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Relationship between serum Vitamin B12 levels and hepatic fibrosis detected by transient elastography (Fibroscan) in non-alcoholic fatty liver disease

Year 2017, Volume: 22 Issue: 3, 141 - 148, 01.05.2017
https://doi.org/10.21673/anadoluklin.297152

Abstract

Aim: Non-alcoholic fatty liver disease (NAFLD) is
one of the most frequent chronic liver disease. Because NAFLD is a complex
disease, finding highly spesific and sensitive biomarkers for diagnosis is very
difficult. We investigated the
possible relation between staging of steatosis and fibrosis determined by
Fibroscan technique and serum vitamin B12 levels as a non-invasive biomarker in
NAFLD patients.

Materials and Method: A total of 129 patients (45,68±12,9 years  and 29F) with NAFLD and 50 healthy subjects
(43,44±15,3 years and 21F) were  included
in this study.  Fibroscan is performed in
all patients for staging of the fatty liver fibrosis. Liver enzymes are also
analyzed in addition to serum vitamin B12 and C-reactive protein (CRP) levels.

Results: There
was no difference in terms of age and gender in NAFLD and control groups. The
serum alanin aminotransferaz, aspartate aminotransferase, gamma-glutamyl
transferase and CRP levels were significantly higher in the NAFLD patients than
controls (p<0.05). On the contrary, 
serum vitamin B12 vitamin levels were lower in patients with NAFLD
compared with controls (352,8±125,2pg/mL vs. 435.2±134,4 p<0.01). There was
a significant difference in mean serum B12 vitamin levels between controls (
435.2±134,4pg/mL) and NAFLD patients from F0 to F3 subgroups
(366,17±129,7pg/mL, 285,22±101pg/mL, p<0.01).







Discussion and Conclusion: The serum vitamin B12 levels were found to be significantly low in
patients with NAFLD when compared to the control group. The reduction in serum
vitamin B12 levels was even more pronounced as hepatic inflammation and
fibrosis increases (F0-F3) but not in advanced fibrosis stage (F4).

