Liver biopsy is the gold standard for diagnosing non-alcoholic steatohepatitis (NASH), but liver biopsy in children is not available in many institutes and many parents are reluctant to agree with the procedure. We investigated the correlation of clinical and pathologic parameters with the severity of non-alcoholic fatty liver disease (NAFLD) in pediatric patients using ultrasonographic examination methods and measured the prevalence of fatty pancreas in pediatric NAFLD.METHODS: Liver biopsy and abdominal ultrasound (US) examinations were performed in 58 children (42 boys, 16 girls; mean age, 12 years; age range, 4–19 years) between March 2006 and August 2017. Fatty liver and fatty pancreas were evaluated by two independent radiologists using US according to 4- and 3-point scales, respectively. We then analyzed the correlations of clinical, laboratory, and histopathologic parameters with the ultrasonographic grade of steatosis.RESULTS: Forty-two children showed simple steatosis (NAFLD activity score [NAS] ≤ 5) while 16 showed NASH (NAS > 5). Higher body mass index (BMI) percentile, waist circumference, hematocrit, insulin resistance, and lower insulin sensitivity index were significantly positively correlated with the grade of fatty liver. NAFLD activity score, amount of steatosis, and fibrosis significantly worsened as the fatty liver grade increased. Higher BMI, lower insulin sensitivity index, and boy were significantly positively correlated with the fatty pancreas grade.CONCLUSION: Altogether, ultrasonographic severity of fatty liver shows good correlation with that of clinical parameters and hepatic pathology.]]>
Academies and Institutes ; Biopsy ; Body Mass Index ; Child ; Fatty Liver ; Female ; Fibrosis ; Hematocrit ; Humans ; Insulin Resistance ; Liver ; Male ; Non-alcoholic Fatty Liver Disease ; Pancreas ; Parents ; Pathology ; Prevalence ; Ultrasonography ; Waist Circumference ; Weights and Measures

The prevalence of non-alcoholic fatty liver disease (NAFLD) is estimated to be 25-30% of the population, and is the most common cause of elevated liver enzymes in Korea. NAFLD is a "hot potato" for pharmaceutical companies. Many clinical trials are underway to develop a first-in-class drug to treat NAFLD. However, there are several challenging issues regarding the diagnosis of NAFLD. Currently, liver biopsy is the gold standard method for the diagnosis of NAFLD and steatohepatitis. Ideally, globally recognized standards for histological diagnosis and methods to optimize observer agreement on biopsy interpretation should be developed. Liver biopsy is the best method rather than a perfect one. Recently, multi-parametric magnetic resonance imagery can estimate the amount of intrahepatic fat successfully and is widely used in clinical trials. But no diagnostic method can discriminate between steatohepatitis and simple steatosis. The other unresolved issue in regard to NAFLD is the absence of satisfactory treatment options. Vitamin E and obeticholic acid have shown protective effects in randomized controlled trials, but this drug has not been approved for use in Korea. This study will provide a description of diagnostic methods and treatments that are currently recommended for NAFLD.
Biomarkers/analysis ; Chenodeoxycholic Acid/analogs & derivatives/therapeutic use ; Clinical Trials as Topic ; Fatty Liver/diagnosis ; Fibrosis ; Humans ; Liver/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; Non-alcoholic Fatty Liver Disease/*diagnosis/drug therapy ; Tomography, X-Ray Computed ; Ultrasonography ; Vitamin E/therapeutic use

PURPOSE: In this study, we aimed to evaluate whether nonalcoholic fatty liver disease (NAFLD) was associated with the presence and morphology of coronary atherosclerotic plaques shown by multidetector computed tomography (MDCT) in asymptomatic subjects without a history of cardiovascular disease. MATERIALS AND METHODS: We retrospectively enrolled 772 consecutive South Korean individuals who had undergone both dualsource 64-slice MDCT coronary angiography and hepatic ultrasonography during general routine health evaluations. The MDCT studies were assessed for the presence, morphology (calcified, mixed, and non-calcified), and severity of coronary plaques. RESULTS: Coronary atherosclerotic plaques were detected in 316 subjects (40.9%) by MDCT, and NAFLD was found in 346 subjects (44.8%) by hepatic ultrasonography. Subjects with NAFLD had higher prevalences of all types of atherosclerotic plaque and non-calcified, mixed, and calcified plaques than the subjects without NAFLD. However, the prevalence of significant stenosis did not differ between groups. After adjusting for age, smoking status, diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome, NAFLD remained a significant predictor for all types of coronary atherosclerotic plaque [odds ratio (OR): 1.48; 95% confidence interval (CI): 1.05-2.08; p=0.025] in binary logistic analysis, as well as for calcified plaques (OR: 1.70; 95% CI: 1.07-2.70; p=0.025) in multinomial regression analysis. CONCLUSION: Our study demonstrated that NAFLD was significantly associated with the presence and the calcified morphology of coronary atherosclerotic plaques detected by MDCT. Further prospective clinical studies are needed to clarify the exact physiopathologic role of NAFLD in coronary atherosclerosis.
Adult ; Aged ; Asian Continental Ancestry Group/statistics & numerical data ; Calcinosis/ethnology/*radiography ; Case-Control Studies ; Coronary Angiography/*methods ; Coronary Artery Disease/ethnology/pathology/*radiography ; Female ; Humans ; Male ; Middle Aged ; Multidetector Computed Tomography/*methods ; Non-alcoholic Fatty Liver Disease/epidemiology/*ultrasonography ; Odds Ratio ; Plaque, Atherosclerotic/*diagnosis/epidemiology ; Prevalence ; Regression Analysis ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Factors ; Ultrasonography

