-4) index. LVDD was defined using serial echocardiography. A parametric Cox proportional hazards model was used. ResultsDuring 11,327 person-years of follow-up, there were 560 (16.0 %) incident cases of LVDD. After adjustment for multiple risk factors, subjects with NAFLD showed an increased adjusted hazard ratio (aHR) of 1.21 (95 % confidence interval [CI]=1.02–1.43) for incident LVDD compared to those without. The risk of LV diastolic dysfunction increased progressively with increasing degree of hepatic steatosis (P< 0.001). Compared to subjects without NAFLD, the multivariable-aHR (95 % CI) for LVDD in subjects with APRI < 0.5 and APRI ≥ 0.5 were 1.20 (1.01–1.42) and 1.36 (0.90–2.06), respectively (P= 0.036), while other fibrosis prediction models (NFS and FIB-4 index) showed insignificant results. ConclusionsThis study demonstrated that NAFLD was associated with an increased risk of LVDD in a large cohort. More severe forms of hepatic steatosis and/or significant liver fibrosis may increase the risk of developing LVDD.

Comparative and Predictive Significance of Serum Leptin Levels in Non-alcoholic Fatty Liver Disease.

Background Non-alcoholic fatty liver disease (NAFLD) has emerged as the single most common chronic non-viral liver disease. The burden of the disease on healthcare-providing services has increased tremendously. Although a liver biopsy is the most authentic laboratory investigation for scoring the disease progression, it is an invasive technique. Researchers are vigorously working to find alternate markers for the scoring purpose. Despite the importance and association of leptin with metabolic syndrome and its related disorders, there have been relatively fewer studies on serum leptin and its association with NAFLD. Objective This study aimed to investigate variations in serum leptin levels between subjects with and without fibrosisin NAFLD and to assess the predictive value of serum leptin levels in NAFLD subjects. Materials and methods The study comprised 130 NAFLD subjects from two tertiary care hospitals in Lahorealong with 86 healthy controls that were age, gender, and BMI matched with the subjects. Based on the NAFLD fibrosis score (NFS), the subjects were divided into two sub-groups, subjects withsimple steatosis and those with fibrosis. Fasting serum leptin, glucose, and insulin levels were measured using enzyme-linked immunosorbent assay (ELISA). The Kruskal-Wallis test was applied to find differences between the three groups and Fisher's exact test for categorical comparison. To assess the predictive value of serum leptin for steatosis and fibrosis in NAFLD subjects, receiver operation characteristic (ROC) curve analysis was implemented. Results The difference in serum leptin level was statistically highly significant(p-value <0.001), with leptin levels of 10 (17.1) ng/mL among controls, 20.5 (21) ng/mL in simple steatosis, and 21 (28.6) ng/mL in fibrosis. The area under the ROC curve was 0.67 and 0.52 for steatosis and fibrosis, respectively. The cut-off value of 12.2 ng/mL showed 70% sensitivity and 50% specificity for steatosis, while at a threshold of 18 ng/mL, leptin demonstrated 40% sensitivity and specificity for fibrosis. Conclusion In conclusion, this study found that serum leptin levels are higher in NAFLD subjects compared to healthy controls, and it is a good independent predictor for the detection of liver steatosis.

A Validation Study of Non-invasive Scoring Systems for Assessing Severity of Hepatic Fibrosis in a Cohort of South Indian Patients With Non-alcoholic Fatty Liver Disease

IntroductionLiver biopsy is the gold standard for diagnosing and staging NAFLD. But liver biopsy has its limitations. Non-invasive tests (NITs) eliminate many of the drawbacks of liver biopsy. We did a retrospective observational study to validate the non-alcoholic fatty liver disease Fibrosis Score (NFS score) and Fibrosis Score 4 (FIB-4 index) against the gold standard liver biopsy in a cohort of south Indian patients with NAFLD. Material and MethodsA retrospective observational analytical study of patients who had a liver biopsy with a diagnosis of NAFLD and had all the data for aetiology assessment and NIT calculation within 4 weeks of biopsy were included in the study. On liver biopsy NAFLD was scored as per NIH’s NASH committee (NASH CRN) grading system. NAFLD Fibrosis Score (NFS) and FIB-4 index were calculated and scores more than 0.676 and 2.67 respectively was taken as the cut-off to predict advanced fibrosis. The sensitivity, specificity, positive predictive value, negative predictive value and area under the ROC curve for NFS score and FIB-4 score to diagnose advanced fibrosis were calculated. ResultsA total of 147 patients were included in the study. Of these 56 (38.1%) patients had advanced fibrosis (Stage 3, 4). Patients with advanced fibrosis were more likely to be older and have DM. Patients with advanced fibrosis had lower platelet count, higher AST, lower albumin and higher AST/ALT ratio. The NFS of > 0.676 had a sensitivity of 68% and specificity of 100% and FIB-4 index of >2.67 had a sensitivity of 67% and specificity of 95.6 % in diagnosing advanced fibrosis in our study. ConclusionThe non-invasive scoring systems NAFLD Fibrosis Score (NFS) and FIB-4 index, can be used as a bedside tool for diagnosing Liver fibrosis in NAFLD allowing liver biopsy to be used in a more targeted manner for patients diagnosed with advanced fibrosis on NITs.