References

  • 1) Abd El-Kader SM, El-Den Ashmawy EM. Non-alcoholic fatty liver disease: The diagnosis and management. World J Hepatol. 2015; 7(6): 846-58.
  • 2) Baffy G, Brunt EM, Caldwell SH. Hepatocellular carcinoma in non-alcoholic fatty liver disease: An emerging menace. J Hepatol. 2012; 56(6): 1384-91.
  • 3) de Carvalho SC, Muniz MT, Siqueira MD, Siqueira ER, Gomes AV, Silva KA, et al. Plasmatic higher levels of homocysteine in non-alcoholic fatty liver disease (NAFLD). Nutr J. 2013; 12:37.
  • 4) Sanal MG. Biomarkers in nonalcoholic fatty liver disease-the emperor has no clothes? World J Gastroenterol. 2015; 21(11): 3223-31.
  • 5) Farrell GC, Chitturi S, Lau GK, Sollano JD. Guidelines for the assessment and management of non-alcoholic fatty liver disease in the Asia-Pacific region: executive summary. J Gastroenterol Hepatol. 2007; 22(6): 775-77.
  • 6) Loria P, Adinolfi LE, Bellentani S, Bugianesi E, Grieco A, Fargion S, et al. Practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease. A decalogue from the Italian Association for the Study of the Liver (AISF) Expert Committee. Dig Liver Dis. 2010; 42(4): 272-82.
  • 7) Osawa H, Mori Y. Sonographic diagnosis of fatty liver using a histogram technique that compares liver and renal cortical echo amplitudes. J Clin Ultrasound. 1996; 24(1): 25-29.
  • 8) el-Hassan AY, Ibrahim EM, al-Mulhim FA, Nabhan AA, Chammas MY. Fatty infiltration of the liver: analysis of prevalence, radiological and clinical features and influence on patient management. Br J Radiol. 1992; 65(777): 774-78.
  • 9) Wong VW, Vergniol J, Wong GL, Foucher J, Chan HL, Le Bail B, et al. Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology. 2010; 51(2): 454-62.
  • 10) Thampanitchawong P, Piratvisuth T. Liver biopsy:complications and risk factors. World J Gastroenterol. 1999; 5(4): 301-304.
  • 11) Saadeh S, Younossi ZM, Remer EM, Gramlich T, Ong JP, Hurley M, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002; 123(3): 745-50.
  • 12) Roldan-Valadez E, Favila R, Martínez-López M, Uribe M, Méndez-Sánchez N. Imaging techniques for assessing hepatic fat content in nonalcoholic fatty liver disease. Ann Hepatol. 2008; 7(3): 212-20.
  • 13) Castéra L, Foucher J, Bernard PH, Carvalho F, Allaix D, Merrouche W, et al. Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations. Hepatology. 2010; 51(3): 828-35.
  • 14) Wong GL. Update of liver fibrosis and steatosis with transient elastography (Fibroscan). Gastroenterol Rep (Oxf). 2013; 1(1): 19-26.
  • 15) de Lédinghen V, Wong VW, Vergniol J, Wong GL, Foucher J, Chu SH, et al. Diagnosis of liver fibrosis and cirrhosis using liver stiffness measurement: comparison between M and XL probe of FibroScan®. J Hepatol. 2012; 56(4): 833-39.
  • 16) Wong VW, Vergniol J, Wong GL, Foucher J, Chan AW, Chermak F, et al. Liver stiffness measurement using XL probe in patients with nonalcoholic fatty liver disease. Am J Gastroenterol. 2012; 107(12): 1862-71.
  • 17) Shipton MJ, Thachil J. Vitamin B12 deficiency - A 21st century perspective. Clin Med. 2015; 15(2): 145-50.
  • 18) Andrès E, Serraj K, Zhu J, Vermorken AJ. The pathophysiology of elevated vitamin B12 in clinical practice. QJM. 2013; 106(6): 505-15.
  • 19) Ermens AA, Vlasveld LT, Lindemans J. Significance of elevated cobalamin (vitamin B12) levels in blood. Clin Biochem. 2003; 36(8): 585-90.
  • 20) Joske RA. The vitamin B12 content of human liver tissue obtaıned by aspiration biopsy. Gut. 1963; 4: 231-35.
  • 21) Holdsworth CD, Atkinson M, Dossett JA, Hall R. Assessment of the diagnostic and prognostic value of serum vitamin B12 levels in liver disease. Gut. 1964; 5: 601-6
  • 22) Catena C, Colussi G, Nait F, Capobianco F, Sechi LA. Elevated Homocysteine Levels Are Associated With the Metabolic Syndrome and Cardiovascular Events in Hypertensive Patients. Am J Hypertens. 2015; 28(7): 943-50.
  • 23) Leach NV, Dronca E, Vesa SC, Sampelean DP, Craciun EC, Lupsor M, et al. Serum homocysteine levels, oxidative stress and cardiovascular risk in non-alcoholic steatohepatitis. Eur J Intern Med. 2014; 25(8): 762-67.
  • 24) Uchihara M, Izumi N. High-sensitivity C-reactive protein (hs-CRP): A promising biomarker for the screening of non-alcoholic steatohepatitis (NASH). Nihon Rinsho. 2006; 64: 1133–38.
  • 25) Wieckowska A, Papouchado BG, Li Z, Lopez R, Zein NN, Feldstein AE. Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am J Gastroenterol. 2008; 103(6): 1372-79.
  • 26) Yoneda M, Mawatari H, Fujita K, Iida H, Yonemitsu K, Kato S, et al. High-sensitivity C-reactive protein is an independent clinical feature of nonalcoholic steatohepatitis (NASH) and also of the severity of fibrosis in NASH. J Gastroenterol. 2007; 42: 573-82.
  • 27) Marchesini G, Marzocchi R, Agostini F, Bugianesi E. Nonalcoholic fatty liver disease and the metabolic syndrome. Curr Opin Lipidol. 2005; 16(4): 421-27.
  • 28) Gulsen M, Yesilova Z, Bagci S, Uygun A, Ozcan A, Ercin CN, et al. Elevated plasma homocysteine concentrations as a predictor of steatohepatitis in patients with non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2005; 20(9): 1448-55.
  • 29) Koplay M, Gulcan E, Ozkan F. Association between serum vitamin B12 levels and the degree of steatosis in patients with nonalcoholic fatty liver disease. J Investig Med. 2011; 59(7): 1137-40.
  • 30) Polyzos SA, Kountouras J, Patsiaoura K, Katsiki E, Zafeiriadou E, Zavos C, et al. Serum vitamin B12 and folate levels in patients with non-alcoholic fatty liver disease. Int J Food Sci Nutr. 2012; 63(6): 659-66.

