Nonalcoholic steatohepatitis and insulin resistance in children

Arata, Mikage; Nakajima, Junya; Nishimata, Shigeo; Nagata, Tomomi; Kawashima, Hisashi

doi:10.4239/wjd.v5.i6.917

Cited by 15 publications

(25 citation statements)

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“…Studies of patients with NAFLD have demonstrated that insulin resistance and pathologic HOMA might be predictors or at least associated with the development of a NAFLD (37, 38), which our study confirmed for our cohort. In addition, we found a significant association between NAFLD and elevated liver enzymes as well as a higher body fat proportion, which is in line with findings of patients without CP but with metabolic syndrome and NAFLD (39). The high rate of NAFLD we found in about 50% of CP patients with HI is higher than previous estimates and indicates that the monitoring of liver function is a critically important component in follow-up care of CP patients.…”

Section: Discussionsupporting

confidence: 89%

Nonalcoholic fatty liver disease and fatigue in long-term survivors of childhood-onset craniopharyngioma

Hoffmann

Bootsveld

Gebhardt

et al. 2015

European Journal of Endocrinology

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Objective: Hypothalamic obesity in childhood craniopharyngioma (CP) patients carries a high risk for development of metabolic syndrome. In metabolic syndrome, the development of nonalcoholic fatty liver disease (NAFLD) is known. The aim of this study is to detect the risk for NAFLD in childhood-onset CP. Design: This cross-sectional study included liver computed tomography (CT); ultrasound analysis of abdomen; measurements of serum parameters, height, weight and body composition; and daily medication of patients with childhood-onset CP. Methods: A total of 384 patients recruited in trials HIT Endo and KRANIOPHARYNGEOM 2000 were analyzed. Ninety-four survivors were included by fulfilling the criteria of proven hypothalamic involvement (HI), a minimum time interval of 5 years between diagnosis and study, and a minimum age of 18 years at the time of evaluation. A total of 19 patients agreed to participate. To quantify the degree of steatosis hepatis, analyses of liver density were performed once by non-contrasted CT of liver sections. Results: NAFLD occurs in about 50% of CP patients with HI and is associated with elevated liver enzymes and homeostasis model assessment index. BMI is not an effective predictive factor but body fat mass measured by near-infrared spectroscopy (NIRS) is. Over half of CP patients (60%) with NAFLD are treated with stimulating agents, with risk of hepatic side effects. Conclusions: NAFLD is a major adverse late effect in childhood-onset CP. NIRS rather than BMI should be used to measure body composition and predict NAFLD. Stimulating agents for treatment of fatigue and daytime sleepiness in CP should be prescribed judiciously.

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Section: Discussionsupporting

confidence: 89%

Nonalcoholic fatty liver disease and fatigue in long-term survivors of childhood-onset craniopharyngioma

Hoffmann

Bootsveld

Gebhardt

et al. 2015

European Journal of Endocrinology

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“…Altogether, the observed differences between NASH in children and adults could be explained by the fact that secretion of CatD into the plasma is dependent on age-related changes of the lysosomes and therefore is dependent on accumulation of specific lipid species. In agreement, several studies indeed describe that the histological and pathological characteristics of NASH are age-dependent12131415. Further studies are warranted to precisely determine the contribution of lysosomes to NASH disease pathology in children and adults.…”

Section: Discussionsupporting

confidence: 63%

“…Recent studies have raised the concept that non-alcoholic fatty liver disease (NAFLD) in children and adults is distinct due to differences in the histological pattern in the liver as well as pathological characteristics of the disease12131415. Thus far, the relationship between plasma CatD and adult NASH has not been explored.…”

mentioning

confidence: 99%

Plasma cathepsin D correlates with histological classifications of fatty liver disease in adults and responds to intervention

Walenbergh

Houben

Rensen

et al. 2016

Sci Rep

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Non-alcoholic steatohepatitis (NASH) is characterized by liver lipid accumulation and inflammation. The mechanisms that trigger hepatic inflammation are poorly understood and subsequently, no specific non-invasive markers exist. We previously demonstrated a reduction in the plasma lysosomal enzyme, cathepsin D (CatD), in children with NASH compared to children without NASH. Recent studies have raised the concept that non-alcoholic fatty liver disease (NAFLD) in adults is distinct from children due to a different histological pattern in the liver. Yet, the link between plasma CatD to adult NASH was not examined. In the current manuscript, we investigated whether plasma CatD in adults correlates with NASH development and regression. Biopsies were histologically evaluated for inflammation and NAFLD in three complementary cohorts of adults (total n = 248). CatD and alanine aminotransferase (ALT) were measured in plasma. Opposite to our previous observations with childhood NASH, we observed increased levels of plasma CatD in patients with NASH compared to adults without hepatic inflammation. Furthermore, after surgical intervention, we found a reduction of plasma CatD compared to baseline. Our observations highlight a distinct pathophysiology between NASH in children and adults. The observation that plasma CatD correlated with NASH development and regression is promising for NASH diagnosis.

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“…For more simplified measurement of IR, fasting insulin and glucose, homeostasis model assessment of IR (HOMA-IR), insulin sensitivity indices-FFA (ISI-FFA), and quantitative insulin sensitivity check index (QUICKI) have been developed 91011. In addition, several previous studies analyzed the association between IR and NASH 12. A recent Korean study clearly showed higher body mass index (BMI), higher HOMA-IR values, and increased triglyceride (TG) ≥150 mg/dL associated with the occurrence of NAFLD in non-obese subjects 13…”

Section: Introductionmentioning

confidence: 99%

Pathologic Impact of Insulin Resistance and Sensitivity on the Severity of Liver Histopathology in Pediatric Non-Alcoholic Steatohepatitis

et al. 2017

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PurposeInsulin resistance (IR) has an important role in the development of non-alcoholic steatohepatitis (NASH). We aimed to analyze the association between liver histopathology and IR in pediatric patients with NASH.Materials and MethodsIn 24 children with non-alcoholic fatty liver disease (NAFLD), we investigated whether the hepatic pathologic characteristics have relations with following three biochemical indices; IR index including homeostasis model assessment of IR (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and insulin sensitivity indices-free fatty acid (ISI-FFA).ResultsAmong 24 patients, 16 (66.6%) had a high NAFLD activity score (NAS), which is diagnostic of NASH. Higher serum triglyceride level was significantly correlated with a high NAS. Higher steatosis grades were significantly associated with low insulin sensitivity (p=0.023). In addition, severe lobular inflammation was associated with higher IR: HOMA-IR (p=0.014) and QUICKI (p=0.023). Severe fibrosis correlated with low insulin sensitivity and high IR indexes: ISI-FFA (p=0.049), HOMA-IR (p=0.028), and QUICKI (p=0.007).ConclusionPatients with high IR had more severe lobular inflammation and hepatic fibrosis. Analyses of biochemical and endocrine parameters can be applied to determine the severity of the hepatic pathologic status in patients with NASH, especially in children who cannot undergo a liver biopsy.

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Nonalcoholic steatohepatitis and insulin resistance in children

Cited by 15 publications

References 46 publications

Nonalcoholic fatty liver disease and fatigue in long-term survivors of childhood-onset craniopharyngioma

Nonalcoholic fatty liver disease and fatigue in long-term survivors of childhood-onset craniopharyngioma

Plasma cathepsin D correlates with histological classifications of fatty liver disease in adults and responds to intervention

Pathologic Impact of Insulin Resistance and Sensitivity on the Severity of Liver Histopathology in Pediatric Non-Alcoholic Steatohepatitis

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