Associations of Nutrient Intake Changes During Childhood with Adolescent Hepatic Fat: The Exploring Perinatal Outcomes Among CHildren Study.

OBJECTIVE: To examine associations of dietary changes from childhood to adolescence with adolescent hepatic fat and whether the PNPLA3 rs738409 risk allele, a strong genetic risk factor for hepatic fat, modifies associations. STUDY DESIGN: Data were from 358 participants in the Exploring Perinatal Outcomes among CHildren (EPOCH) study, a longitudinal cohort in Colorado. Diet was assessed by food frequency questionnaire in childhood (approximately 10 years of age) and adolescence (approximately 16 years of age) and converted to nutrient densities. Hepatic fat was assessed in adolescence by magnetic resonance imaging. Linear regression was used to test associations of dietary changes from childhood to adolescence with adolescent hepatic fat. RESULTS: Increases in fiber, vegetable protein, and polyunsaturated fat intake from childhood to adolescence were associated with lower adolescent hepatic fat, and increases in animal protein were associated with higher hepatic fat (ß per 5-unit increase on log-hepatic fat: -0.12 [95% CI, -0.21 to -0.02] for ▵fiber; -0.26 [95% CI, -0.45 to -0.07] for ▵vegetable protein; -0.18 [95% CI, -0.35 to -0.02] for ▵polyunsaturated fat; 0.13 [95% CI, 0.04-0.22] for ▵animal protein). There was evidence of effect modification by PNPLA3 variant, whereby inverse associations of ▵fiber and ▵vegetable protein and positive associations of ▵saturated fat with adolescent hepatic fat were stronger in risk allele carriers. Most conclusions were similar after adjusting for obesity in adolescence, but associations of ▵saturated fat with hepatic fat were attenuated toward the null. CONCLUSIONS: Our results suggest that nutrient intake changes between childhood and adolescence, particularly decreases in fiber and vegetable protein and increases in saturated fat intake, interact with the PNPLA3 variant to predict higher hepatic fat in adolescence, and may be targets for reducing hepatic fat in high-risk youth.

Health Literacy, Knowledge, and Risk Factors for Fatty Liver Disease among Asian American and Pacific Islanders and Latinos in Los Angeles.

BACKGROUND: Fatty liver disease (FLD) is associated with increased risk for hepatocellular carcinoma (HCC) and is associated with rising rates of diabetes and obesity. The prevalence of FLD is rising among Asian American and Pacific Islanders (AAPIs) and Latinos. This study examined health literacy, knowledge, and risk factors for FLD among AAPIs and Latinos in Los Angeles. METHODS: Data from in-person interviews and clinical measures (body mass index (BMI), body fat percentage, and blood pressure) were obtained from adults aged 18-82 years at four health fairs from November 2018 to March 2019. Interviews assessed knowledge about FLD, access to health resources, and satisfaction with current physician. Correct responses to knowledge questions were summed to generate a FLD knowledge score. Linear regression models were used to examine the association between knowledge score and age, sex, and race/ethnicity. RESULTS: A total of 102 subjects were AAPI and 33 were Latino. Over 65% of participants had heard of FLD but demonstrated limited knowledge about FLD. Only 24% of subjects reported receiving FLD resources in their preferred language. Most subjects failed to identify several risk factors and key symptoms of FLD. Mean knowledge score for subjects who had heard of FLD was 7.58 (95% CI 7.15-8.01) out of a possible 16 points, and for those who had not who had not heard of FLD it was 5.71 (5.00-6.42) (p <0.0001). CONCLUSIONS: A lack of culturally competent resources and effective communication strategies between physicians and patients regarding FLD contributes to a lower awareness about the increased risk of FLD among AAPIs and Latinos. Future studies should investigate optimal methods to educate these communities about FLD and its associations with HCC.

Autoimmune hepatitis, fatty liver, and Fukushima.