Alkole bağlı olmayan karaciğer yağlanmasında transient elastografi (Fibroscan) tekniği ile tespit edilen fibrozis skoru ile serum Vitamin B12 arasındaki ilişkinin araştırılması

Year 2017, Volume: 22 Issue: 3, 141 - 148, 01.05.2017
https://doi.org/10.21673/anadoluklin.297152

Abstract

Amaç:
Alkole bağlı olmayan karaciğer yağlanması (NAFLD) en sık rastlanan kronik
karaciğer hastalığıdır. NAFLD kompleks bir hastalık oldğu için tanıda
kullanılacak spesifik ve duyarlı biyobelirteçler bulmak oldukça güçtür.
Çalışmamızda transient elastografi (FibroScan) tekniği ile belirlenen steatoz
ve fibrozis skorları ile serum Vitamin B12 düzeyinin NAFLD hastalarında
girişimsel olmayan biyobelirteç olarak kullanılabilirliği sorgulanmıştır.

Gereç ve Yöntemler: Çalışmamıza toplam 129 NAFLD hastası
(45,68±12,9 yaş ve 29 kadın) ve 50 sağlıklı gönüllü (43,44±15,3 yaş ve 21
kadın) dahil edilmiştir. Tüm hastaların yağlı karaciğer yağlanması ve fibrozis
evresi FibroScan yöntemiyle belirlenmiştir. Serum Vitamin B12 ve C reaktif
protein (CRP) seviyesininin yanı sıra çeşitli karaciğer enzim düzeyleri de
saptanmıştır.

Bulgular: Yaş ve
cinsiyet açısından NAFLD ile kontrol grupları uyumlu bulunmuştır. NAFLD
hastalarında serum alanin aminotransferaz, aspartat aminotransferaz,
gama-glutamil transferaz ve CRP düzeyleri kontrol grubuna göre anlamlı oranda
(p<0.05) yüksek bulunurken, serum Vitamin B12 düzeyleri ise düşük
(352,8±125,2pg/mL ile 435.2±134,4 p<0.01) bulunmuştur. Ortalama serum B12
düzeylerinin kontrol (435.2±134,4pg/mL) ve NAFLD fibrozis evre F0-F3 alt
grupları (366,17±129,7pg/mL, 285,22±101pg/mL) ile karşılaştırıldığında anlamlı
düzeyde (p<0.01) farklılık  olduğu
görülmüştür.







Tartışma ve sonuç: Serum Bitamin B12 düzeyinin NAFLD hasta grubunda kontrol grubuna göre
anlamlı oranda düşük olduğu saptanmıştır. Serum Vitamin B12 seviyesindeki bu
azalmanın özellikle karaciğer inflamasyonu ve fibrozis evresi yüseldikçe
(F0-F3) daha belirgin olduğu ancak daha ileri fibrozis düzeylerinde (F4)
anlamlı bir fark görülmediği tespit edilmiştir.

