Management Of Nonalcoholic Fatty Liver Disease Research Articles

Non Alcoholic Fatty Liver Disease: A Silent Global Epidemic

Nonalcoholic fatty liver disease (NAFLD) is a common liver disease worldwide affecting adult as well as children with an increasing prevalence. It is associated with insulin resistance and frequently occurs with features of the metabolic syndrome. NAFLD is a spectrum, with NAFL (Non-alcoholic fatty liver) being the initial mildest form, NASH and cirrhosis is being at the other end of the spectrum. Mostly NAFLD is asymptomatic but may present with elevated liver enzyme levels to cirrhosis with its complications and hepatocellular carcinoma. Standard ultrasound including elastography may be used to detect steatosis. Though, liver biopsy is the gold standard for diagnosis of NAFLD but it is not frequently performed. NAFLD patients with evidence of nonalcoholic steatohepatitis and advanced fibrosis are at increased risk of adverse outcomes, including overall mortality. Life style modification and weight loss remains the cornerstone of the management of NAFLD. There are no approved pharmacological drugs for the treatment of NAFLD till now. Although several promising drugs are on the horizon, more trials are needed to validate these medications. Bangladesh J Medicine 2023; 34(2): 73-79

Dihydrotrichodimerol Purified from the Marine Fungus Acremonium citrinum Prevents NAFLD by Targeting PPARα.

The pathogenesis of nonalcoholic fatty liver disease (NAFLD) is closely linked to the imbalance of lipid and glucose metabolism, in which peroxisome proliferator-activated receptors (PPARs) play essential roles. The clinical trials have shown the beneficial effects of the PPARs' ligands on NAFLD. In this study, we screen the extracts from the marine fungus Acremonium citrinum and identify the natural compounds dihydrotrichodimerol (L1A) and trichodimerol (L1B) as the ligands of PPARs, of which L1A is a dual PPARα/γ agonist, whereas L1B is a selective PPARγ agonist. L1A but not L1B significantly prevents hepatic lipid accumulation in an oleic acid-induced NAFLD cell model as well as in a high-fat-diet-induced NAFLD mouse model. Moreover, L1A potently inhibits hepatic steatosis in a PPARα-dependent manner in another NAFLD mouse model constructed by using a choline-deficient and amino acid-defined diet. Mechanistically, L1A transcriptionally up-regulates the expression of SIRT1 in a PPARα-dependent manner, followed by the activation of AMPK and inactivation of ACC, resulting in the inhibition of lipid anabolism and the increase of lipid catabolism. Taken together, our study reveals a dual ligand of PPARα/γ with a distinct structure and therapeutic effect on NAFLD, providing a potential drug candidate bridging the currently urgent need for the management of NAFLD.

Probiotics as Potential Therapy in the Management of Non-Alcoholic Fatty Liver Disease (NAFLD)

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease, the prevalence of which has increased over the years. The management of this pathology is not clear, and a specific pharmacological drug that can treat NAFLD is not available. In this sense, efforts are focused on the potential use of compounds with a natural origin that can contribute to reversing hepatic steatosis. Supplementation with probiotics, live microorganisms, is a potential strategy for the management of NAFLD. Methods: In the present review, the available information on the potential therapeutic effects of probiotics in NAFLD, mainly in animal models and in some clinical trials, is summarized. Results: Studies carried out using animal models of NAFLD induced by a high-fat diet have shown the beneficial effects of probiotic supplementation in reducing liver steatosis and normalizing the blood lipid profile and liver enzyme activities. In addition, a decrease in lipogenesis and an increase in lipolysis have been observed, together with a reduction in the pro-oxidative and pro-inflammatory state and a normalization of intestinal dysbiosis. Clinical trials have reported a decrease in the serum transaminases and an improved lipid profile, as well as a reduction in inflammatory markers. Conclusions: In conclusion, probiotic supplementation can be used as a potential therapy for the management of NAFLD.

