BACKGROUND: The prevalence of metabolic syndrome (MS) and non-alcoholic fatty liver disease (NAFLD) and their associated risk factors are not well-established in young children with obesity. The purpose of this study was to evaluate the prevalence of early onset NAFLD and identify its biochemical predictors in obese children aged less than 10 years. METHODS: Anthropometric measurements, blood pressure, laboratory tests, and abdominal ultrasonography (USG) were performed in all subjects. National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) criteria for MS diagnosis and liver enzymes and USG for NAFLD diagnosis were assessed. RESULTS: A total of 356 children with obesity (233 boys, 123 girls) were included, with 172 children age ≤ 10 years and 184 adolescents. The prevalence of MS was 23.3% in young children and 35.3% in adolescents (P = 0.020); while the prevalence of NAFLD was 36.0% and 70.7%, respectively (P = 0.001). In obese children aged 10 years or less, there were significant differences in levels of serum γ-glutamyltranspeptidase (γGT) (P < 0.001), triglycerides (P = 0.042), and homeostatic model assessment of insulin resistance (P < 0.001) between the non-NAFLD and the NAFLD group. Multivariate logistic regression analysis revealed significant increase in serum γGT and uric acid levels in young children. CONCLUSION: Although MS and NAFLD were more prevalent in adolescents, young children also demonstrated MS and NAFLD as obesity-related complications. Elevated serum γGT and uric acid levels may serve as biochemical predictors in detecting NAFLD in young children with obesity before investigation with abdominal USG.
Adolescent ; Blood Pressure ; Child* ; Cholesterol ; Diagnosis ; Education ; Humans ; Insulin Resistance ; Liver ; Logistic Models ; Non-alcoholic Fatty Liver Disease* ; Obesity* ; Prevalence ; Risk Factors ; Triglycerides ; Ultrasonography ; Uric Acid

Liver fibrosis is a slow, insidious process involving accumulation of extracellular matrix protein in the liver. The stage of liver fibrosis in chronic liver disease (CLD) determines overall morbidity and mortality; the higher the stage, the worse the prognosis. Noninvasive composite scores can be used to determine whether patients with CLD have significant or advanced fibrosis. Patients with low composite scores can be safely followed up in primary care with periodic reassessment. Those with higher scores should be referred to a specialist. As the epidemic of diabetes mellitus, obesity and non-alcoholic fatty liver diseases is rising, CLD is becoming more prevalent. Easy-to-use fibrosis assessment composite scores can identify patients with minimal or advanced fibrosis, and should be an integral part of decision-making. Patients with cirrhosis, high composite scores, chronic hepatitis B with elevated alanine aminotransferase and aspartate aminotransferase, or deranged liver panel of uncertain aetiology should be referred to a specialist.
Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Decision Making ; End Stage Liver Disease ; complications ; diagnosis ; therapy ; Hepatitis B ; complications ; Humans ; Liver ; pathology ; Liver Cirrhosis ; complications ; diagnosis ; therapy ; Non-alcoholic Fatty Liver Disease ; complications ; diagnosis ; therapy ; Prognosis ; Referral and Consultation ; Treatment Outcome

OBJECTIVETo investigate the correlation of serum osteoprotegerin (OPG) with the progression of nonalcoholic fatty liver disease (NAFLD) and the noninvasive prediction and diagnosis of nonalcoholic steatohepatitis (NASH).

METHODSA total of 136 patients with NAFLD were enrolled, and their tissue samples for liver biopsy and serum samples obtained at 1 week after liver biopsy were collected; 83 healthy subjects without the symptoms of fatty liver disease proved by ultrasound examination were enrolled as controls. The physiological indicators including height, body weight, and waist circumference were measured, and body mass index was calculated. The biochemical parameters including alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT, alkaline phosphatase, gamma-glutamyl transferase, total cholesterol, triglyceride (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were measured. Double-antibody sandwich enzyme-linked immunosorbent assay was used to determine the serum level of OPG. The rank sum test, chi-square test, t-test, one-way analysis of variance, Spearman correlation analysis, least significant difference test, and receiver operating characteristic (ROC) curve were applied for statistical analysis of various data.

