Unveiling metabolic dysfunction-associated fatty liver disease: Knowledge gaps and attitudes among Lebanese university students.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a rapidly growing global health problem. Despite its growing incidence and potential for significant repercussions, MAFLD is still widely misunderstood and underdiagnosed. AIM: The purpose of this study was to investigate MAFLD-related knowledge, attitudes, and risk profiles among university students aged 17 to 26. METHODS: A cross-sectional study with 406 university students in Lebanon, equally distributed among males and females, was conducted using a questionnaire that includes demographics, medical information, dietary habits, physical activity, and MAFLD-related knowledge and attitudes. RESULTS: The findings demonstrated a significant lack of knowledge regarding MAFLD, with more than half of participants (54.7%) having no prior knowledge of the illness. Students exhibited unhealthy lifestyle behaviors such as smoking (68%), insufficient physical exercise (44.1%), and poor food habits (52.5%). Having a family history of heart disease, personal history of diabetes mellitus, a balanced diet and prior knowledge of the disease were associated with a higher knowledge score (p<0.05). A higher attitude score existed among those who have a personal or family history of chronic diseases and those who have a prior negative impression about the disease, prior knowledge of the disease, and those who are physically active (p<0.05). CONCLUSION: Despite knowledge gaps, university students in Lebanon have, in general, an appropriate and positive attitude towards MAFLD. We recommend the introduction of focused educational interventions to address the necessity of lifestyle changes among university students and the community as a whole. Developing comprehensive MAFLD prevention methods requires future studies in different age groups and demographics.

Association between Lifestyle Modification and All-Cause, Cardiovascular, and Premature Mortality in Individuals with Non-Alcoholic Fatty Liver Disease.

BACKGROUND: This study is designed to explore the correlation between multiple healthy lifestyles within the framework of "lifestyle medicine", and the mortality risk of nonalcoholic fatty liver disease (NAFLD). METHODS: The National Health and Nutrition Examination Survey (NHANES) database was employed. The analysis consisted of 5542 participants with baseline NAFLD and 5542 matched non-NAFLD participants from the database. Lifestyle information, including five low risk factors advocated by lifestyle medicine (healthy diet, vigorous physical activity, healthy sleep duration, avoiding smoking, and maintaining a non-depressed psychological status), was collected through a baseline questionnaire. Cox proportional hazards regression models and Kaplan-Meier survival curve were used to evaluate risk of mortality. In addition, subgroups were analyzed according to gender, age, body mass index and waist circumference. RESULTS: In total, 502 deaths (n = 181 deaths from cardiovascular disease (CVD)) were recorded among NAFLD participants after the median follow up duration of 6.5 years. In the multivariate-adjusted model, compared to participants with an unfavorable lifestyle (scoring 0-1), NAFLD participants with a favorable lifestyle (scoring 4-5) experienced a 56% reduction in all-cause mortality and a 66% reduction in CVD mortality. Maintaining an undepressed psychological state and adhering to vigorous exercise significantly reduced CVD mortality risk in NAFLD participants (HR, 0.64 [95% CI, 0.43-0.95]; HR, 0.54 [95% CI, 0.33-0.88]) while maintaining healthy sleep reduced premature mortality due to CVD by 31%. CONCLUSIONS: Healthy lifestyle, characterized by maintaining an undepressed mental state and healthy sleep, significantly mitigates the risk of all-cause, CVD, and premature mortality risk among NAFLD patients, with a particularly pronounced effect observed in female and obese subpopulations.