The use of direct antiviral agents (DAAs) for hepatitis C virus has led to a paradigm shift from viral hepatitis to non-viral disease. Autoimmune hepatitis (AIH) remains to be an issue in liver disease after the DAAs era. Moreover, fatty liver had been increasing in incidence and has attracted attention because of its risk for hepatocellular carcinoma. In 2011, the Great East Japan Earthquake, with the associated tsunami and accident at Fukushima Daiichi Nuclear Power Plant, has changed the lifestyle of residents in Fukushima prefecture. In this manuscript, we outlined the recent topics about AIH, fatty liver, and Fukushima.

Effect of chronic psychosocial stress on nonalcoholic steatohepatitis in mice.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation which may progress towards inflammation (nonalcoholic steatohepatitis (NASH)). NAFLD is regarded as a consequence of a sedentary, food-abundant lifestyle which, in the modern world, often coincides with chronically high levels of perceived psychosocial stress. Here, we aimed to characterize the effect of chronic psychosocial stress on the development of NAFLD/NASH in male mice either fed with standard chow or NASH-inducing high fat diet. Chronic psychosocial stress was induced by chronic subordinate colony housing (CSC), a pre-clinically validated paradigm relevant for human affective and somatic disorders. Single housed (SHC) mice served as controls. Under standard chow conditions CSC mice revealed lower hepatic triglyceride levels but higher hepatic TNFα, MCP-1 and HMOX mRNA expression, while serum transaminase levels did not significantly differ from SHC mice. Under the NASH-inducing high-fat diet CSC and SHC mice showed similar body weight-gain and serum levels of glucose and adiponectin. Moreover, liver histology as well as TNFα, MCP-1 and HMOX expression were similar in CSC and SHC mice fed with HFD. Surprisingly, CSC showed even significantly lower transaminase levels than SHC mice fed with the same NASH-inducing diet. Together, these data indicate that under normal dietary conditions the CSC model induces noticeable hepatic oxidative stress and inflammation without causing manifest hepatocellular injury. In contrast, CSC exhibited a protective effect on hepatocellular injury in a dietary NASH-model. Identification of the underlying mechanisms of this phenomenon may lead to novel therapeutic strategies to prevent progression of NAFLD.

Clinical trial: physical, psychological and social needs of patients.

Liver disease has become the fifth most common cause of death in the UK and is associated with significant morbidity. Obesity and type II diabetes have been shown to be on the increase as well, playing a major role in chronic liver disease. Treatment options remain limited for those patients with fatty liver disease. This article uses a reflective case study to demonstrate how the research nurse is able to identify some of the physical, psychological and social needs that impact on a patient's journey throughout his clinical trial participation. The patient's psychological wellbeing became compromised as a result of social stressors at home and coming to terms with his liver condition.

Psychosocial outcomes for children with nonalcoholic fatty liver disease over time and compared with obese controls.

OBJECTIVES: Children with nonalcoholic fatty liver disease (NAFLD) experience compromised quality of life (QOL) akin to those with other chronic disease. Our objectives were to examine the association between NAFLD and QOL as well as other psychosocial outcomes, to compare psychosocial outcomes to obese children without known NAFLD, and to determine whether present standard care for NAFLD results in weight loss and improvement in psychosocial outcomes longitudinally. METHODS: Children with NAFLD between 8 and 18 years and obese control children without known NAFLD were consented to complete a brief psychosocial battery examining depression (Children's Depression Inventory), QOL (Pediatric Quality of Life Inventory; PedsQL), and effect of weight on self-esteem (Body-Esteem Scale for Adolescents and Adults) at baseline; and additionally for the NAFLD group after at least 6 months. RESULTS: A total of 48 children with NAFLD and 40 obese control children were enrolled. The PedsQL scores were not significantly different but the CDI total score and subscales of negative mood, ineffectiveness, and negative self-esteem as well as all of the 3 subscales of BESAA, appearance, attribution, and weight were worse in the NAFLD group compared with obese controls. The PedsQL scores also did not change after standard care in the 33 patients with NAFLD who completed the follow-up evaluations, but the CDI score differed between those whose body mass index improved or not. CONCLUSIONS: Children with NAFLD have higher levels of depression than obese controls. Outcomes did not improve with standard care. Larger longitudinal studies and appropriate interventions are required in this area.

Stage of change and motivation to healthier lifestyle in non-alcoholic fatty liver disease.

