Absence Of Excessive Alcohol Consumption Research Articles

Relationship between non-alcoholic fatty liver disease and hepatocarcinoma: An integrative review

This integrative review explores the connection between Non-Alcoholic Fatty Liver Disease (NAFLD) and Hepatocellular Carcinoma (HCC). NAFLD is characterized by the presence of steatosis in more than 5% of hepatocytes in the absence of excessive alcohol consumption (> 20 g/day in men and > 30 g/day in women) or other chronic liver diseases. On the rise globally, the vast majority is associated with risk factors, mainly obesity and type 2 diabetes mellitus. Advanced NAFLD, including non-alcoholic steatohepatitis, emerges as an important precursor to HCC, in some cases, even before the presence of cirrhosis, due in addition, recent studies highlight NAFLD as a main cause of liver transplantation for HCC. Non-invasive diagnostic methods, such as fibroscan liver elastography, exhibit promise for evaluating hepatic steatosis. Therapeutic interventions aim to slow the progression of NAFLD and mitigate the risks of HCC.

An international multidisciplinary consensus statement on MAFLD and the risk of CVD.

Fatty liver disease in the absence of excessive alcohol consumption is an increasingly common condition with a global prevalence of ~ 25-30% and is also associated with cardiovascular disease (CVD). Since systemic metabolic dysfunction underlies its pathogenesis, the term metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been proposed for this condition. MAFLD is closely intertwined with obesity, type 2 diabetes mellitus and atherogenic dyslipidemia, which are established cardiovascular risk factors. Unlike CVD, which has received attention in the literature on fatty liver disease, the CVD risk associated with MAFLD is often underestimated, especially among Cardiologists. A multidisciplinary panel of fifty-two international experts comprising Hepatologists, Endocrinologists, Diabetologists, Cardiologists and Family Physicians from six continents (Asia, Europe, North America, South America, Africa and Oceania) participated in a formal Delphi survey and developed consensus statements on the association between MAFLD and the risk of CVD. Statements were developed on different aspects of CVD risk, ranging from epidemiology to mechanisms, screening, and management. The expert panel identified important clinical associations between MAFLD and the risk of CVD that could serve to increase awareness of the adverse metabolic and cardiovascular outcomes of MAFLD. Finally, the expert panel also suggests potential areas for future research.

Nonalcoholic fatty liver disease in relation to the remission and progression along the glycemic continuum.

BackgroundThe study aimed to explore the associations of nonalcoholic fatty liver disease (NAFLD) with the remission and progression along the glycemic continuum.MethodsThis prospective cohort study was performed among the general population in 2010–2015. NAFLD was defined as ultrasound‐detected hepatic steatosis with absence of excessive alcohol consumption and other hepatic diseases. Remission of type 2 diabetes referred to glycated hemoglobin <6.5% without hypoglycemic agents for ≥3 months. Prediabetes remission referred to normalization of blood glucose. Multivariable logistic analysis was applied to identify the risk of glycemic metabolic transition.ResultsDuring a median follow‐up of 4.3 years, participants with NAFLD had a significantly higher risk of progressing from normal glucose tolerance to diabetes (3.36 [1.60–7.07]) and lower likelihood of diabetes remission (0.48 [0.30–0.78]). Associations in participants with overweight or obesity and higher probability of hepatic fibrosis remained consistent. Results related to the effect of NAFLD on the specific glucose parameters were generally in line with the changes of glycemic status. NAFLD improvement decreased the risk of prediabetes progressing to diabetes (0.50 [0.32–0.80]) and increased the probability of prediabetes remission (2.67 [1.49–4.79]). NAFLD tended to show the most significant association with glycemic progression and decreased the likelihood in remission of prediabetes and diabetes.ConclusionsPresence of NAFLD increased risk of glycemic progression and decreased likelihood of remission. NAFLD improvement mitigated glycemic deterioration, whereas NAFLD progression impeded the chance of remission. The results emphasized joint management of NAFLD and diabetes and further focused on liver‐specific subgroups of diabetes to tailor early intervention.

