COVID-19-associated hepatic injury differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Tayyaba Ali, M.D.[2]

Overview

COVID-19-associated hepatic Injury must be differentiated from other conditions that cause elevation of liver enzymes.

Differential Diagnosis

COVID-19-associated hepatic Injury must be differentiated from other conditions that cause elevation of liver enzymes.

Disease Clinical manifestations Laboratory findings Additional findings
Symptoms Signs Transaminitis (elevated AST and ALT) Viral markers Autoimmune markers
Nausea & vomiting Abdominal pain Arthralgia Jaundice Hepatomegaly
Acute viral hepatitis Hepatitis A[1][2] +++ ++ + +++ + +++ HAV Ab ---
  • Fecal-oral transmission
  • Usually acute and self limit
  • Fever usually present
Hepatitis B[3] +++ ++ ++ +++ + +++ HBs Ag, HBc Ab, HBe Ag ---
  • Percutaneous transmission most common
  • May cause acute hepatic failure or may become chronic
  • Fever usually present
Hepatitis C[4] +++ ++ ++ +++ + +++ HCV Ab ---
Hepatitis E[5] ++ ++ +/- ++ + +++ HEV Ab ---
  • Fecal-oral transmission
  • May cause fulminant disease in pregnancy
  • Fever usually present
CMV hepatitis[6] +/- ++ - + + ++ CMV-specific immunoglobulin (Ig)M antibody --
  • Usually manifests as mononucleosis syndrome
  • fever usually present
EBV hepatitis[7] +/- ++ - +/- + ++ Heterophile antibody test, monospot test --
  • Systemic manifestations as mononucleosis syndrome
  • Fever usually present
Autoimmune hepatitis[8] - + +/- ++ + +++ --- ANA, ASMA, anti SLA/LP, ANCA, ALKM-1 antibodies
  • Liver biopsy may be required for diagnosis
Alcoholic hepatitis[9] +/- + - + - AST>ALT --- ---
  • History of alcohol intake
Drug induced hepatitis[10] +/- + - + + ++ --- ---
  • May cause either cholestatic or hepatocellular injury
COVID-19-associated hepatic Injury +[11] +[12] +[13] - +[13] ++[14] IgG/IgM Antibodies[15] ---
  • Fever usually present.
  • Live SARS-CoV-2 is also cultured from stool samples in rare cases, providing the evidence that SARS-CoV-2 has the possibility of fecal-oral transmission.[16][17]

References

  1. Jeong SH, Lee HS (2010). "Hepatitis A: clinical manifestations and management". Intervirology. 53 (1): 15–9. doi:10.1159/000252779. PMID 20068336.
  2. Nainan OV, Xia G, Vaughan G, Margolis HS (2006). "Diagnosis of hepatitis a virus infection: a molecular approach". Clin Microbiol Rev. 19 (1): 63–79. doi:10.1128/CMR.19.1.63-79.2006. PMC 1360271. PMID 16418523.
  3. Yuen MF, Chen DS, Dusheiko GM, Janssen HLA, Lau DTY, Locarnini SA; et al. (2018). "Hepatitis B virus infection". Nat Rev Dis Primers. 4: 18035. doi:10.1038/nrdp.2018.35. PMID 29877316.
  4. Mukherjee R, Burns A, Rodden D, Chang F, Chaum M, Garcia N; et al. (2015). "Diagnosis and Management of Hepatitis C Virus Infection". J Lab Autom. 20 (5): 519–38. doi:10.1177/2211068214563794. PMID 25609256.
  5. Kamar N, Dalton HR, Abravanel F, Izopet J (2014). "Hepatitis E virus infection". Clin Microbiol Rev. 27 (1): 116–38. doi:10.1128/CMR.00057-13. PMC 3910910. PMID 24396139.
  6. Gupta P, Suryadevara M, Das A (2014). "Cytomegalovirus-induced hepatitis in an immunocompetent patient". Am J Case Rep. 15: 447–9. doi:10.12659/AJCR.890945. PMC 4206484. PMID 25325934.
  7. Karadeniz A, Yesilbag Z, Kaya FÖ, Akgün FS (2018). "Acute hepatitis due to Epstein-Barr virus with cross-reacting antibodies to cytomegalovirus". Indian J Med Microbiol. 36 (1): 143–144. doi:10.4103/ijmm.IJMM_17_378. PMID 29735847.
  8. Manns MP, Lohse AW, Vergani D (2015). "Autoimmune hepatitis--Update 2015". J Hepatol. 62 (1 Suppl): S100–11. doi:10.1016/j.jhep.2015.03.005. PMID 25920079.
  9. Hosseini N, Shor J, Szabo G (2019). "Alcoholic Hepatitis: A Review". Alcohol Alcohol. 54 (4): 408–416. doi:10.1093/alcalc/agz036. PMC 6671387 Check |pmc= value (help). PMID 31219169.
  10. Katarey D, Verma S (2016). "Drug-induced liver injury". Clin Med (Lond). 16 (Suppl 6): s104–s109. doi:10.7861/clinmedicine.16-6-s104. PMC 6329561. PMID 27956449.
  11. Luo S, Zhang X, Xu H (2020). "Don't Overlook Digestive Symptoms in Patients With 2019 Novel Coronavirus Disease (COVID-19)". Clin Gastroenterol Hepatol. 18 (7): 1636–1637. doi:10.1016/j.cgh.2020.03.043. PMC 7154217 Check |pmc= value (help). PMID 32205220 Check |pmid= value (help).
  12. "Correction to Lancet Infectious Diseases 2020; published online April 29. https://doi.org/10.1016/ S1473-3099(20)30064-5". Lancet Infect Dis. 20 (7): e148. 2020. doi:10.1016/S1473-3099(20)30370-4. PMID 32595044 Check |pmid= value (help). External link in |title= (help)
  13. 13.0 13.1 Li J, Fan JG (2020). "Characteristics and Mechanism of Liver Injury in 2019 Coronavirus Disease". J Clin Transl Hepatol. 8 (1): 13–17. doi:10.14218/JCTH.2020.00019. PMC 7132021 Check |pmc= value (help). PMID 32274341 Check |pmid= value (help).
  14. Bangash MN, Patel J, Parekh D (2020). "COVID-19 and the liver: little cause for concern". Lancet Gastroenterol Hepatol. 5 (6): 529–530. doi:10.1016/S2468-1253(20)30084-4. PMC 7270582 Check |pmc= value (help). PMID 32203680 Check |pmid= value (help).
  15. Lippi G, Simundic AM, Plebani M (2020). "Potential preanalytical and analytical vulnerabilities in the laboratory diagnosis of coronavirus disease 2019 (COVID-19)". Clin Chem Lab Med. 58 (7): 1070–1076. doi:10.1515/cclm-2020-0285. PMID 32172228 Check |pmid= value (help).
  16. Wang W, Xu Y, Gao R, Lu R, Han K, Wu G; et al. (2020). "Detection of SARS-CoV-2 in Different Types of Clinical Specimens". JAMA. doi:10.1001/jama.2020.3786. PMC 7066521 Check |pmc= value (help). PMID 32159775 Check |pmid= value (help).
  17. "Infectious SARS-CoV-2 in Feces of Patient with Severe COVID-19 - Volume 26, Number 8—August 2020 - Emerging Infectious Diseases journal - CDC".