Lifestyle changes in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND: Non-alcoholic fatty liver disease is a liver condition that is increasing worldwide and expected to become the number one cause of cirrhosis and hepatocellular carcinoma in the next 5 years. Currently there are no successful or approved pharmacological treatments. Weight loss is the first-line therapy as a 7 to 10% reduction improves steatosis, inflammation, hepatocyte ballooning, and fibrosis. To achieve this, lifestyle interventions including daily exercise and diet must be encouraged. We aimed to assess the effects of diet, exercise, or a combination of both compared to conventional treatment in patients with non-alcoholic fatty liver disease. METHODS AND FINDING: A literature search was performed in CENTRAL, EMBASE, and PubMed. Randomized controlled trials comparing lifestyle changes with conventional treatment were included, without date restriction. Two authors searched studies according to eligibility criteria, extracted data, and assessed study quality. Subgroup analysis was made by type of intervention, duration of intervention and supervision. We calculated mean differences between the intervention and the control group with their corresponding 95% confidence intervals. Quality of the evidence was assessed using the Cochrane Risk of bias tool. This study is registered in PROSPERO, number CRD42020184241, and checked with the PRISMA checklist. 30 RCTs met the inclusion criteria. Compared to conventional treatment, combined exercise with diet seems to elicit greater reductions in ALT (MD: -13.27 CI 95% -21.39, -5.16), AST (MD: -7.02 CI 95% -11.26, -2.78) and HOMA-IR (MD: -2.07 CI 95% -2.61, -1.46) than diet (ALT MD: -4.48 CI 95% -1.01, -0.21; HOMA-IR MD: -0.61 CI 95% -1.01, -0.21) and exercise (ALT and AST non-significant; HOMA-IR MD = -0.46 CI 95% -0.8, -0.12) alone. Additionally, exercise improved quality of life, cardiorespiratory fitness, and weight (MD: -2.64 CI 95% -5.18, -0.09). CONCLUSION: Lifestyle changes are effective in the treatment of NAFLD. Diet and exercise combined are superior to these interventions alone in improving liver enzymes and HOMA-IR.

Burden of liver disease progression in hospitalized patients with type 2 diabetes mellitus.

BACKGROUND & AIMS: There are uncertainties regarding the burden of liver disease in patients with type 2 diabetes (T2D). Thus, we aimed to quantify the burden of liver disease, identify risk factors, and estimate attributable risks in patients with T2D. METHODS: We measured adjusted hazard ratios of liver disease progression to hepatocellular carcinoma and/or decompensated cirrhosis in a 2010-2020 retrospective, bicentric, longitudinal, cohort of 52,066 hospitalized patients with T2D. RESULTS: Mean age was 64±14 years and 58% were men. Alcohol use disorders accounted for 57% of liver-related complications and were associated with all liver-related risk factors. Non-metabolic liver-related risk factors accounted for 37% of the liver burden. T2D control was not associated with liver disease progression. The incidence (95% CI) of liver-related complications and of competing mortality were 3.9 (3.5-4.3) and 27.8 (26.7-28.9) per 1,000 person-years at risk, respectively. The cumulative incidence of liver disease progression exceeded the cumulative incidence of competing mortality only in the presence of well-identified risk factors of liver disease progression, including alcohol use. The incidence of hepatocellular carcinoma was 0.3 (95% CI 0.1-0.5) per 1,000 person-years in patients with obesity and it increased with age. The adjusted hazard ratios of liver disease progression were 55.7 (40.5-76.6), 3.5 (2.3-5.2), 8.9 (6.9-11.5), and 1.5 (1.1-2.1), for alcohol-related liver disease, alcohol use disorders without alcohol-related liver disease, non-metabolic liver-related risk factors, and obesity, respectively. The attributable fractions of alcohol use disorders, non-metabolic liver-related risk factors, and obesity to the liver burden were 55%, 14%, and 7%, respectively. CONCLUSIONS: In this analysis of data from 2 hospital-based cohorts of patients with T2D, alcohol use disorders, rather than obesity, contributed to most of the liver burden. These results suggest that patients with T2D should be advised to drink minimal amounts of alcohol. LAY SUMMARY: There is uncertainty on the burden of liver-related complications in patients with type 2 diabetes. We studied the risks of liver cancer and complications of liver disease in over 50,000 patients with type 2 diabetes. We found that alcohol was the main factor associated with complications of liver disease. This finding has major implications on the alcohol advice given to patients with type 2 diabetes.

Perceptions of Exercise and Its Challenges in Patients With Nonalcoholic Fatty Liver Disease: A Survey-Based Study.

Exercise is a foundational treatment for nonalcoholic fatty liver disease (NAFLD); however, the majority of patients are unable to initiate and maintain effective exercise habits and remain at increased risk for progressive liver disease. Barriers and limitations to exercise in patients with NAFLD have not been fully identified. We performed a single survey of 94 patients with biopsy-proven NAFLD to understand baseline physical activity and sedentary behavior, self-perceived fitness, limitations to exercise, potential solutions to increase physical activity behavior, and perception of exercise as a foundational treatment for NAFLD. For exploratory analyses, we evaluated differences in responses to the survey by grouping severity of hepatic fibrosis as follows: nonalcoholic fatty liver (NAFL); early stage (nonalcoholic steatohepatitis [NASH] F0, NASH F1, NASH F2); and late stage (NASH F3, NASH F4). Zero weekly total physical activity was reported by 29% of patients with NAFLD. Late-stage NASH had significantly lower vigorous (P = 0.024), walking (P = 0.029), total weekly activity (P = 0.043), and current fitness level (P = 0.022) compared to early stage NASH. Overall, 72% of patients with NAFLD reported limitations to exercise, with the greatest proportion citing lack of energy (62%), fatigue (61%), prior/current Injury (50%), and shortness of breath (49%). A preference for personal training to increase their physical activity was indicated by 66% of patients with NAFLD, and 63% preferred exercise over medication to treat NAFLD. Conclusion: The majority of patients with NAFLD have limitations to exercise but prefer exercise as a treatment option for NAFLD in the form of personal training. Patients with NAFLD may have unique physiologic limitations to exercise that worsen with fibrosis severity. Exercise interventions or services that are personalized and scalable may improve sustainability of exercise habits in the long term.

