Markers Of Nonalcoholic Fatty Liver Disease Research Articles

Cross-sectional association between prolactin levels and non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus: a retrospective analysis of patients from a single hospital in China

ObjectiveThis study aimed to retrospectively assess the association between prolactin (PRL) and non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM).Design and settingA retrospective, cross-sectional study...

Evaluation of the effect of phytosomal curcuminoids on oxidative stress and inflammatory markers in NAFLD: A randomized double-blind placebo-controlled trial

• Non-alcoholic fatty liver disease (NAFLD) is one of the major public health challenges of the 21st century. • Oxidative stress (OS) is widely regarded as one of the most important factors in the pathophysiology of this disease. • The potential of curcumin in reducing inflammation and oxidative stress has been investigated in many studies. • Daily use of phytosomal curcuminoids in patients with NAFLD resulted in a significant increase in CAT activity and a significant reduction in MCP-1. The aim of this study was to evaluate the effects of the phytosomal curcuminoids on oxidative stress and inflammatory biomarkers along with routine biochemical factors in non-alcoholic fatty liver disease (NAFLD). Seventy-two patients were selected and randomly divided into Placebo and Curcumin groups (250 mg of phytosomal curcuminoids daily for two months). Biochemical, inflammatory biomarkers including interleukin (IL) 6, IL-10, TNFα (tumor necrosis factor alpha), MCP-1 (monocyte chemoattractant protein-1) and high-sensitivity C-reactive protein (hsCRP) and oxidative stress measurements including malondialdehyde (MDA), superoxide dismutase (SOD) and Catalase (CAT) were measured between two groups before and after the intervention. Curcumin treatment statistically significant increased the activity of CAT enzyme compared with the Placebo group after intervention ( p value = 0.001). However, no significant changes were observed in MDA and SOD biomarkers. Moreover, there was a statistically significant reduction in monocyte chemoattractant protein-1 (MCP-1) levels as a chemokine in the Curcumin group compared with the Placebo group after treatment ( p value = 0.007). Daily use of 250 mg of phytosomal curcuminoids for two months in patients with NAFLD resulted in a significant increase of CAT activity and a significant reduction of MCP-1.

Single-cell transcriptome and cell type-specific molecular pathways of human non-alcoholic steatohepatitis

The aim of this study is to characterize cell type-specific transcriptional signatures in non-alcoholic steatohepatitis (NASH) to improve our understanding of the disease. We performed single-cell RNA sequencing on liver biopsies from 10 patients with NASH. We applied weighted gene co-expression network analysis and validated our findings using a publicly available RNA sequencing data set derived from 160 patients with non-alcoholic fatty liver disease (NAFLD) and 24 controls with normal liver histology. Our study provides a comprehensive single-cell analysis of NASH pathology in humans, describing 19,627 single-cell transcriptomes from biopsy-proven NASH patients. Our data suggest that the previous notion of ”NASH-associated macrophages” can be explained by an up-regulation of normally existing subpopulations of liver macrophages. Similarly, we describe two distinct populations of activated hepatic stellate cells, associated with the level of fibrosis. Finally, we find that the expression of several circulating markers of NAFLD are co-regulated in hepatocytes together with predicted effector genes from NAFLD genome-wide association studies (GWAS), coupled to abnormalities in the complement system. In sum, our single-cell transcriptomic data set provides insights into novel cell type-specific and general biological processes associated with inflammation and fibrosis, emphasizing the importance of studying cell type-specific biological processes in human NASH.

Cadmium, lead, and mercury mixtures interact with non-alcoholic fatty liver diseases

There is a scarcity of studies on the interactions between heavy metals and non-alcoholic fatty liver disease (NAFLD). Using a variety of statistical approaches, we investigated the impact of three common heavy metals on liver enzymes and NAFLD markers in a Korean adult population. We observed that cadmium, mercury, and lead all demonstrated positive correlations with liver enzymes and NAFLD indices. Our findings were mostly robust in secondary analysis, which included three novel mixture modeling approaches (WQS, qgcomp, and BKMR) as well as in silico investigation of molecular mechanisms (genes, miRNAs, biological processes, pathways, and illnesses). The 16 genes interacted with a mixture of heavy metals, which was linked to the development of NAFLD. Co-expression was discovered in nearly half of the interactions between the 18 NAFLD-linked genes. Key molecular pathways implicated in the pathogenesis of NAFLD generated by the heavy metal combination include activated oxidative stress, altered lipid metabolism, and increased cytokines and inflammatory response. Heavy metal exposure levels were related to liver enzymes and NAFLD indices, and cutoff criteria were revealed. More studies are needed to validate our findings and gain knowledge about the effects of chronic combined heavy metal exposure on adult and child liver function and the likelihood of developing NAFLD. To reduce the occurrence of NAFLD, early preventative and regulatory actions (half-yearly screening of workers at high-risk facilities; water filtration; avoiding excessive amounts of seafood, etc.) should be taken.