References

  • 1) Abd El-Kader SM, El-Den Ashmawy EM. Non-alcoholic fatty liver disease: The diagnosis and management. World J Hepatol. 2015; 7(6): 846-58.
  • 2) Baffy G, Brunt EM, Caldwell SH. Hepatocellular carcinoma in non-alcoholic fatty liver disease: An emerging menace. J Hepatol. 2012; 56(6): 1384-91.
  • 3) de Carvalho SC, Muniz MT, Siqueira MD, Siqueira ER, Gomes AV, Silva KA, et al. Plasmatic higher levels of homocysteine in non-alcoholic fatty liver disease (NAFLD). Nutr J. 2013; 12:37.
  • 4) Sanal MG. Biomarkers in nonalcoholic fatty liver disease-the emperor has no clothes? World J Gastroenterol. 2015; 21(11): 3223-31.
  • 5) Farrell GC, Chitturi S, Lau GK, Sollano JD. Guidelines for the assessment and management of non-alcoholic fatty liver disease in the Asia-Pacific region: executive summary. J Gastroenterol Hepatol. 2007; 22(6): 775-77.
  • 6) Loria P, Adinolfi LE, Bellentani S, Bugianesi E, Grieco A, Fargion S, et al. Practice guidelines for the diagnosis and management of nonalcoholic fatty liver disease. A decalogue from the Italian Association for the Study of the Liver (AISF) Expert Committee. Dig Liver Dis. 2010; 42(4): 272-82.
  • 7) Osawa H, Mori Y. Sonographic diagnosis of fatty liver using a histogram technique that compares liver and renal cortical echo amplitudes. J Clin Ultrasound. 1996; 24(1): 25-29.
  • 8) el-Hassan AY, Ibrahim EM, al-Mulhim FA, Nabhan AA, Chammas MY. Fatty infiltration of the liver: analysis of prevalence, radiological and clinical features and influence on patient management. Br J Radiol. 1992; 65(777): 774-78.
  • 9) Wong VW, Vergniol J, Wong GL, Foucher J, Chan HL, Le Bail B, et al. Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease. Hepatology. 2010; 51(2): 454-62.
  • 10) Thampanitchawong P, Piratvisuth T. Liver biopsy:complications and risk factors. World J Gastroenterol. 1999; 5(4): 301-304.
  • 11) Saadeh S, Younossi ZM, Remer EM, Gramlich T, Ong JP, Hurley M, et al. The utility of radiological imaging in nonalcoholic fatty liver disease. Gastroenterology. 2002; 123(3): 745-50.
  • 12) Roldan-Valadez E, Favila R, Martínez-López M, Uribe M, Méndez-Sánchez N. Imaging techniques for assessing hepatic fat content in nonalcoholic fatty liver disease. Ann Hepatol. 2008; 7(3): 212-20.
  • 13) Castéra L, Foucher J, Bernard PH, Carvalho F, Allaix D, Merrouche W, et al. Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations. Hepatology. 2010; 51(3): 828-35.
  • 14) Wong GL. Update of liver fibrosis and steatosis with transient elastography (Fibroscan). Gastroenterol Rep (Oxf). 2013; 1(1): 19-26.
  • 15) de Lédinghen V, Wong VW, Vergniol J, Wong GL, Foucher J, Chu SH, et al. Diagnosis of liver fibrosis and cirrhosis using liver stiffness measurement: comparison between M and XL probe of FibroScan®. J Hepatol. 2012; 56(4): 833-39.
  • 16) Wong VW, Vergniol J, Wong GL, Foucher J, Chan AW, Chermak F, et al. Liver stiffness measurement using XL probe in patients with nonalcoholic fatty liver disease. Am J Gastroenterol. 2012; 107(12): 1862-71.
  • 17) Shipton MJ, Thachil J. Vitamin B12 deficiency - A 21st century perspective. Clin Med. 2015; 15(2): 145-50.