Co-supplementation of camelina oil and a prebiotic is more effective for in improving cardiometabolic risk factors and mental health in patients with NAFLD: a randomized clinical trial.

This trial evaluated the effects of co-supplementing Camelina sativa oil (CSO) and a prebiotic as modulators of the gut microbiota on cardiometabolic risk factors and mental health in NAFLD patients. In all, 44 subjects with NAFLD were allocated to either an intervention (20 g d-1 CSO + resistant dextrin) or a placebo (20 g d-1 CSO + maltodextrin) group and received a calorie-restricted diet (-500 kcal d-1) for 12 weeks. Fasting plasma levels of gucose, insulin, hs-CRP, endotoxin, antioxidant enzyme activity, total antioxidant capacity (TAC), malondialdehyde (MDA), 8-iso-prostaglandin F2α, and uric acid were measured at the baseline and post-intervention. The depression, anxiety and stress scale (DASS) and the general health questionnaire (GHQ) were used to assess mental health. Co-supplementing CSO and resistant dextrin significantly decreased the level of insulin concentration (-0.84 µU ml-1, p = 0.011), HOMA-IR (-0.27, p = 0.021), hs-CRP (-1.25 pg ml-1, p = 0.023), endotoxin (-3.70 EU mL-1, p = 0.001), cortisol (-2.43, p = 0.033), GHQ (-5.03, p = 0.035), DASS (-9.01, p = 0.024), and MDA (-0.54 nmol mL-1, p = 0.021) and increased the levels of TAC (0.16 mmol L-1, p = 0.032) and superoxide dismutase (106.32 U g-1 Hb, p = 0.45) in the intervention group compared with the placebo group. No significant changes were observed in the levels of other biomarkers. Co-supplementing CSO and resistant dextrin in combination with a low-calorie diet may improve metabolic risk factors and mental health in NAFLD patients.

Opioid Use Is More Common in Nonalcoholic Fatty Liver Disease Patients with Cirrhosis, Higher BMI, and Psychiatric Disease.

BACKGROUND: Opioid use is a topic of growing concern among patients with nonalcoholic fatty liver disease (NAFLD). Given safety concerns of opioids, proactively identifying subgroups of patients with an increased probability of opioid use may encourage practitioners to recommend alternative therapies for pain, thus reducing the likelihood of opioid misuse. This work assessed the prevalence and patient characteristics associated with opioid use in a real-world cohort of patients with NAFLD. METHODS: TARGET-NASH, an observational study of participants at 55 academic and community sites in the United States, includes patients with NAFLD defined by pragmatic case definitions. Opioid use was defined as any documented opioid prescriptions in the year prior to enrollment. The association between patient characteristics and the odds of opioid use were modeled with stepwise multivariable logistic regression and tree ensemble methods (Classification and regression tree/Boosted Tree). RESULTS: The cohort included 3,474 adult patients with NAFLD including 18.0% with documented opioid use. Variables associated with opioid use included presence of cirrhosis (OR 1.51, 95% CI 1.16-1.98), BMI ≥32 kg/m2 (OR 1.29, 95% CI 1.05-1.59), depression (OR 1.87, 95% CI 1.50-2.33), and anxiety (OR 1.59, 95% CI 1.27-1.98). In the boosted tree analysis, history of back pain, depression, and fibromyalgia had the greatest relative importance in predicting opioid use. CONCLUSION: Prescription opioids were used in nearly 1 of 5 patients with NAFLD. Given the safety concerns of opioids in patients with NAFLD, alternative therapies including low-dose acetaminophen and nonpharmacologic treatments should be considered for these patients.

