Skip to main content

Advertisement

SpringerLink
Log in

The Role of Micronutrients in Chronic Liver Disease

  • Published:
Current Hepatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The importance of general nutrition in chronic liver disease is well established. The role of this review is to identify and summarise recent developments in the associations between specific micronutrients and chronic liver disease; and whether there is data to support therapeutic interventions.

Recent Findings

There is a significant association between micronutrient deficiencies and chronic liver disease. Rates of deficiency in vitamin D, zinc, selenium, and vitamin A have been noted to be as high as 85–95% in patients with decompensated liver disease. A correlation exists between severity of the micronutrient deficiency and the severity of the liver disease as well as risk of liver-related complications and mortality.

Summary

Micronutrient deficiencies have a strong correlation with chronic liver disease and liver outcomes; however, it remains unclear whether the exact mechanism of this relationship and further high-quality research is required to better assess this and identify whether widespread intervention in micronutrient deficiencies influences disease outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Atiemo K, Skaro A, Maddur H, Zhao L, Montag S, Vanwagner L, et al. Mortality risk factors among patients with cirrhosis and a low model for end-stage liver disease sodium score (≤15): an analysis of liver transplant allocation policy using aggregated electronic health record data. Am J Transplant. 2017;17(9):2410–9. https://doi.org/10.1111/ajt.14239.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Tsiaousi ET, Hatzitolios AI, Trygonis SK, Savopoulos CG. Malnutrition in end stage liver disease: recommendations and nutritional support. J Gastroenterol Hepatol. 2008;23(4):527–33. https://doi.org/10.1111/j.1440-1746.2008.05369.x.

    Article  PubMed  Google Scholar 

  3. Merli M, Riggio O, Dally L. Does malnutrition affect survival in cirrhosis? Hepatology. 1996;23(5):1041–6. https://doi.org/10.1002/hep.510230516.

    Article  CAS  PubMed  Google Scholar 

  4. Merli M, Giusto M, Gentili F, Novelli G, Ferretti G, Riggio O, et al. Nutritional status: its influence on the outcome of patients undergoing liver transplantation. Liver Int. 2010;30(2):208–14. https://doi.org/10.1111/j.1478-3231.2009.02135.x.

    Article  CAS  PubMed  Google Scholar 

  5. Carvalho L, Parise ER. Evaluation of nutritional status of nonhospitalized patients with liver cirrhosis. Arq Gastroenterol. 2006;43(4):269–74. https://doi.org/10.1590/s0004-28032006000400005.

    Article  PubMed  Google Scholar 

  6. Llibre-Nieto G, Lira A, Vergara M, Solé C, Casas M, Puig-Diví V, et al. Micronutrient deficiencies in patients with decompensated liver cirrhosis. Nutrients. 2021;13(4):1249. https://doi.org/10.3390/nu13041249.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Cheung K, Lee SS, Raman M. Prevalence and mechanisms of malnutrition in patients with advanced liver disease, and nutrition management strategies. Clin Gastroenterol Hepatol. 2012;10(2):117–25. https://doi.org/10.1016/j.cgh.2011.08.016.

    Article  PubMed  Google Scholar 

  8. Koop AH, Mousa OY, Pham LE, Corral-Hurtado JE, Pungpapong S, Keaveny AP. An argument for vitamin D, A, and sinc monitoring in cirrhosis. Ann Hepatol. 2018;17(6):920–32. https://doi.org/10.5604/01.3001.0012.7192.

    Article  CAS  PubMed  Google Scholar 

  9. Gad AI, Elmedames MR, Abdelhai AR, Marei AM. The association between vitamin D status and non-alcoholic fatty liver disease in adults: a hospital-based study. Egypt Liver J. 2020;10(1). https://doi.org/10.1186/s43066-020-00033-z.

  10. Kubesch A, Quenstedt L, Saleh M, Rüschenbaum S, Schwarzkopf K, Martinez Y, et al. Vitamin D deficiency is associated with hepatic decompensation and inflammation in patients with liver cirrhosis: a prospective cohort study. PLOS ONE. 2018;13(11):e0207162. https://doi.org/10.1371/journal.pone.0207162.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Stokes CS, Krawczyk M, Reichel C, Lammert F, Grünhage F. Vitamin D deficiency is associated with mortality in patients with advanced liver cirrhosis. Eur J Clin Invest. 2014;44(2):176–83. https://doi.org/10.1111/eci.12205.

    Article  CAS  PubMed  Google Scholar 

  12. Finkelmeier F, Kronenberger B, Zeuzem S, Piiper A, Waidmann O. Low 25-Hydroxyvitamin D levels are associated with infections and mortality in patients with cirrhosis. PLOS ONE. 2015;10(6):e0132119. https://doi.org/10.1371/journal.pone.0132119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Paternostro R, Wagner D, Reiberger T, Mandorfer M, Schwarzer R, Ferlitsch M, et al. Low 25-OH-vitamin D levels reflect hepatic dysfunction and are associated with mortality in patients with liver cirrhosis. Wien Klin Wochenschr. 2017;129(1–2):8–15. https://doi.org/10.1007/s00508-016-1127-1.