Effects of Food Insecurity on Hepatic Steatosis and Fibrosis in People With HIV

Background & AimsFood insecurity (FI) is a risk factor for nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis in the general population, but its impact on liver disease in people with HIV (PWH) is unknown. MethodsWe examined the association of FI with prevalence of NAFLD and fibrosis in a diverse cohort of PWH. PWH aged ≥18 years on antiretroviral therapy, HIV RNA<200 copies/mL, and without other known liver diseases were screened for NAFLD (CAP≥263 decibels/meter) and advanced fibrosis (LSM≥11 kilopascals) by vibration controlled transient elastography at eight US centers. Participants were categorized as food insecure using the Six-Item Short Form Household Food Security Survey. We used multivariable logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) of NAFLD and advanced fibrosis by FI status. ResultsAmong 654 PWH, NAFLD was present in 348 (53%) and advanced fibrosis in 41 (6%). FI was present in 203 (31%) of participants, including 97/348 (28%) with NAFLD and 18/41 (44%) with advanced fibrosis. In multivariable analysis, FI was associated with lower odds of NAFLD (OR=0.57,95%CI:0.37-0.88) and a greater, but nonsignificant, odds of advanced fibrosis (OR=1.38,95%CI:0.65-2.90). We identified a significant interaction between FI and diabetes (p=0.02) on fibrosis risk, with a greater odds of fibrosis among food insecure PWH and diabetes (OR=3.83,95%CI:1.15-12.73) but not among food insecure nondiabetics (OR=1.12,95%CI:0.47-2.98). ConclusionsFI is highly prevalent among PWH and associated with lower odds of NAFLD, and among PWH with diabetes, a greater odds of advanced fibrosis. FI may contribute to hepatic fibrosis through mechanisms other than steatosis in PWH.

Assessment of Liver Fibrosis Grading with Non Invasive Scoring Systems Among Non Alcoholic Fatty Liver Disease (NAFLD) Patients

Background: The evaluation of degree of liver fibrosis is an important prognostic factor in the management of NAFLD patients. Noninvasive risk stratification is needed to triage individuals with advanced fibrosis for optimal treatment and surveillance. Objective: To find the frequency of fibrosis in NAFLD patients using multiple non-invasive tests and to match the performance of noninvasive tests in diagnosing liver fibrosis. Methods: An observational study done in Out-patient Clinics of National Institute of Liver and GI diseases (NILGID), Dow University Hospital from January 2021 to January 2022. All consecutive NAFLD patients during the study period were enrolled. Liver fibrosis was assessed in each patient with non invasive scoring including APRI score (AST to platelet ratio index), AST/ALT ratio, NFS (NAFLD fibrosis scores) and FIB-4. Results: 322 patients (mean age 44.84 ±10.94 years) were included. The mean values for ALT and AST levels were 40.67 ± 31.69IU/L and 31.85 ± 22.60 respectively. The best diagnostic accuracy was observed with FIB4 score having AUROC of 0.904. A robust correlation was observed between APRI index and FIB-4 score (r = 0.734, p-value &lt; 0.01), and between FIB-4 score and NFS score (r = 0.700, p- value &lt;0.01). Whereas correlation of APRI index with NFS score was moderate (r=0.394), and with AST/ALT ratio was weak (r = 0.201). Conclusion: Noninvasive markers, FIB4 and NFS score demonstrate a dependable ability to diagnose and rule out liver fibrosis, which proves to be an economical approach in management of patients with NAFLD.