Nonalcoholic fatty liver disease (NAFLD)

Purpose: Many studies have reported the relationship between nonalcoholic fatty liver disease (NAFLD) and bone mineral density (BMD) among adults. However, fewer studies on this topic have been reported in adolescents. We thus conducted a meta-analysis to show the association between NAFLD and BMD in adolescents with obesity.

Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of hepatocellular carcinoma (HCC), liver-related mortality, and liver transplantation. There is reasonable epidemiological cohort data to recommend surveillance of patients with NAFLD based upon the incidence of HCC. The American Gastroenterology Association (AGA) expert review published in 2020 recommend that NAFLD patients with cirrhosis or advanced fibrosis estimated by non-invasive tests (NITs) should consider HCC surveillance. NITs include fibrosis-4 (FIB-4) index, the enhanced liver fibrosis (ELF) test, FibroScan, and MR elastography. The recommended surveillance modality is abdominal ultrasound (US) given that it is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with NAFLD. In NAFLD patients with a high likelihood of having an inadequate US or if US is attempted but inadequate, CT or MRI may be utilized. The GALAD score, consisting of age, gender, AFP, lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II), can help to identify high risk of incident HCC in NAFLD patients. Innovative parameters including Mac-2 binding protein glycated isomer , type IV collagen 7S, free apoptosis inhibitor of macrophage, combination of single nucleoside polymorphisms are expected to be established. Considering a large number of NAFLD population, optimal screening tests must meet several criteria including high

liver, a condition called nonalcoholic fatty liver disease (NAFLD). NAFLD is a clinicopathologic entity that includes a spectrum of liver damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and rarely, progression to cirrhosis. Recent studies emphasize the role of insulin resistance, oxidative stress and subsequent lipid peroxidation, proinflammatory cytokines, adipokines and mitochondrial dysfunction in the development and progression of NAFLD. About 20% all adults have NAFLD and 2% to 3% of adults have NASH. A strong correlation exists between overweight, in particular visceral fat accumulation, and prevalence of NASH.

Abstract: Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disorder. Strongly linked to obesity and diabetes, NAFLD has the characteristics of complex diseases with substantial heterogeneity. Accordingly, our ability to predict the risk of advanced NAFLD and provide efficient treatment may improve by a better understanding of the relationship between genotype and phenotype. MicroRNAs (miRNAs) play a major role in the fine-tuning of gene expression and they have recently emerged as novel biomarkers and therapeutic tools in the management of NAFLD. These short non-coding RNA sequences act by partial repression or degradation of targeted mRNAs. Deregulation of miRNAs has been associated with different stages of NAFLD, while their biological role in the pathogenesis remains to be fully understood. Systems biology analyses based on predicted target genes have associated hepatic miRNAs with molecular pathways involved in NAFLD progression such as cholesterol and lipid metabolism, insulin signaling, oxidative stress, inflammation, and pathways of cell survival and proliferation. Moreover, circulating miRNAs have been identified as promising noninvasive biomarkers of NAFLD and linked to disease severity. This rapidly growing field is likely to result in major advances in the pathomechanism, prognostication, and treatment of NAFLD.

While liver steatosis might look like alcoholic liver disease, it can occur in people who drink little or no alcohol. This condition, described as nonalcoholic fatty liver disease (NAFLD), is an emerging health prob- lem. Erroneously seen in the past as a benign con- dition, NAFLD has the potential to progress through the inflammatory phase of nonalcoholic steatohepatitis (NASH) to fibrosis, cirrhosis, and hepatocellular carci- noma. 2,3 Although there are as yet no diagnostic and

