Prognosis Of Nonalcoholic Fatty Liver Disease Research Articles

Dapagliflozin ameliorates hepatic steatosis via suppressing LXRα-mediated synthesis of lipids and bile acids

Nonalcoholic fatty liver disease (NAFLD) prevalence is rising globally with no pharmacotherapies approved. Hepatic steatosis is closely associated with progression and prognosis of NAFLD. Dapagliflozin, kind of sodium-glucose cotransporter 2 (SGLT2) inhibitor, was found to improve NAFLD in clinical trials, while the underlying mechanism remains poorly elucidated. Here, we reported that dapagliflozin effectively mitigated liver injury and relieved lipid metabolism disorders in vivo. Further investigation showed that dapagliflozin markedly suppressed Liver X Receptor α (LXRα)-mediated synthesis of de novo lipids and bile acids (BAs). In AML12 cells, our results proved dapagliflozin decreased lipid contents via inhibiting the expression of LXRα and downstream liposynthesis genes. Proteosome inhibitor MG132 eliminated the effect of dapagliflozin on LXRα-mediated signaling pathway, which suggested that dapagliflozin downregulated LXRα expression through increasing LXRα degradation. Knockdown of LXRα with siRNA abolished the reduction of lipogenesis from dapagliflozin treatment, indicating that LXRα might be the pivotal target for dapagliflozin to exhibit the aforementioned benefits. Furthermore, the data showed that dapagliflozin reversed gut dysbiosis induced by BAs disruption and altered gut microbiota profile to reduce intestinal lipids absorption. Together, our study deciphered a novel mechanism by which dapagliflozin relieved hepatic steatosis and highlighted the potential benefit of dapagliflozin in treating NAFLD.

Serum uric acid levels and prognosis of patients with non-alcoholic fatty liver disease

Uric acid (UA) is associated with non-alcoholic fatty liver disease (NAFLD). However, it is unclear whether UA plays a predictive role in NAFLD prognosis. This study aimed to explore the relationship between UA levels and mortality in NAFLD patients without severe renal disease. Data were obtained from the Third National Health and Nutrition Examination Survey (NHANES). Time-dependent Cox regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for mortality. Overall, 2493 individuals with NAFLD and estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 were included in this study. The median follow-up period was 26.58 years. Patients were divided into high and low-UA groups according to UA levels. Time-independent Cox regression showed that UA level was not an independent risk factor for mortality in NAFLD patients without decreased eGFR (P > 0.05). After matching for age and sex using the propensity score matching method, UA remained not independently associated with death in NAFLD patients (P > 0.05). Similar results were found for cardiovascular-related and cancer-related deaths. Although UA is closely related to NAFLD, UA levels are not independently associated with the long-term survival of patients with NAFLD without decreased eGFR.

Neutrophils: tissue and circulating signatures of pediatric non-alcoholic fatty liver disease.

The recent rise in non-alcoholic fatty liver disease (NAFLD) among children and adolescents led to a thorough investigation of the peculiarities of the cellular infiltrate which characterize the disease at young ages. This review aims to highlight the key involvement of neutrophils in the pathogenesis of pediatric NAFLD and the potential biomarker role of neutrophil-to-lymphocyte ratio (NLR) in the same pediatric disorder. Neutrophils, which are first responders to inflammation, constitute an abundant component of an infiltrate which is particularly disposed within the portal area of children with NAFLD. The involvement of neutrophils in triggering liver fibrosis has been related amongst others to reactive oxygen species (ROS) production, to the stimulation of hepatic stellate cells, and to their synthesis of neutrophil elastase. As immune imbalance characterizes NAFLD, potentially emerging non-invasive biomarkers such as NLR have been proposed for the detection and prognosis of NAFLD. In adults, several studies asserted the role of NLR in the prediction of advancing liver fibrosis and mortality in subjects with NAFLD. In children, data is scarce with contradicting findings, as some studies failed to identify significant shifting in NLR values in children with NAFLD when compared with obese controls without liver impairment. However, NLR seems to significantly increase in children with obesity and different degrees of NAFLD when compared to healthy counterparts and their changes seem to be reversible with weight loss. Still, paucity of pediatric studies calls for future research addressing the role of NLR in predicting NAFLD development and progression in children with obesity.