RESULTSSerum OPG level was correlated with AST and TG (P < 0.05), and was highly correlated with hepatocyte fatty degeneration, ballooning degeneration, intralobular inflammation, portal inflammation, and fibrosis degree (P < 0.01). With the increasing NAFLD activity score (NAS), serum OPG level decreased, and there was a highly negative correlation between them (r = -0.928, P < 0.01). Serum OPG level was significantly lower in NASH patients than non-NASH patients. The area under the ROC curve of serum OPG level was 0.963, and according to the Youden index, its optimal sensitivity and specificity were 96.1% and 97.4%, respectively, at an optimal cut-off value of 242.96 ng/L, which suggested a high diagnostic power.

CONCLUSIONIn NASH patients, serum OPG level decreases significantly. Serum OPG level can be used as an independent predictive factor to evaluate NASH and its severity, as well as a noninvasive diagnostic index for NASH.

Alanine Transaminase ; blood ; Alkaline Phosphatase ; blood ; Aspartate Aminotransferases ; blood ; Biopsy ; Body Mass Index ; Case-Control Studies ; Cholesterol ; blood ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Fibrosis ; Humans ; Inflammation ; pathology ; Liver ; pathology ; Non-alcoholic Fatty Liver Disease ; blood ; diagnosis ; Osteoprotegerin ; blood ; ROC Curve ; Triglycerides ; blood ; gamma-Glutamyltransferase ; blood

BACKGROUND/AIMS: A low vitamin D level has been associated with metabolic syndrome and diabetes. However, an association between a low vitamin D level and nonalcoholic fatty liver disease (NAFLD) has not yet been definitively established. This study aimed to characterize the relationship between a vitamin D level and NAFLD in Korea. METHODS: A cross-sectional study involving 6,055 health check-up subjects was conducted. NAFLD was diagnosed on the basis of typical ultrasonographic findings and a history of alcohol consumption. RESULTS: The subjects were aged 51.7±10.3 years (mean±SD) and 54.7% were female. NAFLD showed a significant inverse correlation with the vitamin D level after adjusting for age and sex [odds ratio (OR)=0.85, 95% confidence interval (CI)=0.75-0.96]. The age- and sex-adjusted prevalence of NAFLD decreased steadily with increasing vitamin D level [OR=0.74, 95% CI=0.60-0.90, lowest quintile (≤14.4 ng/mL) vs highest quintile (≥28.9 ng/mL), p for trend <0.001]. Multivariate regression analysis after adjusting for other metabolic factors revealed that NAFLD showed a significant inverse correlation with both the vitamin D level (>20 ng/mL) [OR=0.86, 95% CI=0.75-0.99] and the quintiles of the vitamin D level in a dose-dependent manner (p for trend=0.001). CONCLUSIONS: The serum level of vitamin D, even when within the normal range, was found to be inversely correlated with NAFLD in a dose-dependent manner. Vitamin D was found to be inversely correlated with NAFLD independent of known metabolic risk factors. These findings suggest that vitamin D exerts protective effects against NAFLD.
Adult ; Aged ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Non-alcoholic Fatty Liver Disease/blood/*diagnosis/diagnostic imaging ; Odds Ratio ; Regression Analysis ; Ultrasonography ; Vitamin D/*blood

