Early Diagnosis Of Non-alcoholic Fatty Liver Disease Research Articles

ONOO–-activatable and LD-traced NIR fluorescent probe for mechanism study and early diagnosis of NAFLD and diabetes induced liver injury

Lipid metabolism disorder and oxidative stress play an essential role in the occurrence and development of metabolic diseases such as nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). Here, we constructed an ONOO-activatable and lipid drops (LDs) traced near-infrared (NIR) fluorescent probe BDP-NIR-Py+ through structural modification, and evaluated oxidative stress and lipid metabolism disorders in relevant disease by monitoring changes in ONOO and LDs levels in cells and mice. With the dual monitoring of ONOO and LDs, BDP-NIR-Py+ realized real-time visualization of the occurrence and development of NAFLD and T2DM, and early diagnosis of liver injury, which is faster and more sensitive than tissue analysis and blood detection. Collectively, the ability of BDP-NIR-Py+ to simultaneously monitor ONOO and LDs makes it has unlimited potential in the early diagnosis and mechanism research of diseases such as NAFLD and T2DM in which oxidative stress and lipid metabolism disorder interact.

Nonalcoholic fatty liver disease from a primary care perspective.

Nonalcoholic fatty liver disease (NAFLD) affects up to one-third of the US population. Approximately one-fifth of patients with NAFLD have nonalcoholic steatohepatitis (NASH), characterized by hepatocyte damage and inflammation with or without fibrosis. NASH leads to greater risk of liver-related complications and liver-related mortality, with the poorest outcomes seen in patients with advanced fibrosis. NASH is also associated with other metabolic comorbidities and conveys an increased risk of adverse cardiovascular outcomes and extrahepatic cancers. Despite its high prevalence, NAFLD is frequently underdiagnosed. This is a significant concern, given that early diagnosis of NAFLD is a key step in preventing progression to NASH. In this review, we describe the clinical impact of NASH from the perspective of both the clinician and the patient. In addition, we provide practical guidance on the diagnosis and management of NASH for primary care providers, who play a pivotal role in the frontline care of patients with NASH, and we use case studies to illustrate real-world scenarios encountered in the primary care setting.

Identification of biomarkers in nonalcoholic fatty liver disease: A machine learning method and experimental study.

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease. However, the early diagnosis of NAFLD is challenging. Thus, the purpose of this study was to identify diagnostic biomarkers of NAFLD using machine learning algorithms. Differentially expressed genes between NAFLD and normal samples were identified separately from the GEO database. The key DEGs were selected through a protein‒protein interaction network, and their biological functions were analysed. Next, three machine learning algorithms were selected to construct models of NAFLD separately, and the model with the smallest sample residual was determined to be the best model. Then, logistic regression analysis was used to judge the accuracy of the five genes in predicting the risk of NAFLD. A single-sample gene set enrichment analysis algorithm was used to evaluate the immune cell infiltration of NAFLD, and the correlation between diagnostic biomarkers and immune cell infiltration was analysed. Finally, 10 pairs of peripheral blood samples from NAFLD patients and normal controls were collected for RNA isolation and quantitative real-time polymerase chain reaction for validation. Taken together, CEBPD, H4C11, CEBPB, GATA3, and KLF4 were identified as diagnostic biomarkers of NAFLD by machine learning algorithms and were related to immune cell infiltration in NAFLD. These key genes provide novel insights into the mechanisms and treatment of patients with NAFLD.

Non-Alcoholic Fatty Liver Disease and Extrahepatic Cancers: A Wolf in Sheep's Clothing?

Non-alcoholic fatty liver disease (NAFLD) is now considered the main driver and leading cause of chronic liver disease globally. The umbrella term NAFLD describes a range of liver conditions closely related to insulin resistance, metabolic syndrome, diabetes mellitus, obesity, and dyslipidemia. At the same time, several malignancies, including hepatocellular carcinoma and colorectal cancer, are considered to be common causes of death among patients with NAFLD. At first, our review herein aims to investigate the role of NAFLD in developing colorectal neoplasms and adenomatous polyps based on the current literature. We will also explore the connection and the missing links between NAFLD and extrahepatic cancers. Interestingly, any relationship between NAFLD and extrahepatic malignancies could be attributable to several shared metabolic risk factors. Overall, obesity, insulin resistance, metabolic syndrome, and related disorders may increase the risk of developing cancer. Therefore, early diagnosis of NAFLD is essential for preventing the progression of the disease and avoiding its severe complications. In addition, cancer screening and early detection in these patients may improve survival and reduce any delays in treatment.