Associations between non-alcoholic fatty liver disease and cognitive impairment and the effect modification of inflammation

This study aimed to evaluate the association between non-alcoholic fatty liver disease (NAFLD) and cognitive impairment and explore the effect modification by the inflammatory status. A total of 4400 community-based participants aged 50–64 years from the Cardiovascular and Metabolic Disease Etiology Research Center were included in this cross-sectional study. NAFLD was identified as the Fatty Liver Index 30 or higher in the absence of excessive alcohol consumption. Cognitive impairment was defined as the total score of the Mini-Mental State Examination (cutoff 24). The inflammatory status was evaluated using white blood cell (WBC) and high-sensitivity C-reactive protein (hsCRP). Multivariate logistic regression analyses were performed. Stratified analyses by the WBC count (the highest quartile) and the hsCRP level (≥ 1.0 mg/dL vs. < 1.0 mg/dL) were conducted. Participants with NAFLD showed an increased prevalence of cognitive impairment (odds ratio [OR] = 1.26; 95% confidence interval [CI] = 1.04–1.52) compared with the non-NAFLD population. In women, this association was significantly stronger in the highest quartile WBC group than in lower WBC group (OR = 1.81; 95% CI = 1.19–2.74 vs. OR = 1.02; 95% CI = 0.78–1.33, p-interaction = 0.05). NAFLD was positively associated with a higher proportion of cognitive impairment, and this association was stronger in women with higher inflammatory status.

The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and the leading cause of liver-related morbidity and mortality. We aimed to predict the burden of NAFLD by examining and estimating the temporal trends of its worldwide prevalence and incidence. In this systematic review and meta-analysis, we searched MEDLINE, EMBASE, Scopus, and Web of Science without language restrictions for reports published between date of database inception and May 25, 2021. We included observational cross-sectional or longitudinal studies done in study populations representative of the general adult population, in whom NAFLD was diagnosed using an imaging method in the absence of excessive alcohol consumption and viral hepatitis. Studies were excluded if conducted in paediatric populations (aged <18 years) or subgroups of the general population. Summary estimates were extracted from included reports by KR and independently verified by HA using the population, intervention, comparison, and outcomes framework. Primary outcomes were the prevalence and incidence of NAFLD. A random-effects meta-analysis was used to calculate overall and sex-specific pooled effect estimates and 95% CIs. The search identified 28 557 records, of which 13 577 records were screened; 299 records were also identified via other methods. In total, 72 publications with a sample population of 1 030 160 individuals from 17 countries were included in the prevalence analysis, and 16 publications with a sample population of 381 765 individuals from five countries were included in the incidence analysis. The overall prevalence of NAFLD worldwide was estimated to be 32·4% (95% CI 29·9-34·9). Prevalence increased significantly over time, from 25·5% (20·1-31·0) in or before 2005 to 37·8% (32·4-43·3) in 2016 or later (p=0·013). Overall prevalence of NAFLD was significantly higher in men than in women (39·7% [36·6-42·8] vs 25·6% [22·3-28·8]; p<0·0001). The overall incidence of NAFLD was estimated to be 46·9 cases per 1000 person-years (36·4-57·5); 70·8 cases per 1000 person-years (48·7-92·8) in men and 29·6 cases per 1000 person-years (20·2-38·9) in women (p<0·0001). There was considerable heterogeneity between studies of both NAFLD prevalence (I2=99·9%) and NAFLD incidence (I2=99·9%). Worldwide prevalence of NAFLD is considerably higher than previously estimated and is continuing to increase at an alarming rate. Incidence and prevalence of NAFLD are significantly higher among men than among women. Greater awareness of NAFLD and the development of cost-effective risk stratification strategies are warranted to address the growing burden of NAFLD. Canadian Institutes of Health.

Endoplasmic reticulum stress in nonalcoholic (metabolic associated) fatty liver disease (NAFLD/MAFLD).