Potential therapeutic targets for nonalcoholic fatty liver disease: Glucagon-like peptide 1.

Nonalcoholic fatty liver disease (NAFLD) is the most rapidly growing contributor to liver mortality and morbidity. Hepatocellular injury in nonalcoholic steatohepatitis (NASH) is caused by an increase in metabolic substrates (glucose, fructose, and fatty acids), leading fatty acids to participate in pathways that cause cellular injury and a poor response to injury. The pathogenesis of this disease is largely associated with obesity, type 2 diabetes, and increasing age. To date, there are no Food and Drug Administration-approved treatments for NAFLD/NASH or its associated fibrosis. Since one of the pathogenic drivers of NASH is insulin re-sistance, therapies approved for the treatment of type 2 diabetes are being evaluated in patients with NASH. Currently, the glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide is a safe, well-studied therapeutic for NAFLD/ NASH patients. Existing research demonstrates that semaglutide can increase the resolution of NASH but not improve fibrosis. However, improving the fibrosis of NAFLD is the only way to improve the long-term prognosis of NAFLD. Given the complex pathophysiology of NASH, combining therapies with complementary mechanisms may be beneficial. Researchers have conducted trials of semaglutide in combination with antifibrotic drugs. However, the results have not fully met expectations, and it cannot be ruled out that the reason is the short trial time. We should continue to pay increasing attention to GLP-1RAs.

Comprehensive Strategy for Identifying Extracellular Vesicle Surface Proteins as Biomarkers for Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is a liver disorder that has become a global health concern due to its increasing prevalence. There is a need for reliable biomarkers to aid in the diagnosis and prognosis of NAFLD. Extracellular vesicles (EVs) are promising candidates in biomarker discovery, as they carry proteins that reflect the pathophysiological state of the liver. In this review, we developed a list of EV proteins that could be used as diagnostic biomarkers for NAFLD. We employed a multi-step strategy that involved reviewing and comparing various sources of information. Firstly, we reviewed papers that have studied EVs proteins as biomarkers in NAFLD and papers that have studied circulating proteins as biomarkers in NAFLD. To further identify potential candidates, we utilized the EV database Vesiclepedia.org to qualify each protein. Finally, we consulted the Human Protein Atlas to search for candidates' localization, focusing on membrane proteins. By integrating these sources of information, we developed a comprehensive list of potential EVs membrane protein biomarkers that could aid in diagnosing and monitoring NAFLD. In conclusion, our multi-step strategy for identifying EV-based protein biomarkers for NAFLD provides a comprehensive approach that can also be applied to other diseases. The protein candidates identified through this approach could have significant implications for the development of non-invasive diagnostic tests for NAFLD and improve the management and treatment of this prevalent liver disorder.

Dietary cholesterol drives the development of nonalcoholic steatohepatitis by altering gut microbiota mediated bile acid metabolism in high-fat diet fed mice

Nonalcoholic fatty liver disease (NAFLD) is the most widespread chronic liver disorder globally. Unraveling the pathogenesis of simple fatty liver to nonalcoholic steatohepatitis (NASH) has important clinical significance for improving the prognosis of NAFLD. Here, we explored the role of a high-fat diet alone or combined with high cholesterol in causing NASH progression. Our results demonstrated that high dietary cholesterol intakes accelerate the progression of spontaneous NAFLD and induces liver inflammation in mice. An elevation of hydrophobic unconjugated bile acids cholic acid (CA), deoxycholic acid (DCA), muricholic acid and chenodeoxycholic acid, was observed in high-fat and high-cholesterol diet fed mice. Full-length sequencing of the 16S rDNA gene of gut microbiota revealed a significant increase in the abundance of Bacteroides, Clostridium, and Lactobacillus that possess bile salt hydrolase activity. Furthermore, the relative abundance of these bacterial species was positively correlated with content of unconjugated bile acids in liver. Moreover, the expression of genes related to bile acid reabsorption (organic anion-transporting polypeptides, Na+-taurocholic acid cotransporting polypeptide, apical sodium dependent bile acid transporter and organic solute transporter β) was found to be increased in mice with a high-cholesterol diet. Lastly, we observed that hydrophobic bile acids CA and DCA induce an inflammatory response in free fatty acids-induced steatotic HepG2 cells. In conclusion, high dietary cholesterol promotes the development of NASH by altering gut microbiota composition and abundance and thereby influencing with bile acid metabolism.