Chronic Infection Considerations in Nonalcoholic Fatty Liver Disease Patients

Nonalcoholic fatty-liver disease (NAFLD) has become one of the most common and important chronic liver diseases worldwide. Some chronic infectious diseases are associated with the risk of NAFLD. These can induce abnormal glucose and lipid metabolism, insulin resistance, inflammatory activation and other responses, which increase the risk of progression of liver fibrosis. The present study describes the pathogenesis and management of NAFLD with chronic infectious diseases, such as hepatitis B virus, hepatitis C virus, Helicobacter pylori, and human immunodeficiency virus infections.

Multidisciplinary intensive lifestyle intervention improves markers of nonalcoholic fatty liver disease (NAFLD) in patients with type 1 diabetes and obesity: a retrospective matched-cohort study

BackgroundThe prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing among patients with type 1 diabetes (T1D) paralleling the increasing prevalence of obesity among this population. However, little is known about the impact of intensive lifestyle intervention (ILI) on NAFLD in patients with T1D.MethodsUsing Hepatic Steatosis Index (HSI), a noninvasive surrogate predictor of NAFLD, we retrospectively evaluated 88 adult patients with T1D and obesity after one year of participating in a 12-week ILI program in real-world clinical practice. Using the NAFLD guidelines of the American Association for the Study of Liver Diseases (AASLD), we excluded 11 participants. We matched the remaining ILI cohort (age 43 ± 12 years, females 65%, diabetes duration 22 ± 9 years, A1C 8.2 ± 0.9%, body weight 101 ± 17 kg, BMI 35.3 ± 4.9 kg/m2) in 1:1 ratio with a similar cohort of patients with T1D and obesity who received standard diabetes care (SC) at the same practice and during the same period. Matching criteria included: sex, age, BMI, A1C and duration of T1D. HSI [8 + ALT/AST + BMI (+ 2 if female, + 2 if T2D)] was calculated at baseline and after 12 months of intervention.ResultsAt baseline, HSI was similar between the two cohorts (46.2 ± 6.1 in the ILI cohort and 44.9 ± 5.7 in the SC cohort). After 12 months, the ILI group lost an average of 5.6 ± 2.7 kg (5.8%, p < 0.05) while the SC group maintained their baseline body weight (p < 0.001 between groups). HSI decreased significantly from baseline in the ILI group (-2.7 ± 1.1, p = 0.01), but did not change in the SC group (0.6 ± 0.9, p = 0.53, p < 0.001 between groups). Percentage of patients with high likelihood of NAFLD diagnosis decreased from 100% at baseline to 88.3% in the ILI group, and was 10.4% less compared to SC (p < 0.01). Total daily insulin dose decreased in the ILI cohort compared to the SC cohort (-6.1 ± 4.2 versus 1.34 ± 4.3 units/day, p < 0.01).ConclusionsTwelve weeks of ILI improved HSI and decreased total daily insulin requirements in patients with T1D and obesity at one year. Short-term ILI should be implemented in the management of NAFLD for obese patients with type 1 diabetes.

Performance Comparison of Three Classification Algorithms for Non-alcoholic Fatty Liver Disease Patients Using Data Mining Tool

This study aims to carry out a comparative analysis of the three classification algorithms used in research on Nonalcoholic Fatty Liver Disease (NAFLD) Patients. NAFLD is a liver condition associated with the accumulation of fat in the liver in individuals who do not consume excessive alcohol. The algorithms used in the analysis are Decision Tree, Naïve Bayes, and k-Nearest Neighbor (k-NN), with data processing using RapidMiner software. The data used is sourced from Kaggle which comes from the Rochester Epidemiology Project (REP) database with research conducted in Olmsted, Minnesota, United States. The measurement results show that the Decision Tree algorithm has an accuracy of 92.56%, a precision of 93.24%, and a recall of 99.08%. The Naïve Bayes algorithm has an accuracy of 89.93%, a precision of 95.40% and a recall of 93.56%. While the k-Nearest Neighbor algorithm has an accuracy of 91.33%, a precision of 91.94%, and a recall of 99.27%. ROC curve analysis, all algorithms show "Excellent" classification quality. However, only the k-NN algorithm reached 1.0, showing excellent classification results in solving the problem of classifying Nonalcoholic Fatty Liver Disease patients. This study concluded that the k-NN algorithm is a better choice in solving the problem of classifying Non-alcoholic Fatty Liver Disease patients compared to the Decision Tree and Naïve Bayes algorithms. This study provides valuable insights in the development of classification methods for the early diagnosis and management of NAFLD.