Important Food Sources of Fructose-Containing Sugars and Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Controlled Trials.

Background: Fructose providing excess calories in the form of sugar sweetened beverages (SSBs) increases markers of non-alcoholic fatty liver disease (NAFLD). Whether this effect holds for other important food sources of fructose-containing sugars is unclear. To investigate the role of food source and energy, we conducted a systematic review and meta-analysis of controlled trials of the effect of fructose-containing sugars by food source at different levels of energy control on non-alcoholic fatty liver disease (NAFLD) markers. Methods and Findings: MEDLINE, Embase, and the Cochrane Library were searched through 7 January 2022 for controlled trials ≥7-days. Four trial designs were prespecified: substitution (energy-matched substitution of sugars for other macronutrients); addition (excess energy from sugars added to diets); subtraction (excess energy from sugars subtracted from diets); and ad libitum (energy from sugars freely replaced by other macronutrients). The primary outcome was intrahepatocellular lipid (IHCL). Secondary outcomes were alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Independent reviewers extracted data and assessed risk of bias. The certainty of evidence was assessed using GRADE. We included 51 trials (75 trial comparisons, n = 2059) of 10 food sources (sugar-sweetened beverages (SSBs); sweetened dairy alternative; 100% fruit juice; fruit; dried fruit; mixed fruit sources; sweets and desserts; added nutritive sweetener; honey; and mixed sources (with SSBs)) in predominantly healthy mixed weight or overweight/obese younger adults. Total fructose-containing sugars increased IHCL (standardized mean difference = 1.72 [95% CI, 1.08 to 2.36], p < 0.001) in addition trials and decreased AST in subtraction trials with no effect on any outcome in substitution or ad libitum trials. There was evidence of influence by food source with SSBs increasing IHCL and ALT in addition trials and mixed sources (with SSBs) decreasing AST in subtraction trials. The certainty of evidence was high for the effect on IHCL and moderate for the effect on ALT for SSBs in addition trials, low for the effect on AST for the removal of energy from mixed sources (with SSBs) in subtraction trials, and generally low to moderate for all other comparisons. Conclusions: Energy control and food source appear to mediate the effect of fructose-containing sugars on NAFLD markers. The evidence provides a good indication that the addition of excess energy from SSBs leads to large increases in liver fat and small important increases in ALT while there is less of an indication that the removal of energy from mixed sources (with SSBs) leads to moderate reductions in AST. Varying uncertainty remains for the lack of effect of other important food sources of fructose-containing sugars at different levels of energy control.

Correlation of Cytokeratin-18 as a Marker of Cardiovascular Risk Assessment in Nonalcoholic Fatty Liver Disease in Nonobese and Nondiabetic Patients

Background: The evidence of nonalcoholic fatty liver disease (NAFLD) in absence of obesity and diabetes is not fairly adequate; furthermore, there is not much data on the markers of NAFLD for this patient population, especially in Indian patients. We aimed to evaluate the severity of NAFLD in nonobese and nondiabetic patients and determine the correlation of its severity with cytokeratin-18 (CK-18). We also aimed to analyze the data for correlation between the conventional marker alanine aminotransferase (ALT), cardiovascular surrogate markers carotid intima-media thickness (CIMT), and CK-18 in adults with NAFLD. Materials and Methods This prospective, single-center, and noninterventional study enrolled 200 nonobese, nondiabetic adults with ultrasonography-confirmed NAFLD (presence of any two of the features – increased liver echogenicity with a clear contrast between kidney and liver, clouding of vessels, or deep weakening of the ultrasound signal) and 100 healthy controls and was conducted in the Department of Gastroenterology at Sher-i-Kashmir Institute of Medical Sciences, Kashmir, India. Results The CK-18 levels progressively increased with the severity of fatty liver, 68.54 (Grade 1), 167.5 (Grade 2), and 324.44 (Grade 3). In patients with Grade 2 and 3 NAFLD, the levels of CK-18 were significantly higher compared to controls as well as Grade 1 (P = 0.00). The correlation between ALT, CIMT (right and left), and CK-18 levels using Pearson's correlation coefficient showed that CIMT had a significant (P ≤ 0.0001) and positive correlation with both ALT and CK-18. The CIMT and ALT are highly correlated, whereas the CIMT and CK-18 are moderately correlated. Conclusion Apart from ALT, elevated CK-18 in patients with NAFLD appears to be promising as a signal for cardiovascular risk evaluation even in nonobese, nondiabetic adults.