BACKGROUNDS & AIMS: Healthy diet and physical activity are the treatment cornerstones of non-alcoholic fatty liver disease (NAFLD); their effectiveness is however limited by difficulties in implementing lifestyle changes. We aimed at determining the stage of change and associated psychological factors as a prerequisite to refine strategies to implement behavior changes. METHODS: We studied 138 consecutive NAFLD patients (73% male, age 19-73 years). The diagnosis was confirmed by liver biopsy in 64 cases (steatohepatitis, 47%). All cases completed the validated EMME-3 questionnaire, consisting of two parallel sets of instruments (for diet and physical activity, respectively) and providing stages of change according to transtheoretical model. Logistic regression analysis was used to identify factors associated with stages making behavioral changes more demanding. RESULTS: The individual profiles were variable; for diet, no cases had precontemplation as prevalent stage of change (highest score in individual profiles); 36% had contemplation. For physical activity, 50% were classified in either precontemplation or contemplation. Minor differences were recorded in relation to associated metabolic complications or steatohepatitis. Logistic regression identified male sex (odds ratio, 4.51; 95% confidence interval, 1.69-12.08) and age (1.70; 1.20-2.43 per decade) as the independent parameters predicting precontemplation or contemplation for diet. No predictors were identified for physical activity. CONCLUSIONS: NAFLD cases have scarce readiness to lifestyle changes, particularly with regard to physical activity. Defining stages of change and motivation offers the opportunity to improve clinical care of NAFLD people through individual programs exploiting the powerful potential of behavioral counseling, an issue to be tested in longitudinal studies.

Psychological and psychiatric aspects of treatment of obesity and nonalcoholic fatty liver disease.

Chronic illnesses incur a tremendous cost to American lives in dollars and quality of life. Outcomes in these illnesses are often affected by psychological, behavioral, and pharmacologic issues related to mental illness and psychological symptoms. This article focuses on psychological and psychiatric issues related to the treatment of obesity and nonalcoholic fatty liver disease (NAFLD), including available weight-loss interventions, the complex relationship between psychiatric disorders and obesity, and special considerations regarding use of psychiatric drugs in patients with or at risk for NAFLD and obesity. Recommendations for collaborative care of individuals with comorbid NAFLD and psychological disorders/symptoms are discussed.

Regional reduction in gray and white matter volume in brains of cirrhotic patients: voxel-based analysis of MRI.

Chronic hepatic encephalopathy is a characteristically reversible neuropsychiatric disorder that occurs mainly in patients with liver cirrhosis. The brain regions critically involved in the pathophysiology of cirrhosis are not clear. Magnetic resonance imaging (MRI) with voxel-based morphometry (VBM) is a valuable tool for evaluating structural brain changes in many neurodegenerative diseases. We performed an MRI scan on 18 patients with liver cirrhosis and 16 age-matched healthy controls. We evaluated brain regional structural changes, regional differences and the relationship of these changes with the blood levels of ammonia and the results of neuropsychological tests in patients with cirrhosis. The VBM showed reduction in the volume of gray matter in the cerebellum and occipital lobe and in the volume of white matter in the cingulate, parietal, temporal, occipital lobe and precentral area in cirrhotic patients compared with controls. There were significant correlations between the volume of these regions with the plasma levels of ammonia and the results of neuropsychological tests. Voxel-based analysis of MRI revealed evidence for structural abnormalities of brain in patients with cirrhosis. Abnormal function in the above regions may account for the ammonia-mediated changes and neuropsychological deficits in hepatic encephalopathy.

Low incidence of non-alcoholic steatohepatitis in a Danish liver unit.