Patient-reported outcomes in patients with non-alcoholic fatty liver disease: A narrative review of Chronic Liver Disease Questionnaire-non-alcoholic fatty liver disease/non-alcoholic steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and one of the leading causes of hepatocellular carcinoma and liver transplantation. Moreover, patients with NAFLD frequently complain of non-specific symptoms including fatigue, abdominal discomfort, as well as anxiety, and NAFLD is reported to affect patient-reported outcomes (PROs). Thus, for clarifying the total burden of NAFLD, it is crucial to assess all associated outcomes, including not only clinical and economic outcomes but also PROs. PROs are thought to reflect what is happening in one's daily life and is an important way patients and health-care professionals communicate. There are various instruments for the assessment of PROs. Recently, a NAFLD/non-alcoholic steatohepatitis (NASH)-specific instrument called "Chronic Liver Disease Questionnaire (CLDQ)-NAFLD/NASH" has been developed. CLDQ-NAFLD/NASH comprises six domains: (i) abdominal symptoms, (ii) activity/energy, (iii) emotional health, (iv) fatigue, (v) systemic symptoms, and (vi) worry. CLDQ-NAFLD/NASH has demonstrated excellent internal consistency, face validity, content validity, and test-retest reliability. It has been sufficiently validated in two international phase 3 clinical trials. In this review, we summarize features of various instruments for assessing PROs by focusing on CLDQ-NAFLD/NASH. We also examine the validity of CLDQ-NAFLD/NASH in Japanese patients and alterations in CLDQ-NAFLD/NASH score in Japanese patients with significant hepatic fibrosis. Moreover, we discuss the utility of CLDQ-NAFLD/NASH in phase 3 clinical trials and in a real-world clinical setting.

Readiness to Change and Prospective Effects of Weight Management Programs in Pediatric Nonalcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is an increasing problem in pediatrics with limited treatment options. We prospectively assessed outcomes in patients managed in a hepatology clinic (HC) alone vs. those managed in combination with a multidisciplinary weight management program (MWMP). We describe each group's readiness to change at the time of NAFLD diagnosis. Patients diagnosed with NAFLD were given a modified Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES) at enrollment (T1) to assess readiness to change. They were then followed at 3-9 months (T2) and at 10-15 months (T3). Linear mixed models were used to evaluate changes in body mass index (BMI), BMI z-score, and transaminases over time and between the two groups. There were no significant treatment group main effects or treatment × time interactions for our primary end points for HC alone (n = 75) or with MWMP (n = 18). There was a significant main effect for time for BMI z-score, with BMI z-scores declining on average by 0.0568 (P = 0.004) from visit to visit. Low SOCRATES subscales scores in HC alone (n = 33) or with MWMP (n = 4) suggested a patient population with low recognition of disease and likelihood of taking steps for change. Patients with obesity and NAFLD had low scores on all three SOCRATES subscales. Despite this, both groups had improvement in BMI z-score without significant difference between the two treatment groups in other primary end points. Further study is needed to identify the most effective patient selection and treatment strategies for pediatric patients with NAFLD, including pharmacotherapy and surgery.

Non-alcoholic fatty liver disease (NAFLD) as a neglected metabolic companion of psychiatric disorders: common pathways and future approaches.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in over 5% of the parenchyma in the absence of excessive alcohol consumption. It is more prevalent in patients with diverse mental disorders, being part of the comorbidity driving loss of life expectancy and quality of life, yet remains a neglected entity. NAFLD can progress to non-alcoholic steatohepatitis (NASH) and increases the risk for cirrhosis and hepatic carcinoma. Both NAFLD and mental disorders share pathophysiological pathways, and also present a complex, bidirectional relationship with the metabolic syndrome (MetS) and related cardiometabolic diseases. MAIN TEXT: This review compares the demographic data on NAFLD and NASH among the global population and the psychiatric population, finding differences that suggest a higher incidence of this disease among the latter. It also analyzes the link between NAFLD and psychiatric disorders, looking into common pathophysiological pathways, such as metabolic, genetic, and lifestyle factors. Finally, possible treatments, tailored approaches, and future research directions are suggested. CONCLUSION: NAFLD is part of a complex system of mental and non-communicable somatic disorders with a common pathogenesis, based on shared lifestyle and environmental risks, mediated by dysregulation of inflammation, oxidative stress pathways, and mitochondrial function. The recognition of the prevalent comorbidity between NAFLD and mental disorders is required to inform clinical practice and develop novel interventions to prevent and treat these complex and interacting disorders.

