J Endocrinol Metab
Journal of Endocrinology and Metabolism, ISSN 1923-2861 print, 1923-287X online, Open Access
Article copyright, the authors; Journal compilation copyright, J Endocrinol Metab and Elmer Press Inc
Journal website http://www.jofem.org


Volume 6, Number 5, October 2016, pages 133-134

Think About the Application of Vitamin E to Heterozygous Familial Hypobetalipoproteinemia to Prevent Liver Cirrhosis and Hepatocellular Carcinoma

Hidekatsu Yanai

Department of Internal Medicine, National Center for Global Health and Medicine Kohnodai Hospital, 1-7-1 Kohnodai, Ichikawa, Chiba 272-0034, Japan

Manuscript accepted for publication October 19, 2016
Short title: Vitamin E to Familial Hypobetalipoproteinemia
doi: http://dx.doi.org/10.14740/jem380w

Familial hypobetalipoproteinemia (FHBL) is a rare genetic disease characterized by low levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B. In homozygous FHBL, dietary fat restriction and long-term high-dose vitamin E and A supplementation are recommended to prevent the progression of neuromuscular and retinal degenerative disease [1]. However, it has been considered that heterozygous FHBL subjects are usually asymptomatic, and do not require vitamin E supplementation [1]. The accumulated literatures suggest the development of fatty liver diseases including non-alcoholic steatohepatitis (NASH)-related cirrhosis and hepatocellular carcinoma (HCC) in heterozygous FHBL individuals [1-11].

A 33-year-old skinny man was referred to me for the treatment of heterozygous FHBL. He had been diagnosed to have fatty liver disease and heterozygous FHBL 6 years ago. However, he was told that there was no treatment for FHBL by the doctor. His serum levels of total cholesterol, LDL-cholesterol and apo B (normal range: 73 - 109 mg/dL) were 102, 27 and 22 mg/dL, respectively, supporting the diagnosis of heterozygous FHBL. He complained of steatorrhea and general fatigue. I started the treatment using dairy 150 mg of vitamin E, which ameliorated steatorrhea and general fatigue. He gained body weight by 3 kg. His father was diagnosed to have HCC when he was 63 years old; however, hepatitis B and C viruses, and alcoholism were not detected, suggesting the development of HCC due to NASH.

Vitamin E supplementation has been recommended for persons with homozygous FHBL because this disease leads to low serum lipid-soluble vitamin E. However, it has not been recommended that persons with heterozygous FHBL receive vitamin E supplementation [1, 12]. I think that a significance of vitamin E for fatty liver diseases including NASH, liver cirrhosis and HCC in heterozygous FHBL individuals has been forgotten. To our knowledge, there are no literatures about the application of vitamin E to prevent NASH in heterozygous FHBL. The efficacy of vitamin E is reasonably well established in a selected group of patients with NASH, who are not FHBL patients [13]. To prevent NASH, liver cirrhosis and HCC, we should think about the application of vitamin E to heterozygous FHBL patients who may have low serum vitamin E levels and may be also prone to develop NASH.

Conflicts of Interest

The author declares that there are no conflicts of interest concerning this article.