INTRODUCTION: Non-alcoholic fatty liver disease encompasses a spectrum of histological lesions ranging from steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. Simple steatosis is generally benign, while NASH can progress to severe liver disease. The aim of the present study was to quantify the number of patients with NASH and assess the prognosis associated with the condition in a large Danish referral centre for liver disease. MATERIAL AND METHODS: Through the pathology archives at Hvidovre Hospital, 348 patients with steatohepatitis diagnosed during the 1976-1987-period were identified. Data were systematically collected by review of available medical records. These data were supplemented by data from the Danish National Hospital Registry and the Registry of Causes of Death. RESULTS: A total of 100 patients referred from other hospitals were excluded as their records were missing and 236 patients were excluded, mainly due to a history of alcohol abuse; this left 14 patients to constitute the study population. At the end of the follow-up period which had a median duration of 16.7 years, ten of the patients had died: four of cardiovascular disease, four of extra-hepatic neoplasm and two of unknown causes. There were no liver-related deaths and only one patient developed cirrhosis. CONCLUSION: In a specialised referral centre, only few patients were diagnosed with NASH 25-30 years ago and those who were identified had a low risk of progression to cirrhosis and premature death. FUNDING: The local research council and the foundation for the study of liver diseases at Hvidovre Hospital provided funding for this study. TRIAL REGISTRATION: not relevant.

Non-alcoholic fatty liver disease impairs hippocampal-dependent memory in male rats.

Non-alcoholic fatty liver disease (NAFLD) is a disorder observed in children and adults characterized by an accumulation of liver fat (>5% wet weight) in the absence of excessive alcohol intake. NAFLD affects 10 to 30% of the American population and is the most common cause of liver disease in the United States. NAFLD leads to serious disturbances in cardiovascular and hormonal function; however, possible effects on brain function have been overlooked. The aims of the present study were to test whether diet-induced NAFLD impairs hippocampal-dependent memory and to determine whether any observed deficits are associated with changes in hippocampal insulin signaling or concentrations of brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1). Post-weanling male Sprague-Dawley rats were fed a high fructose (60% of calories) or control diet for 12 weeks and then trained and tested in a spatial water maze. NAFLD was confirmed with postmortem measures of liver mass and liver lipid concentrations. NAFLD did not affect acquisition of the spatial water maze, but did impair retention tested 48 h later. Specifically, both groups demonstrated similar decreases in latency to swim to the escape platform over training trials, but on the memory test NAFLD rats took longer to reach the platform and made fewer visits to the platform location than control diet rats. There were no differences between the groups in terms of insulin-stimulated phosphorylation of insulin receptor ß subunit (IR-ß) and protein kinase B (PKB/AKT) in hippocampal slices or hippocampal BDNF or IGF-1 concentrations. Thus, these data indicate that NAFLD impairs hippocampal-dependent memory function and that the deficit does not appear attributable to alterations in hippocampal insulin signaling or hippocampal BDNF or IGF-1 concentrations.

Association of short sleep duration with obesity, diabetes, fatty liver and behavioral factors in Japanese men.

OBJECTIVE: Sleep is one of the major means to maintain health. The association of short sleep duration with obesity, diabetes, fatty liver and behavioral factors requires further exploration. METHODS: A total of 8157 Japanese men who underwent health evaluations were divided into 3 groups by sleep duration <5 hours, 5~<7 hours and ≥7 hours. Poor sleep was self-reported, being defined as difficulty of getting to sleep or awakening easily. The age-adjusted and age and poor sleep-adjusted odds ratios of the 3 groups for obesity, diabetes, fatty liver, mental stress, poor sleep, regular exercise and late dinner time were investigated. RESULTS: Compared to the sleep duration 5~<7 hours group, the age-adjusted odds ratios of the <5 hours group were significantly higher for obesity (1.42), diabetes (1.63), mental stress (1.75), poor sleep (1.85), late dinner time (1.47), and significantly lower for regular exercise (0.61); while those of the ≥7 hours group were significantly lower for obesity (0.73), fatty liver (0.82), mental stress (0.73), poor sleep (0.69), late dinner time (0.45), and significantly higher for regular exercise (1.27). Above significances still existed after adjustment for age and poor sleep. CONCLUSION: Short sleep duration is associated with obesity, diabetes, fatty liver and multiple behavioral factors. The optimal sleep duration for health promotion and effective actions for obtaining optimal sleep, including modifications of behavioral and environmental factors, should be one of the major concerns of public health.

Urinary excretion of 5-hydroxy-3-indoleacetic acid in dystimic/depressed, adult obese women: what correlations to hepatic steatosis?