Association between iron metabolism and cognitive impairment in older non-alcoholic fatty liver disease individuals: A cross-sectional study in patients from a Chinese center.

Sparse is the research on the relationship between iron metabolism and mild cognitive impairment (MCI) in adults aged over 60 years with non-alcoholic fatty liver disease (NAFLD). The soluble transferrin receptor (sTfR), serum iron (SI), serum ferritin (SF), transferrin (TRF) and hemoglobin (HB) are indicators of iron metabolism.This study examined whether iron metabolism is associated with cognitive impairment in older individuals.A cross-sectional study was held in patients from a Chinese center. Individuals with NAFLD aged over 60 years were included if they did not have excessive alcohol intake and were free of stroke or dementia. Their cognitive function was assessed by the same neurologist. 3.0T H proton magnetic resonance spectroscopy (H-MRS) was performed to evaluate the hippocampus of the participants without contraindication. t test and Chi-square test were used to analyze the data. Binary logistic regression was used for correlation analysis.Fifty four (54%) of participants were diagnosed with MCI by the psychiatrist. MCI was significantly associated with higher sTfR after adjustment of all the covariates (OR = 2.565, 95%CI: 1.334∼4.934; P = .005). No statistically significant associations were observed between MCI and age or blood glucose or choline (Cho) /creatine (Cr) of theright hippocampus head.Increased age and low levels of sTfR and HB were associated with MCI in NAFLD individuals aged over 60 years.

Association between Smoking and Liver Fibrosis among Patients with Nonalcoholic Fatty Liver Disease.

Objective: We aimed at analyzing the role of smoking in hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) and at exploring the related risk factors. Methods: This was a cross-sectional study that included a total of 225 patients with NAFLD. Among them, 127 were nonsmokers and 98 were smokers. Liver significant fibrosis was diagnosed when the liver stiffness (LS) value was higher than 7.4 kPa. The diagnostic criterion for NAFLD was a controlled attenuation parameter (CAP) value of >238 dB/m. The CAP and LS values were measured using FibroScan. Results: FibroScan showed that the LS value in the smokers was significantly higher than that in the nonsmokers (10.12 ± 10.38 kPa vs. 7.26 ± 6.42 kPa, P=0.013). The proportions of patients with liver significant fibrosis and advanced liver fibrosis among the smokers were significantly higher than those among the nonsmokers (P=0.046). Univariate analysis showed that age, weight, high AST level, low PLT level, and smoking were the risk factors associated with liver fibrosis in the smokers with NAFLD while multivariate analysis showed that age (OR = 1.029, P=0.021), high AST level (OR = 1.0121, P=0.025), and smoking (OR = 1.294, P=0.015) were the independent risk factors associated with liver fibrosis in the patients with NAFLD. Moreover, high AST level (OR = 1.040, P=0.029), smoking index (OR = 1.220, P=0.019), and diabetes mellitus (OR = 1.054, P=0.032) were the independent risk factors for liver fibrosis among the smokers with NAFLD. Conclusion: This study showed that smoking was closely associated with liver fibrosis among the patients with NAFLD. For patients with NAFLD who smoke, priority screening and timely intervention should be provided if they are at risk of liver fibrosis.

Curcumin and inflammation in non-alcoholic fatty liver disease: a randomized, placebo controlled clinical trial.

BACKGROUND: The aim of the present study was to evaluate the effects of curcumin supplementation on inflammatory indices, and hepatic features in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: Fifty patients with NAFLD were randomized to receive lifestyle modification advice plus either 1500 mg curcumin or the same amount of placebo for 12 weeks. RESULTS: Curcumin supplementation was associated with significant decrease in hepatic fibrosis (p < 0.001), and nuclear factor-kappa B activity (p < 0.05) as compared with the baseline. Hepatic steatosis and serum level of liver enzymes, and tumor necrosis-α (TNF-α) significantly reduced in both groups (p < 0.05). None of the changes were significantly different between two groups. CONCLUSION: Our results indicated that curcumin supplementation plus lifestyle modification is not superior to lifestyle modification alone in amelioration of inflammation. TRIAL REGISTRATION: IRCT20100524004010N24, this trial was retrospectively registered on May 14, 2018.

A Structured Literature Review of the Epidemiology and Disease Burden of Non-Alcoholic Steatohepatitis (NASH).