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic fat accumulation in the absence of excessive alcohol consumption and is strongly associated with obesity, type 2 diabetes (T2DM) and other metabolic syndrome features. NAFLD is becoming increasingly prevalent and currently constitutes the leading cause of hepatocellular carcinoma (HCC). Recently, the term metabolic (dysfunction) associated fatty liver disease (MAFLD) has been proposed reflecting more accurately the underlying pathogenesis and the cardiometabolic disorders associated to NAFLD/MAFLD. Given the vital metabolic functions of the liver to maintain the body homeostasis, an extended endoplasmic reticulum (ER) network is mandatory in hepatocytes to retain its capacity to adapt to the multiple extracellular and intracellular signals mediating metabolic changes. Dysfunction of hepatocyte ER homeostasis and disturbance of its interaction with mitochondria have been recognized to be involved in the NAFLD pathophysiology. Apart from hepatocytes, hepatic stellate cells, and Kupffer cells have been shown to play an important role in the occurrence of NAFLD and progression to nonalcoholic steatohepatitis (NASH) with possibly different roles in the different stages of the NAFLD spectrum. Furthermore, excess lipid accumulation in the liver causes lipotoxicity which interacts with ER stress and culminates in inflammation and hepatocellular damage, mechanisms crucially implicated in NASH pathogenesis. Finally, the circadian clock machinery regulates ER stress-related pathways and vice versa, thus controlling the homeostasis of the liver metabolism and being implicated in the NAFLD progression. This review presents a comprehensive overview of the current knowledge supporting the impact of ER stress signaling on NAFLD, whilst summarizing potential therapeutic interventions targeting this process.

Empirically-Derived Dietary Patterns in Relation to Non-Alcoholic Fatty Liver Diseases Among Adult Participants in Amol, Northern Iran: A Structural Equation Modeling Approach

Dietary modifications remain the mainstay in managing nonalcoholic fatty liver disease (NAFLD). Published data on the effect of overall dietary patterns on NAFLD is scarce. The present study aims to extract the dietary patterns and investigate their association to NAFLD by gender, using structural equation modeling, among adult participants in Amol, northern Iran. In this cross-sectional study, data from 3,149 participants in the Amol cohort study (55.3% men, n = 1,741) were analyzed. Usual dietary intake was assessed by a validated 168-items semiquantitative food frequency questionnaire. We classified major dietary patterns by explanatory factor analysis (EFA) and confirmatory factor analysis (CFA). NAFLD diagnosis was based on ultrasound scanning, including increased hepatic echogenicity, abnormal appearance of hepatic arteries, and diaphragm in the absence of excessive alcohol consumption. Multivariable logistic regression and structural equation modeling (SEM) were used to explore the relationship between dietary patterns and NAFLD. Three distinct dietary patterns, including western, healthy, and traditional/mixed dietary patterns, were identified. Adult male who adhere to the western dietary pattern were more affected with NAFLD risk [Q1, Q2, Q3, Q4, odds ratio (OR) = 1, 1.16, 1.34, 1.39; 95% confidence interval (CI) = 0.83–1.61, 0.96–1.85, 0.98–1.96, ptrend = 0.04, respectively]. A full mediating effect of healthy dietary pattern, western dietary pattern, and traditional dietary pattern via dietary acid load (DAL) proxy (of dietary patterns to DAL: βstd = −0.35, p < 0.006, βstd = 0.15, p = 0.009, and βstd = 0.08, p = 0.001, respectively), on NAFLD was found through mediation analysis using SEM. A western dietary pattern comprising frequent intake of salty and sweet snacks, soft drinks, refined grains, processed meats, cooked and fried potatoes, eggs, and coffee was associated with a higher odds of NAFLD in an Iranian male population. Additionally, our findings might provide a mechanistic explanation for the association between dietary patterns and NAFLD via DAL proxy. However, further prospective studies, including assessing acid-base biomarkers, are needed.

Association of metabolic dysfunction-associated fatty liver disease with kidney disease.

Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of fat in more than 5% of hepatocytes in the absence of excessive alcohol consumption and other secondary causes of hepatic steatosis. In 2020, the more inclusive term metabolic (dysfunction)-associated fatty liver disease (MAFLD) - defined by broader diagnostic criteria - was proposed to replace the term NAFLD. The new terminology and revised definition better emphasize the pathogenic role of metabolic dysfunction and uses a set of definitive, inclusive criteria for diagnosis. Diagnosis of MAFLD is based on evidence of hepatic steatosis (as assessed by liver biopsy, imaging techniques or blood biomarkers and scores) in persons who are overweight or obese and have type 2 diabetes mellitus or metabolic dysregulation, regardless of the coexistence of other liver diseases or excessive alcohol consumption. The known association between NAFLD and chronic kidney disease (CKD) and our understanding that CKD can occur as a consequence of metabolic dysfunction suggests that individuals with MAFLD - who by definition have fatty liver and metabolic comorbidities - are at increased risk of CKD. In this Perspective article, we discuss the clinical associations between MAFLD and CKD, the pathophysiological mechanisms by which MAFLD may increase the risk of CKD and the potential drug treatments that may benefit both conditions.

Regulation of Mitochondrial Function by Natural Products for the Treatment of Metabolic Associated Fatty Liver Disease.

Metabolic associated fatty liver disease (MAFLD) is a multifactorial systemic disorder that occurs in the absence of excessive alcohol consumption. The disease is characterized by fatty degeneration and fat accumulation in liver parenchymal cells, the incidence of which is increasing annually, particularly in younger adults. MAFLD is caused by genetic and metabolism related disorders, of which mitochondrial dysfunction is the major contributor. Natural products can relieve MAFLD through restoring mitochondrial function. In this article, we describe the relationship between mitochondria and MAFLD and discuss the beneficial effects of natural products as a future anti-MAFLD strategy. Significance Statement. We herein propose that the development of mitochondrial regulators/nutrients from natural products can remedy mitochondrial dysfunction which represents an attractive strategy for the treatment of MAFLD. Furthermore, the mitochondrial regulation of natural products can provide new insight into the underlying mechanisms of action of natural products used for future MAFLD therapeutics.

Поширеність неалкогольної жирової хвороби печінки у хворих на предіабет

Актуальність. Цукровий діабет (ЦД) є одним із глобальних і надзвичайних викликів у галузі охорони здоров’я. Предіабет— це рання стадія в континуумі гіперглікемії, при якій організм схильний до підвищеного ризику розвитку ЦД. Неалкогольна жирова хвороба печінки (НАЖХП) становить собою низку порушень функції печінки, які характеризуються стеатозом печінки або накопиченням жиру в клітинах печінки за відсутності надмірного вживання алкоголю, вірусної етіології чи вживання наркотиків. На сьогодні проведено не так багато досліджень із метою вивчення поширеності НАЖХП в осіб із предіабетом. Дане дослідження є зусиллям у цьому напрямку. Матеріали та методи. Проведене поперечне обсерваційне дослідження. 100 пацієнтів із предіабетом були включені в дослідження протягом періоду з листопада 2017 року по березень 2019 року після отримання інформованої згоди. Дані дослідження включали визначення біохімічних показників, рівня глікемії в плазмі натще, електролітів та HbA1c, інсуліну в сироватці крові, проведення загального аналізу крові, функціональних тестів печінки та нирок, 2-годинного орального глюкозотолерантного тесту. Результати. Дослідження включало 38 чоловіків та 62 жінки, середній вік досліджуваної популяції становив 46 років. Установлено, що середній індекс маси тіла (ІМТ) становить 24,29±3,98 кг/м2, окружність талії— 81,26±8,71 см. Виявлений вірогідний зв’язок між показниками ехоструктури печінки при ультразвуковому дослідженні (УЗД) та ІМТ (р=0,003) і статтю. Установлено, що 30% обстежених мають порушену чутливість до інсуліну, у 22% виявлені ранні прояви резистентності до інсуліну, у 48%— виражена інсулінорезистентність. Показано статистично значущу кореляцію між результатами УЗД й еластографії. Виявлено статистичну кореляцію між HOMA-IR та показниками ехоструктури на УЗД, а також середньою жорсткістю печінки при еластографії. Висновки. Виявлено вірогідну кореляцію між резистентністю до інсуліну та наявністю НАЖХП. Спостерігалися вірогідні зв’язки між різними демографічними характеристиками та ступенем стеатозу. Існує необхідність провести подальші дослідження в більш широкому масштабі, щоб обґрунтувати отримані результати цього дослідження. Очікується, що це значною мірою сприятиме підвищенню обізнаності й оптимізації стратегій охорони здоров’я.