The synthesis of serotonin at CNS level is influenced by diet. Moreover, insulin resistance is associated with lower serotonin levels. Visceral obesity, strictly linked to hepatic steatosis is specifically associated with mild to severe somatic affective-depressive symptom clusters. Previous data support the view that depression involves serotonergic systems, reflecting low levels of urinary 5- hydroxy-3-indoleacetic acid (5-HIAA). The 24-h urinary excretion of 5-HIAA was evaluated in 76 dystimic/depressed, obese/overweight females, divided into two groups, i.e., on a hyper-caloric diet, associated with a life style characterized by leisure time sedentary behavior (LTSB, 35 women), or on a normo-caloric diet, assisted by program-based strategies aimed at promoting physical activity participation (PAP, 41 women). Beck Depression Inventory (BDI) was carried out to score the severity of dystimia/depression. Anthropometric measures, metabolic indices, severity of hepatic steatosis at sonography and HOMA were studied. Urinary levels of 5-HIAA in controls and PAP groups were comparable with a great overlap, while in the LTSB group the urinary excretion of 5-HIAA was significantly reduced in respect to that of the PAP group and obviously compared to that of the control group, 3.4±1.4 mg/L versus 6.2±2.7 mg/L and 6.4±2.6 mg/L, respectively, ANOVA test, P= 0.001. Among metabolic indices, cholesterol, HDL-cholesterol, triglycerides and uric acid were not able to predict urinary concentrations of 5-HIAA, which were not associated with hepatic steatosis; vice versa, ferritin levels, and mainly HOMA values, were independent predictors of the urinary excretion of 5-HIAA (ß=0.235 and 0.45, respectively). Dystimia/depression severity was negatively predicted by urinary 5-HIAA levels in the sense that the highest BDI values were forecast by the lowest values of urinary 5-HIAA (ß= -0.72).The importance of measuring the 24-h urinary excretion of 5-HIAA in follow-ups could rely on a method simultaneously mirroring the well-being status, the adherence to physical activity, which leads to improved insulin sensitivity, and the eating habits acquired by dystimic/depressed overweight/obese patients. In contrast, the significance of the urinary 5-HIAA is reduced in evaluating the severity of hepatic steatosis, likely because it is a structured process.

Depression in patients with nonalcoholic fatty liver disease and chronic viral hepatitis B and C.

BACKGROUND: Patients with chronic liver disease (CLD) and depression may be at a higher risk for various complications, including impaired quality of life and more advanced liver disease. The purpose of this study was to determine the prevalence of depression in CLD patients (non-alcoholic fatty liver disease (NAFLD), Hepatitis B (HBV), and Hepatitis C (HCV)) and to identify potential clinical and laboratory correlates of depression in these patients. METHODS: We used a database of CLD patients that contains extensive clinical (including self-reported depression) and laboratory data for each patient. We compared the prevalence of depression in patients with HBV, HCV, and NAFLD. We also used regression models to find independent predictors of depression in these patients. RESULTS: Of 878 CLD patients, 207 (23.6%) had a diagnosis of depression (NAFLD 27.2%, HCV 29.8%, and HBV 3.7%). Examination of predictors of depression differed by the type of chronic liver disease. For NAFLD, independent predictors of depression were the presence of hypertension, smoking, history of lung disease, being female, and non-African-American. For HBV patients, the only independent predictor of depression was excessive alcohol consumption (defined as >10 g/d), while for HCV patients, independent predictors were being female and non-Asian, presence of fatigue, and excessive alcohol intake. CONCLUSIONS: This study demonstrates that individuals with NAFLD and HCV have a higher prevalence of depression than HBV patients and the rates of depression reported for the general population. The most consistent correlates of depression status in CLD patients are being female and excessive alcohol consumption.

Cognitive-behavioral treatment of nonalcoholic Fatty liver disease: a propensity score-adjusted observational study.