In pediatric populations, previous studies have reported that NAFLD is related to risk factors such as: whole body and central obesity [6,22], insulin resistance and type II diabetes [23]. Studies also suggest that chil- dren who enter puberty with excessive fat and/or present genetic basis are more likely to develop NAFLD [8,24]. Nonetheless, the amount of fat accumulated in the deep abdominal region seems to be a key-factor in NAFLD diagnosis. Furthermore, the profound endocrine, meta- bolic and morphologic changes that occurred over time, particularly in adolescence might explain the gender dif- ferences found in the occurrence of NAFLD [25]. Table 2 Comparisons of body composition and metabolic syndrome components of obese adolescents with (presence) and without (absence) nonalcoholic fatty liver disease, adjusted by sex, age, pubertal stage and total body fat mass

Abstract: Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common cause of chronic liver disease due to an increase in the prevalence of obesity. The development of NASH leads to an increase in morbidity and mortality. While the first line of treatment is lifestyle modifications, including dietary changes and increased physical activity, there are no approved pharmacological treatment agents for NAFLD and NASH currently. Due to its complex pathophysiology, different pathways are under investigation for drug development with the focus on metabolic pathways, inflammation, and slowing or reversing fibrosis. There are several agents advancing in clinical trials, and promising results have been seen with drugs that affect hepatic steatosis, inflammation, and fibrosis. This review will provide an overview on NAFLD and some of the mechanisms of disease that are being targeted with pharmacologic agents.

Nonalcoholic fatty liver disease (NAFLD) is believed to be the most common chronic liver disease, affecting at least one-third of the population worldwide. The more aggressive form is known as nonalcoholic steatohepatitis (NASH) and characterized by hepatocyte necrosis and inflammation. The presence of fibrosis is not uncommon. Fibrosis indicates a more aggressive course and patients with NASH that are at high-risk of cirrhosis and premature mortality, as well as at increased risk of hepatocellular carcinoma (HCC). Patients with type 2 diabetes mellitus (T2DM) are at the highest risk for the development of NASH, even in the setting of normal plasma aminotransferase levels. The presence of dysfunctional adipose tissue in most overweight and obese subjects, combined with insulin resistance, hyperglycemia, and atherogenic dyslipidemia, contribute to their increased cardiovascular risk. Many therapeutic agents have been tested for the treatment of NASH but few studies have focused in patients with T2DM. At the present moment, the only FDA-approved agents that in controlled studies have shown to significantly improve liver histology in patients with diabetes are pioglitazone and liraglutide. Current research efforts are centering on the mechanisms for intrahepatic triglyceride accumulation and for the development of steatohepatitis, the role of mitochondrial dysfunction in NASH, and the impact of improving glycemic control per se on the natural history of the disease. This brief review summarizes our current knowledge on the pharmacological agents available for the treatment of NASH to assist healthcare providers in the management of these challenging patients.

30. Pacifico L, Bonci E, Di Martino M, Versacci P, Andreoli G, Silvestri LM, et al. A double- blind, placebo-controlled randomized trial to evaluate the efficacy of docosahexae- noic acid supplementation on hepatic fat and associated cardiovascular risk factors in overweight children with nonalcoholic fatty liver disease. Nutr Metab Cardiovasc Dis 2015;25(8):734-41. Epub 2015 Apr 25.

We selected a total of 377 unrelated adult subjects from August 2012 to August 2015, including 182 pa- tients of different genders and different ages (85 males, 97 females,) diagnosed with NAFLD and 195 healthy controls matched for genders and ages (88 males, 107 females,) who underwent B-type ultrasonography. We collected subjects from the department of gastroenter- ology and the medical center of Qingdao municipal hospital. All individuals were unrelated and ethnically Han Chinese adults. The diagnosis of NAFLD was made by ultrasonic imaging according to EASL and AASLD criteria. Other causes of liver disease were ex- cluded, including increased alcohol intake (>210/140 g/ week for males/females), as confirmed by at least one family member or friend and carboxydesialylated trans- ferrin determination, viral and autoimmune hepatitis,

