The Visceral Adiposity Index in Non-Alcoholic Fatty Liver Disease and Liver Fibrosis—Systematic Review and Meta-Analysis

(1) Background: In order to avoid a liver biopsy in non-alcoholic fatty liver disease (NAFLD), several noninvasive biomarkers have been studied lately. Therefore, we aimed to evaluate the visceral adiposity index (VAI) in NAFLD and liver fibrosis, in addition to its accuracy in predicting NAFLD and NASH. (2) Methods: We searched PubMed, Embase, Scopus, and Cochrane Library, identifying observational studies assessing the VAI in NAFLD and liver fibrosis. QUADAS-2 was used to evaluate the quality of included studies. The principal summary outcomes were mean difference (MD) and area under the curve (AUC). (3) Results: A total of 24 studies were included in our review. VAI levels were significantly increased in NAFLD (biopsy-proven and ultrasound-diagnosed), simple steatosis vs. controls, and severe steatosis vs. simple steatosis. However, no significant MD was found according to sex, liver fibrosis severity, simple vs. moderate and moderate vs. severe steatosis, pediatric NAFLD, and NASH patients. The VAI predicted NAFLD (AUC 0.767) and NASH (AUC 0.732). (4) Conclusions: The VAI has a predictive value in diagnosing NAFLD and NASH, with significantly increased values in adult NAFLD patients, simple steatosis compared to controls, and severe steatosis compared to simple steatosis.

FAT score: an Indian insight to a novel diagnostic score to differentiate non-alcoholic steatohepatitis (NASH) from simple steatosis

Background The aim of this study was to propose a simple predictive score to differentiate NASH from simple steatosis. Results This study included 64 patients who had biopsy-proven NAFLD, of which 34 patients had steatohepatitis and 30 had simple steatosis. Clinical, anthropometric, and biochemical variables of the study population were analyzed. Univariate analysis showed platelet count, ferritin, and transaminases (ALT&AST) were predictors of NASH. This led to the proposal of a new diagnostic tool, FAT score (F signifies Ferritin, A indicates AST&ALT, T denotes t in Platelet) with AUROC of 0.95. The ROC curves for the significant variables were plotted and cutoff values were identified. Each component is awarded a score of 0 or 1, based on this cutoff value. The component is awarded a score of 1 if the component score is above the cutoff value and 0, if the score is below cutoff. The maximum score which can be obtained is 4. A score of ≥ 3 was able to predict NASH from simple steatosis with a sensitivity of 76.5% and a specificity of 100%. The score was validated with a cohort of 84 liver biopsy patients wherein a cutoff ≥ 3 was found to give a specificity of 100% in the validation cohort. Conclusions FAT score is a simple predictive model to differentiate NASH from simple steatosis (cutoff of more than or equal to 3) without performing a liver biopsy. A FAT score less than 3 rules out the need for biopsy.

Impact of Nonalcoholic Steatohepatitis on the Outcome of Patients Undergoing Roux-en-Y Gastric Bypass Surgery: a Propensity Score–Matched Analysis

Purpose It is currently unknown whether NASH (nonalcoholic steatohepatitis), as compared to simple steatosis, is associated with impaired postoperative weight loss and metabolic outcomes after RYGB surgery. To compare the effectiveness of Roux-en-Y gastric bypass (RYGB) on patients with NASH versus those with simple nonalcoholic fatty liver (NAFL). Materials and Methods We retrospectively retrieved data from 515 patients undergoing RYGB surgery with concomitant liver biopsy. Clinical follow-up and metabolic assessment were performed prior to surgery and 12 months after surgery. We used multivariate analysis of variance (MANOVA) and propensity score matching and we assessed for changes in markers of hepatocellular injury and metabolic outcomes. Results There were 421 patients with simple NAFL, and 94 with NASH. Baseline alanine and aspartate aminotransferases were significantly higher in patients with NASH (p < 0.01). Twelve months after the RYGB surgery, as determined by both MANOVA and propensity score matching, patients with NASH exhibited a significantly greater reduction in alanine aminotransferase (ß-coefficient − 12 iU/l [− 22 to − 1.83], 95% CI, adjusted p = 0.021) compared to their NAFL counterparts (31 matched patients in each group with no loss to follow-up at 12 months). Excess weight loss was similar in both groups (ß-coefficient 4.54% [− 3.12 to 12.21], 95% CI, adjusted p = 0.244). Change in BMI was comparable in both groups (− 14 (− 16.6 to − 12.5) versus − 14.3 (− 17.3 to − 11.9), p = 0.784). Conclusion After RYGB surgery, patients with NASH experience a greater reduction in markers for hepatocellular injury and similar weight loss compared to patients with simple steatosis.