The effectiveness of cognitive-behavior treatment (CBT) in nonalcoholic fatty liver disease (NAFLD), largely related to overweight/obesity and considered the hepatic expression of the metabolic syndrome (MS), has so far been tested in very limited samples. In a tertiary referral center, consecutively observed NAFLD subjects were offered a CBT program aimed at weight loss and increased physical activity, based on 13 group sessions; 68 cases entered the treatment protocol, those who refused (n = 82) were given recommendations for diet and physical activity. Treatment goals (weight loss ≥7% initial body weight, normalization of liver enzymes, and improved parameters of MS) were tested by logistic regression at 6 months (all cases) and at 2 years, both on intention-to-treat and in completers (Diet, 78; CBT, 65). The results were adjusted for the propensity score of attending the CBT program, based on civil, anthropometric and clinical variables. At baseline the CBT group had a larger prevalence of obesity and more severe insulin resistance (homeostasis model assessment (HOMA)). At follow-up, CBT was associated with a higher probability of weight loss and normal liver enzymes (6-month: odds ratio (OR), 2.56; 95% confidence interval (CI), 1.15-5.69; 2-year intention-to-treat: OR, 3.57, 95% CI, 1.59-8.00), after adjustment for propensity and changes in body weight. A similar trend was observed in the outcome goals of insulin resistance and the score of MS, which were both reduced. In conclusion, subjects with NAFLD participating in a CBT program significantly improve their general and liver parameters. The beneficial effects are largely maintained at 2-year follow-up, in keeping with the lifestyle-related pathogenesis of disease.

Depression and anxiety in nonalcoholic steatohepatitis: is there any association?

AIM: Several authors consider that depression and anxiety may induce inflammatory states, and thus can influence the progression of nonalcoholic fatty liver disease (NAFLD). The purpose of this paper was to evaluate if there was an association between anxiety, depression and NAFLD, in patients with normal and elevated serum transaminases. METHODS: We selected a group of patients with NAFLD and a group of female patients with chronic viral hepatitis (B or C). Clinical and biological parameters were collected. All patients filled in several questionnaires assessing total distress, and the presence of symptoms of depression and anxiety. We compared all these scores in female versus males, in patients with normal and elevated liver serum transaminases (LST), and in female patients with NAFLD versus female patients with chronic hepatitis. RESULTS: The NAFLD group included 63 patients (38 females). The viral hepatitis group included 18 female patients. Female patients had significantly higher scores in all questionnaires when compared with male patients. There was a strong association between feminine gender and depression, with a relative risk of 3.2 (95% CI = 1.6-6.7). Depression, anxiety and distress scores were not statistically different in patients with NAFLD and normal LST as compared with patients with NAFLD and elevated LST. No differences were noticed when comparing the scores of depression, anxiety, or distress in females with NAFLD and females with viral hepatitis. There were no correlations between the scores for personality traits and serological tests in either of groups. CONCLUSION: Symptoms of depression and anxiety are common in our region, and are more often seen in female patients. We cannot support any relationship between NAFLD and depression or anxiety. Prospective studies should be done in order to assess the real influence of depression and anxiety on the outcome of patients with NAFLD or chronic viral hepatitis.

Symptoms and quality of life in obese children and adolescents with non-alcoholic fatty liver disease.

BACKGROUND: Data on the quality of life (QOL) of children with non-alcoholic fatty liver disease (NAFLD) are needed to estimate the true burden of illness in children with NAFLD. AIM: To characterize QOL and symptoms of children with NAFLD and to compare QOL in children with NAFLD with that in a sample of healthy children. METHODS: Quality of life and symptoms were assessed in children with biopsy-proven NAFLD enrolled in the NASH Clinical Research Network. PedsQL scores were compared with scores from healthy children. For children with NAFLD, between-group comparisons were made to test associations of demography, histological severity, symptoms and QOL. RESULTS: A total of 239 children (mean age 12.6 years) were studied. Children with NAFLD had worse total (72.8 vs. 83.8, P < 0.01), physical (77.2 vs. 87.5, P < 0.01) and psychosocial health (70.4 vs. 81.9, P < 0.01) scores compared with healthy children. QOL scores did not significantly differ by histological severity of NAFLD. Fatigue, trouble sleeping and sadness accounted for almost half of the variance in QOL scores. Impaired QOL was present in 39% of children with NAFLD. CONCLUSIONS: Children with NAFLD have a decrement in QOL. Symptoms were a major determinant of this impairment. Interventions are needed to restore and optimize QOL in children with NAFLD.