BACKGROUND/AIMS: Vitamin E improves the biochemical profiles and liver histology in nonalcoholic steatohepatitis, but the role of vitamin E is not clearly defined in the management of nonalcoholic fatty liver disease (NAFLD) which includes both simple steatosis and steatohepatitis. Co-morbid metabolic syndrome increases the probability of steatohepatitis in NAFLD. In this study, we aimed to determine the short-term effects of vitamin E and off-treatment durability of response in a propensity-score matched cohort of NAFLD patients with metabolic syndrome. METHODS: A retrospective cohort was constructed by retrieving 526 consecutive NAFLD patients from the electronic medical record data warehouse of a tertiary referral hospital in South Korea. Among them, 335 patients (63.7%) had metabolic syndrome and were eligible for vitamin E therapy. In order to assess the effect of vitamin E, propensity score matching was used by matching covariates between control patients (n=250) and patients who received vitamin E (n=85). RESULTS: The PS-matched vitamin E group (n=58) and control group (n=58) exhibited similar baseline metabolic profiles. After 6 months of vitamin E therapy, the mean ALT levels decreased significantly compared to PS-matched control (P<0.01). The changes in metabolic profiles (body weight, lipid and glucose levels) did not differ between control and vitamin E groups during the study period. CONCLUSIONS: Short-term vitamin E treatment significantly reduces ALT levels in NAFLD patients with metabolic syndrome, but metabolic profiles are not affected by vitamin E.
Adult ; Aged ; Alanine Transaminase/blood ; Aspartate Aminotransferases/blood ; Body Weight ; Cohort Studies ; Female ; Humans ; Lipoproteins, HDL/blood ; Lipoproteins, LDL/blood ; Liver/pathology ; Male ; Metabolic Syndrome X/*complications/diagnosis/drug therapy ; Middle Aged ; Non-alcoholic Fatty Liver Disease/*complications/diagnosis/*drug therapy ; Propensity Score ; Republic of Korea ; Retrospective Studies ; Vitamin E/*therapeutic use

Previous epidemiologic studies have shown the clinical association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). However, there is only limited information about the effect of NAFLD on the development of hypertension. Accordingly, we investigated the clinical association between NAFLD and prehypertension. A prospective cohort study was conducted on the 11,350 Korean men without prehypertension for 5 yr. The incidences of prehypertension were evaluated, and Cox proportional hazard model was used to measure the hazard ratios (HRs) for the development of prehypertension according to the degree of NAFLD (normal, mild, moderate to severe). The incidence of prehypertension increased according to NAFLD states (normal: 55.5%, mild: 63.7%, moderate to severe: 70.3%, P<0.001). Even after adjusting for multiple covariates, the HRs (95% confidence interval) for prehypertension were higher in the mild group (1.18; 1.07-1.31) and moderate to severe group (1.62; 1.21-2.17), compared to normal group, respectively (P for trend <0.001). The development of prehypertension is more potentially associated with the more progressive NAFLD than normal and milder state. These findings suggest the clinical significance of NAFLD as one of risk factors for prehypertension.
Adult ; Blood Glucose ; Blood Pressure ; Cohort Studies ; Diabetes Mellitus, Type 2/complications/diagnosis ; Humans ; Incidence ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/complications/*diagnosis ; Prehypertension/diagnosis/*epidemiology/etiology ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Smoking

BACKGROUND/AIMS: Nonalcoholic fatty liver disease (NAFLD) may be one of the important causes of cryptogenic hepatocellular carcinoma (HCC). The aim of this study was to evaluate whether patients with cryptogenic HCC share clinical features similar to that of NAFLD. METHODS: Cryptogenic HCC was defined as HCC that occurs in patients with the following conditions: HBsAg(-), anti-HCV(-), and alcohol ingestion of less than 20 g/day. All patients diagnosed with cryptogenic HCC from 2005 to 2012 (cryptogenic HCC group), and all patients diagnosed with HBV associated HCC between 2008 and 2012 (HBV-HCC group) were enrolled in the present study. Clinical features, BMI, lipid profiles, presence of diabetes mellitus, hypertension, and metabolic syndrome were compared between the two groups. RESULTS: Cryptogenic HCC group was composed of 35 patients (19 males and 16 females) with a mean age of 70+/-11 years. HBV-HCC group was composed of 406 patients (318 males and 88 females) with a mean age of 56+/-7 years. Patients in the cryptogenic HCC group were older (p=0.001) and female dominant (p=0.042) than those in the HBV-HCC group. There were no differences in the laboratory test results including lipid profiles and Child-Turcotte-Pugh class between the two groups. Patients in the cryptogenic HCC group had higher prevalence of diabetes (37% vs. 17%, p=0.015), hypertension (49% vs. 27%, p=0.051), metabolic syndrome (37% vs. 16%, p=0.001), and higher BMI (25.3 kg/m2 vs. 24.1 kg/m2, p=0.042) than those in the HBV-HCC group. The tumor stage was more advanced (stage III and IV) at diagnosis in the cryptogenic HCC group than in the HBV-HCC group (60% vs. 37%, p=0.007). CONCLUSIONS: Cryptogenic HCC has clinical features similar to that of NAFLD and is diagnosed at a more advanced tumor stage.
Age Factors ; Aged ; Body Mass Index ; Carcinoma, Hepatocellular/*diagnosis/etiology/pathology ; Diabetes Complications ; Diabetes Mellitus/pathology ; Female ; Hepatitis B/complications ; Humans ; Hypertension/complications ; Lipids/blood ; Liver Neoplasms/*diagnosis/etiology/pathology ; Male ; Metabolic Syndrome X/complications ; Middle Aged ; Neoplasm Staging ; Non-alcoholic Fatty Liver Disease/*diagnosis/pathology ; Risk Factors ; Severity of Illness Index ; Sex Factors