Noninvasive tests predict liver-related events and mortality in patients with nonalcoholic fatty liver disease: sub-analysis of the CLIONE-Asia study.

Noninvasive tests (NITs) have prognostic potential, but whether NITs are comparable with liver biopsy is unclear. This study aimed to examine the prognostic accuracy of NITs for liver-related mortality (LRM) and events (LREs) in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD). We investigated 1313 patients with NAFLD. Patients were assigned to low-risk, indeterminate-risk, and high-risk groups using conventional cutoff values of each FIB-4 and NAFLD fibrosis score (NFS) and to stage 0-2 and stage 3-4 groups using the fibrosis stage. Survival and Cox regression analyses of the prognostic potential of NITs for LRM/LREs were conducted. During a median follow-up of 4.5years, regarding to FIB-4, the incidence rate (/1000 person-years) in the low risk was zero for LRM and 0.5 for LREs. In contrast, the rate in stage 0-2 was 1.3 for LRM and 2.8 for LRE. The adjusted hazard ratios (aHRs) for LREs in the high risk compared with the low risk were 32.85 (P<0.01). The aHRs in stage 3-4 compared with stage 0-2 were 2.68 (P=0.02) for LREs and 2.26 (P=0.582) for LRM. In the same fibrosis stage, the incidence of LRM/LREs was more frequent with a higher risk stratification. The same trend was observed for NFS. NITs accurately predict LRM and LREs as well as a liver biopsy in Japanese patients with NAFLD. Patients in the low risk may not require close follow-up for at least 5years. The simple NITs could be an acceptable alternative method to performing a liver biopsy for the prognosis of NAFLD.

Food and Gut Microbiota-Derived Metabolites in Nonalcoholic Fatty Liver Disease.

Diet and lifestyle are crucial factors that influence the susceptibility of humans to nonalcoholic fatty liver disease (NAFLD). Personalized diet patterns chronically affect the composition and activity of microbiota in the human gut; consequently, nutrition-related dysbiosis exacerbates NAFLD via the gut–liver axis. Recent advances in diagnostic technology for gut microbes and microbiota-derived metabolites have led to advances in the diagnosis, treatment, and prognosis of NAFLD. Microbiota-derived metabolites, including tryptophan, short-chain fatty acid, fat, fructose, or bile acid, regulate the pathophysiology of NAFLD. The microbiota metabolize nutrients, and metabolites are closely related to the development of NAFLD. In this review, we discuss the influence of nutrients, gut microbes, their corresponding metabolites, and metabolism in the pathogenesis of NAFLD.

NEAT1: A Novel Long Non-coding RNA Involved in Mediating Type 2 Diabetes and its Various Complications.

Nuclear-enriched abundant transcript 1 (abbreviated as NEAT1) is a long-chain noncoding RNA involved in various physiological and pathological processes. This study aimed to clarify the effect and molecule system of NEAT1 within non-alcoholic fatty liver disease (NAFLD) as well as type 2 diabetes (T2DM). In this review, current studies concerning mechanisms of NEAT1l, in the development of type 2 diabetes and its complications have been summarized and analyzed. Also, we searched the papers based on NEAT1 related to NAFLD. The related studies were obtained through a systematic search of Pubmed. NEAT1 displays a close correlation with how T2DM occurs and develops, and it was confirmed to be significantly up-regulated in T2DM and its various complications (e.g., diabetics nephropathy, diabetics cardiomyopathy, diabetics retinopathy as well as diabetic neuropathy). Besides, NEAT1 is capable of impacting the occurrence, development and prognosis of NAFLD and T2DM. LncRNA NEAT1 is likely to act as a novel therapeutic target for T2DM and its complications. Moreover, non-alcoholic fatty liver disease is also correlated with NEAT1.