Non-alcoholic fatty liver disease and psoriasis - is there a shared proinflammatory network?

Psoriasis is an immune-mediated systemic inflammatory disease that is not limited to the skin but may be associated with arthritis, cardiovascular diseases, metabolic syndrome including diabetes and obesity and, as identified more recently, non-alcoholic fatty liver disease (NAFLD) that occurs in approximately 50 % of all patients with psoriasis. NAFLD is characterized by accumulation of fat in hepatocytes in the absence of excessive alcohol consumption. Over the last two decades, NAFLD has developed to the most common chronic liver disease with an estimated prevalence of 25% in the Western population. NAFLD ranges from non-inflammatory or bland hepatic steatosis to inflammation of hepatic tissue (non-alcoholic steatohepatitis, NASH) and consecutive liver fibrosis. It is controversial whether the underlying systemic inflammation of psoriasis is contributing to development of NAFLD or if comorbid diseases such as obesity enhance NAFLD development. Recent findings indicate that cytokine-mediated inflammation through TNFα, interleukin (IL)-6 and IL-17 might be the common link between psoriasis and NAFLD. Considering the shared inflammatory pathways, IL-17 pharmacological blockade, which is already well-established for psoriasis, may be a promising strategy to treat both psoriasis and NAFLD. Therefore, early detection of NAFLD and a better understanding of its pathophysiology in the context of the systemic inflammation in psoriasis is important with regard to individualized treatment approaches.

Fatty Acids and a High-Fat Diet Induce Epithelial-Mesenchymal Transition by Activating TGFβ and β-Catenin in Liver Cells.

Nonalcoholic fatty liver disease is defined as the accumulation of excessive fat in the liver in the absence of excessive alcohol consumption or any secondary cause. Although the disease generally remains asymptomatic, chronic liver inflammation leads to fibrosis, liver cirrhosis, and even to the development of hepatocellular carcinoma (HCC). Fibrosis results from epithelial–mesenchymal transition (EMT), which leads to dedifferentiation of epithelial cells into cells with a mesenchymal-like phenotype. During EMT, epithelial cells with high expression of E-cadherin, influenced by growth factors, cytokines, and inflammatory processes, undergo morphological changes via enhanced expression of, e.g., vimentin, fibronectin, and N-cadherin. An inducer of EMT and, consequently, of fibrosis development is transforming growth factor beta (TGFβ), a pleiotropic cytokine associated with the progression of hepatocarcinogenesis. However, the understanding of the molecular events that direct the development of steatosis into steatohepatitis and liver fibrosis remains incomplete. Our study revealed that both prolonged exposure of hepatocarcinoma cells to fatty acids in vitro and high-fat diet in mice (20 weeks) result in inflammation. Prolonged treatment with fatty acids increased the levels of TGFβ, MMP9, and β-catenin, important EMT inducers. Moreover, the livers of mice fed a high-fat diet exhibited features of liver fibrosis with increased TGFβ and IL-1 levels. Increased expression of IL-1 correlated with a decrease in monocyte chemoattractant protein-induced protein 1 (MCPIP1), a negative regulator of the inflammatory response that regulates the stability of proinflammatory transcripts encoding IL-1. Our study showed that a high-fat diet induced EMT by increasing the levels of EMT-activating transcription factors, including Zeb1, Zeb2, and Snail and changed the protein profile to a profile characteristic of the mesenchymal phenotype.

