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Paediatrics & Child Health logoLink to Paediatrics & Child Health
. 2017 Apr 13;22(2):59–60. doi: 10.1093/pch/pxx034

Fatty liver in a non-obese patient

Cody Jackson 1, Michael T Geraghty 2, Robert A Hegele 3, Dina El Demellawy 4, Carolina Jimenez-Rivera 5,
PMCID: PMC5804803  PMID: 29479178

CASE PRESENTATION

A 15-year-old male with a body mass index of 19.5 kg/m2 (25th percentile) presented with asymptomatic elevated liver enzymes found on routine bloodwork; alanine transaminase was 98 U/L (upper normal limit: 55 U/L) and aspartate transaminase was 52 U/L (upper normal limit: 50 U/L). Complete blood count was normal without acanthocytes. Physical examination was normal except for an enlarged thyroid gland. There was no history of nausea, abdominal pain, diarrhea, systemic complaints or neurological symptoms. He denied alcohol intake or recreational drug use and was on no medications. Repeat transaminase levels over a 4-month period persisted slightly elevated with normal gamma glutamyltransferase, alkaline phosphatase and bilirubin levels. Further investigations for underlying liver disease including Wilson’s disease, autoimmune hepatitis, viral aetiologies and alpha-1 antitrypsin deficiency were negative. A liver ultrasound demonstrated coarse echogenicity without focal lesions, consistent with fatty infiltration. MRI suggested fatty liver without biliary duct pathology. A liver biopsy revealed nonalcoholic steatohepatitis (NASH) with fibrosis and early cirrhosis. Further investigations suggested the underlying diagnosis.

DISCUSSION

A lipid profile revealed total, low-density lipoprotein (LDL) and high-density lipoprotein cholesterol of 1.4, 0.78 and 0.84 mmol/L, respectively, and triglycerides 0.76 mmol/L (all below fifth percentile). Vitamin A and D levels were normal as was the international normalized ratio; however, his vitamin E level was low (8 mmol/L, normal: 12 to 46 mmol/L). Obesity and being overweight are the most common causes of nonalcoholic fatty liver. Patients are usually asymptomatic and very few complain of vague abdominal pain. Liver enzymes can be elevated and liver imaging demonstrates fatty infiltration most times. Definite diagnosis of NASH is made by a liver biopsy to assess the degree of inflammatory/fibrotic changes. Differential diagnoses include viral aetiologies (hepatitis C), autoimmune diseases, side effects of medications or toxins, nutritional (protein-calorie malnutrition, starvation, parenteral nutrition) and metabolic disorders. Optimal treatment consists of dietary modifications and exercise prescription to reduce weight. High-dose vitamin E, alone or in combination with exercise and diet, has been tried with some success in obese children with NASH (1).

In this particular case, given this patient’s abnormally low lipid profile and low vitamin E levels, abetalipoproteinaemia (ABL) was suspected. Molecular studies showed two mutations in the microsomal triglyceride transfer protein (MTP) gene (c.1618C>T:p.Arg540Cys; c.1901A>G:p.Asn634Gly). Parental genotyping confirmed these mutations were on opposite chromosomes, consistent with compound heterozygosity for mutant MTP underlying a mild ABL phenotype.

ABL is an autosomal recessive disorder characterized by a malfunction of the lipoprotein assembling protein MTP. This protein catalyzes the transfer of lipids between membranes and is crucial for the biogenesis of lipoproteins and chylomicrons. Classical ABL is characterized by steatorrhea and failure to thrive in infancy, together with undetectable LDL cholesterol and acanthocytosis on peripheral blood smear. Patients with ABL have severe deficiencies of vitamins A, D, E and K, typically with clinical findings such as retinopathy, coagulopathy and neuropathy (2). Treatment includes fat restriction and high oral doses of such vitamins. In contrast, the patient reported here had a very mild ABL phenotype, with relative deficiency of LDL cholesterol and deficiency of vitamin E only. Patients with ABL and the related condition hypobetalipoproteinaemia are prone to develop fatty liver due to inability to mobilize triglycerides from hepatocytes as they cannot synthesize apolipoprotein (apo) B-containing lipoproteins. Rarely, fatty liver in these conditions can progress to fibrosis and cirrhosis (2).

The patient was last seen at age 17 and had been on vitamin E supplementation (800 IU daily) for over 1 year; his transaminases were found to be near normal. A repeat liver biopsy then showed significantly reduced fibrosis (1/4 on the NASH clinical research network staging system compared with 3/4 on the initial biopsy). No interface hepatitis was appreciated on this biopsy, demonstrating significant improvement when compared with the previous biopsy; the fat content was unchanged.

This case exemplifies that milder phenotypes of ABL may sometimes underlie NASH, particularly in non-obese patients. Defects in apo B metabolism should be suspected when total cholesterol, triglyceride and LDL cholesterol are markedly reduced with associated fat-soluble vitamin deficiencies. Interestingly, the improved hepatic histology with vitamin E replacement in our patient suggests that vitamin E deficiency may play a role in the pathogenesis of liver disease in ABL and possibly in NASH.

CLINICAL PEARLS

  • Nonalcoholic fatty liver is often associated with obesity and being overweight; however, it can occur in patients with normal body mass index in which case a rare metabolic disorder such as abetalipoproteinaemia should be considered.

  • Underlying liver disease should be ruled out in any patient with suspected nonalcoholic fatty liver; abnormally low lipids in the presence of elevated liver enzymes and a fatty liver should raise suspicion for abetalipoproteinaemia or the related disorder hypobetalipoproteinaemia.

  • Fat restriction and supplementation of vitamin deficiencies are standard treatment for genetic hypolipidaemia; high-dose vitamin E may have reduced the progression of liver fibrosis in nonalcoholic steatohepatitis in this patient with mild abetalipoproteinaemia.

References

  • 1. Mitchel EB, Lavine JE. Review article: The management of paediatric nonalcoholic fatty liver disease. Aliment Pharmacol Ther 2014;40:1155–70. [DOI] [PubMed] [Google Scholar]
  • 2. Lee J, Hegele RA. Abetalipoproteinemia and homozygous hypobetalipoproteinemia: A framework for diagnosis and management. J Inherit Metab Dis 2014;37:333–9. [DOI] [PubMed] [Google Scholar]

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