Exosomal FZD-7 Expression Is Modulated by Different Lifestyle Interventions in Patients with NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial condition characterized from hypertriglyceridemia and hepatic fat accumulation, in the absence of alcohol intake. NAFLD starts as steatosis (NAFL), and the continued injury relative to the toxic fat induces inflammation, steatohepatitis (NASH), and HCC. One of the factors determining liver degeneration during the evolution of NAFLD is a modification of Wnt/Frizzled (FZD) signaling. In particular, an inhibition of Wnt signaling and an overexpression of a specific FZD receptor protein, namely, the FZD7, have been observed in NAFLD. Actually, the prognosis and the follow-up of NAFLD is not easy, and the liver biopsy is the gold standard for an accurate detection of liver fibrosis. In this study, the modulation of the FZD7 expression levels in plasma-derived exosomes of NAFLD-affected patients, before and after specific lifestyle interventions, were experimentally evaluated by Western blotting analysis. The experimental data were analyzed by an accurate statistical study that indicated, in the exosomes derived from plasma of NAFLD patients with moderate or severe steatosis, an average expression level of FZD7 that was significantly higher than healthy subjects at baseline; conversely, the values were normalized after 90 days of specific lifestyle interventions. The overall results suggested that the FZD7 delivered by exosomes represents a good candidate as a new and effective biomarker for diagnosis and prognosis of NAFLD.

Assessing liver fibrosis in all patients with type 2 diabetes and fatty liver disease: It's time to act now.

Assessing liver fibrosis in all patients with type 2 diabetes and fatty liver disease: It's time to act now.

Bioinformatics Analysis Explores Potential Hub Genes in Nonalcoholic Fatty Liver Disease.

Background: Nonalcoholic fatty liver disease (NAFLD) is now recognized as the most prevalent chronic liver disease worldwide. However, the dysregulated gene expression for NAFLD is still poorly understood. Material and methods: We analyzed two public datasets (GSE48452 and GSE89632) to identify differentially expressed genes (DEGs) in NAFLD. Then, we performed a series of bioinformatics analyses to explore potential hub genes in NAFLD. Results: This study included 26 simple steatosis (SS), 34 nonalcoholic steatohepatitis (NASH), and 13 healthy controls (HC). We observed 6 up- and 19 down-regulated genes in SS, and 13 up- and 19 down-regulated genes in NASH compared with HC. Meanwhile, the overlapping pathways between SS and NASH were PI3K-Akt signaling pathway and pathways in cancer. Then, we screened out 10 hub genes by weighted Gene Co-Expression Network Analysis (WGCNA) and protein-protein interaction (PPI) networks. Eventually, we found that CYP7A1/GINS2/PDLIM3 were associated with the prognosis of hepatocellular carcinoma (HCC) in the TCGA database. Conclusion: Although further validation is still needed, we provide useful and novel information to explore the potential candidate genes for NAFLD prognosis and therapeutic options.

Evaluation of the Role of Hyaluronic Acid as A potential Biomarker for Diagnosis of Non-Alcoholic Fatty Liver Disease

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, ranging from simple steatosis and non-alcoholic steatohepatitis (NASH) to cirrhosis, with its complications including hepatocellular carcinoma (HCC). The non-invasive diagnostic markers of NAFLD are gaining interest due to the invasive nature and potential side effects of liver biopsy, and are the current gold standard of diagnosis. Objective: This study aimed to evaluate hyaluronic acid (HA) as a potential non-invasive biomarker for diagnosis and prognosis of NAFLD and to compare it with the traditional non-invasive techniques. Patients and methods: This study included 63 subjects divided into 3 groups; including 21 patients with fatty liver, 21 patients with NASH, in addition to 21 healthy controls. Non-invasive assessment of liver fibrosis was done to all study subjects using aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 score (FIB4), in addition to measurement of HA serum levels. Results: As regard assessment of liver fibrosis, there was a highly significant statistical difference between groups as regard APRI and Fib4 scores. As for HA there was a highly significant statistical difference between study groups. HA receiver operating characteristics curves (ROC) achieved excellent diagnostic performance for fatty liver with 100% sensitivity and specificity at cutoff of 25 ng/ml for fatty liver, versus a sensitivity of 95.2% and specificity of 85.7% for NASH at cutoff of 110 ng/ml. Conclusion: HA can be used as an accurate and specific non-invasive biomarker for the diagnosis of NAFLD and staging of the severity of disease compared with the traditional known non-invasive scores.