CONSORT-Characteristics and metabolic phenotype of gut microbiota in NAFLD patients.

Patients with nonalcoholic fatty liver disease (NAFLD) have symptoms of a gut microbiota disorder with abnormal amino acid and glycolipid metabolism. This study was designed to analyze the characteristics of gut microbiota in patients with NAFLD, predict the gut microbiota phenotype, explore its role in the diagnosis of NAFLD, and establish its significance in disease progression.The characteristics of the gut microbiota in NAFLD patients (n = 28, 45.8 ± 14.2 years, male/female = 18/10) and healthy subjects (n = 20, 49.6 ± 4.8 years, male/female = 14/6) during March–May 2020 were analyzed using 16S rRNA sequencing technology and the phenotypes with large differences were predicted using the Tax4Fun method. The metabolites in the fecal samples of the patients were analyzed using mass spectrometry, and their correlation with different microorganisms was examined. The accuracy of the gut microbiota in diagnosing NAFLD was investigated by receiver operating characteristic curve analysis.We found that the microbial diversity and Bacteroides/Firmicutes (BF) ratio changed significantly (P < .05) in the feces of NAFLD patients. Phenotypic prediction showed that there were significant differences in the phenotypes of amino acid, glucose, and lipid metabolism of gut microbiota in the NAFLD group (P < .05). receiver operating characteristic curve analysis revealed that combination of Bacteroides and the BF ratio resulted in 88% and 100% sensitivity and specificity, respectively, when used for NAFLD diagnosis. Metabolomics and bioinformatics analysis revealed changes in the metabolism of nicotinate, nicotinamide, and pyrimidine; signaling pathways of calcium and oxytocin; pancreatic secretion with metabolites such as uracil, xanthine, and biliverdin; and enzymes such as xanthine dehydrogenase and xanthine oxidase (P < .05).Therefore, the phenotypic changes may be a potential marker for NAFLD and we considered that a combined analysis of Bacteroides and BF ratio had good diagnostic accuracy for NAFLD.

Risk assessment with gut microbiome and metabolite markers in NAFLD development.

A growing body of evidence suggests interplay between the gut microbiota and the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the role of the gut microbiome in early detection of NAFLD is unclear. Prospective studies are necessary for identifying reliable, microbiome markers for early NAFLD. We evaluated 2487 individuals in a community-based cohort who were followed up 4.6 years after initial clinical examination and biospecimen sampling. Metagenomic and metabolomic characterizations using stool and serum samples taken at baseline were performed for 90 participants who progressed to NAFLD and 90 controls who remained NAFLD free at the follow-up visit. Cases and controls were matched for gender, age, body mass index (BMI) at baseline and follow-up, and 4-year BMI change. Machine learning models integrating baseline microbial signatures (14 features) correctly classified participants (auROCs of 0.72 to 0.80) based on their NAFLD status and liver fat accumulation at the 4-year follow up, outperforming other prognostic clinical models (auROCs of 0.58 to 0.60). We confirmed the biological relevance of the microbiome features by testing their diagnostic ability in four external NAFLD case-control cohorts examined by biopsy or magnetic resonance spectroscopy, from Asia, Europe, and the United States. Our findings raise the possibility of using gut microbiota for early clinical warning of NAFLD development.