Ectopic fat deposition and its related abnormalities of lipid metabolism followed by nonalcoholic fatty pancreas.

The positive energy balance between caloric intake and caloric output increasing storage of triglycerides (TG) in adipocytes has made nonalcoholic fatty liver disease (NAFLD) one of the major public health problems in China. Excessive lipid deposition in the pancreas is referred to as nonalcoholic fatty pancreas disease (NAFPD). Early assessment of pancreatic fat infiltration will have an increasing role in the clinical management of the metabolic dysregulation and prevention pancreatic complications. We retrospectively collected data of inpatients with NAFPD from EUS database between September 2012 and August 2020 at our endoscopic center. The prevalence of NAFPD and factors associated with its development were statistically analyzed. The echogenicity of the pancreas was compared to that of the left renal cortex during the EUS examination by using an existing criterion. Four thousand, seven hundred and four consecutive individuals underwent EUS were enrolled. The prevalence of NAFPD was 1.2% (57/4704) . Factors independently associated with NAFPD on multivariate analysis were increasing TG (odds ratios [OR] 4.65, P = 0.014), NAFLD (OR 16.76, P = 0.005) and decreasing apolipoprotein A-1 (OR 0.002, P = 0.0127). We found no association between NAFPD and age, sex, total cholesterol or hypertension. We found a meaningful relationship between NAFLD, dyslipidemia, and NAFPD in Chinese. We hypothesized that NAFPD was strongly correlated with ectopic fat deposition and its related abnormalities of lipid metabolism. Early diagnosis of NAFLD provides opportunities to control the progression of NAFPD.

Comparison of Transient Elastography and Liver Biopsy in Assessing Fibrosis in Patients with Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease. Ultrasound-based transient elastography (TE) or TE of the liver is a noninvasive tool for effectively evaluating liver stiffness and fibrosis. The study aimed to compare the accuracy of TE as assessed by Fibroscan with liver biopsy in staging fibrosis in patients with NAFLD. Consecutive NAFLD patients (N = 72) were prospectively enrolled. TE evaluation was performed with Fibroscan and compared with liver biopsy, which is a reference standard. Fibrosis was staged according to the METAVIR scoring system (Meta-analysis of Histological Data in Viral Hepatitis). TE scores and biopsy-related fibrosis stages were correlated. Diagnostic accuracy (sensitivity, specificity, positive and negative predictive values) of TE was evaluated. Data were analyzed using software R v3.6.3. Liver biopsy showed that 36.11% of patients did not exhibit fibrosis, whereas 25, 16.67, 15.28, and 6.94% of patients had stage F1 (por-tal/mild fibrosis), F2 (periportal/moderate fibrosis), F3 (bridging/severe fibrosis), and F4 (cirrhosis/advanced fibrosis), respectively. TE showed that 50% of patients had cirrhosis, whereas 20.83,15.28, and 13.86% of patients had mild, moderate, and severe fibrosis, respectively. TE had 71% accuracy, 89% sensitivity, and 38% specificity in diagnosing the severity of fibrosis. Hence, it can be implemented as a noninvasive alternative diagnostic tool for understanding the severity of fibrosis in patients with NAFLD. Moreover, it can also be used for quick early diagnosis of NAFLD, reliable staging of fibrosis, and understanding the need for liver transplantation in patients with NAFLD.

Non-invasive Methods in Diagnosis of Nonalcoholic Fatty Liver Disease

ABSTRACT Background: Non-alcoholic fatty liver disease (NAFLD) is a risk factor for increased morbidity and mortality plus cardiovascular disease and malignancy. Despite all of these, most patients have good prognosis if diagnosed at early stages. Objective: The study was designed to evaluate different non-invasive methods as a diagnostic tool of non-alcoholic fatty liver disease among diabetic and non-diabetic patients. Patients and Methods: The study was done on 100 patients were divided into two groups of 50 diabetics and 50 non-diabetics with fatty liver disease on abdominal ultrasonography finding. These patients were assessed with transient elastography (TE) after lab tests and then scoring systems (Fib-4 and NAFLD fibrosis score) and liver stiffness scores were compared between the two groups. Results: There was statistically significant difference between the two groups as regard Fib-4 and NAFLD fibrosis score (p F2) than those with (F2 or less) (p < 0.001). Conclusion: A combination of Fibroscan, Fib-4 and NAFLD fibrosis score provides a valuable non-invasive method in diagnosis of NAFLD patients, and this can eliminate the need for liver biopsy in patients without clear indication, especially diabetic patients that can help in early diagnosis of NAFLD before development of fibrosis.