Outcomes of Japanese patients with non-alcoholic fatty liver disease according to genetic background and lifestyle-related diseases

Introduction and objectivesGenetic background may be involved in the mechanisms of liver injury and the development of non-alcoholic fatty liver disease (NAFLD). However, its contributions to the long-term outcome of NAFLD have been unclear. MethodsWe enrolled 314 Japanese patients with biopsy-confirmed NAFLD from 2000 to 2018 (161 men [51.3%]; median age, 53 [14–84] years; 114 with advanced fibrosis [37.5%]) in the patients without hepatocellular carcinoma at diagnosis. Genomic DNA was extracted from peripheral blood and single nucleotide polymorphisms (SNPs) were analyzed. Associations of mortality with patatin-like phospholipase 3 (PNPLA3) and aldehyde dehydrogenase 2 (ALDH2) were analyzed. Finally, a subgroup analysis according to lifestyle-related disease was performed. ResultsDuring the median 7 years of follow-up, 20 patients (6.4%) died (13 liver-related [4.1%] and 7 non-liver-related deaths [2.2%]). Patients with ALDH2 (non-GG genotype) who had reduced alcohol metabolism tended to have a poor prognosis (p = 0.06). Patients carrying both risk SNPs of PNPLA3 (GG) and ALDH2 (non-GG) had a significantly poor prognosis (p = 0.01). In the subgroup analysis, patients with PNPLA3 (GG) who were non-diabetics (p = 0.06) or non-dyslipidemic (p = 0.03), with ALDH2 (non-GG) who were non-dyslipidemic (p = 0.01) or hypertensive (p = 0.03), also had a poor prognosis. The Cox analysis revealed that ALDH2 (non-GG) was associated with a poor prognosis (Hazard ratio: 4.568, 95% Confidence Interval: 1.294–16.131, p = 0.02) similar to the liver function tests. ConclusionsGenetic background may affect NAFLD prognosis and ALDH2 SNP could predict the outcome.

Correlation between Obstructive Sleep Apnea and Non-Alcoholic Fatty Liver Disease before and after Metabolic Bariatric Surgery.

Emerging evidence has revealed that obstructive sleep apnea (OSA) is associated with non-alcoholic fatty liver disease (NAFLD). However, the impact of OSA on NAFLD among obese patients undergoing metabolic and bariatric surgery (MBS), especially during follow-up period, remains unclear. To analyze the correlation based on preoperative characteristics and postoperative conditions among bariatric patients with comorbid OSA and NAFLD. Clinical data of patients who underwent MBS in our institution between January 2016 and June 2019 were reviewed retrospectively. Correlation analysis and linear regressions were used to identify how OSA links with NAFLD before and after treatment of MBS. Of 308 patients, 181 were diagnosed with OSA and enrolled in the present study, and 127 completed follow-up visits at 6months. The proportion of NAFLD in the mild-moderate OSA and severe OSA groups was 75.0% and 96.0%, respectively. MBS was effective at improving sleep apnea and nocturnal hypoxia, as well as liver steatosis and fibrosis (P< 0.05). And we also found that there were significant correlations not only between OSA- and NAFLD-related characteristics at baseline but also between their improvements after surgery, eventually leading to similar prognosis of NAFLD for both groups (P< 0.05), no matter what presurgical differences existed. In addition, the results of the univariate and multivariate linear regression analyses supported preoperative liver/spleen Hounsfield units ratio (LSR) by computerized tomography (CT) as an independent predictor of the effect of MBS on liver steatosis. In conclusion, MBS plays a pivotal role in the control of medical conditions in obese patients with OSA and NAFLD. Given the correlation between OSA and NAFLD in the present study, in the case of both the severity at baseline as well as the improvement after surgery, OSA may pose an impact on the prognosis of NAFLD in bariatric patients.