Further Insights Into the Impact of Bariatric Surgery on the Progression of Nonalcoholic Fatty Liver Disease

Seeberg KA, Borgeraas H, Hofsø H, et al. Gastric bypass versus sleeve gastrectomy in type 2 diabetes: effects on hepatic steatosis and fibrosis: a randomized controlled trial. Ann Intern Med 2022;175:74–83. Bariatric surgery has an increasingly recognized role in treating metabolic syndrome, and benefits nonalcoholic fatty liver disease (NAFLD) specifically (Gastroenterology 2020;159:1290–1301). However, the extent to which bariatric surgery might impact NAFLD progression and whether various bariatric approaches affect this differently remain relatively unexplored. Seeberg et al undertook a single-center randomized trial in which 100 participants with type 2 diabetes mellitus (T2DM) and obesity were randomized 1:1 to either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) and followed up to 1 year postoperatively. Although the primary trial outcomes related to T2DM remission have been published (Lancet Diabetes Endocrinol 2019;7:912–924), this present study described predefined outcomes related to hepatic steatosis (assessed via liver fat fraction on magnetic resonance imaging), enhanced liver fibrosis test (as a proxy of hepatic fibrosis), and other noninvasive NAFLD markers. At 1-year follow-up, there was a 20% reduction (95% CI, 23% to 17%) in liver fat fraction in the SG group and 22% (95% CI, 24% to 19%) observed in the RYGB group, with no significant difference between groups. Almost all patients—94% of the SG group and 100% of the RYGB group—had no or low-grade steatosis at 1 year (compared with ∼25% of participants at baseline). The enhanced liver fibrosis score category remained stable in 77% of patients, but 18% experienced worsening of fibrosis at 1 year, with no substantial between-group difference. Weight loss, improvements in lipid profile, and remission rates for T2DM favored RYGB compared with SG. Collectively, these data demonstrate that both evaluated forms of bariatric surgery are of comparable high efficacy in improving hepatic steatosis, although this may not translate into short-term improvements in hepatic fibrosis. Study limitations include it being a single-center trial, possible underpowering for NAFLD-related outcomes (given the primary outcome relating to T2DM), and the reliance on a noninvasive marker (enhanced liver fibrosis) as the main measure of hepatic fibrosis, with no liver biopsies obtained. Given that steatohepatitis typically progresses to fibrosis over the course of years rather than months in NAFLD, results of the already planned longer-term follow-up will be of great pertinence for gauging the full impact of bariatric surgery. Splitting Hairs: Folliculin Parts the Good From the Bad in mTORC1 Control Over Lipid MetabolismGastroenterologyVol. 163Issue 2PreviewGosis BS, Wada S, Thorsheim C, et al. Inhibition of nonalcoholic fatty liver disease in mice by selective inhibition of mTORC1. Science 2022;376(6590):eabf8271. Full-Text PDF

Serum Ferritin and NAFLD in Patients Undergoing Bariatric Surgery.

Non-alcoholic fatty liver disease (NAFLD) has become a challenge in public health, as the prevalence of obesity and overweight has been increasing. It has been observed that serum ferritin (SF) levels are commonly elevated in NAFLD patients. To assess the relationship between SF levels and NAFLD, exploring the role of SF as a non-invasive marker of NAFLD. Clinical, anthropometric, laboratory, and histological data of patients with obesity who underwent bariatric surgery in a reference center in Brazil were retrospectively evaluated. Data were collected in the preoperative period up to the first year postoperatively. A total of 431 patients were analyzed. The prevalence of hyperferritinemia was 18% in the preoperative period and 14% 1 year after the surgery. After multiple regression analysis, elevated SF was not an independent predictor of steatosis, non-alcoholic steatohepatitis (NASH), or liver fibrosis. Increased SF levels are common in patients with NAFLD; however, SF was not considered an independent predictor of steatosis, NASH, or fibrosis.

Endogenous Liver Protections Against Lipotoxicity and Oxidative Stress to Avoid the Progression of Non-alcoholic Fatty Liver to more Serious Disease.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder characterized by an ectopic accumulation of lipids in at least 5% of hepatocytes. The first phase of the disease, called hepatic steatosis, progresses over time to chronic conditions, such as steatohepatitis, cirrhosis, and finally, hepatic insufficiency and cancer. The accumulation of free fatty acids in hepatocytes, particularly saturated fatty acids, is a key process in the development and progression of NAFLD. Furthermore, the accumulation of oxidative stress markers in NAFLD is closely linked to lipotoxicity due to impaired lipid metabolism and increased generation of reactive oxygen species (ROS). However, endogenous mechanisms are activated early in the liver to protect against lipotoxicity and oxidative stress, thus preventing liver mass loss and disease progression. Thus, in order to develop appropriate therapies, the purpose of this review is to discuss recent data from the literature regarding the importance of intrinsic mechanisms deployed by the liver in protecting itself against the adverse effects related to chronic lipid accumulation and ROS generation.