Clinical Significance of HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA Panel in NAFLD/NASH Diagnosis: Egyptian Pilot Study

Background: Non-alcoholic steatohepatitis ((NASH) is the progressive form of (non-alcoholic fatty liver disease) (NAFLD), which can progress to liver cirrhosis and hepatocellular carcinoma. There is no available reliable non-invasive diagnostic tool to diagnose NASH, and still the liver biopsy is the gold standard in diagnosis. In this pilot study, we aimed to evaluate the Nod-like receptor (NLR) signaling pathway related RNA panel in the diagnosis of NASH. Methods: Bioinformatics analysis was done, with retrieval of the HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA panel based on the relation to the NLR-signaling pathway. Hepatitis serum markers, lipid profile, NAFLD score and fibrosis score were assessed in the patients’ sera. Reverse transcriptase real time polymerase chain reaction (RT-PCR) was done to assess the relative expression of the RNA panel among patients who had NAFLD without steatosis, NAFLD with simple steatosis, NASH and healthy controls. Results: We observed up-regulation of Lnc-SPARCL1-1:2 lncRNA that led to upregulation of miR-6881-5P with a subsequent increase in levels of HSPD1, MMP14, and ITGB1 mRNAs. In addition, ROC curve analysis was done, with discriminative cutoff values that aided discrimination between NASH cases and control, and also between NAFLD, simple steatosis and NASH. Conclusion: This pilot study concluded that HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 panel expression has potential in the diagnosis of NASH, and also differentiation between NAFLD, simple steatosis and NASH cases.

IGFBP-2 as a biomarker in NAFLD improves hepatic steatosis:an integrated bioinformatics and experimental study

Background and aims: Non-alcoholic fatty liver disease (NAFLD) has become a common chronic liver disease in the world. Simple steatosis is the early phase of NAFLD. However, the molecular mechanisms underlying the development of steatosis have not yet been fully elucidated. Methods: Two public datasets (GSE48452 and GSE89632) through the Gene Expression Omnibus (GEO) database were used to identify differentially expressed genes (DEGs) in the development of steatosis. A total of 72 participants including 38 normal histological controls and 34 simple steatosis patients were included in this study. GO, KEGG and PPI network analysis were performed to explore the function of DEGs. The results were further confirmed in high-fat diet (HFD)-fed mice and oleate-treated HepG2 cells. Results: Total 57 DEGs including 31 up- and 26 down-regulated genes between simple steatosis patients and healthy controls were determined. GO and KEGG analysis showed that most of DEGs were enriched in the ligand-receptor signaling pathways. PPI network construction was used to identify the hub genes of the DEGs. MYC, ANXA2, GDF15, AGTR1, NAMPT, LEPR, IGFBP-2, IL1RN, MMP7 and APLNR were identified as hub genes. And IGFBP-2 expression was found to be reversely associated with hepatic steatosis, fasting insulin, HOMA-IR index and ALT levels. In HFD-fed mice, hepatic IGFBP-2 was also downregulated and negatively associated with hepatic triglyceride levels. Moreover, overexpression IGFBP-2 ameliorated the oleate induced accumulation of triglycerides in hepatocytes. Conclusions: This study identified novel gene signatures in the hepatic steatosis and will provide new understanding and molecular clues of hepatic steatosis.