BACKGROUND/AIMS: The red-blood-cell distribution width (RDW) is a newly recognized risk marker in patients with cardiovascular disease, but its role in nonalcoholic fatty liver disease (NAFLD) has not been well defined. The aim of the present study was to determine the association between RDW values and the level of fibrosis in NAFLD according to BARD and FIB-4 scores. METHODS: This study included 24,547 subjects who had been diagnosed with NAFLD based on abdominal ultrasonography and questionnaires about alcohol consumption. The degree of liver fibrosis was determined according to BARD and FIB-4 scores. The association between RDW values and the degree of fibrosis in NAFLD was analyzed retrospectively. RESULTS: After adjusting for age, hemoglobin level, mean corpuscular volume, history of hypertension, history of diabetes, and high-sensitivity C-reactive protein, the RDW values were 12.61+/-0.41% (mean+/-SD), 12.70+/-0.70%, 12.77+/-0.62%, 12.87+/-0.82%, and 13.25+/-0.90% for those with BARD scores of 0, 1, 2, 3, and 4, respectively, and 12.71+/-0.72%, 12.79+/-0.66%, and 13.23+/-1.52% for those with FIB-4 scores of <1.30, 1.31-2.66, and > or =2.67, respectively (P<0.05). The prevalence of advanced fibrosis (BARD score of 24 and FIB-4 score of > or =1.3) increased with the RDW [BARD score: 51.1% in quartile 1 (Q1) vs. 63.6% in Q4; FIB-4 score: 6.9% in Q1 vs. 10.5% in Q4; P<0.001]. After adjustments, the odds ratio of having advanced fibrosis for those in Q4 compared to Q1 were 1.76 (95%CI=1.55-2.00, P<0.001) relative to BARD score and 1.69 (95%CI=1.52-1.98, P<0.001) relative to FIB-4 score. CONCLUSIONS: Elevated RDW is independently associated with advanced fibrosis in NAFLD.
Adult ; Alcohol Drinking ; C-Reactive Protein/analysis ; Diabetes Mellitus/pathology ; Erythrocyte Indices ; Fatty Liver/complications/*diagnosis/ultrasonography ; Female ; Humans ; Hypertension/pathology ; Liver Cirrhosis/*diagnosis/epidemiology/etiology ; Male ; Middle Aged ; Odds Ratio ; Prevalence ; Questionnaires ; Severity of Illness Index

OBJECTIVETo explore demographic and metabolic factors associated with increased alanine aminotransferase (ALT) activity in non-diabetic non-alcoholic fatty liver disease (NAFLD) patients.

METHODSOverall 372 patients who consecutively attended to Gastroenterology Clinic of Baqiyatallah University of Medical Sciences, Tehran, Iran awere diagnosed as NAFLD entered into analysis. Exclusion criteria were having diabetes mellitus and fasting blood glucose over 126 mg/dL, active hepatitis B virus infection, having hepatitis C virus positive serology, and to be under corticosteroid therapy. ALT levels were considered pathologically high when it was over 30 IU/L for men and over 19 IU/L for women.

RESULTSBivariate analyses using t test and chi-square test showed that patients with pathologically augmented ALT levels had significantly higher NAFLD grades in their ultrasonographic evaluations (P=0.003). Moreover, these patients represented significantly higher homeostatic model assessment levels (P=0.003), levels of serum insulin (P=0.002), fasting blood glucose (P<0.001), and uric acid (P=0.02). The prevalence of insulin resistance was also higher in patients with increased serum ALT concentrations. Multifactorial logistic regression models showed that ultrasonographic grading of NAFLD (P=0.027) and insulin resistance (P=0.013) were the only variables significantly associated with abnormal ALT levels.

CONCLUSIONSThis study shows that the associations of increased ALT serum levels in NAFLD patients are different from what are supposed before. By excluding diabetic patients from our population, we find that increased ALT levels are not associated with dyslipidemias but are independently associated with insulin resistance and NAFLD grading on ultrasonographic evaluations. Further studies are needed to confirm our results.

