A Diet High in Fat and Fructose Induces Early Hepatic Mitochondrial Aging.

ABSTRACT: To investigate the effect of high fructose diet on ultrastructure and content of hepatic mitochondria, we randomized 6-8 weeks old male C57Bl6/J mice to ad lib chow or high-fat-high-fructose (HF2) diet for 32 weeks. HF2-fed mice gained more weight, had higher plasma alanine aminotransferase, and fasting glucose levels and increased hepatic triglyceride content at all time points compared to chow-fed mice. HF2-fed mice had lower mitochondrial to nuclear DNA ratio compared to chow-fed mice. HF2-fed mice had lower average mitochondrial surface area and the number of mitochondria compared to chow-fed mice. HF2-fed mice had higher expression of the hepatic endoplasmic reticulum stress marker Chop, compared to chow-fed mice. A diet high in fat and fructose leads to enhanced hepatic mitochondrial aging, depletion, and dysfunction, which may be important determinants of nonalcoholic steatohepatitis pathogenesis.

Quantitative Liver MRI-Biopsy Correlation in Pediatric and Young Adult Patients With Nonalcoholic Fatty Liver Disease: Can One Be Used to Predict the Other?

OBJECTIVE: The purpose of this study is to determine the relationships between quantitative liver MRI measurements and liver biopsy findings in pediatric and young adult patients with nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: Data were obtained from a registry that prospectively enrolls pediatric and young adult patients with biopsy-confirmed NAFLD at our tertiary medical center with parent or guardian and subject informed consent, as appropriate. Patients enrolled between November 2007 and June 2016 with a quantitative liver MRI examination within 6 months of biopsy were included (n = 69). Liver stiffness (kilopascals), volume (milliliters), and fat fraction (percentage) were extracted from MRI records. Multiple linear regression was used to determine the relationships between NAFLD activity score and quantitative MRI measures, and between MRI liver stiffness and histopathologic scores (steatosis, lobular inflammation, portal inflammation, hepatocyte ballooning, and fibrosis). Histopathologic data were extracted from medical records, with severity graded by hepatopathologists using Non-alcoholic Steatohepatitis (NASH) Clinical Research Network criteria. Ordinal logistic regression was used to assess the relationship between categoric NAFLD severity (simple steatosis vs NASH vs NASH with significant fibrosis) and MRI measures. RESULTS: The mean (± SD) patient age at the time of MRI was 14.3 ± 2.8 years (range, 8-21 years); 25 (36.2%) patients were female. Liver biopsy was performed within a mean of 64.4 days of the MRI examination. There was a positive correlation between histopathologic steatosis and MRI liver fat fraction (ρ = 0.57; p < 0.0001). MRI fat fraction was the only significant imaging predictor of NAFLD activity score (p = 0.017). Fibrosis score was the only significant histopathologic predictor of MRI liver stiffness (p = 0.001). MRI liver volume was the only imaging predictor of categoric NAFLD severity (odds ratio = 1.001; 95% CI, 1.000-1.002; p = 0.007). CONCLUSION: There was significant positive correlation between histopathologic and MRI liver fat measurements in our cohort. MRI liver stiffness did not predict the severity of fatty liver disease in children and young adults.

Fatty liver disease in children--what should one do?

The world's population is increasingly overweight and obese. According to the World Health Organization (WHO) as of 2010, 43 million children under the age of five were overweight. Once considered to be limited to developed countries, overweight and obese children are now found in low- and middle-income countries, though most commonly in urban areas. Furthermore the WHO now cites the conditions of overweight and obesity as being associated with more deaths around the globe than those associated with being underweight. With this increased prevalence of overweight and obese children has come a host of other medical problems including nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). This review will focus on NAFLD and NASH, their definitions, epidemiology, diagnosis and treatment. The authors will also discuss NAFLD in the Indian subcontinent, and the future of NAFLD and NASH.