FIB-4 index is a marker for a subsequent decrease in insulin secretion in a non-diabetic Japanese population

Non-alcoholic fatty liver disease (NAFLD) is associated with a high risk of type 2 diabetes (DM), therefore, early diagnosis of NAFLD is important to prevent incident DM. FIB-4 index, a biomarker, often used to evaluate severity of NAFLD, may be useful to evaluate risk for incident DM in ordinary clinical setting. Here, we determined the association of FIB-4 index with changes in indices representing glucose metabolism with aging in a non-diabetic population. From among the participants of the population-based Iwaki study of Japanese people conducted during 2014–2017, 1,268 non-diabetic individuals with complete data sets (age: 51.4 ± 15.9 years; men/women: 485/773) were enrolled in a cross-sectional study. In addition, of the participants, 439 who attended consecutive appointments between 2014 and 2017 were enrolled in a longitudinal study that aimed to evaluate the changes in insulin secretion and resistance with aging (age: 53.1 ± 13.7 years; men/women: 178/261). The cross-sectional study showed significant correlations of FIB-4 index with homeostasis model of assessment (HOMA) indices, even after adjustment for multiple factors (HOMA-β: β = − 0.254, p < 0.001; HOMA-R: β = − 0.247, p < 0.001). The longitudinal study showed a significant association between FIB-4 index and the change in HOMA-β (p < 0.001) but not HOMA-R (p = 0.639) during the 3-year study period. Use of the optimal cut-off value of the FIB-4 index for the prediction of decreased insulin secretion (HOMA-β < 30), determined using receiver operating characteristic analysis (1.592), showed that individuals at risk had a hazard ratio of 2.22 (confidence interval 1.17−4.06) for decreased insulin secretion, after adjustment for confounders. FIB-4 index may represent a useful predictor of a subsequent decrease in insulin secretion, at least in a non-diabetic Japanese population.

Predicting and elucidating the etiology of fatty liver disease: A machine learning modeling and validation study in the IMI DIRECT cohorts.

Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in individuals with and without type 2 diabetes (T2D). Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and, ultimately, hepatocellular carcinomas. We sought to expand etiological understanding and develop a diagnostic tool for NAFLD using machine learning. We utilized the baseline data from IMI DIRECT, a multicenter prospective cohort study of 3,029 European-ancestry adults recently diagnosed with T2D (n = 795) or at high risk of developing the disease (n = 2,234). Multi-omics (genetic, transcriptomic, proteomic, and metabolomic) and clinical (liver enzymes and other serological biomarkers, anthropometry, measures of beta-cell function, insulin sensitivity, and lifestyle) data comprised the key input variables. The models were trained on MRI-image-derived liver fat content (<5% or ≥5%) available for 1,514 participants. We applied LASSO (least absolute shrinkage and selection operator) to select features from the different layers of omics data and random forest analysis to develop the models. The prediction models included clinical and omics variables separately or in combination. A model including all omics and clinical variables yielded a cross-validated receiver operating characteristic area under the curve (ROCAUC) of 0.84 (95% CI 0.82, 0.86; p < 0.001), which compared with a ROCAUC of 0.82 (95% CI 0.81, 0.83; p < 0.001) for a model including 9 clinically accessible variables. The IMI DIRECT prediction models outperformed existing noninvasive NAFLD prediction tools. One limitation is that these analyses were performed in adults of European ancestry residing in northern Europe, and it is unknown how well these findings will translate to people of other ancestries and exposed to environmental risk factors that differ from those of the present cohort. Another key limitation of this study is that the prediction was done on a binary outcome of liver fat quantity (<5% or ≥5%) rather than a continuous one. In this study, we developed several models with different combinations of clinical and omics data and identified biological features that appear to be associated with liver fat accumulation. In general, the clinical variables showed better prediction ability than the complex omics variables. However, the combination of omics and clinical variables yielded the highest accuracy. We have incorporated the developed clinical models into a web interface (see: https://www.predictliverfat.org/) and made it available to the community. ClinicalTrials.gov NCT03814915.