OBJECTIVETo assess the predictive value of hemoglobin (HGB) levels for non-alcoholic fatty liver disease (NAFLD) by performing a prospective cohort study of NAFLD incidence in a healthy population.

METHODSA total of 2840 individuals in the Xinjiang province were enrolled in the study from 2008 to 2011, based on liver ultrasound showing no evidence of fatty liver disease and the discovery of no major risk factors upon interview. All participants completed an epidemiological questionnaire survey, a physical examination, an abdominal ultrasonography, and gave blood for biochemistry testing. The hazard ratios of NAFLD were compared when the participants were grouped according to HGB level (g/L in quintiles): Q1, less than or equal to 145 for males and less than or equal to 123 for females; Q2, > 145 to less than or equal to 151 for males and > 123 to less than or equal to 129 for females; Q3, > 151 to less than or equal to 155 for males and >129 to less than or equal to 134 for females; Q4, > 155 to less than or equal to 161 for males and > 134 to less than or equal to 139 for females; Q5, > 161 for males and > 139 for females. Between-group comparison of measurement data was carried out by t-test and of percentage or count data by chi-square test. Between group comparison of the HGB level was carried out by one-way ANOVA. The prospective association between HGB levels and NAFLD was assessed by conditioned logistic regression analysis.

RESULTSThe values of body mass index, blood pressure, and triglyceride level were significantly higher in the participants with elevated serum uric acid quartiles. Within the 3-year study period, NAFLD was newly diagnosed in 19.6% of the male participants and 10.1% of the female participants; the difference between males and females reached the threshold of statistical significance (X2 = 51.043, P less than 0.01). The incidence of NAFLD in the quintile groups was 6.10% in Q1, 10.50% in Q2, 13.13% in Q3, 16.95% in Q4, and 22.03% in Q5 (X2 = 70.495, P less than 0.01), and the increasing trend with elevated HGB quartiles was significant (P less than 0.01). In multivariate logistic regression analysis, with adjustment for sex, age, race, metabolic syndrome and its components, the hazard ratios for incidence of fatty liver comparing Q2 to Q5 of HGB concentration to Q1 were 1.125, 1.325, 1.516 and 1.982.

CONCLUSIONElevated HGB concentration is predictive of NAFLD in otherwise healthy subjects and may be used for screening during a routine health check-up.

Adult ; Early Diagnosis ; Female ; Hemoglobins ; analysis ; Humans ; Logistic Models ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease ; blood ; diagnosis ; Predictive Value of Tests ; Prospective Studies ; Surveys and Questionnaires

OBJECTIVETo analyze the relationship between normal serum uric acid (SUA) levels and nonalcoholic fatty liver disease (NAFLD) among postmenopausal women, and determine the possible risk factors of NAFLD in this patient population.

METHODSChinese postmenopausal women who participated in the annual health check-up program from March 2009 to February 2010 were retrospectively assessed to identify individuals with SUA within normal range for study inclusion. For the total 1425 study participants, the recorded data of anthropometric parameters, metabolic factors, and serum biochemical parameters were collected. Results from abdominal ultrasonography examination were used to group participants according to presence of fatty liver. Women with fatty liver were divided into NAFLD and non-NAFLD groups. Further sub-grouping was performed according to SUA quartiles, as follows: Q1 group: less than 226.1 mumol/L); Q2 group: 226.1 mumol/L less than or equal to SUA less than 267.8 mumol/L; Q3 group: 267.8 mumol/Lless than or equal to SUA less than 303.5 mumol/L); Q4 group: 303.5 mumol/Lless than or equal toSUAless than or equal to357.0 mumol/L. The independent-sample t-test was used to compare normally distributed variables between groups, and the Mann-Whitney U test was used to analyze variables with skewed distribution. Categorical variables were examined by the R * C x2 test. Binary logistic analysis was used to determine the risk factors for fatty liver and to adjust for possible confounders. The multiple non-parameter independent-sample test (Kruskal-Wallis test) was used to compare the differences of SUA levels among NAFLD groups with different disease severity.