INTRODUCTION: Non-Alcoholic Steatohepatitis (NASH) is a chronic, progressive disease characterized by fatty liver and liver cell injury, advancing to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Diagnosis involves liver biopsy; however, as a result of its high cost and invasiveness, NASH remains underdiagnosed, and accurate burden of disease (BoD) data are lacking. Our aim was to understand the epidemiological and BoD landscape in NASH and identify knowledge gaps. METHODS: The Ovid search engine was used to conduct a structured review, following quality systematic principles. It included publications that reported on epidemiology, quality of life (QoL) and BoD outcomes in NASH adults. Searches were limited to English language studies published between January 2007 and September 2017. Additional grey literature searches were conducted. A total of 53 references were selected; 38 were peer-reviewed and 15 were grey literature sources. RESULTS: NASH is estimated to affect 3-5% of the global population, most suffering from several comorbidities. Advancing fibrosis drives clinical outcomes, with approximately 20% of patients developing cirrhosis and/or HCC, the latter being a leading cause of death in NASH. A recent model predicted the 15-year survival of advanced fibrosis patients at F3 and F4 as 51.0% and 28.4%, respectively. The limited data consistently show that NASH patients experience significantly poorer QoL and higher costs compared to non-NASH patients. CONCLUSION: This first broad-ranging examination of NASH literature revealed a paucity of evidence, with poor-quality, small studies found. The overwhelming impact of NASH and its patient and healthcare burden is evident. Further evidence is needed to improve our understanding of NASH, especially as fibrosis stages advance. FUNDING: Gilead Science Inc.

Non-Alcoholic Fatty Liver Disease in Overweight Children: Role of Fructose Intake and Dietary Pattern.

The role of nutrition and diet in the development of non-alcoholic fatty liver disease (NAFLD) is still not fully understood. In the present study, we determined if dietary pattern and markers of intestinal permeability differ between overweight children with and without NAFLD. In addition, in a feasibility study, we assessed the effect of a moderate dietary intervention only focusing on nutrients identified to differ between groups on markers of intestinal barrier function and health status. Anthropometric data, dietary intake, metabolic parameters, and markers of inflammation, as well as of intestinal permeability, were assessed in overweight children (n = 89, aged 5⁻9) and normal-weight healthy controls (n = 36, aged 5⁻9). Sixteen children suffered from early signs of NAFLD, e.g., steatosis grade 1 as determined by ultrasound. Twelve children showing early signs of NAFLD were enrolled in the intervention study (n = 6 intervention, n = 6 control). Body mass index (BMI), BMI standard deviation score (BMI-SDS), and waist circumference were significantly higher in NAFLD children than in overweight children without NAFLD. Levels of bacterial endotoxin, lipopolysaccharide-binding protein (LBP), and proinflammatory markers like interleukin 6 (IL-6) and tumor necrosis factor α (TNFα) were also significantly higher in overweight children with NAFLD compared to those without. Total energy and carbohydrate intake were higher in NAFLD children than in those without. The higher carbohydrate intake mainly resulted from a higher total fructose and glucose intake derived from a significantly higher consumption of sugar-sweetened beverages. When counseling children with NAFLD regarding fructose intake (four times, 30⁻60 min within 1 year; one one-on-one counseling and three group counselings), neither alanine aminotransferase (ALT) nor aspartate aminotransferase (AST) activity in serum changed; however, diastolic blood pressure (p < 0.05) and bacterial endotoxin levels (p = 0.06) decreased markedly in the intervention group after one year. Similar changes were not found in uncounseled children. Our results suggest that a sugar-rich diet might contribute to the development of early stages of NAFLD in overweight children, and that moderate dietary counseling might improve the metabolic status of overweight children with NAFLD.

Quality of life in patients with nonalcoholic fatty liver disease: A systematic review.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent medical condition, which may lead to severe complications including cirrhosis and hepatocellular carcinoma. Its chronic course and its association with obesity and diabetes mellitus augment the long-term impact of NAFLD on patients' health and quality of life (QoL) and put great strain on healthcare systems worldwide. Research is growingly focusing on NAFLD patients' QoL in an attempt to describe the full spectrum of disease burden and tackle its future consequences. Relevant studies are characterized by sample heterogeneity and provide conflicting findings which should be interpreted with the use of a systematic and integrative approach. In this context, our aim was to conduct a systematic literature review on the topic of NAFLD patients' QoL. METHODS: We performed a systematic search of PubMed, ScienceDirect and GoogleScholar databases according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol. RESULTS: Our search yielded 14 suitable articles reporting data from almost 5000 patients. All authors agree that NAFLD patients' QoL is impaired especially in the physical sub-domain. In addition, several demographic, clinical and histopathological parameters have emerged as major determinants of patients' QoL. However, future studies are needed to further clarify these issues. CONCLUSIONS: NAFLD patients report poor physical QoL. QoL impairment is associated with a variety of disease-related parameters, mostly the presence of fatigue and cirrhosis.