Hyperlipidemia is one of the most common comorbid- ities related to NAFLD, increasing the risk of cardiovascu- lar disease and premature death. 4 Our results showed that the intake of garlic powder leads to a positive effect on LDL-c and total cholesterol concentrations. A recent meta- analysis indicated that garlic reduces LDL-c and total cho- lesterol, whereas its effect on HDL-c depends on the type of garlic. 28 Similarly, in another meta-analysis, garlic powder intake has resulted in a signi fi cant reduction in LDL-c by 15.8 mg/dL and total cholesterol by 8.1 mg/dL, without changing the serum HDL-c. 24 Although ample evidence has shown the consistency in serum cholesterol parameters with garlic treatment, there are some controversies in serum triglycerides. 29 The subgroup analysis of the previous meta- analysis has shown that the aforesaid issue may be due to the difference in the type of garlic, duration of the study, baseline serum triglycerides of the study population, and dosage. 28 The results obtained in our study showed a signi fi cant reduction in serum triglycerides with the intake of garlic. The current fi ndings were supported by a similar study in which the administration of garlic powder at 800 mg/day for 4 months reduced TG by 38 mg/dL. 30 The hypolipidemic property of garlic has been linked to the down-regulation of hepatic lipogenic and cholestero- genic genes and the enhancement of bile acid excretion from the gastrointestinal tract. 31,32

After consumption of a MCT-rich oil diet in mice, plasma triacylglycerol levels were elevated, as were hepatic lipogenic enzymes activities, acetyl-coenzyme A carboxyl- ase, fatty acid synthase and diacylglycerol acyltransferase; however the levels of plasma and hepatic cholesterol were reduced [28]. A MCFA-rich diet with replacement of diet- ary long-chain triacylglycerols has been shown to reduce the levels of steatosis and the markers of hepatic injury, such as hepatic transaminases. This replacement appeared to result in a substantial upregulation of fatty acid liver oxi- dation, sufficient to reduce the development of steatosis [29]. The substitution of saturated for unsaturated fats pro- vides a dose-responsive protective effect on the develop- ment of alcoholic liver disease in a murine model of ethanol consumption in vivo [30]. The severity of steatosis varies widely depending on the dietary saturated fat con- tent, so delineation of the type of dietary fat is an important factor that affects hepatic pathology by inducing or promot- ing the development and progression of NAFLD (Fig. 1).

In conclusion, this 23-year cohort study shows that overweight/ obese children are more likely to have NAFLD and ALT elevation in adulthood. However, this association could be largely reduced by becoming nonobese during adulthood. These findings underscore the importance of both early prevention and lifelong treatment of overweight and obesity to reduce the risk of adverse liver outcome in adulthood.

ALT is a relatively liver-specific aminotransferase. Eleva- tion of ALT activity in serum is the result of leakage from damaged cells and therefore reflects hepatocyte damage. Elevated transaminase levels correlated strongly with NAFLD [2]. ALT levels were significantly lower in the res- veratrol group as compared to the control group (34 IU/L versus 40 IU/L) and similar to steatosis group levels. In the group treated with resveratrol, lower glucose levels and higher serum albumin levels as compared to untreated rats were also found. Studies have reported increases in serum TNF-D levels in humans with insulin resistance [24]. Hyperglycemia and insulin resistance are associated to the presence of NAFLD [2,25]. Changes in plasma lev- els of markers predicting for the onset of diabetes occurred with a high carbohydrate-fat free diet [25]. Glucose levels were decreased in the resveratrol group [26], as occurred in our study. Other studies have also noted that resvera- trol improved insulin sensitivity, lowered plasma glucose, and increased mitochondrial capacity in obese mice [27]. Insulin resistance was not analyzed in our study.

and/or irregular working hours may have adverse effects on health. In Taiwan, there are few published population-based studies addressing the prevalence and possible etiology of NAFLD in the elderly Chinese population which, as in other countries, also faces the burden of liver disease. Due to the increased frequency of NAFLD in elderly subjects, it is useful for identifying treatment needs and rehabilitation services, and for planning and implementing comprehensive NAFLD preventive care programs. Preventive health examinations are an important health promotion strategy, 21,22 and could help