Prevalence of nonalcoholic fatty liver disease and the related risk factors among healthy adults: A cross-sectional study in Chongqing, China.

Epidemiological characteristics of nonalcoholic fatty liver disease (NAFLD) in Chongqing, a west-central city of China, remain unclear. The objective of this study was to investigate the prevalence of NAFLD and the related risk factors among healthy adults for physical examination in Chongqing. A total of 110,626 subjects were enrolled in the present study. Each of the participants underwent physical examination, laboratory measurements, and abdominal ultrasonography. The chi-square test was employed to compare differences in the NAFLD prevalence, and logistic regression analysis was used to estimate the odds ratio for risk factors of NAFLD. The prevalence of NAFLD in individuals in the population of Chongqing was 28.5%, and the prevalence in men (38.1%) was significantly higher than that in women (13.6%) (OR = 2.44; 95% CI: 2.31-2.58). NAFLD was more common in men aged 51-60 years and women over 60 years. Approximately 79.1% of the people with obesity and 52.1% of the people with central obesity had NAFLD. The prevalence of NAFLD in people with hypertension and cholelithiasis was 48.9 and 38.4%, respectively. Logistic regression showed that gender, age, body max index (BMI), central obesity, hypertension, impaired fasting glucose/diabetes mellitus (DM), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hyperuricemia (HUA), alanine transaminase (ALT), and cholelithiasis were independently associated with the presence of NAFLD. The prevalence of NAFLD among healthy adults in Chongqing was high. To improve the prevention and management of NAFLD, special attention should be paid to the factors associated with the presence of NAFLD, including higher BMI, higher waist circumference, higher blood glucose, hypertension, hypertriglyceridemia, hyperuricemia, cholelithiasis, and elevated ALT.

Electrocardiographic changes in patients with non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) has become a major public health problem worldwide. NAFLD is the most common chronic liver disease in developed countries and is estimated to affect 25 to 30 % of the adult population. Currently, NAFLD is considered as a multisystem disease that affects not only the liver, but also the cardiovascular system. Ultimately, these changes may be responsible for the increased cardiac morbidity and mortality associated with NAFLD. Consistent with this finding, and based on the fact that cardiovascular disease (CVD) complications often determine outcomes in patients with NAFLD, the clinical guidelines of the Russian Scientific Liver Society and the Russian Gastroenterological Association, as well as the European Clinical Practice Guidelines for the management of NAFLD recommend that a cardiovascular risk assessment should be performed in all NAFLD patients.

Associations of physical activity domains and muscle strength exercise with non-alcoholic fatty liver disease: a nation-wide cohort study