1432-P: ALT Elevation Suggestive of NAFLD in Overweight and Obese Youth on Second-Generation Antipsychotics

Second-generation antipsychotics (SGAs) increase risk for insulin resistance and metabolic syndrome. Less is known about the risk of nonalcoholic fatty liver disease (NAFLD) in youth treated with SGAs. MOBILITY is a large, multi-center, pragmatic study designed to assess the effect of metformin added to lifestyle instruction compared to lifestyle instruction alone on weight gain and metabolic parameters in youth with overweight and obesity (ages 8-19) and bipolar-spectrum disorders receiving SGAs. We examined baseline ALT as a marker for NAFLD in 840 youth in the study (78% with obesity; 46% female; 68% white; 17% black; 11% Hispanic) . Overall, 44% of subjects had mild ALT elevation (ALT&amp;gt;22 females; ALT&amp;gt;25 males) , and 10% had significantly elevated ALT≥ 45 (2× ULN) . Male sex (p&amp;lt;0.001) , obesity (p=0.007) , and white race (p=0.009) were significantly associated with ALT elevation. Hispanic ethnicity and age were not significantly associated with ALT elevation. There was no difference in duration of exposure to SGAs (&amp;lt; 1 year vs. &amp;gt; 1 year of exposure) . There was a trend towards an association between prediabetes and significant ALT elevation (2× ULN; p=0.06) ; however, glucose was not associated with ALT elevation overall. Although we had no imaging or biopsy data in these patients, our study demonstrates that a clinically relevant percentage of youth with overweight and obesity treated with SGAs have elevated ALT suggestive of NAFLD; in fact, the prevalence of elevated ALT is higher than expected with obesity alone. Given that NAFLD is the most common liver disease now in youth and can progress to cirrhosis and liver failure, our findings suggest that pediatric psychiatrists who treat these patients must screen for NAFLD with ALT and refer patients for further evaluation and management as needed. Disclosure N.A.Crimmins: None. M.Mouzaki: None. M.P.Delbello: Board Member; Sage Pharmaceuticals, Consultant; Alkermes, Sunovion Pharmaceuticals Inc., Research Support; Alkermes, Johnson &amp; Johnson, Lundbeck, Shire plc., Speaker's Bureau; Sunovion Pharmaceuticals Inc. C.Correll: Consultant; Alkermes, Janssen Pharmaceuticals, Inc., Lundbeck, Medscape, Mylan N.V., Neurocrine Biosciences, Inc., Otsuka America Pharmaceutical, Inc., Sunovion Pharmaceuticals Inc., Takeda Pharmaceutical Company Limited, Teva Pharmaceutical Industries Ltd. J.Welge: None. Funding Mobility: Improving Patient-Centered Outcomes Among Overweight and Obese Youth with Bipolar Spectrum Disorders Treated with Second-Generation Antipsychotics. [PICORI (Delbello) ].

29-OR: Impact of Carbohydrate-Restricted Nutrition Therapy Delivered via Continuous Remote Care on Metabolic Markers in Veterans with Type 2 Diabetes: A Nationwide, Real-World Study

Type 2 Diabetes (T2D) affects one in four Veterans and often occurs with dyslipidemia, chronic kidney disease, and nonalcoholic fatty liver disease (NAFLD) . In a pilot program, the Veterans Health Administration partnered with Virta Health to provide carbohydrate restricted nutrition therapy via continuous remote care to Veterans to reverse T2D by reducing glucose and dependence on medication, as demonstrated in prior research. This retrospective analysis assessed the 1- and 2-year effects on lipids and renal and hepatic markers in a real-world sample of Veterans with T2D using medical record data. Changes in metabolic markers from enrollment to 1- and 2-years (E, 1y, 2y) were assessed with paired t-tests with Holm-Bonferroni correction for multiple comparisons. Veterans retained at least two years at time of analysis were included (n=254, 58.5% of 434 eligible enrolled, 60±8 years, 12% female) . HDL-C (E: 42±16, 1y: 46±12, 2y: 44±11 mg/dl; ps&amp;lt;0.001) and triglycerides (E: 205±168, 1y: 186±184, 2y: 160±119 mg/dl; 2y p&amp;lt;0.05) improved. Total cholesterol (E: 165±46 mg/dl) and nonHDL-C (E: 124±46 mg/dl) were unchanged. Serum creatinine (E: 1.0±0.3 mg/dl) and eGFR (E: 85±18 ml/min/1.73m2) were stable; BUN increased (E: 17.3±6.1; 1y: 19.6±8.4, 2y: 18.9±7.6 mg/dl, ps&amp;lt;0.05) but remained within normal limits. Liver enzymes (ALP at E: 77.8±24.6 U/L; ALT at E: 32.3±17.1 U/L) were within normal limits and unchanged except AST decreased (E: 26.6±14.1, 1y: 21.7±8.7, 2y: 21.8±9.3 U/L, 2y p&amp;lt;0.05) . Veterans with T2D who underwent two years of diabetes reversal treatment improved atherogenic dyslipidemia and AST with no adverse effects on other markers of NAFLD and renal function, suggesting long term broad metabolic health benefit of this care model in the real world. Disclosure M.Vantieghem: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. A.L.Mckenzie: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. R.E.Ratner: Employee; Virta Health Corp.