    Article  CAS  PubMed  Google Scholar 

  14. Zhang Z, Wu L, Wang G, Hu P. Effect of vitamin D deficiency on spontaneous peritonitis in cirrhosis: a meta-analysis. Gastroenterol Rev. 2021;16(1):10–4. https://doi.org/10.5114/pg.2020.101632.

    Article  CAS  Google Scholar 

  15. • Mohamed AA, Al-Karmalawy AA, El-Kholy AA, El-Damas DA, Abostate HM, Mostafa SM, et al. Effect of Vitamin D supplementation in patients with liver cirrhosis having spontaneous bacterial peritonitis: a randomized controlled study. Eur Rev Med Pharmacol Sci. 2021;25(22):6908–19. https://doi.org/10.26355/eurrev_202111_27239. One of very few studies to demonstrate a clinically significant mortality benefit from vitamin D supplementation in chronic liver disease.

    Article  CAS  PubMed  Google Scholar 

  16. Grover I, Gunjan D, Singh N, Benjamin J, Ramakrishnan L, Pandey RM, et al. Effect of vitamin D supplementation on vitamin D level and bone mineral density in patients with cirrhosis: a randomized clinical trial. Am J Gastroenterol. 2021;116(10):2098–104. https://doi.org/10.14309/ajg.0000000000001272.

    Article  CAS  PubMed  Google Scholar 

  17. •• Bjelakovic M, Nikolova D, Bjelakovic G, Gluud C. Vitamin D supplementation for chronic liver diseases in adults. Cochrane Database Syst Rev. 2021;2021(10). https://doi.org/10.1002/14651858.cd011564.pub3. A comprehensive systematic review of the effects of vitamin D supplementation in chronic liver disease highlighting the lack of convincing and high quality data in the area.

  18. Bloom A, Bloom S, Silva H, Nicoll AJ, Sawhney R. Zinc supplementation and its benefits in the management of chronic liver disease: an in-depth literature review. Ann Hepatol. 2021;25:100549. https://doi.org/10.1016/j.aohep.2021.100549.

    Article  CAS  PubMed  Google Scholar 

  19. Grüngreiff K, Reinhold D, Wedemeyer H. The role of zinc in liver cirrhosis. Ann Hepatol. 2016;15(1):7–16. https://doi.org/10.5604/16652681.1184191.

    Article  CAS  PubMed  Google Scholar 

  20. •• Diglio DC, Fernandes SA, Stein J, Azeredo-da-Silva A, de Mattos AA, Tovo CV. Role of zinc supplementation in the management of chronic liver diseases: a systematic review and meta-analysis. Ann Hepatol. 2020;19(2):190–6. https://doi.org/10.1016/j.aohep.2019.08.011. A systematic review of zinc supplementation in chronic liver disease highlighting lack of strong data but some suggestion of benefit in hepatic encephalopathy.

    Article  CAS  PubMed  Google Scholar 

  21. Fang A, Zhu H. Serum copper and zinc levels and risk of hepatocellular carcinoma: a 1:1 matched case-control study. Curr Dev Nutr. 2020;4:nzaa061_25. https://doi.org/10.1093/cdn/nzaa061_025.

  22. • Nishikawa H, Asai A, Fukunishi S. The significance of zinc in patients with chronic liver disease. Nutrients. 2022;14(22):4855. https://doi.org/10.3390/nu14224855. Review noting the link between hypozincemia and HCC occurrence in viral-induced chronic liver disease.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Schomburg L, Schweizer U, Köhrle J. Selenium and selenoproteins in mammals: extraordinary, essential, enigmatic. Cell Mol Life Sci. 2004;61(16):1988–95. https://doi.org/10.1007/s00018-004-4114-z.

    Article  CAS  PubMed  Google Scholar 

  24. Berger MM, Shenkin A, Schweinlin A, Amrein K, Augsburger M, Biesalski HK, et al. ESPEN micronutrient guideline. Clin Nutr. 2022;41(6):1357–424. https://doi.org/10.1016/j.clnu.2022.02.015.

    Article  CAS  PubMed  Google Scholar 

  25. •• Lin Y, He F, Lian S, Xie B, Liu T, He J, et al. Selenium status in patients with chronic liver disease: a systematic review and meta-analysis. Nutrients. 2022;14(5):952. https://doi.org/10.3390/nu14050952. A systematic review and meta-analysis establishing the state of selenium deficiency in chronic liver disease and link with hepatitis and HCC.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. • Shih C-W, Chen Y-J, Chen W-L. Inverse association between serum selenium level and severity of liver fibrosis: a cross-sectional study. Nutrients. 2022;14(17):3625. https://doi.org/10.3390/nu14173625. First study utilising transient elastography to show a correlation between the severity of selenium deficiency and the severity of liver fibrosis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. • Reja M, Makar M, Visaria A, Marino D, Rustgi V. Increased serum selenium levels are associated with reduced risk of advanced liver fibrosis and all-cause mortality in NAFLD patients: National Health and Nutrition Examination Survey (NHANES) III. Ann Hepatol. 2020;19(6):635–40. https://doi.org/10.1016/j.aohep.2020.07.006. Third National Health and Nutrition Examination Survey (NHANES III), a cross sectional study based on a national survey including more than 33,000 demonstrating the relationship between selenium deficiency and liver fibrosis in NAFLD.