Effect of traditional Chinese medicine formula Sinisan on chronic restraint stress-induced nonalcoholic fatty liver disease: a rat study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) represents one of the most common forms of liver disease worldwide, and it is always regarded as a consequence of a sedentary, food-abundant lifestyle, sitting for an extended time, and a low physical activity level, which often coincide with chronic and long-lasting psychological stress. A Chinese medicine Sinisan (SNS) may be a potential formula for treating this kind of disease. METHODS: In this study, a long-term chronic restraint stress protocol was used to investigate the mechanism underlying stress-induced NALFD. To investigate the effect of SNS treatment on stress-induced NAFLD, we measured the liver and serum values of total cholesterol (TC), triglyceride (TG), liver free fatty acids (FFA), low-density lipoprotein, superoxide dismutase, tumor necrosis factor-α, malondialdehyde, interleukin (IL)-6, and serum values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase. Results are shown as a mean ± standard deviation. Significant differences between the groups were evaluated using the Student t-test. For multiple comparisons, one-way analysis of variance (ANOVA) was used. If the results of ANOVA indicated significant differences, post hoc analysis was performed with the Tukey test or Dunnett test, and p < 0.05 was considered statistically significant. RESULTS: Long-term chronic stress led to steatosis and non-alcoholic steatohepatitis. Additionally, SNS treatment significantly increased body weight gain (p < 0.01) and sucrose preference (p < 0.001), and it reduced the liver values of TC, TG, and FFA (p < 0.05). SNS also reduced the serum values of AST and ALT (p < 0.001), and the liver value of IL-6 (p < 0.01). CONCLUSIONS: This study's results demonstrate that psychological stress may be a significant risk factor of NAFLD. Furthermore, the traditional Chinese medicine formula SNS may have some beneficial effect in antagonizing psychological stress and stress-related NAFLD.

Role of illness perception and self-efficacy in lifestyle modification among non-alcoholic fatty liver disease patients.

AIM: To describe the relationships between non-alcoholic fatty-liver disease (NAFLD) patient's disease consequences and treatment perceptions, self-efficacy, and healthy lifestyle maintenance. METHODS: A cross-sectional study among 146 ultrasound diagnosed NAFLD patients who visited the fatty liver clinic at the Tel-Aviv Medical Center. Eighty-seven of these individuals, participated in a clinical trial of physical activity and underwent fasting blood tests, analyzed at the same lab. Exclusion criteria included positivity for serum HBsAg or anti-HCV antibodies; fatty liver suspected to be secondary to hepatotoxic drugs; excessive alcohol consumption (≥ 30 g/d in men or ≥ 20 g/d in women) and positive markers of genetic or immune-mediated liver diseases. Patients were asked to complete a self-report structured questionnaire, assembled by the Israeli Center for Disease Control. Nutrition habits were measured using six yes/no questions (0 = no, 1 = yes) adopted from the national survey questionnaire. Participants in the clinical trial completed a detailed semi-quantitative food frequency questionnaire (FFQ) reporting their habitual nutritional intake during the past year. Self-efficacy was assessed by the Self-Efficacy Scale questionnaire, emotional representation, degree of illness understanding, timeline perception, treatment perception and symptoms were measured by the Brief Illness Perception questionnaire. Illness consequences were measured by the Personal Models of Diabetes Interview questionnaire. A path analysis was performed to describe the interrelationships between the patients' illness perceptions, and assess the extent to which the data fit a prediction of nutritional habits. RESULTS: The study sample included 54.1% men, with a mean age of 47.76 ± 11.68 years (range: 20-60) and mean body mass index of 31.56 ± 4.6. The average perceived nutrition habits score was 4.73 ± 1.45 on a scale between 0-6, where 6 represents the healthiest eating habits. Most of the study participants (57.2%) did not feel they fully understood what NAFLD is. Better nutritional habits were positively predicted by the degree of illness understanding (ß = 0.26; P = 0.002) and self-efficacy (ß = 0.25; P = 0.003). Perceptions of more severe illness consequences were related with higher emotional representation (ß = 0.55; P < 0.001), which was related with lower self-efficacy (ß = -0.17; P = 0.034). The perception of treatment effectiveness was positively related with self-efficacy (ß = 0.32; P < 0.001). In accordance with the correlation between self-efficacy and the perceived nutrition habits score, self-efficacy was also correlated with nutrient intake evaluated by the FFQ; negatively with saturated fat (percent of saturated fat calories from total calories) (r = -0.28, P = 0.010) and positively with fiber (r = 0.22, P = 0.047) and vitamin C intake (r = 0.34, P = 0.002). In a sub analysis of the clinical trial participants, objectively measured compliance to physical activity regimen was positively correlated with the self-efficacy level (r = 0.34, P = 0.046). CONCLUSION: Self-efficacy and illness understanding are major determinants of lifestyle-modification among NAFLD patients. This information can assist clinicians in improving compliance with lifestyle changes among these patients.