It is unclear if various types and domains of exercise have an identical effect on non-alcoholic fatty liver disease (NAFLD). Thus, this study aimed to investigate associations of different physical activity domains and muscle strength exercise with NAFLD using a nation-wide cohort database. Adults aged 20–79 years who participated in the Korean National Health and Nutrition Examination Survey between 2014 and 2018 were analyzed. Hepatic steatosis index was used to identify NAFLD. Physical activity was assessed with the Global Physical Activity Questionnaire. Of 21,015 participants, 4942 (23.5%) had NAFLD. Participants with ≥ 150 min/week of total physical activity had a lower risk of NAFLD than those with < 150 min/week (the fully adjusted OR: 0.86, 95% CI 0.78–0.95). When the individual domain of physical activity was assessed, ≥ 150 min/week of recreation activity was associated with a reduced risk of NAFLD (OR: 0.77, 95% CI 0.67–0.88), whereas ≥ 150 min/week of travel or work activity was not. The fully adjusted OR for NAFLD comparing participants with ≥ 2/week to those with < 2/week of muscle strength exercise was 0.83 (95% CI 0.73–0.94). Muscle strength exercise ≥ 2/week showed a lower risk of NAFLD for all levels of total and each specific domains of physical activity except for ≥ 150 min/week of work activity. An increased level of physical activity and muscle strength exercise was associated with a reduced risk of NAFLD, albeit the effect varied depending on domains of physical activity. Thus, physical activity should be differentiated by domains for the management of NAFLD. Muscle strength exercise could also be a good option for individuals who could not perform moderate-to-vigorous physical activity.

Different Dietary Approaches, Non-Alcoholic Fatty Liver Disease and Cardiovascular Disease: A Literature Review.

Non-alcoholic fatty liver disease (NAFLD) is the first cause of chronic liver disease and is also associated with other harmful entities such as obesity, metabolic syndrome, dyslipidemia, and diabetes. NAFLD is a significant public health concern worldwide, impacting individuals of all ages, and its prevalence is projected to increase in the near future due to its connection with obesity. Intrinsic (genetics) and external (lifestyle) factors may also modulate NAFLD, and, in turn, may partly explain the observed relationship between NAFLD and cardiovascular disease (CVD). Although many drugs are been tested to treat NAFLD, to date, no drug has indication to specifically treat this disorder. Thus, the current management of NAFLD relies on lifestyle modifications and specifically on weight loss, physical activity, and the intake of a healthy diet. In the present narrative review, we will discuss the effects of certain dietary patterns on NAFLD incidence and progression.

Multi-model in silico characterization of 3-benzamidobenzoic acid derivatives as partial agonists of Farnesoid X receptor in the management of NAFLD

Non-alcoholic fatty liver disease (NAFLD) is a pathological condition which is strongly correlated with fat accumulation in the liver that has become a major health hazard globally. So far, limited treatment options are available for the management of NAFLD and partial agonism of Farnesoid X receptor (FXR) has proven to be one of the most promising strategies for treatment of NAFLD. In present work, a range of validated predictive cheminformatics and molecular modeling studies were performed with a series of 3-benzamidobenzoic acid derivatives in order to recognize their structural requirements for possessing higher potency towards FXR. 2D-QSAR models were able to extract the most significant structural attributes determining the higher activity towards the receptor. Ligand-based pharmacophore model was created with a novel and less-explored open access tool named QPhAR to acquire information regarding important 3D-pharmacophoric features that lead to higher agonistic potential towards the FXR. The alignment of the dataset compounds based on pharmacophore mapping led to 3D-QSAR models that pointed out the most crucial steric and electrostatic influence. Molecular dynamics (MD) simulation performed with the most potent and the least potent derivatives of the current dataset helped us to understand how to link the structural interpretations obtained from 2D-QSAR, 3D-QSAR and pharmacophore models with the involvement of specific amino acid residues in the FXR protein. The current study revealed that hydrogen bond interactions with carboxylate group of the ligands play an important role in the ligand receptor binding but higher stabilization of different helices close to the binding site of FXR (e.g., H5, H6 and H8) through aromatic scaffolds of the ligands should lead to higher activity for these ligands. The present work affords important guidelines towards designing novel FXR partial agonists for new therapeutic options in the management of NAFLD. Moreover, we relied mainly on open-access tools to develop the in-silico models in order to ensure their reproducibility as well as utilization.

Intermittent fasting for the management of NAFLD: Is there enough evidence?