PREVALENCE OF NAFLD AND IT’S ASSOCIATION WITH INSULIN RESISTANCE IN PATIENTS WITH DIABETES

Objectives: Non Alcoholic Fatty Liver Disease (NAFLD) is characterized by fatty infiltration of the liver, mostly in the form of triglycerides (TG), which exceeds 5% of the liver weight.NAFLD is strongly associated with Insulin Resistance(IR).Patients with NAFLD also having type 2 diabetes carry added risk of progressive forms of the disease particularly cirrhosis. They also have poor glycemic control owing to IR. So it is logical to identifying the patients with diabetes having NAFLD could estimates the future risk and help in prevention of chronic liver disease and delaying the progression to NASH and cirrhosis and various complications of Diabetes.&#x0D; Methods: This was a cross sectional observational study conducted in department of medicine, N.S.C.B., MCH, Jabalpur in which 100 cases of diabetes were taken who satisfied inclusion and exclusion criteria. Abdominal USG was used for evidence of fatty liver and it’s grading and fasting serum levels of insulin (FIL) and fasting blood sugar(FBS) were used to calculate HOMA IR value to find presence of IR.&#x0D; Results: Our study showed prevalence of NAFLD was 56%(n-56),Among these,in 58.92%(n-33) cases NAFLD is associated with IR(chi square value-4.1,p value-0.041).Prevalence of NAFLD was slightly more in females-56.6%(n-30) as compare to males-55.32%(n-26).Strong association of NAFLD with IR is found among females as compare to males (p-0.022 and p-0.79 respectively). Waist circumference, Mean BMI, FBS, Triglycerides, FIL and HOMA IR levels in cases with NAFLD (95.11±12.46, 24.83±2.42, 176.13±66.79, 180.07±51.35, 13.59±15.42, 5.33±5.21)were higher as compare to non NAFLD (85.84±9.86, 22.41±2.16, , 134.8±34.41,139.09±39.27, 6.79±4.49, 2.37±1.94)respectively. The mean AST and ALT levels were higher in NAFLD group than Non NAFLD group (t= 2.23,2.19) respectively with p value &lt;0.05.Prevalence of NAFLD was 88.23%(n-15)in obese population.&#x0D; Conclusion: Given the high prevalence of NAFLD in patients with diabetes, the possibility of NAFLD should be suspected in all of them. These patients with NAFLD have high propensity of IR than Non NAFLD patients, so are at higher risk of developing complications of diabetes, NASH and cirrhosis. Also obese diabetic patients have higher incidence of NAFLD and IR as compared to non-obese patients. It seems reasonable to expect that early diagnosis of NAFLD and early intervention with strict glycemic control and weight loss would prevent complications.

Fatty Liver Index (FLI) in Predicting Non-alcoholic Fatty Liver Disease (NAFLD)

Background: Non-alcoholic fatty liver disease (NAFLD) is considered as the most common chronic liver disease, which can contribute to some clinical conditions varying from simple steatosis to hepatic cirrhosis. Consequently, the early diagnosis of NAFLD is vital. The present study aimed at investigating the ability of FLI (fatty liver index) in predicting NAFLD. Methods: A total of 212 individuals over the age of 18 years (103 males and 109 females) were recruited from those admitted to a gastrointestinal clinic in Mashhad, northeastern Iran. Anthropometric parameters were measured and blood samples were collected. Hepatic steatosis and fibrosis were identified by FibroScan. FLI from body mass index, waist circumference (WC), triglyceride, and gamma glutamyltransferase data were calculated. Logistic regression was applied to establish a relationship among FLI, hepatic steatosis, and fibrosis. The sensitivity and specificity of FLI and its optimal cut-off point were detected by receiver operating characteristic analysis. Results: The mean age of the participants was 39.26 ± 14.18 years. FLI was significantly associated with NAFLD (OR = 1.062, 95%CI: 1.042 - 1.082, P < 0.001) and hepatic fibrosis (OR = 1.022, 95%CI: 1.011 - 1.032, P < 0.001). The AUC of FLI was 0.85 (95%CI = 0.79 - 0.9) in the diagnosis of NAFLD, and its optimal cut-off point was 26.2 (sensitivity = 0.83, specificity = 0.7). Also, the optimal cut- off point of FLI was 30.4 in males (sensitivity = 0.82, specificity = 0.71) and 20.7 in females (sensitivity = 0.89, specificity = 0.66). Conclusions: Fatty liver index (FLI) is a suitable and simple predictor for liver steatosis. However, performance of FLI in predicting NAFLD is not more effective than WC. Although FLI is a predictor for liver steatosis, it has a positive association with liver fibrosis and can perhaps predict liver fibrosis too.

Too much medicine: overdiagnosis and overtreatment of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is now the most common cause of liver disease. This remarkable rise in prevalence over the past 20 years is largely through the recognition of fatty liver in the absence of excessive alcohol consumption as a disease. The natural history of NAFLD is incompletely understood, and although a small proportion of individuals with NAFLD will develop complications of liver disease, most will not. This raises the prospect of widespread overdiagnosis of NAFLD. Clinical practice guidelines from the European specialist societies representing hepatology, endocrinology, and obesity endorse screening for NAFLD in at-risk groups, and this further increases the likelihood of overdiagnosis and consequent overtreatment through false-positive testing. Predictable outcomes of overdiagnosis include physical harms through investigation and treatment, and psychosocial harms through disease labelling. Prospective studies are required to better understand both the benefits and risks associated with an early diagnosis of NAFLD.