INSULIN AND INSULIN RECEPTOR GENE POLYMORPHISMS AND SUSCEPTIBILITY TO NONALCOHOLIC FATTY LIVER DISEASE.

Nonalcoholic fatty liver disease (NAFLD) is an increasing global health concern defined by excessive hepatic fat content in the absence of excessive alcohol consumption. Given the pivotal role of insulin resistance in NAFLD, we hypothesized that insulin (INS) and insulin receptor (INSR) gene polymorphisms may be associated with NAFLD risk. A total of 312 subjects, including 153 cases with biopsy-proven NAFLD and 159 controls were enrolled in this case-control study. Four polymorphisms in INS (rs3842752, rs689) and INSR (rs1052371, rs1799817) genes were genotyped using PCR-RFLP method. The cases with NAFLD were older and had higher BMI, systolic blood pressure, diastolic blood pressure, as well as higher serum levels of aspartate aminotransferase, alanine aminotransferase, and gamma glutamyl transferase than the controls (P<0.001). The "TT" genotype of INSR rs1799817 compared with "CC" genotype occurred more frequently in the controls than the cases with NAFLD and the difference remained significant after adjustment for confounding factors (P=0.018; OR=0.10, 95%CI=0.02-0.76). However, no significant difference was found for INS rs3842752, INS rs689, and INSR rs1052371 gene polymorphisms between the cases with NAFLD and the controls either before or after adjustment for the confounders. These findings corroborate the hypothesis that genetic polymorphisms related to insulin resistance play a role in NAFLD susceptibility. Specifically, the INSR rs1799817 "TT" genotype had a protective effect for NAFLD. However, our results remain to be validated in other studies.

Hepatocyte Injury and Hepatic Stem Cell Niche in the Progression of Non-Alcoholic Steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by lipid accumulation in hepatocytes in the absence of excessive alcohol consumption. The global prevalence of NAFLD is constantly increasing. NAFLD is a disease spectrum comprising distinct stages with different prognoses. Non-alcoholic steatohepatitis (NASH) is a progressive condition, characterized by liver inflammation and hepatocyte ballooning, with or without fibrosis. The natural history of NAFLD is negatively influenced by NASH onset and by the progression towards advanced fibrosis. Pathogenetic mechanisms and cellular interactions leading to NASH and fibrosis involve hepatocytes, liver macrophages, myofibroblast cell subpopulations, and the resident progenitor cell niche. These cells are implied in the regenerative trajectories following liver injury, and impairment or perturbation of these mechanisms could lead to NASH and fibrosis. Recent evidence underlines the contribution of extra-hepatic organs/tissues (e.g., gut, adipose tissue) in influencing NASH development by interacting with hepatic cells through various molecular pathways. The present review aims to summarize the role of hepatic parenchymal and non-parenchymal cells, their mutual influence, and the possible interactions with extra-hepatic tissues and organs in the pathogenesis of NAFLD.

Evaluation of microRNA-34a as a molecular link between insulin resistance and nonalcoholic fatty liver disease