Abstract The pathogenesis of the non-alcoholic fatty liver disease (NAFLD) has been described as multifactorial, with genetic and environmental factors acting synergistically and causing excessive hepatic lipid accumulation, insulin resistance, and downstream pathogenetic insults. High-calorie diets, particularly those rich in foods with high (saturated) fat and sugar content, and sugar-sweetened beverages, are among the behavioral risk factors with a crucial role in the disease pathogenesis. In addition, meal frequency and meal timing appear to be relevant factors associated with NAFLD. Current guidelines recommend a hypocaloric, preferably Mediterranean diet as the main dietary intervention approach, but various other dietary models have been evaluated in patients with NAFLD. Among these, several intermittent fasting regimens have shown promising results. Diets based on Time-Restricted Feeding and Intermittent Energy Restriction have demonstrated some improvements in body adiposity, liver enzymes, and hepatic steatosis, but most studies included a small number of subjects, were of relatively short-duration, and used surrogate markers of NAFLD. The best intermittent fasting regimen for NAFLD is not yet known, and further well-designed research that evaluates the feasibility (mainly on long-term), safety and efficacy outcomes of these dietary interventions is still needed. Our review has evaluated the up-to-date information regarding the intermittent fasting dietary intervention in NAFLD and generated some key-point messages that are relevant to physicians and dietitians involved in the care of patients with NAFLD.

Frequency of Liver Fibrosis by Non Invasive Marker in Patients with Non-Alcohol Fatty Liver Diseases

Nonalcoholic fatty liver disease (NAFLD) is one of the most important causes of liver disease. NAFLD is commonly associated with obesity, insulin resistance and other metabolic abnormalities such as hypertriglyceridemia and hyperuricemia. Patients with NAFLD can be properly rationalized and with early exploration and management of fatty liver the progression and complications of NAFLD in relation to liver fibrosis can be reduced on priority basis because the APRI is noninvasive and a simple calculation of two laboratorial variables. Objective: To determine the frequency of liver fibrosis by non-invasive marker in patients with non-alcohol fatty liver disease. Methods: This cross-sectional descriptive study was conducted upon 164 patients with NAFLD, presented at Department of Medicine, Liaquat University Hospital, Hyderabad. All the patients with NAFLD were evaluated and explored for liver fibrosis through APRI by taking 2cc venous blood sample in a sterilized syringe by principal investigator and send to laboratory for analysis to get the AST and platelet count. An APRI score greater than 0.7 was set cut off for significant hepatic fibrosis. The data were collected on pre-designed proforma. The study lasted 6 months from 26th February 2020 to 31st August 2020. Results: The mean age of the patients was 48.15±11.13 years. Frequency of liver fibrosis by non-invasive marker in patients with non-alcohol fatty liver disease was 10.98% (18/164). The mean APRI score was found to be 1.8±0.6. Conclusions: It was concluded that APRI is noninvasive and a simple calculation of two laboratory variables and can easily be used at the bedside or in an outpatient setting to assess the liver fibrosis. In this way, the management of NAFLD can be improved.

Abstract P325: Adverse Clinical Outcomes in Non-Alcoholic Fatty Liver Disease Patients Admitted With Heart Failure and Chronic Kidney Disease