  • 18) Andrès E, Serraj K, Zhu J, Vermorken AJ. The pathophysiology of elevated vitamin B12 in clinical practice. QJM. 2013; 106(6): 505-15.
  • 19) Ermens AA, Vlasveld LT, Lindemans J. Significance of elevated cobalamin (vitamin B12) levels in blood. Clin Biochem. 2003; 36(8): 585-90.
  • 20) Joske RA. The vitamin B12 content of human liver tissue obtaıned by aspiration biopsy. Gut. 1963; 4: 231-35.
  • 21) Holdsworth CD, Atkinson M, Dossett JA, Hall R. Assessment of the diagnostic and prognostic value of serum vitamin B12 levels in liver disease. Gut. 1964; 5: 601-6
  • 22) Catena C, Colussi G, Nait F, Capobianco F, Sechi LA. Elevated Homocysteine Levels Are Associated With the Metabolic Syndrome and Cardiovascular Events in Hypertensive Patients. Am J Hypertens. 2015; 28(7): 943-50.
  • 23) Leach NV, Dronca E, Vesa SC, Sampelean DP, Craciun EC, Lupsor M, et al. Serum homocysteine levels, oxidative stress and cardiovascular risk in non-alcoholic steatohepatitis. Eur J Intern Med. 2014; 25(8): 762-67.
  • 24) Uchihara M, Izumi N. High-sensitivity C-reactive protein (hs-CRP): A promising biomarker for the screening of non-alcoholic steatohepatitis (NASH). Nihon Rinsho. 2006; 64: 1133–38.
  • 25) Wieckowska A, Papouchado BG, Li Z, Lopez R, Zein NN, Feldstein AE. Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am J Gastroenterol. 2008; 103(6): 1372-79.
  • 26) Yoneda M, Mawatari H, Fujita K, Iida H, Yonemitsu K, Kato S, et al. High-sensitivity C-reactive protein is an independent clinical feature of nonalcoholic steatohepatitis (NASH) and also of the severity of fibrosis in NASH. J Gastroenterol. 2007; 42: 573-82.
  • 27) Marchesini G, Marzocchi R, Agostini F, Bugianesi E. Nonalcoholic fatty liver disease and the metabolic syndrome. Curr Opin Lipidol. 2005; 16(4): 421-27.
  • 28) Gulsen M, Yesilova Z, Bagci S, Uygun A, Ozcan A, Ercin CN, et al. Elevated plasma homocysteine concentrations as a predictor of steatohepatitis in patients with non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2005; 20(9): 1448-55.
  • 29) Koplay M, Gulcan E, Ozkan F. Association between serum vitamin B12 levels and the degree of steatosis in patients with nonalcoholic fatty liver disease. J Investig Med. 2011; 59(7): 1137-40.
  • 30) Polyzos SA, Kountouras J, Patsiaoura K, Katsiki E, Zafeiriadou E, Zavos C, et al. Serum vitamin B12 and folate levels in patients with non-alcoholic fatty liver disease. Int J Food Sci Nutr. 2012; 63(6): 659-66.
There are 30 citations in total.

Details

Subjects Health Care Administration
Journal Section ORIGINAL ARTICLE
Authors

Filiz Fusun Bolukbas This is me

Seyda İgnak

Ozlem Unay Demirel

Yavuz Furuncuoglu

Ferhan Mantar This is me

Sercen Cansu Sertel This is me

Filiz Yarimcan Saglam This is me

Cengiz Bolukbas This is me

Publication Date May 1, 2017
Acceptance Date April 9, 2017
Published in Issue Year 2017 Volume: 22 Issue: 3

Cite

Vancouver Bolukbas FF, İgnak S, Unay Demirel O, Furuncuoglu Y, Mantar F, Sertel SC, Yarimcan Saglam F, Bolukbas C. Relationship between serum Vitamin B12 levels and hepatic fibrosis detected by transient elastography (Fibroscan) in non-alcoholic fatty liver disease. Anatolian Clin. 2017;22(3):141-8.

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