Moderate alcohol consumption aggravates high-fat diet induced steatohepatitis in rats.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) develops in the absence of chronic and excessive alcohol consumption. However, it remains unknown whether moderate alcohol consumption aggravates liver inflammation in pre-existing NASH condition. METHODS: Sprague-Dawley rats were first fed ad libitum with Lieber-DeCarli high-fat diet (71% energy from fat) for 6 weeks to induce NASH, as demonstrated previously. Afterwards, these rats were continuously fed with high-fat diet (HFD, 55% total energy from fat) or high fat plus alcohol diet (HFA, 55% energy from fat and 16% energy from alcohol) for an additional 4 weeks. Pathological lesions including fat accumulation and inflammatory foci in liver were examined and graded. Lipid peroxidation and apoptotic hepatocytes in the liver were assessed. The mRNA expressions of tumor necrosis factor-alpha (TNFalpha) and TNF receptor 1 (TNF-R1), Fas death receptor (Fas) and Fas ligant (FasL), IL-1beta and IL-12 were determined by real-time PCR. Protein levels of total and cleaved caspase-3, CYP2E1, Bax, and Bcl-2 were measured by western blotting. RESULTS: The number of hepatic inflammatory foci and apoptotic hepatocytes were significantly increased in rats fed with HFA as compared with those in HFD-fed rats. The aggravated inflammatory response and cellular apoptosis mediated by HFA were associated with elevated mRNA expression of Fas/FasL and cleaved caspase-3 protein. Although no significant differences were observed between HFD and HFA groups, the levels of lipid peroxidation, Bax and Bcl-2 protein concentration, and mRNA levels of other inflammatory cytokines were significantly higher in these 2 groups than those in the control group. CONCLUSIONS: These data suggest that even moderate alcohol consumption can cause more hepatic inflammation and cellular apoptosis in a pre-existing NASH condition.

Nutritional assessments of patients with non-alcoholic fatty liver disease.

BACKGROUND: Obesity is not only associated with nonalcoholic fatty liver disease (NAFLD) but it also adversely affects the progression of other liver diseases. There are limited data regarding the dietary habits of patients with chronic liver disease. METHODS: Nutrition surveys containing 13 different food groups were mailed. Nutrition scores were calculated based on weekly servings. Foods were also divided into USDA food pyramid categories with conversion of each group into calories expended. Clinico-demographic data were available. NAFLD patients were compared to patients with chronic viral hepatitis. RESULTS: A total of 233 subjects were included: age 52.5 +/- 10.0 years, Body mass index (BMI) 28.1 +/- 6.5, MS 24.2%, 31.8% NAFLD, 48.1% hepatitis C virus (HCV), and 20.2% hepatitis B virus (HBV). Six nutrition indices were different among the groups. NAFLD and HCV consumed more low-nutrient food (p = 0.0037 and 0.0011) and more high-sodium food than HBV (p = 0.0052 and 0.0161). Multivariate analysis showed that NAFLD and HCV consumed more high-fat sources of meat/protein than HBV (p = 0.0887 and 0.0626). NAFLD patients consumed less calories from fruits compared to HCV and HBV patients (p = 0.0273 and 0.0023). Nine nutrition indices differed according to BMI. Univariate analysis showed that obese/overweight patients consumed more high-fat sources of meat/protein (p = 0.0078 and 0.0149) and more high-sodium foods (p = 0.0089 and 0.0062) compared to the normal-weight patients. In multivariate analysis, normal-weight patients consumed more fruits than obese (p = 0.0307). Overweight patients also consumed more calories of meat and oil than normal-weight patients (p = 0.0185 and 0.0287). CONCLUSION: NAFLD and HCV patients have similar dietary habits. Patients with HBV have the healthiest dietary habits. Specific dietary interventions should focus on decreasing intake of low-nutrient and high-sodium food, as well as high-fat sources of meat/protein.