Alterations in lipid, carbohydrate and iron metabolism in patients with non-alcoholic steatohepatitis (NASH) and metabolic syndrome

Eur J Intern Med. 2011 Jun;22(3):305-10. doi: 10.1016/j.ejim.2011.01.011. Epub 2011 Feb 12.

Abstract

Background: NASH (non-alcoholic steatohepatitis) is considered the hepatic manifestation of the metabolic syndrome (MS). We aimed to analyze lipid, carbohydrate, and iron metabolism in NASH.

Patients, methods: 37 patients with MS (17 M/20 F, 51+/-15 years), elevated transaminases; 25 patients had histologically proven NASH (NAS score≥5), 12 patients had toxic background (nonNASH). 37 age, sex, BMI-matched healthy controls. Lipid variables, LDL-subfractions, iron, ferritin, transferrin (T), transferrin saturation (TS), and hepcidin (H) were measured in patients/controls. Oral glucose tolerance tests were performed.

Results: NASH patients with steatosis gr. 2 and 3 (>33% hepatic fat) had higher sd-LDL (mg/dl) concentrations than patients with steatosis gr. 1 (<33%) (p=0.002), nonNASH patients (p=0.03) and controls (p=0.001). Sd absolute (mg/dl) correlated directly with the steatosis grade only in patients with NASH and steatosis >33% (p=0.04). NASH-patients showed higher insulin, C-peptide and IRI values than nonNASH patients (p=0.034; 0.032; 0.04). H was increased in patients versus controls (p<0.001). H correlated with ferritin in MS-patients (p=0.01), correlated directly with sd-LDL (mg/dl) (p=0.017) and IRI (p<0.001) and indirectly with HDL (p=0.05) in NASH. No associations between hepatic inflammation/iron content on liver biopsy and variables of lipid metabolism were found but hepcidin correlated with hepatic inflammation in all patients and with NAS scores in NASH.

Conclusions: NASH-patients show insulin resistance and increased sd-LDL subfractions, suggesting an atherogenic profile. The correlation of H with sd-LDL and IRI, without relation to hepatic iron content suggests a putative link between inflammation, carbohydrate and lipid metabolism in NASH.

MeSH terms

  • Adult
  • Aged
  • Antimicrobial Cationic Peptides / blood
  • C-Peptide / blood
  • Carbohydrate Metabolism / physiology*
  • Cholesterol, LDL / blood
  • Fatty Liver / etiology
  • Fatty Liver / metabolism*
  • Female
  • Ferritins / blood
  • Glucose Tolerance Test
  • Hepcidins
  • Humans
  • Insulin / blood
  • Iron / metabolism*
  • Lipid Metabolism / physiology*
  • Male
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / metabolism*
  • Metabolome / physiology
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease
  • Transferrin / metabolism

Substances

  • Antimicrobial Cationic Peptides
  • C-Peptide
  • Cholesterol, LDL
  • HAMP protein, human
  • Hepcidins
  • Insulin
  • Transferrin
  • Ferritins
  • Iron