Combined Effects of Chronic Kidney Disease and Nonalcoholic Fatty Liver Disease on the Risk of Cardiovascular Disease in Patients with Diabetes.

Background: We investigated the combined effect of chronic kidney disease (CKD) and nonalcoholic fatty liver disease (NAFLD) on the risk of cardiovascular disease (CVD) in patients with type 2 diabetes. Methods: Data were obtained from the Korean National Health Insurance Service. Patients with diabetes who participated in health screenings from 2009 to 2011 were included. The fatty liver index (FLI) was used as a surrogate marker for NAFLD. Results: During a mean follow-up of 6.9 years, 40,863 incidents of myocardial infarction (MI), 58,427 strokes, and 116,977 deaths were reported in 1,607,232 patients with type 2 diabetes. After adjusting for conventional risk factors, patients with CKD and NAFLD showed the highest risk of MI and stroke (hazard ratio (HR) = 1.49; 95% confidence interval (CI): 1.42–1.57 and stroke, HR = 1.48; 95% CI: 1.41–1.54, respectively) compared with those without either CKD or NAFLD. Both overall and cardiovascular mortality were highest in the CKD/NAFLD group compared with other groups (HR = 2.00; 95% CI: 1.94–2.06, and HR = 2.20; 95% CI: 2.07–2.35, respectively). Advanced liver fibrosis was significantly associated with an increased risk of CVD in patients with NAFLD. Proteinuria was significantly associated with incidence of CVD events in patients with CKD. Conclusions: The combination of CKD and NAFLD was associated with an increased risk of CVD and mortality in patients with type 2 diabetes. Close monitoring and appropriate management of CKD and NAFLD may be warranted to prevent CVD in these patients.

Association between the fatty liver index and the risk of severe complications in COVID-19 patients: a nationwide retrospective cohort study

BackgroundResearch on the association of non-alcoholic fatty liver disease (NAFLD) with prognosis in COVID-19 has been limited. We investigated the association between the fatty liver index (FLI), a non-invasive and simple marker of NAFLD, and the severe complications of COVID-19 patients in South Korea.MethodsWe included 3122 COVID-19-positive patients from the nationwide COVID-19 cohort dataset in South Korea between January and June 2020. The FLI was calculated using triglyceride, body mass index, glutamyl transpeptidase, and waist circumference, which were obtained from the national health screening program data. Severe complications related to COVID-19 were defined as the composite of mechanical ventilation, intensive care unit treatment, high-oxygen flow therapy, and death within 2 months after a COVID-19 infection. We performed a multivariate logistic regression analysis for the development of severe complications in COVID-19 patients.ResultsThe mean ± standard deviation of FLI were 25.01 ± 22.64. Severe complications from COVID-19 occurred in 223 (7.14%) patients, including mechanical ventilation in 82 (2.63%) patients, ICU admission in 126 (4.04%), high-flow oxygen therapy in 75 (2.40%), and death in 94 (3.01%) patients, respectively. The multivariate analysis indicated that the highest tertile (T3) of FLI was positively associated with severe complications from COVID-19 (adjusted odds ratio (OR): 1.77, 95% confidence interval (CI) (1.11–2.82), P = 0.017) compared with the lowest tertile (T1).ConclusionsOur study demonstrated that FLI, which represents NAFLD, was positively associated with an increased risk of severe complications from COVID-19. FLI might be used as a prognostic marker for the severity of COVID-19.