  1. Burnett JR, Hooper AJ. Vitamin E and oxidative stress in abetalipoproteinemia and familial hypobetalipoproteinemia. Free Radic Biol Med. 2015;88(Pt A):59-62.
  2. Welty FK. Hypobetalipoproteinemia and abetalipoproteinemia. Curr Opin Lipidol. 2014;25(3):161-168.
    doi pubmed
  3. Martin-Morales R, Garcia-Diaz JD, Tarugi P, Gonzalez-Santos P, Saavedra-Vallejo P, Magnolo L, Mesa-Latorre JM, et al. Familial hypobetalipoproteinemia: analysis of three Spanish cases with two new mutations in the APOB gene. Gene. 2013;531(1):92-96.
    doi pubmed
  4. Harada N, Soejima Y, Taketomi A, Yoshizumi T, Uchiyama H, Ikegami T, Saibara T, et al. Recurrent familial hypobetalipoproteinemia-induced nonalcoholic fatty liver disease after living donor liver transplantation. Liver Transpl. 2009;15(7):806-809.
    doi pubmed
  5. Di Leo E, Magnolo L, Pinotti E, Martini S, Cortella I, Vitturi N, Rabacchi C, et al. Functional analysis of two novel splice site mutations of APOB gene in familial hypobetalipoproteinemia. Mol Genet Metab. 2009;96(2):66-72.
    doi pubmed
  6. Katsuda S, Kawashiri MA, Inazu A, Tada H, Tsuchida M, Kaneko Y, Nozue T, et al. Apolipoprotein B gene mutations and fatty liver in Japanese hypobetalipoproteinemia. Clin Chim Acta. 2009;399(1-2):64-68.
    doi pubmed
  7. Sen D, Dagdelen S, Erbas T. Hepatosteatosis with hypobetalipoproteinemia. J Natl Med Assoc. 2007;99(3):284-286.
  8. Whitfield AJ, Barrett PH, Robertson K, Havlat MF, van Bockxmeer FM, Burnett JR. Liver dysfunction and steatosis in familial hypobetalipoproteinemia. Clin Chem. 2005;51(1):266-269.
    doi pubmed
  9. Tarugi P, Lonardo A, Gabelli C, Sala F, Ballarini G, Cortella I, Previato L, et al. Phenotypic expression of familial hypobetalipoproteinemia in three kindreds with mutations of apolipoprotein B gene. J Lipid Res. 2001;42(10):1552-1561.
  10. Ahmed A, Keeffe EB. Asymptomatic elevation of aminotransferase levels and fatty liver secondary to heterozygous hypobetalipoproteinemia. Am J Gastroenterol. 1998;93(12):2598-2599.
    doi pubmed
  11. Heeks LV, Hooper AJ, Adams LA, Robbins P, Barrett PH, van Bockxmeer FM, Burnett JR. Non-alcoholic steatohepatitis-related cirrhosis in a patient with APOB L343V familial hypobetalipoproteinaemia. Clin Chim Acta. 2013;421:121-125.
    doi pubmed
  12. Clarke MW, Hooper AJ, Headlam HA, Wu JH, Croft KD, Burnett JR. Assessment of tocopherol metabolism and oxidative stress in familial hypobetalipoproteinemia. Clin Chem. 2006;52(7):1339-1345.
    doi pubmed
  13. Gawrieh S, Chalasani N. Pharmacotherapy for Nonalcoholic Fatty Liver Disease. Semin Liver Dis. 2015;35(3):338-348.
    doi pubmed

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Journal of Endocrinology and Metabolism is published by Elmer Press Inc.


Browse  Journals  


Journal of Clinical Medicine Research

Journal of Endocrinology and Metabolism

Journal of Clinical Gynecology and Obstetrics


World Journal of Oncology

Gastroenterology Research

Journal of Hematology


Journal of Medical Cases

Journal of Current Surgery

Clinical Infection and Immunity


Cardiology Research

World Journal of Nephrology and Urology

Cellular and Molecular Medicine Research


Journal of Neurology Research

International Journal of Clinical Pediatrics



Journal of Endocrinology and Metabolism, bimonthly, ISSN 1923-2861 (print), 1923-287X (online), published by Elmer Press Inc.                     
The content of this site is intended for health care professionals.
This is an open-access journal distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, which permits unrestricted
non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Creative Commons Attribution license (Attribution-NonCommercial 4.0 International CC-BY-NC 4.0)

This journal follows the International Committee of Medical Journal Editors (ICMJE) recommendations for manuscripts submitted to biomedical journals,
the Committee on Publication Ethics (COPE) guidelines, and the Principles of Transparency and Best Practice in Scholarly Publishing.

website: www.jofem.org   editorial contact: editor@jofem.org
Address: 9225 Leslie Street, Suite 201, Richmond Hill, Ontario, L4B 3H6, Canada

© Elmer Press Inc. All Rights Reserved.

Disclaimer: The views and opinions expressed in the published articles are those of the authors and do not necessarily reflect the views or opinions of the editors and Elmer Press Inc. This website is provided for medical research and informational purposes only and does not constitute any medical advice or professional services. The information provided in this journal should not be used for diagnosis and treatment, those seeking medical advice should always consult with a licensed physician.