PERFORMACE OF TRIGLYCERIDE-GLUCOSE INDEX ON DIAGNOSIS AND STAGING OF NAFLD IN OBESE PATIENTS

ABSTRACT BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in the world, and its prevalence is increasing alongside obesity. In United States, NAFLD is already the second leading cause of liver transplantation. The spectrum of the disease ranges from simple steatosis, which has a benign course, to steatohepatitis, which may progress to cirrhosis and its complications. The rising of noninvasive methods for diagnosing and staging non-alcoholic steatohepatitis (NASH) and fibrosis decreases the need of liver biopsy, as well as the costs and the occurrence of complications related to it. OBJECTIVE: To analyze the performance of the triglyceride-glucose index to evaluate steatosis, NASH and liver fibrosis in obese patients with NAFLD. METHODS: This is a retrospective cross-sectional study. Every medical record of patients who were candidates for bariatric surgery at a leading hospital in Southern Brazil were analyzed. The triglyceride-glucose index (TyG Index), a method composed only of two simple laboratory tests (serum triglycerides and fasting glucose levels), was performed prior to surgery. The TyG Index performance regarding the anatomopathological findings was evaluated, and the AUROC curve was calculated to evaluate the best cut-off point for diagnosing steatosis, non-alcoholic steatohepatitis and liver fibrosis grade. Also, the NAFLD fibrosis Score (NFS) was evaluated. RESULTS: A total of 423 patients were evaluated. The TyG Index with a cut-off point of 8.76 excluded significant simple steatosis (grade 2-3) in obese patients, with 67.6% sensitivity, 65.1% specificity, 46.3% positive predictive value (PPV), 81.8% negative predictive value (NPV), 65.8% accuracy and 0.66 AUROC (P=0.005). In the evaluation of NASH, the TyG Index with a cut-off point of 8.82 excluded significant NASH (grade 2-3) with 57.3% sensitivity, 58.6% specificity, 33.7% PPV, 78.8% NPV, 58.2% accuracy and 0.58 AUROC (P=0.022). When evaluating liver fibrosis, the TyG Index with a cut-off point of 8.91 showed a sensitivity of 61.8%, a specificity of 62.5%, a PPV of 13.8 and a NPV of 94.4% for exclusion of advanced fibrosis (F3-4), with a 62.4% accuracy and 0.69 AUROC (P<0.001). When analyzing the performance of NFS in the diagnosis of advanced fibrosis, the cut-off point <-1.455 excluded advanced fibrosis with sensitivity of 59.4%, specificity of 51%, PPV of 11%, NPV of 92.4% and accuracy of 51.7%. However, the cut-off point of 0.676 to diagnose advanced fibrosis presented sensitivity of 21.9%, specificity of 83%, PPV of 11.7%, NPV of 91.2% and 77.3% accuracy. The AUROC was 0.54 (P=0.480). CONCLUSION: TyG Index did not perform well in the diagnosis of significant steatosis and NASH. However, it was able to exclude advanced fibrosis in obese patients who are candidates for bariatric surgery.

Dietary Patterns in Patients With Different Forms of Non-alcoholic Fatty Liver Disease

Objectives The aim of the study was to compare food patterns in patients with simple steatosis (SS) and non-alcoholic steatohepatitis (NASH). Methods Prospective study was approved by LEC and enrolled subjects with confirmed non-alcoholic fatty liver disease (SS or NASH group). Nutrilogic software (Nutrilogic, Russia) was used for diet assessment. Dietary patterns were assessed according to the Healthy Eating Index (HEI): amounts of the major groups of foods and food products (grains, fruits, vegetables, dairy products, meats, fats and confectioneries) consumption were compared to the levels described in the HEI, and individual deviation rates were obtained. Nonparametric statistics (Mann-Whitney U test) was used to compare deviation rates found in subjects of SS and NASH groups. Results Subjects in NASH group (n = 22) were younger (Mean ± SD: 48.6 ± 13.4 y.o.) than those in SS group (n = 156; 56.5 ± 12.3 y.o., P = 0.008). Main macronutrients consumption did not differ between the groups. Although dietary patterns of major groups of foods consumption did not differ between SS and NASH groups, analysis of the foods subgroups revealed dissimilarity in the structure of vegetables and fats consumption. Patients with NASH consumed larger amounts of potatoes (0.14 ± 0.08 vs 0.11 ± 0.15, P = 0.006), and lower – of onions (0.02 ± 0.03 vs 0.07 ± 0.1, P = 0.006); they also consumed lower amounts of dairy butter (0.14 ± 0.44 vs 0.15 ± 0.21, P = 0.009) compared to subjects with simple steatosis. No other difference in the structure of vegetables (beans, root crops, leafy and other vegetables), fats (animal fats, vegetable oils, margarines) and other major groups of foods consumption was revealed. Conclusions Dietary patterns of patients with non-alcoholic steatohepatitis and simple steatosis differ. The obtained results may help in diet modification in patients with NAFLD in case of confirmation in larger multicenter trials. Funding Sources Russian Science Foundation, grant #1976-30014.