Cholesterol impairs hepatocyte lysosomal function causing M1 polarization of macrophages via exosomal miR-122-5p

Nonalcoholic steatohepatitis (NASH) is a major threat to health worldwide. Lipotoxicity and macrophage-mediated inflammation play key roles in the pathogenesis of NASH. In this study, we found that individuals with higher serum LDL-C levels have a higher prevalence of nonalcoholic fatty liver disease (NAFLD) and elevated levels of glutamic-pyruvic transaminase, glutamic-oxalacetic transaminase and alkaline phosphatase. A logistic regression analysis revealed that serum LDL-C level is an independent risk factor for the prevalence and prognosis of NAFLD. In vitro, we used ox-LDL and MβCD-cholesterol to treat Huh7 cells and found that cholesterol loading reduced lysosomal quantity and impaired lysosomal acidification, reducing the number of multivesicular bodies (MVBs) colocalizing with lysosomes. The bafilomycin A1 inhibition of lysosomal function also inhibited lysosomal MVBs degradation, promoting the release of exosomes from the Huh7 cells. Next, we found that cholesterol loading promoted exosome release from the Huh7 cells. The exosomes from the cholesterol-loaded cells increased the ratio of the THP-1 cells positive for the M1 marker (iNOS-1) without affecting the ratio of the cells positive for the M2 marker (CD206). Moreover, an elevated level of miR-122-5p was observed in exosomes derived from the Huh7 cells loaded with cholesterol. While the miR-122-5p mimics promoted THP-1 M1 polarization, downregulating miR-122-5p in the Huh7 cells inhibited the exosome-induced activation of macrophages and macrophage-related inflammation. These findings suggest that cholesterol plays an important role in the development and progression of NASH. Cholesterol-induced lysosomal dysfunction increases exosome release from hepatocytes, resulting in M1 polarization and macrophage-induced inflammation in a miR-122-5p-dependent manner.

The diagnostic and initial approach of the patient with non-alcoholic fatty liver disease: role of the primary care provider.

Non-alcoholic fatty liver disease (NAFLD) represents a broad spectrum of liver damage, ranging from simple steatosis to steatohepatitis and fibrosis; as well, there is a close association between NAFLD, obesity, metabolic syndrome and type 2 diabetes mellitus. There is a certain degree of uncertainty regarding the natural history and prognosis of NAFLD; however, several methods are currently used for its diagnostic approach. In the first instance, non-invasive tests could be used to identify patients at low risk of developing fibrosis and to establish more easily the need for a liver biopsy, whose accuracy in the evaluation of fibrosis has been questioned, mainly due to errors of intra and interobserver sampling, technical problems and cost, which limits its use. Therefore, it is essential to determine the diagnostic strategy for patients with NAFLD.

Dual Energy Transfer-Based Fluorescent Nanoprobe for Imaging miR-21 in Nonalcoholic Fatty Liver Cells with Low Background.

Nonalcoholic fatty liver disease (NAFLD) can progress gradually to liver failure, early warning of which is critical for improving the cure rate of NAFLD. In situ imaging and monitoring of overexpressed miR-21 is an advanced strategy for NAFLD diagnosis. However, this strategy usually suffers from the high background imaging in living cells owing to the complexity of the biological system. To overcome this problem, herein, we have developed a one-donor-two-acceptor nanoprobe by assembling gold nanoparticles (AuNPs) coupled with BHQ2 (AuBHQ) and quantum dots (QDs) through DNA hybridization for imaging of miR-21 in living cells. The fluorescence of QDs was quenched up to 82.8% simultaneously by the AuNPs and the BHQ2 via nanometal surface energy transfer and fluorescence resonance energy transfer, reducing the background signals for target imaging. This low background fluorescent nanoprobe was successfully applied for imaging the target miR-21 in nonalcoholic fatty liver cells by catalyzing the disassembly of QDs with the AuBHQ and the fluorescence recovery of QDs. In addition, the sensitivity of this nanoprobe has also been enhanced toward detecting miR-21 in the range of 2.0-15.0 nM with the detection limit (LOD, 3σ) of 0.22 nM, which was 13.5 times lower than that without BHQ2. The proposed approach provides a new way for early warning, treatments, and prognosis of NAFLD.

