Utility of magnetic resonance imaging in the evaluation of hepatic fat content

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Utility of Magnetic Resonance Imaging in the Evaluation of Hepatic Fat Content

To the Editor:

We enjoyed the article on the link between glucose dysregulation and hepatic steatosis by Cali and colleagues in a recent issue of HEPATOLOGY.1 In 118 obese adolescents, the authors assessed carbohydrate metabolism with the oral glucose tolerance test and hepatic fat content with magnetic resonance imaging (MRI). They stratified the sample in tertiles of hepatic fat content and observed how races were differently distributed; the amount of visceral fat, ratio of visceral fat to subcutaneous fat, insulin resistance, 2-hour plasma glucose, and interleukin-6 increased, whereas both the total adiponectin and high-molecular-weight adiponectin decreased across tertiles. The topic addressed is hot. In the face of epidemic obesity in youth, there is a need to ascertain the link between nonalcoholic fatty liver disease (NAFLD) and prediabetes, mainly impaired glucose tolerance, to find new means of prevention. What we regret noting is that the study design and the analytical approach do not allow the determination of whether the strongest determinant of metabolic impairment and, in particular, glucose dysregulation in NAFLD adolescents is the amount of intrahepatic fat or the visceral fat content. Both hepatic and visceral fats have been found to be significantly associated in this study and in a number of previous studies,2 so it is hard determining which one, the hepatic or the visceral fat, affects more glucose dysregulation. However, evidence suggests that increased hepatic fat content is associated more closely with diabetes (mainly increased gluconeogenesis) than with visceral obesity.3 Yet normal-weight individuals presenting with normal levels of alanine aminotransferase and increased hepatic fat have reduced suppression of endogenous glucose production.4 In this context, performing fast MRI may be worthwhile because it can add valuable information and is less expensive and faster than conventional MRI. This technique (and maybe even ultrasound) can provide a better estimate of the total amount of hepatic fat than liver biopsy. In fact, when we looked for an association between the 2-hour plasma glucose and the degree of steatosis as estimated by liver biopsy in a sample of 218 obese children and adolescents [age, 12 ± 3.4 years; body mass index z score, 1.84 ± 0.6; total cholesterol, 162 ± 38 mg/dL; triglycerides, 109 ± 76 mg/dL; alanine aminotransferase, 85 ± 74 IU/L; aspartate aminotransferase, 51 ± 31 IU/L; homeostasis model assessment of insulin resistance, 2.8 ± 2; Insulin Sensitivity Index (ISI) composite, 4.02 ± 2.2; NAFLD activity score, 3.8 ± 1.6; steatosis grade (1/2/3), 70/83/67; necro-inflammation grade (0/1/2/3), 23/159/33/5; and fibrosis grade (0/1/2/3), 69/124/9/18], no significant relationships and/or differences across degrees of steatosis were found. The reason that this occurs is likely the variability in bioptic sampling, whereas MRI provides information on the entire amount of hepatic fat. Of course, we have to agree with the authors that studies are needed to compare the ability of MRI versus conventional biopsy in quantifying fat liver content, but MRI and liver biopsy probably must be performed with completely different aims: (1) for endocrinologists, determining the degree of metabolic abnormalities, including the risk of diabetes, and (2) for hepatologists, determining the degree of parenchymal derangement toward necro-inflammation and fibrosis.

What we would like to suggest to the authors is to try dissecting the single contribution of the liver and the muscle to insulin resistance, as described by Abdul-Ghani et al.,5 because hepatic insulin resistance is, of course, expected to rise across tertiles. Furthermore, as we look for prediabetes in young individuals with NAFLD, we should consider performing liver biopsy in all subjects in this age range with prediabetes.

Still, there is no answer to the basic question: which comes first, the chicken or the egg? Longitudinal observation of large cohorts of patients is needed to answer which comes first, the visceral fat or the hepatic fat.

Melania Manco M.D., Ph.D.*, Valerio Nobili M.D.†, * Scientific Directorate, Bambino Gesù Hospital, Rome, Italy, † Liver Unit, Bambino Gesù Hospital, Rome, Italy.

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