Background: Patients with heart failure (HF) are increasingly affected by (CKD). There is a growing evidence connecting Non-Alcoholic Fatty Liver Disease (NAFLD) with poor health outcomes. Nevertheless, there is limited scientific evidence of clinical outcomes in NAFLD population with HF and CKD. Therefore, we sought to investigate this population. Methods: We queried NIS between 2016-2019 for adult patients who were hospitalized with HF and CKD and had NAFLD. The primary outcome was inpatient mortality. The secondary outcomes were cardiogenic shock, cardiac arrest, gastrointestinal bleeding (GIB), acute kidney injury (AKI), invasive mechanical ventilation, length of stay (LOS) and total hospital charge. Multivariable logistic and Poisson regression analyses were used to estimate clinical outcomes. P-value &lt; 0.05 was significant. Results: There were 9,221,158 patients with HF and CKD, of which 405,290 (4.3%) had NAFLD. NAFLD and non-NAFLD cohorts were with mean age of 68.4 vs. 72.7 yrs; males 57.2% vs 53.5%; Caucasians 60.1% vs 63.4%; systolic HF 44.2% vs 41.7%; obesity 21.3% vs 23.0%; dyslipidemia 43.3% vs 56.1%; anemia 24.3% vs 22.4%, DM 59.3% vs 57.7%; AF 43.6% vs 43.5%; history of MI 12.6% vs 16.1%; stroke 1.9% vs 2.2%, COPD 30.5% vs 34.3%, respectively. NAFLD cohort had significantly higher mortality and worse clinical outcomes (Table 1). Conclusion: HF patients with co-existent CKD who were affected by NAFLD demonstrated significantly worse clinical outcomes and higher resource utilization. They were younger, male, with prevalent systolic HF, anemia, diabetes, AF. NAFLD is associated with increased GIB and AKI and may raise risk for systolic dysfunction and coagulopathy. Early NAFLD detection and management in HF and CKD population may improve clinical outcomes. Clinicians should be aware of this negative predictor when managing patients with HF&amp;CKD. Further research is needed to describe this population.

Association between smoking cessation and non-alcoholic fatty liver disease using NAFLD liver fat score.

Smoking is well known to be associated with a higher prevalence and incidence of liver diseases such as advanced fibrosis. However, the impact of smoking on developing nonalcoholic fatty liver disease remains controversial, and clinical data on this is limited. Therefore, this study aimed to investigate the association between smoking history and nonalcoholic fatty liver disease (NAFLD). Data from the Korea National Health and Nutrition Examination Survey 2019-2020 were used for the analysis. NAFLD was diagnosed according to an NAFLD liver fat score of >-0.640. Smoking status was classified as into nonsmokers, ex-smokers, and current smokers. Multiple logistic regression analysis was conducted to examine the association between smoking history and NAFLD in the South Korean population. In total, 9,603 participants were enrolled in this study. The odds ratio (OR) for having NAFLD in ex-smokers and current smokers in males was 1.12 (95% confidence interval [CI]: 0.90-1.41) and 1.38 (95% CI: 1.08-1.76) compared to that in nonsmokers, respectively. The OR increased in magnitude with smoking status. Ex-smokers who ceased smoking for <10 years (OR: 1.33, 95% CI: 1.00-1.77) were more likely to have a strong correlation with NAFLD. Furthermore, NAFLD had a dose-dependent positive effect on pack-years, which was 10 to 20 (OR: 1.39, 95% CI: 1.04-1.86) and over 20 (OR: 1.51, 95% CI: 1.14-2.00). This study found that smoking may contribute to NAFLD. Our study suggests cessation of smoking may help management of NAFLD.

Non-obese or lean non-alcoholic fatty liver disease was associated with increased risk of cancer in patients with type 2 diabetes mellitus

IntroductionRisk of non-obese or lean non-alcoholic fatty liver disease (NAFLD) for cancer in patients with type 2 diabetes mellitus (T2DM) is less known. We aimed to evaluate independent associations of...

Type 2 diabetes originated from non-alcoholic fatty liver disease

Abstract Both non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are highly prevalent metabolic liver diseases. Accumulating epidemiological evidence now indicates that NAFLD and T2DM are strongly associated, yet the causative relationship remains to be elucidated. Liver serves as a hub for nutrient and energy metabolism in the body. Here we demonstrated the pathogenesis linking NAFLD to T2DM through a series of studies and the attenuation of T2DM progression after NALFD improvement in cohort study. We proposed the urgent necessity of NAFLD management and NAFLD drug development, which might be novel therapeutic avenues for T2DM.

