Skip to main content

Liver injury without liver failure in COVID-19 patients: how to explain, in some cases, elevated ammonia without hepatic decompensation

We read with great interest the recent research letter by Cardoso et al. who describe the liver injury seen with COVID-19 [1]. We would like to provide some additional information. In our large cohort of COVID-19 patients, we had several patients who did not regain consciousness as expected, even when sedation had been stopped for 4–5 days. Electroencephalogram (EEG) in these patients demonstrated a metabolic pattern. In the process of working through the differential diagnoses, we measured serum ammonia levels and were surprised to see that in two patients the ammonia level was elevated 3 times above the normal limit. While those patients had liver injury but absolutely no sign of liver failure, nor were they receiving medications that could explain hyperammonemia, such as valproate or amiodarone [2]. Both patients had experienced very severe diarrhea several days prior to admission. Baseline Glasgow Coma Score (GCS) was difficult to determine as both patients were intubated by an emergency team on site. CT scan of the brain was unremarkable. Both patients were treated with classical medical therapy including lactulose, but, despite increasing doses of lactulose for 3 days, ammonia levels remained unchanged. We decided that if there was no progress within 72 h, continuous renal replacement therapy (CRRT) would be started to remove ammonia. As the ammonia was below 200 mg/dL, there was no acute indication to start CRRT to avoid brain edema. We were surprised to see that both patients regained consciousness 48 and 72 h later respectively, and ammonia levels normalized. Retrospectively, we hypothesize that the pre-admission diarrhea may have resulted in secondary carnitine deficiency, as described in the literature [3], leading to hyperammonemia unresponsive to medical therapy [4]. CRRT dramatically reduces ammonia levels, but ultimately can worsen the situation by further reducing the level of carnitine [5]. As we did not measure serum carnitine levels and we did not supply the patients with carnitine supplementation, the diagnosis of carnitine deficiency in these cases remains only a hypothesis. Clinicians should keep this diagnosis in mind in COVID-19 patients with severe diarrhea.

Availability of data and materials

Not applicable.

Abbreviations

EEG:

Electroencephalogram

CRRT:

Continuous renal replacement therapy

References

  1. 1.

    Cardoso FS, Pereira R, Germano N. Liver injury in critically ill patients with COVID-19: a case series. Crit Care. 2020;24:190.

    Article  Google Scholar 

  2. 2.

    Cappe M, Hantson P, Komuta M, Vincent MF, Laterre PF, Ould-Nana I. Hyperammonemic encephalopathy and lipid dysmetabolism in a critically ill patient after a short course of amiodarone. J Crit Care Med (Targu Mures). 2019;5(4):161–5. https://doi.org/10.2478/jccm-2019-0026 eCollection 2019 Oct.

    Article  Google Scholar 

  3. 3.

    Fitzgerald JF, Troncone R, Roggero P, Pozzi E, Garavaglia B, Parini R, et al. Clinical quiz. Secondary carnitine deficiency due to celiac disease. J Pediatr Gastroenterol Nutr. 2003;36(5):636–46.

    Article  Google Scholar 

  4. 4.

    Limketkai BN, Zucker SD. Hyperammonemic encephalopathy caused by carnitine deficiency. J Gen Intern Med. 2008;23(2):210–3. Published online 2007 Dec 13. https://doi.org/10.1007/s11606-007-0473-0.

    Article  PubMed  Google Scholar 

  5. 5.

    Sgambat K, Moudgil A. Carnitine deficiency in children receiving continuous renal replacement therapy. Hemodial Int. 2016;20:63–7.

    Article  Google Scholar 

Download references

Acknowledgements

We would like to thank Dr. Melissa Jackson for the critical review of the manuscript.

Funding

None.

Author information

Affiliations

Authors

Contributions

PMH, SR, and DDB designed the paper. All authors participated in drafting and reviewing. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Patrick M. Honore.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare to have no competing interests.

Additional information

Publisher’s Note

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

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Honore, P.M., Barreto Gutierrez, L., Kugener, L. et al. Liver injury without liver failure in COVID-19 patients: how to explain, in some cases, elevated ammonia without hepatic decompensation. Crit Care 24, 352 (2020). https://doi.org/10.1186/s13054-020-03088-x

Download citation