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is a chronic progressive disease of the liver that occurs in the absence of excessive alcohol consumption, evolving from simple hepatic steatosis, non-alcoholic steatohepatitis (NASH), fibrosis to cirrhosis and hepatocellular carcinoma (HCC). With a global prevalence of 25.24% (22.10-28.65), NAFLD has become a major public health problem. The principal risk factors associated with NAFLD include metabolic syndrome such as obesity, type-2 diabetes and hyperlipidemia. In particular, the prevalence of obesity in European patients with NAFLD varied from 25% to 94%. Insulin resistance resulting in a hyperinsulinemic state increases de novo lipogenesis, which further exacerbates hepatic lipid deposition and boosts the development of the disease. Objective The aim of this study is to evaluate Circulating microRNA-34a as a molecular link between insulin resistance and nonalcoholic fatty liver disease. Methods This study was carried out on 40 participants between June 2017 and June 2018. They were classified into 2 groups: Group I included 20 patients newly diagnosed as Nonalcoholic fatty liver disease (NAFLD) and had not received any treatment. Group II included 20 apparently healthy volunteers defined as those with normal transaminases, normal hepatic ultrasound and negative for HBsAg, HCV¬Ab. Results Results were compared to results of similar researches; where this study found that there was statistically significant increase in MiR-34a levels in group I Clan group II with p-value &amp;lt; 0.001. Also there was statistically significant positive correlation between MiR-34a and age, BMI, HOMA-IR, NAFLD-fibrosis score, ALT, AST, TGs, F.ins and F.Glu. The best cut off point to differentiate between normal and NAFLD group regarding MIR34-a was found &amp;gt; 1.46 with sensitivity of 80%, specificity of 100% and area under curve (AUC) of 92.2%. Conclusion Circulating microRNA-34a provides a good molecular link between insulin resistance and nonalcoholic ratty liver disease. All data were statistically analyzed. Results were compared to results of similar researches; where this study found that the best cut off point to differentiate between normal and NAFLD group regarding MIR34-a was found &amp;gt; 1.46 with sensitivity of 80%, specificity of 100% and area under curve (AUC) of 92.2%.

Role of hepatic colour duplex ultrasound in assessment of non alcoholic fatty liver disease-nafld

Abstract Background Gray-scale ultrasonography (US) is an initial, easy to use and widely available imaging modality for NAFLD, the presence of fat infiltration in the liver in the absence of excessive alcohol consumption and other causes of liver disease, is the most common cause of fatty liver, with a prevalence as high as 15-25% in many populations. Objective to determine the effect of obesity and NAFLD on the Doppler waveform pattern of the liver vascularity. Methods A case control study, conducted at Ain Shams University in the period between july and December 2018 . In both groups, liver span &amp; subcutaneous fat was measured by ultrasonographic examination. Hepatic vein waveform pattern &amp; portal vein mean flow velocity were assessed &amp; hepatic artery resistance index was measured by duplex Doppler ultrasonography examination. Results Our study included 50 patients , 20 were control &amp; 30 were cases.. The mean age of cases was 45.30 ± 10.15 SD &amp; the mean age of control was 32.70 ± 10.95 SD rendering the mean age of cases &amp; control of high statistical significance (p value=0.000). The Subcutaneous fat showed high significant statistical difference between cases &amp; control groups with mean subcutaneous fat in control =0.75 ± 0.14 SD &amp; mean subcutaneous fat in cases= 1.23 ± 0.42 SD with p –value = 0.000. The liver span showed high significant statistical difference between cases &amp; control groups with mean in control =15.11 ± 0.85 SD &amp; mean liver span in cases= 17.46 ± 1.67SD ( p value = 0.000). Hepatic vein wave pattern was normal in all 20 control (100%). In the 30 cases,the Hepatic vein wave pattern was triphasic in 12 patients (40%) &amp; biphasic or monophasic In 18 patients (60%) with high statistical significance (p-value =0.000). There was negative correlation between the hepatic vein velocity &amp; BMI with ( p value=0.0032). There was no statistically significant difference between cases &amp; control as regards all Doppler indices including the Hepatic artery RI(resistive index), Hepatic artery PSV(peak systolic velocity), Portal vein velocity(maximum &amp; minimum)&amp; hepatic vein velocity (maximum velocity) where the p value was more than 0.05. Conclusion Patients with NAFLD have a high rate of abnormal hepatic vein Doppler waveform patterns ,which can be biphasic or monophasic rather than alterations in hepatic artery resistance index values by duplex Doppler ultrasonography. Also the fatty infiltration of hepatocytes can increase liver span &amp; the subcutaneous fat.