NONINVASIVE METHODS IN THE DIAGNOSIS OF NON-ALCOHOLIC FATTY LIVER DISEASE

Non-alcoholic fatty liver disease (NAFLD) being increasingly diagnosed worldwide is considered as the most common liver disease in Western countries. The incidence is growing rapidly due to the continuing epidemic of the obesity and diabetes mellitus type 2. There is the extremely topical question of the affordable, effective and early diagnosis of NAFLD. Over the past few years, significant progress has been made in the understanding of its risk factors, pathogenesis, clinical course, methods of diagnosis and treatment of NAFLD. The article gives an overview of modern and promising methods for diagnosing NAFLD, useful for physicians of various specialties who have to deal with NAFLD patients. Key problems of diagnostics are formulated and directions for further research are determined. There is discussed the role of biomarkers as promising noninvasive diagnostic methods, that provides to assess the severity of necrotic inflammatory processes and liver fibrosis in NAFLD patients.

Synergy between NAFLD and AFLD and potential biomarkers

Fatty liver (hepatosteatosis) is the earliest abnormality in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) due either to metabolic risk factors associated with insulin resistance and/or metabolic syndrome in the absence of alcohol consumption or to chronic alcohol abuse. When unchecked, both NAFLD and AFLD lead to steatohepatitis, fibrosis, cirrhosis, hepatocellular carcinoma (HCC) and eventual death. A number of common mechanisms contribute to the above various stages of hepatocyte injury, including lipotoxicity, endotoxin release, oxidative and ER stress leading to increased pro-inflammatory cytokines that stimulate hepatic fibrogenesis and cirrhosis by activating the quiescent hepatic stellate cells (HSC) into myofibroblasts. Significantly, patients with either NAFLD or AFLD respond favorably to early treatment modalities to reduce hepatic fat accumulation and consequent increased inflammatory signalling and activation of hepatic stellate cells. Although the pathogenic pathways associated with NAFLD and AFLD are seemingly similar, differentiation of the molecular mechanism/s of the pathogenesis of these liver diseases is critical in identifying the unique molecular signatures, especially in the early diagnosis of NAFLD and AFLD. Current clinical practice requires the invasive biopsy procedure for the conclusive diagnosis of NAFLD and AFLD. Micro RNAs (miRNAs) are ∼22 nucleotide non-coding sequences that bind to the 3'-untranslated region of target transcripts and regulate gene expression by degradation of target mRNAs or inhibition of translation. Emerging studies may prove to establish miRNAs as excellent non-invasive tools for the early diagnosis of various stages of liver diseases.

Nonalcoholic Fatty Liver Disease in Children with Hypopituitarism

Purpose: It has been reported that children with hypopituitarism have features of metabolic syndrome, including obesity, impaired glucose tolerance, and dyslipidemia. The aim of this study was to investigate the clinical features and liver histology of pediatric non-alcoholic fatty liver disease (NAFLD) associated with hypopituitarism.Methods: We reviewed the clinical data of 11 children diagnosed with NAFLD among patients with hypopituitarism.Results: The mean age at the time of diagnosis of hypopituitarism was 10.4±3.2 years, and the mean age at the time of diagnosis of NAFLD was 13.1±2.7 years. A craniopharyngioma was the most common cause of pituitary dysfunction. At the time of diagnosis of NAFLD, 9 patients (82%) had a body mass index greater than the 85th percentile, 5 patients (45%) had elevated fasting blood glucose levels, and 9 patients (82%) had hypertriglyceridemia. The mean height SD score was significantly lower at the time of diagnosis of NAFLD than at the time of diagnosis of hypopituitarism. Of the six patients who were biopsied, one had cirrhosis, two had non-alcoholic steatohepatitis (NASH) with bridging fibrosis, two had NASH with mild portal fibrosis, and one had simple steatosis.Conclusion: Children with hypopituitarism are at risk of short stature, obesity, dyslipidemia, and NAFLD. The early diagnosis of NAFLD is important in children with hypopituitarism because advanced fibrosis is common. (Korean J Pediatr Gastroenterol Nutr 2010; 13: 51∼57)Key Words: Child, Fatty liver, Hypopituitarism, Obesity