Acute liver cell damage in patients with anorexia nervosa: a possible role of starvation-induced hepatocyte autophagy.
ABSTRACT Acute liver insufficiency is a rare complication of anorexia nervosa. The mechanisms for this complication are unclear. The aim of this study was to describe patient characteristics and clarify the mechanisms involved.
Liver specimens from 12 patients (median age, 24 years; median body mass index, 11.3 kg/m(2)), with a prothrombin index <50% and/or an International Normalized Ratio >1.7 and anorexia nervosa as the only cause for acute liver injury were analyzed. A detailed pathologic examination was performed, including under electron microscopy.
Liver cell glycogen depletion was a constant finding. There was a contrast between the increase in serum alanine aminotransferase (56 times normal on average; 1,904 IU/L) and the absence of significant hepatocyte necrosis on histology. Centrilobular changes (trabecular atrophy and/or sinusoidal fibrosis) were observed in 6 patients. There were rare or no (<5%) terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive hepatocytes, suggesting that apoptosis was not the primary mechanism. Hepatocytes from 4 patients showed numerous autophagosomes, a morphologic hallmark of autophagy, on electron microscopy. In contrast, the mitochondria, endoplasmic reticulum, and nuclei were normal in most cells. These features were absent in 11 control patients. The outcome was favorable in all patients, with a rapid return to normal liver function.
Anorexia nervosa with extremely poor nutritional status should be added to the list of conditions causing acute liver insufficiency. Our findings show that starvation-induced autophagy in the human liver may be involved in liver cell death during anorexia nervosa, even though other mechanisms of liver cell damage could also play a role.
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ABSTRACT: Autophagy, a lysosomal catabolic pathway for long-lived proteins and damaged organelles, is crucial for cell homeostasis, and survival under stressful conditions. During starvation, autophagy is induced in numerous organisms ranging from yeast to mammals, and promotes survival by supplying nutrients and energy. In the early neonatal period, when transplacental nutrients supply is interrupted, starvation-induced autophagy is crucial for neonates' survival. In adult animals, autophagy provides amino acids and participates in glucose metabolism following starvation. In patients with anorexia nervosa, autophagy appears initially protective, allowing cells to copes with nutrient deprivation. However, when starvation is critically prolonged and when body mass index reaches 13 kg/m(2) or lower, acute liver insufficiency occurs with features of autophagic cell death, which can be observed by electron microscopy analysis of liver biopsy samples. In acetaminophen overdose, a classic cause of severe liver injury, autophagy is induced as a protective mechanism. Pharmacological enhancement of autophagy protects against acetaminophen-induced necrosis. Autophagy is also activated as a rescue mechanism in response to Efavirenz-induced mitochondrial dysfunction. However, Efavirenz overdose blocks autophagy leading to liver cell death. In conclusion, in acute liver injury, autophagy appears as a protective mechanism that can be however blocked or overwhelmed.BioMed Research International 01/2014; 2014:701064. · 2.71 Impact Factor
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ABSTRACT: Objective Anorexia nervosa (AN) is a complex disorder involving severe psychological manifestations and multiple organ damage, including liver dysfunction. The primary aim of this study consisted in assessing plasma levels of vitamin B12 and folates with respect to liver function enzymes considering the liver-storage properties of this vitamin.Method We recruited 70 restrictive type AN adolescents and the severity of psychopathological traits was assessed using EDI-3 scale. Plasma levels of vitamin B12, folates, transaminases (AST, ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP) and cholinesterase (CHE) were determined.ResultsAbout 38.5% of patients displayed vitamin B12 values (H-B12) above the upper range of normal reference; 4.3% of patients had increased values of folates; 20 and 11.4% of patients displayed ALT and AST values above reference limits; none had GGT values above normal range. Albeit low CHE and ALP values were found in 55 and 20% of patients, respectively, a linear correlation with both transaminases was present only for vitamin B12 and folates; furthermore, H-B12 patients had both higher AST and ALT values. EDI- 3 subscores significantly correlated with vitamin B12 and folates plasma values and H-B12 patients displayed EDI-3 higher values.DiscussionThese data suggest that plasma levels of vitamin B12 might be an early marker of liver dysfunction, possibly also related to more severe psychopathological aspects. The identification of patients with higher fasting plasma vitamin B12 levels could therefore lead to earlier and more careful refeeding interventions. Further studies will clarify the potential role of this vitamin in AN clinical practice. © 2014 Wiley Periodicals, Inc. (Int J Eat Disord 2014)International Journal of Eating Disorders 11/2014; · 3.03 Impact Factor
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ABSTRACT: Elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels are frequently reported in patients with anorexia nervosa (AN) and in subjects who are overweight or with hyperlipidemia, which can be found to be associated with binge eating disorder (BED) and bulimia nervosa (BN). Liver functioning and psychopathological features have been evaluated in 43 patients with AN, 33 with BN, and 32 with BED. Body mass index was found to be inversely associated with AST and ALT in AN, and directly associated with AST and ALT in BED. A positive association between ALT and AST and body shape concern in AN was observed. Liver enzymes could be considered as an index of severity in AN and BED patients. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association.European Eating Disorders Review 08/2014; · 1.38 Impact Factor