SCCA-IgM as a Potential Biomarker of Non-Alcoholic Fatty Liver Disease in Patients with Obesity, Prediabetes and Diabetes Undergoing Sleeve Gastrectomy

Background: Non-alcoholic fatty liver disease (NAFLD) has a high prevalence in obesity and its presence should be screened. Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for obesity, but its effects on NAFLD are still to be firmly established. The diagnosis of non-alcoholic steatohepatitis (NASH) is currently performed by liver biopsy, a costly and invasive procedure. Squamous cell carcinoma antigen-IgM (SCCA-IgM) is a biomarker of viral hepatitis to hepatocellular carcinoma development and its role in NAFLD to NASH progression has not yet been investigated. Objective: The aim of this study was to evaluate SCCA-IgM as a non-invasive biomarker of NAFLD/NASH in patients with different degrees of metabolic-complicated obesity before and after LSG. Method: Fifty-six patients with obesity were studied before and 12 months after LSG; anthropometric, biochemical, clinical, and imaging data were collected. Results: At baseline steatosis was strongly associated with the glycaemic profile (p = 0.016) and was already present in prediabetic patients with obesity (82%). Only 3 patients had an SCCA-IgM level above the normal cut-off. SCCA-IgM titre did not change according to glycaemic profile or steatosis. Metabolic and inflammatory factors and transaminases significantly reduced after LSG-induced weight loss, except for SCCA-IgM. The ALT/AST ratio decreased post-LSG correlated with BMI (r = 0.297, p = 0.031), insulin (r = 0.354, p = 0.014), and triglycerides (r = 0.355, p = 0.009) reduction. Conclusions: Our results confirm the tight link between NAFLD and metabolic complications, suggesting prediabetes as a new risk factor of steatosis. SCCA-IgM does not seem to have a role in the identification and prognosis of NAFLD.

Fibroscan of Liver in Type 2 Diabetes Mellitus and Its Correlation with Risk Factors

Introduction: Non-alcoholic fatty liver disease (NAFLD) is regarded as the hepatic manifestation of metabolic syndrome. Insulin resistance is regarded as central to the development of NAFLD. Type 2 Diabetes Mellitus (DM) is an important cause of NAFLD. The pathology in NAFLD ranges from hepatic steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis and primary liver cancer. Diagnosis of NAFLD requires demonstration of increased liver fat in the absence of hazardous levels of alcohol consumption. Liver biopsy is the gold standard for diagnosis of NAFLD but it is fraught with various difficulties and is a risky procedure. Fibroscan (?Abbott) or transient elastography is a non-invasive tool which measures the hepatic stiffness. Objective: To estimate the degree of hepatic stiffness due to NAFLD and to identify the factors affecting it. Patients: 50 patients of newly diagnosed Type 2 diabetes mellitus without a history of chronic hepatitis or alcohol intake were included in the study. Results: In our study, 40% of the patients were obese with 46% of the total patients having an elevated AST, 66% having an elevated ALT and 18% having an elevated alkaline phosphatase. Dyslipidemia was very common with 14% of total patients having a high cholesterol, 36% having elevated triglycerides, 64% having a low HDL with none with an elevated LDL. 50% of patients had steatosis on ultrasound. On comparing liver stiffness, a significantly high hepatic stiffness (>7.9 kPa) was found in 34% of patients with severe fibrosis (≥12 kPa) in 10% of patients. Multivariate analysis showed significant positive correlation of fibroscan value with total cholesterol and ALT levels and there was a significant negative correlation with AST levels and serum HDL levels. Conclusion: Fibroscan may be helpful in diagnosing and guiding treatment of NAFLD. Larger studies to evaluate its efficacy in determining prognosis of NAFLD are warranted.