Non-alcoholic Fatty Liver Disease (NAFLD) is associated with impairment of Health Related Quality of Life (HRQOL).

BACKGROUND: NAFLD impacts patient reported outcomes (PROs). Our aim was to assess the impact of NAFLD on patients' HRQOL. METHODS: National Health and Nutrition Examination Survey (NHANES) 2001-2011 data were used to identify adult patients with NAFLD [Fatty Liver Index (FLI) > 60 in absence of other liver disease and excessive alcohol >20 g/day for men, >10 g/day for women]. Patients with other chronic diseases (ex. HIV, cancer, end-stage kidney disease) were excluded. Subjects without any of these conditions were healthy controls. HCV RNA (+) patients were HCV-controls. All patients completed NHANES HRQOL-4 questionnaire. Linear regression determined the association between NAFLD and HRQOL components adjusting for age, gender, race, and BMI. RESULTS: Participants with complete data were included (n = 9661); 3333 NAFLD (age 51 years and BMI 34 kg/m(2)); 346 HCV+ (age 49 years; BMI 27 kg/m(2)) and 5982 healthy controls (age 48 years and BMI 26 kg/m(2)). The proportion of subjects rating their health as "fair" or "poor" in descending order were HCV controls (30 %) NAFLD (20 %) and healthy controls (10 %) (p < 0.001). HRQOL-4 components scores 2-4 were lowest for HCV, followed by NAFLD and then healthy controls (p-values p = 0.011 to < .0001). After adjustment for age, gender, race, and BMI, NAFLD patients were 18-20 % more likely to report days when their physical health wasn't good or were unable to perform daily activities as a result (p < .0001). CONCLUSIONS: NAFLD causes impairment of HRQOL. As NAFLD is becoming the most important cause of CLD, its clinical and PRO impact must be assessed.

Weight loss results in significant improvements in quality of life for patients with nonalcoholic fatty liver disease: A prospective cohort study.

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and associated with decreased quality of life (QOL). The currently available treatment is weight loss through lifestyle modification. However, longitudinal QOL data are lacking on whether weight loss improves QOL. We prospectively enrolled 151 patients with NAFLD from 2009 to 2014. All patients received a liver biopsy, lifestyle assessment, blood tests, and QOL tools, including the Chronic Liver Disease Questionnaire (CLDQ), a validated health-related quality of life measurement. All patients were followed with a repeat CLDQ at 6 months. The cohort included 91 (60%) men, ages 51.5 ± 12.6 years, 46 (30%) of whom were diabetic. Thirty (21%) had advanced fibrosis or cirrhosis and 67 (47%) had a NAFLD Activity Score >4. Overall, 47 (31%) patients achieved at least a 5% reduction in weight. The cohort's median baseline total CLDQ value was 5.6 (interquartile range: 4.8-6.2). Those who achieved at least a 5% reduction in weight had a 0.45 (95% confidence interval [CI]: 0.24-0.66; P < 0.0001) point improvement in the total CLDQ, compared to 0.003 (95% CI: -0.12-0.12; P = 0.95) in those who did not. Nondiabetic patients with nonalcoholic steatohepatitis and without advanced fibrosis are most likely to achieve QOL benefits from weight loss. For every decrement in body mass index (BMI), there was a corresponding increase of 0.09 (95% CI: 0.03-0.16) points in the CLDQ scale (P = 0.005), adjusting for histology, diabetes, sex, age, and change in alanine aminotransferase level and change in FIB-4 index. A decrease by 5 points in BMI leads to a 10% adjusted improvement in QOL. CONCLUSION: Patients with NAFLD can experience significant improvements in QOL that appear specific to weight loss and not biochemical improvements.