Diagnostic methods and pharmacological management of non-alcoholic fatty liver disease – There is still room for improvement

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of excessive alcohol consumption and it may progress to non-alcoholic steatohepatitis, cirrhosis, liver failure, and cancer. Despite the alarming rate of the disease observed in the last decades due to the increase in the prevalence of the metabolic syndrome,there are unmet needs in the diagnosis and the management of the disease. The gold standard for the diagnosis of the disease remains the liver biopsy. The ultrasound, the laboratory tests (serum aminotransferases, gamma-glutamyl transpeptidase, and ferritin levels, cytokeratin-18 fragment and fibrosis growth factor 21), the clinical (Fatty Liver Index [FLI], NAFLD fibrosis score [NFS] and Fibrosis 4 calculator [FIB-4]) and the non-invasive scores (NIS-4, FS3) are being developed and evaluated and they are very promising for both detecting the presence and assessing the severity of the disease. For the management of NASH, no pharmacological treatment has been approved. Vitamin E, thiazolidinediones, sodium-glucose transport protein-2 (SGLT-2) inhibitors, inhibitors of dipeptidyl peptidase 4 (DPP-4), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), statins, and many other agents under investigation may have a role in the management of NAFLD alongside their primary indications.

MR spectroscopy of the liver - a reliable non-invasive alternative for evaluating non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common conditions worldwide that targets the liver parenchyma. NAFLD represents an intrahepatic triglyceride accumulation in the absence of excessive alcohol consumption and other diseases that affect the liver parenchyma. The current “gold standard” for evaluating the amount of intrahepatic fat is represented by liver biopsy, but many patients are reluctant and hardly accept undergoing this procedure due to its invasive nature. The current study addresses this aspect by evaluating the reliability of liver magnetic resonance spectroscopy (MRS) in diagnosing NAFLD, compared to the traditional invasive liver biopsy. The present study included a total of 38 patients based on several well-defined inclusion and exclusion criteria. We used the same NAFLD grading system for both liver MRS and liver biopsy: grade 0: <5% hepatocytes are affected; grade I: 5–33% hepatocytes are affected; grade II: 34–66% hepatocytes are affected; grade III: >66% hepatocytes are affected. Regarding the NAFLD grade, over three-quarters of patients were classified as grade I and grade II, with a strong predilection for men. The current results indicated a significant association between the NAFLD grade indicated by liver MRS and the NAFLD grade indicated by liver biopsy. At the end of our study, we recommend using liver MRS for evaluating and grading NAFLD in association with other parameters like serum triglycerides and body mass index grade as this protocol can enhance early detection and provide an accurate grading that will lead to a proper management of this disease.

A comprehensive bioinformatics analysis on multiple Gene Expression Omnibus datasets of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Fatty liver disease is one of the leading causes of chronic damage in western countries. Approximately 25% of adults in the United States have fatty livers in the absence of excessive alcohol consumption, a condition termed nonalcoholic fatty liver disease (NAFLD). Little is known about the prevalence and genetic background of NAFLD or the factors that determine its development. In this study, we used the Gene-Cloud of Biotechnology Information bioinformatics platform to carry out a comprehensive bioinformatics analysis identifying differentially expressed genes (DEGs), key biological processes and intersecting pathways. We imported 3 Gene Expression Omnibus datasets (GSE66676, GSE49541, and GSE83452). Then, we assessed the expression of the DEGs in clinical samples. We found that CD24 was the only gene co-expressed in all 3 datasets. “Glycolysis/gluconeogenesis”, “p53 signaling pathway” and “glycine, serine and threonine metabolism” were 3 common pathways related to the fatty liver process. In NAFLD tissues, CD24, COL1A1, LUM, THBS2 and EPHA3 were upregulated, and PZP was downregulated. CD24 is a core gene among these DEGs and have not yet been studied of its impact on NAFLD. Co-expressed genes, common biological processes and intersecting pathways identified in the study might play an important role in NAFLD progression. Further studies are needed to elucidate the mechanism of these potential genes and pathways in NAFLD.

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.