Bioinformatics screening and analysis of key differentially expressed genes characteristics in nonalcoholic fatty liver disease

Objective: To screen and analyze the key differentially expressed genes characteristics in nonalcoholic fatty liver disease (NAFLD) with bioinformatics method. Methods: NAFLD-related expression matrix GSE89632 was downloaded from the GEO database. Limma package was used to screen differentially expressed genes (DEGs) in healthy, steatosis (SS), and nonalcoholic steatohepatitis (NASH) samples. WGCNA was used to analyze the output gene module. The intersection of module genes and differential genes was used to determine the differential genes characteristic, and then GO function and KEGG signaling pathway enrichment analysis were performed. The protein-protein interaction network (PPI) was constructed using the online website STRING and Cytoscape software, and the key (Hub) genes were screened. Finally, R software was used to analyze the receiver operating characteristic curve (ROC) of the Hub gene. Results: 92 differentially expressed genes characteristic were obtained through screening, which were mainly enriched in inflammatory response-related functions of "lipopolysaccharide response and molecular response of bacterial origin", as well as cancer signaling pathways of "proteoglycan in cancer" and "T-cell leukemia virus infection-related". 10 hub genes (FOS, CXCL8, SERPINE1, CYR61, THBS1, FOSL1, CCL2, MYC, SOCS3 and ATF3) had good diagnostic value. Conclusion: The differentially expressed hub genes among the 10 NAFLD disease-related characteristics obtained with bioinformatics analysis may become a diagnostic and prognostic marker and potential therapeutic target for NAFLD. However, further basic and clinical studies are needed to validate.

Elevated Serum Regulator of Calcineurin 2 is Associated With an Increased Risk of Non-Alcoholic Fatty Liver Disease.

Background: The promoting effect of the regulator of calcineurin 2 (RCAN2) in hepatic steatosis has been observed in animal studies. However, the association of RCAN2 with non-alcoholic fatty liver disease (NAFLD) in humans remains unclear. This study aimed to evaluate the expression of RCAN2 in the liver of mice with hepatic steatosis and in the serum of NAFLD patients and to explore the relationship between serum RCAN2 levels and NAFLD. Methods: The mRNA and protein expression of RCAN2 were detected by quantitative real-time PCR (qRT-PCR) and Western blot. NAFLD was diagnosed by abdominal ultrasonography. Circulating RCAN2 levels were measured by ELISA kits. The relationship between serum RCAN2 levels and NAFLD was assessed. Results: qRT-PCR and Western blot analysis showed that compared with the corresponding controls, the mRNA and protein expression of RCAN2 were significantly increased in the liver tissues of db/db and mice on a high-fat diet. Serum RCAN2 levels were markedly elevated in NAFLD patients compared with non-NAFLD subjects. Binary logistic regression analysis showed that serum RCAN2 levels were significantly associated with NAFLD. Receiver operation characteristic (ROC) curve analysis showed that serum RCAN2 might act as a predictive biomarker for NAFLD [area under the curve (AUC) = 0.663, 95% CI = 0.623–0.702], and the serum RCAN2/(AST/ALT) ratio displayed improved predictive accuracy (AUC = 0.816, 95% CI = 0.785–0.846). Conclusion: Elevated serum RCAN2 levels were associated with an increased risk of NAFLD. Serum RCAN2, especially the serum RCAN2/(AST/ALT) ratio, might be a candidate diagnostic marker for NAFLD.

Correlation of serum uric acid level with non-alcoholic fatty liver disease (NAFLD) in patients attending at a tertiary level hospital

Non-alcoholic fatty liver disease (NAFLD) is considered as a common cause of chronic liver disease. It is potentially progressive towards non-alcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis and its complications including hepatocellular carcinoma (HCC). So, the need for predictive factors of NAFLD is important. Among the different serum markers in NAFLD, serum uric acid (SUA) has emerged as a possible predictor of severity of liver damage. This observational cross sectional study was carried out involving 100 patients from the department of gastroenterology, BSMMU, Dhaka, with the intention to determine the association of serum uric acid (SUA) level with non-alcoholic fatty liver disease. Among them, 55 were having NAFLD; and 45 subjects without NAFLD were considered as control. The diagnosis of NAFLD was based on the guidelines for the assessment and management of NAFLD in the Asia-pacific region. Serum uric acid, liver enzymes, glycaemic status, serum lipid profile and anthropometric measurements were compared between NAFLD group &amp; control. The mean age was found 41.34 + 10.88 years in both the groups. Male were 62% &amp; female were 38% among the study population. Forty percent of the study subjects were overweight, 23% were obese and 37% had normal body weight. NAFLD patients had significantly higher serum uric level (6.9 + 0.89 mg/dl) in comparison to non-NAFLD group (4.3 +0.87 mg/dl). The study showed that serum uric acid level was significantly associated with NAFLD. Serum uric acid may be used as a useful additional marker to assess the risk of development of NAFLD in the clinical setting of metabolic syndrome. BSMMU J 2021; 14(4): 125-131