RESULTSThe prevalence of NAFLD among Chinese postmenopausal women with normal SUA was 32.8%, with NAFLD prevalences of 20.4% (70/343) in women with Q1 SUA, 26.3% (104/395) with Q2 SUA, 35.2% (128/364) with Q3 SUA, and 51.4% (166/323) with Q4 SUA. The prevalence of fatty liver showed a significant increasing trend according to the SUA quartile (x2 = 76.470, P-trend less than 0.01). Women in the SUA Q3 and Q4 groups had significantly higher risk of fatty liver presence than women in the Q1 group (P less than 0.01 for both, with or without adjustment of confounders). Disease severity did not appear to be related to disease severity, as the SUA levels in women with mild, moderate or severe fatty liver were not significantly different (286.8+/-48.2 mumol/L vs. 277.9+/-53.0 mumol/L vs. 281.4+/-48.2 mumol/L, respectively; x2 = 3.025, P more than 0.05).

CONCLUSIONSUA levels were independently correlated with NAFLD in Chinese postmenopausal women. SUA levels in the higher quartiles of the normal range may be an independent risk factor of NAFLD.

Aged ; Female ; Humans ; Middle Aged ; Non-alcoholic Fatty Liver Disease ; blood ; diagnosis ; Postmenopause ; Retrospective Studies ; Risk Factors ; Uric Acid ; blood

BACKGROUND/AIMS: Waist circumference (WC) is a risk factor for metabolic syndrome and is related to insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD). The purpose of this study was to determine the association between WC and IR and NAFLD in apparently healthy Korean adults. METHODS: The volunteers included in this cross-sectional study comprised 9,159 adults (5,052 men, 4,107 women) who participated in a comprehensive health checkup program. IR was evaluated by the homeostasis model assessment of IR (HOMA-IR) and was considered to be present when the HOMA-IR score was >2. NAFLD was evaluated by ultrasound examination. Elevated alanine aminotransferase (ALT) was defined as >40 IU/L in men and >35 IU/L in women. Logistic regression was performed to determine the odds ratios (ORs) and 95% confidence intervals (95% CIs) for NAFLD, IR, and ALT according to categorized levels of WC. RESULTS: NAFLD was found in 2,553 (27.9%) of the participants (82.6% men, 17.4% women), while IR and elevated ALT were found in 17.2% (68.1% men, 31.9% women) and 10% (83% men, 17% women), respectively. After adjusting for confounding factors, the prevalence of NAFLD, IR, and elevated ALT was significantly associated with increases in WC quartile: highest quartile for NAFLD in men, OR=15.539, 95% CI=12.687-19.033; highest quartile for NAFLD in women, OR=48.732, 95% CI=23.918-99.288 (P<0.001); and highest quartile for IR in men, OR=17.576, 95% CI=13.283-23.255; highest quartile for IR in women, OR=11.078, 95% CI=7.813-15.708 (P<0.001); highest quartile for elevated ALT in men, OR=7.952, 95% CI=6.046-10.459; and highest quartile for elevated ALT in women, OR=8.487, 95% CI=4.679-15.395 (P<0.001). CONCLUSIONS: WC contributes to IR and NAFLD in apparently healthy Korean adults, and thus may be an important factor in the development of IR and NAFLD.
Adult ; Alanine Transaminase/blood ; Area Under Curve ; Asian Continental Ancestry Group ; Body Mass Index ; Cross-Sectional Studies ; Fatty Liver/*diagnosis ; Female ; Humans ; *Insulin Resistance ; Male ; Middle Aged ; Odds Ratio ; Republic of Korea ; Risk Factors ; *Waist Circumference