Adult ; Alanine Transaminase ; metabolism ; Blood Glucose ; Dyslipidemias ; metabolism ; Female ; Humans ; Insulin Resistance ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease ; diagnostic imaging ; metabolism ; pathology ; Risk Factors ; Ultrasonography

PURPOSE: We examined the relationship between portal venous velocity and hepatic-abdominal fat in patients with nonalcoholic fatty liver disease (NAFLD), using spectral Doppler ultrasonography (US) and magnetic resonance imaging (MRI). MATERIALS AND METHODS: In this prospective study, 35 patients with NAFLD and 29 normal healthy adults (control group) underwent portal Doppler US. The severity of hepatic steatosis in patients with NAFLD was assessed by MRI through chemical shift imaging, using a modification of the Dixon method. Abdominal (intra-abdominal and subcutaneous) fat was measured by MRI. RESULTS: The difference in portal venous velocity between the patients with NAFLD and the control group was significant (p < 0.0001). There was no correlation between the degree of abdominal or hepatic fat and portal venous velocity (p > 0.05). There were strong correlations between the hepatic fat fraction and subcutaneous adiposity (p < 0.0001), intraperitoneal fat accumulation (p = 0.017), and retroperitoneal fat accumulation (p < 0.0001). CONCLUSION: Our findings suggest that patients with NAFLD have lower portal venous velocities than normal healthy subjects.
Abdominal Fat/pathology ; Adult ; Aged ; Blood Flow Velocity/*physiology ; Case-Control Studies ; Fatty Liver/*physiopathology/*ultrasonography ; Female ; Humans ; Image Interpretation, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Obesity/complications ; Overweight/complications ; Portal Vein/*ultrasonography ; Prospective Studies ; *Ultrasonography, Doppler

BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH) is the progressive form of non-alcoholic fatty liver disease (NAFLD), and its prevalence is increasing worldwide. Liver biopsy remains the best way to diagnose NASH and establish the presence of fibrosis, but has not been performed easily in children because of its invasiveness. We analyzed the ultrasonographic and histopathologic findings of pediatric NAFLD patients, and studied to find their association with clinical characteristics and laboratory findings. METHODS: The study involved 18 obese children ranging from 7 to 15 years of age, who were diagnosed with NASH by liver biopsy. We performed the abdomen ultrasonography before the liver biopsy. We reviewed their pathology slides and classified them by NASH CRN (Clinical Research Network) scoring system. We also reviewed the abdomen ultrasonographic findings of the patients and classified them into grade of 1, 2, and 3. We reviewed the medical records of the patients and investigated their clinical characteristics and laboratory findings. RESULTS: The ultrasonographic grades had significant association with NAFLD activity score, grade of steatosis amount, ballooning change, and portal inflammation. Serum triglyceride level was significantly higher in patients who showed high grade steatosis and high NAFLD activity score. CONCLUSIONS: This study showed that serum triglycerides and ultrasonographic findings are highly correlated with pathologic findings in children with NAFLD.
Adolescent ; Biopsy, Fine-Needle ; Child ; Disease Progression ; Fatty Liver/diagnosis/pathology/ultrasonography ; Female ; Humans ; Male ; Obesity/complications ; Retrospective Studies ; *Severity of Illness Index ; Triglycerides/blood

No abstract available.
Citric Acid Cycle/physiology ; Cytochrome P-450 Enzyme System/metabolism ; Fatty Liver/diagnosis/pathology/ultrasonography ; Humans ; Obesity/*complications ; Severity of Illness Index

BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH) is commonly diagnosed using the semi-quantitative grading and staging system proposed by Brunt et al. in 1999. The Pathology Committee of the NASH established the nonalcoholic fatty liver diseases (NAFLD) activity score (NAS) in 2005. The aim of this study was to elucidate the validity and reliability of the NAS in Korean NAFLD patients. METHODS: Fifty-six patients on whom sonography-guided liver biopsy for well-defined NAFLD was performed between 1999 and 2007 were identified retrospectively. Two pathologists evaluated each biopsy sample. NAFLD was evaluated using both the grading system developed by Brunt et al. and the NAS. Each pathologist was blinded to the patients' clinical data and scored independently. We evaluated the body mass index (BMI), liver enzymes, lipid profile, peripheral insulin resistance, leptin, insulin/c-peptide ratio, ferritin, and fasting blood glucose. RESULTS: The patients were aged 32.1+/-12.5 years (mean+/-SD) and comprised 44 males (78.6%). Patients with different grades at the two grading systems had mild steatosis or ballooning changes with fibrosis, and 36.6% of them were borderline cases (NAS of 3 or 4). The interobserver agreement on diagnostic category was 0.748 (P<0.001) for the NAS (using weighted kappa statistics). Elevated fasting glucose, ALT, and triglyceride were associated with the NAS. CONCLUSIONS: The simple and reproducible NAS was found to be a useful pathologic grading system in Korean NAFLD patients. However, the proportion of borderline cases based on the NAS was high. The "wait and see" strategy is necessary for evaluating the long-term prognosis.
Adult ; Alanine Transaminase/blood ; Asian Continental Ancestry Group ; Blood Glucose/analysis ; Fatty Liver/*pathology/ultrasonography ; Female ; Ferritins/blood ; Fibrosis ; Humans ; Insulin Resistance ; Male ; Middle Aged ; Reproducibility of Results ; Republic of Korea ; Retrospective Studies ; *Severity of Illness Index ; Triglycerides/blood ; Validation Studies as Topic

No abstract available.
Aged ; Cholecystitis/*diagnosis/radiography/ultrasonography ; Endosonography ; Fatty Liver/pathology ; Female ; Humans ; Recurrence ; Tomography, X-Ray Computed