    Article  CAS  PubMed  Google Scholar 

  28. Steinbrenner H, Duntas LH, Rayman MP. The role of selenium in type-2 diabetes mellitus and its metabolic comorbidities. Redox Biol. 2022;50:102236. https://doi.org/10.1016/j.redox.2022.102236.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Jacobs ET, Lance P, Mandarino LJ, Ellis NA, Chow HHS, Foote J, et al. Selenium supplementation and insulin resistance in a randomized, clinical trial. BMJ Open Diabetes Res Care. 2019;7(1):e000613. https://doi.org/10.1136/bmjdrc-2018-000613.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Licata A, Zerbo M, Como S, Cammilleri M, Soresi M, Montalto G, et al. The role of vitamin deficiency in liver disease: to supplement or not supplement? Nutrients. 2021;13(11):4014. https://doi.org/10.3390/nu13114014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Saeed A, Bartuzi P, Heegsma J, Dekker D, Kloosterhuis N, De Bruin A, et al. Impaired hepatic vitamin A metabolism in NAFLD mice leading to vitamin A accumulation in hepatocytes. Cell Mol Gastroenterol Hepatol. 2021;11(1):309-25.e3. https://doi.org/10.1016/j.jcmgh.2020.07.006.

    Article  CAS  PubMed  Google Scholar 

  32. Blaner WS. Vitamin A signaling and homeostasis in obesity, diabetes, and metabolic disorders. Pharmacol Ther. 2019;197:153–78. https://doi.org/10.1016/j.pharmthera.2019.01.006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kubota H, Chiba H, Takakuwa Y, Osanai M, Tobioka H, Kohama G, et al. Retinoid X receptor alpha and retinoic acid receptor gamma mediate expression of genes encoding tight-junction proteins and barrier function in F9 cells during visceral endodermal differentiation. Exp Cell Res. 2001;263(1):163–72. https://doi.org/10.1006/excr.2000.5113.

    Article  CAS  PubMed  Google Scholar 

  34. Simbrunner B, Semmler G, Stadlmann A, Scheiner B, Schwabl P, Paternostro R, et al. Vitamin A levels reflect disease severity and portal hypertension in patients with cirrhosis. Hep Intl. 2020;14(6):1093–103. https://doi.org/10.1007/s12072-020-10112-3.

    Article  Google Scholar 

  35. •• Song J, Jiang ZG. Low vitamin A levels are associated with liver-related mortality: a nationally representative cohort study. Hepatol Commun. 2023;7(5). https://doi.org/10.1097/hc9.0000000000000124. A large cohort study demonstrating the association between retinol deficiency and liver fibrosis and liver-related mortality.

  36. • Kataria Y, Deaton RJ, Enk E, Jin M, Petrauskaite M, Dong L, et al. Retinoid and carotenoid status in serum and liver among patients at high-risk for liver cancer. BMC Gastroenterol. 2016;16(1). https://doi.org/10.1186/s12876-016-0432-5. A cross sectional study demonstrating the association between low retinoid levels and liver fibrosis in HCV infected patients including before the development of liver fibrosis.

  37. Perumpail B, Li A, John N, Sallam S, Shah N, Kwong W, et al. The role of vitamin E in the treatment of NAFLD. Diseases. 2018;6(4):86. https://doi.org/10.3390/diseases6040086.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Bischoff SC, Bernal W, Dasarathy S, Merli M, Plank LD, Schütz T, et al. ESPEN practical guideline: clinical nutrition in liver disease. Clin Nutr. 2020;39(12):3533–62. https://doi.org/10.1016/j.clnu.2020.09.001.

    Article  PubMed  Google Scholar 

  39. Lai JC, Tandon P, Bernal W, Tapper EB, Ekong U, Dasarathy S, et al. Malnutrition, frailty, and sarcopenia in patients with cirrhosis: 2021 practice guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021;74(3):1611–44. https://doi.org/10.1002/hep.32049.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gastroenterology, John Hunter Hospital, Newcastle, NSW, Australia

    Bassem Ibrahim, Dhanashree Tikhe & Steven Bollipo

  2. Department of Gastroenterology, Royal Darwin Hospital, Tiwi, Darwin, NT, Australia

    Bassem Ibrahim

  3. School of Medicine & Public Health, University of Newcastle, Callaghan, Australia

    Steven Bollipo

Authors
  1. Bassem Ibrahim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dhanashree Tikhe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Steven Bollipo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bassem Ibrahim.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ibrahim, B., Tikhe, D. & Bollipo, S. The Role of Micronutrients in Chronic Liver Disease. Curr Hepatology Rep 22, 216–220 (2023). https://doi.org/10.1007/s11901-023-00605-8

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11901-023-00605-8

Keywords

Search

Navigation