The pathogenesis of NAFLD leading to metabolic abnormalities has not been fully elucidated. It is char- acterized by excessive accumulation of free fatty acid within the liver where they are reesterified with glycerol to produce triglyceride (TG). This lipid abnormality leads to the condition of IR by alterations in insulin receptors of peripheral tissues. Increased deposition of fatty acids within the hepatocytes causes oxidative stress with the release of free radicals leading to ATP depletion, mito- chondrial dysfunction and hepatic injury-all contribute to the development of inflammation followed by fibro- sis [5]. The hepatic steatosis caused by oxidative stress and their underlying mechanism for the development of inflammation still remains unclear. Recent studies revealed that defective insulin action reduces the lipolysis of hepatic fat by decreasing β-oxidation which enhances the release of nonesterified fatty acid (NEFA) from adi- pose tissue so that more NEFA are transported through the bloodstream and taken up by the liver. In a secondary event of hepatic fat accumulation causes oxidative stress and mitochondrial dysfunction thereby releasing of reac- tive oxygen species (ROS) through lipid peroxidation and the generation of proinflammatory cytokines leading to inflammation [6].

Synbiotics on Obesity, Insulin Resistance Syndrome, Type 2 Diabetes and Non-Alcoholic Fatty Liver 755. Disease: A Review of Human Clinical Trials[r]

Abstract: Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum ranging from simple steatosis to cirrho- sis. Hepatocellular lipid accumulation is a hallmark of both nonalcoholic steatosis and steatohepatitis (NASH). The latter develops upon pro-inflammatory cell infiltration and is widely considered as the first relevant pathophysiological step in NAFLD-progression. The chemokine CCL5/RANTES plays an important role in the progression of hepatic in- flammation and fibrosis. We here aimed to investigate its expression in NAFLD. Incubation of primary human hepato- cytes with palmitic acid induced a dose-dependent lipid accumulation, and corresponding dose-dependent RANTES induction in vitro. Furthermore, we observed significantly elevated hepatic RANTES expression in a dietary model of NAFLD, in which mice were fed a high-fat diet for 12 weeks. This diet induced significant hepatic steatosis but only minimal inflammation. In contrast to the liver, RANTES expression was not induced in visceral adipose tissue of the group fed with high-fat diet. Finally, RANTES serum levels were elevated in patients with ultrasound-diagnosed NAFLD. In conclusion, our data indicate hepatocytes as cellular source of elevated hepatic as well as circulating RANTES levels in response to hepatic steatosis. Noteworthy, upregulation of RANTES in response to lipid accumula- tion occurs in the absence of relevant inflammation, which further indicates that hepatic steatosis per se has patho- physiological relevance and should not be considered as benign.

Nonalcoholic fatty liver disease (NAFLD) is characterized as pathological excessive liver lipid accumulation com- bined with chronic inflammatory state of subjects who without history of alcohol abuse [1]. However, the under- lying mechanism of NAFLD is unclear. NAFLD is strongly linked to insulin resistance, and obesity, being prevalent in up to 95% of obese patients [2]. Certain potential mecha- nisms may interpret why obesity is a doughty hazard factor for the development of NAFLD [3], which include increased production of adipokines/cytokines, FFA; as well

Hence Nonalcoholic fatty liver disease is considering as Yakrit vikaras occur due to Atisantarpana (over nutrition). NAFLD is not comparable to any condition in Ayurveda, but we consider it as Santarpanajanya Vyadhi (disease caused by over nourishment) because similarity in the Nidana (etiology) and Samprapti (pathogenesis). Hence we can treat the condition with the help of traditional remedies includes Langhana, Pachana, Deepana, Mridu Virechana/ classical Virechana. In the today’s scenario the modern medi- cine have not specific treatment of this disease, that’s why its need of time to explore some herbal sources is priority to prevent a cure the NAFLD.