Oxidative Stress Modulation by ncRNAs and Their Emerging Role as Therapeutic Targets in Atherosclerosis and Non-Alcoholic Fatty Liver Disease.

Atherosclerosis and non-alcoholic fatty liver disease (NAFLD) are pathologies related to ectopic fat accumulation, both of which are continuously increasing in prevalence. These threats are prompting researchers to develop effective therapies for their clinical management. One of the common pathophysiological alterations that underlies both diseases is oxidative stress (OxS), which appears as a result of lipid deposition in affected tissues. However, the molecular mechanisms that lead to OxS generation are different in each disease. Non-coding RNAs (ncRNAs) are RNA transcripts that do not encode proteins and function by regulating gene expression. In recent years, the involvement of ncRNAs in OxS modulation has become more recognized. This review summarizes the most recent advances regarding ncRNA-mediated regulation of OxS in atherosclerosis and NAFLD. In both diseases, ncRNAs can exert pro-oxidant or antioxidant functions by regulating gene targets and even other ncRNAs, positioning them as potential therapeutic targets. Interestingly, both diseases have common altered ncRNAs, suggesting that the same molecule can be targeted simultaneously when both diseases coexist. Finally, since some ncRNAs have already been used as therapeutic agents, their roles as potential drugs for the clinical management of atherosclerosis and NAFLD are analyzed.

The Non-Invasive Assessment of Circulating D-Loop and mt-ccf Levels Opens an Intriguing Spyhole into Novel Approaches for the Tricky Diagnosis of NASH.

Nonalcoholic fatty liver disease (NAFLD) is the commonest liver disease worldwide affecting both adults and children. Nowadays, no therapeutic strategies have been approved for NAFLD management, and hepatic biopsy remains the gold standard procedure for its diagnosis. NAFLD is a multifactorial disease whose pathogenesis is affected by environmental and genetic factors, and it covers a spectrum of conditions ranging from simple steatosis up to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Several studies underlined the urgent need to develop an NAFLD risk prediction model based on genetics, biochemical indicators, and metabolic disorders. The loss of mitochondrial dynamics represents a typical feature of progressive NAFLD. The imbalance of mitochondrial lifecycle together with the impairment of mitochondrial biomass and function trigger oxidative stress, which in turn damages mitochondrial DNA (mtDNA). We recently demonstrated that the main genetic predictors of NAFLD led to mitochondrial dysfunction. Moreover, emerging evidence shows that variations in the displacement loop (D-loop) region impair mtDNA replication, and they have been associated with advanced NAFLD. Finally, lower levels of mitophagy foster the overload of damaged mitochondria, resulting in the release of cell-free circulating mitochondrial DNA (mt-ccf) that exacerbates liver injury. Thus, in this review we summarized what is known about D-loop region alterations and mt-ccf content during NAFLD to propose them as novel non-invasive biomarkers.

Nutritional Genomics in Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is a common chronic condition associated with genetic and environmental factors in which fat abnormally accumulates in the liver. NAFLD is epidemiologically associated with obesity, type 2 diabetes, and dyslipidemia. Environmental factors, such as physical inactivity and an unbalanced diet, interact with genetic factors, such as epigenetic mechanisms and polymorphisms for the genesis and development of the condition. Different genetic polymorphisms seem to be involved in this context, including variants in PNPLA3, TM6SF2, PEMT, and CHDH genes, playing a role in the disease's susceptibility, development, and severity. From carbohydrate intake and weight loss to omega-3 supplementation and caloric restriction, different dietary and nutritional factors appear to be involved in controlling the onset and progression of NAFLD conditions influencing metabolism, gene, and protein expression. The polygenic risk score represents a sum of trait-associated alleles carried by an individual and seems to be associated with NAFLD outcomes depending on the dietary context. Understanding the exact extent to which lifestyle interventions and genetic predispositions can play a role in the prevention and management of NAFLD can be crucial for the establishment of a personalized and integrative approach to patients.