The Role of Aspartate Transaminase to Platelet Ratio Index (APRI) for the Prediction of Non-Alcoholic Fatty Liver Disease (NAFLD) in Severely Obese Children and Adolescents.

The aspartate transaminase to platelet ratio index (APRI) has been proposed as an easy-to-use biochemical marker in obese adults with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatotic hepatitis (NASH). The objective of the present study was to evaluate the clinical and predictive value of APRI in a paediatric obese population. Seven hundred fifty-seven obese children and adolescents (BMI standard deviation score, SDS: >2.0; age range: 10–18.5 years), not consuming alcohol and without hepatitis B or C, were recruited after having been screened for NAFLD by ultrasonography. A series of demographic, biochemical and clinical parameters was compared between the two subgroups (with or without NAFLD); the same parameters were correlated with APRI; and finally, univariable and multivariable logistic regression was used to evaluate the predictors of NAFLD. NAFLD was diagnosed in about 39% of the entire paediatric population, predominantly in males and in subjects suffering from metabolic syndrome. APRI was correlated with the waist circumference (WC), high-density lipoprotein cholesterol (HDL-C), uric acid, total bilirubin, C reactive protein (CRP) and systolic blood pressure (SBP). Furthermore, APRI was higher in males than females, but independent from steatosis severity and metabolic syndrome. With the univariable analysis, the BMI SDS, triglycerides (TG), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), APRI, uric acid and metabolic syndrome were positive predictors of NAFLD, with female sex being negative predictor. At multivariable analysis; however, only BMI SDS, TG, HOMA-IR and APRI were positive predictors of NAFLD, with female sex being a negative predictor. The accuracy of APRI as a biochemical marker of NAFLD was about 60%.In conclusion, in a large (Italian) paediatric obese population, parameters, such as BMI SDS, TG, HOMA-IR and APRI, were positive predictors of NAFLD, with female sex being a negative predictor and most of the prediction explained by APRI. Nevertheless, APRI appears to be a simple biochemical marker of liver injury rather than of NAFLD/NASH and, moreover, is endowed with a limited accuracy for the prediction/diagnosis of NAFLD.

Associations of Serum Vitamin D Level with Sarcopenia, Non-Alcoholic Fatty Liver Disease (NAFLD), and Sarcopenia in NAFLD Among People Aged 50 Years and Older: The Korea National Health and Nutrition Examination Survey IV-V.

Background: The role of serum 25-hydroxyvitamin D [25(OH)D] levels in the development of sarcopenia in non-alcoholic fatty liver disease (NAFLD) remains controversial. We investigated the association between vitamin D levels, occurrence of sarcopenia, NAFLD, and sarcopenia in NAFLD in adults aged >50 years. Methods: This study used data pertaining to 5396 adults aged >50 years (1870 men and 3526 women) from the 2008-2011 Korea National Health and Nutrition Examination Survey. Appendicular skeletal muscle mass adjusted by weight (ASM/Wt) was used to diagnose sarcopenia, and NAFLD was diagnosed using the NAFLD fat score. Results: The lowest quintile of serum 25(OH)D level (4.85-15.26 ng/mL) was associated with an increased occurrence of sarcopenia [odds ratio (OR) 2.65; 95% confidence interval (CI) 1.64-4.27], NAFLD (OR 1.82; 95% CI 1.19-2.96), and sarcopenia in NAFLD (OR 2.25; 95% CI 1.26-4.03) in men. In women, sarcopenia (OR 1.80; 95% CI 1.29-2.51) was also significantly associated with serum vitamin D levels, whereas high levels of vitamin D were not significantly related to NAFLD. Conclusions: Serum vitamin D levels are associated with sarcopenia, NAFLD, and sarcopenia in NAFLD. Vitamin D level can be a useful marker of sarcopenia and NAFLD, especially in men.