Validity of routine biochemical and ultrasound scores for prediction of hepatic fibrosis and steatosis in NAFLD

Background We evaluated the validity of some non-invasive scores and ultrasound findings to predict fibrosis and steatosis in a cohort of NAFLD patients who underwent liver biopsy. Ninety-seven NAFLD patients were enrolled and classified into NASH (66) and simple steatosis groups (31) based on liver biopsy. ROC curves were constructed for Fibrosis-4 index (FIB4), aspartate aminotransferase to platelet ratio index (APRI), and NAFLD fibrosis score (NFS) in fibrosis prediction, also for (hepatic steatosis index; HSI, fatty liver index; FLI) and ultrasonographic subcutaneous and visceral adipose tissue measurements (SAT and VAT) for steatosis prediction. Results FIB4 had AUC of 0.6, APRI and NFS at cutoffs of 0.3 and -.2.4 had AUC of 0.64 and 0.63 in detecting the presence of any grade of fibrosis, and of (0.52, 0.55, and 0.58) for significant fibrosis. FIB4 at a cut-off of (0.76) had the highest AUC in detecting any grade of fibrosis in the simple steatosis group (0.81). SAT (at cutoff of 2.1 and 2.5) was superior to VAT. HSI (at cutoff 45.35 and 45.7) was superior to FLI in detecting moderate or marked steatosis. Conclusion FIB4 and NFS can be used in screening for silent liver disease with ongoing fibrosis in simple steatosis. They are unsatisfactory predictors for significant fibrosis in NAFLD. SAT is better than VAT in predicting moderate steatosis and is slightly better than biochemical HSI.

Non-targeted Serum Metabolomics Identifies Candidate Biomarkers Panels Associated with Nonalcoholic Fatty Liver Disease: A Pilot Study in Russian Male Patients

Aims: The aim of the present study was to explore changes in the serum metabolome of patients with NAFLD relative to healthy controls to identify biomarkers associated with steatosis or Non-Alcoholic Steatohepatitis (NASH). Background: The serum metabolome reflects changes at the organismal level. This is especially important in Non-Alcoholic Liver Disease (NAFLD), where changes in hormones, cytokines, enzymes and other metabolic alterations can affect the liver, as well as adipose tissue, skeletal muscle and other systems. Objective: The objectives were to conduct non-targeted serum metabolomics, data processing, and identification of candidate biomarkers, as well as panels and assessment of their prognostic value. Materials and Methods: Non-targeted metabolomic analysis of blood serum samples from 21 male patients with NAFLD (simple steatosis or NASH) and seven male Control group was performed using gas chromatography-mass spectrometry. Results: A total of 319 serum metabolites were detected in NAFLD and Control groups, several of which differed significantly between groups. The most discriminating biomarkers were 3-hydroxybutyric acid, 2-hydroxybutyric acid, 2,3-dihydroxybutyric acid, arabitol and 3-methyl-2-oxovaleric acid. Using a panel of three, four or more markers could distinguish patients with NAFLD from controls, and patients with NASH from those with simple steatosis. Conclusion: We identified candidate biomarkers for simple steatosis and NASH. Since NAFLD is a multifactorial disease, it is preferable to use a marker panel rather than individual metabolites. Markers may not only result from dysregulation of metabolic pathways in patients with NAFLD, they may also reflect adaptive responses to disease, including functional changes in the intestinal microbiota.