Post-COVID-19 cholangiopathy
In our clinical experience with the Gamma variant in Brazil, we have come across many cases of this novel clinical entity. There was one case in 2020 that has left a mark in our practice, published in the beginning of 2021 in Portuguese (1). A 63-year-old male previously healthy patient developed a severe case of coronavirus disease 2019 (COVID-19) respiratory disease, needing prolonged mechanical ventilation and high-dose vasopressor drugs. He was admitted to the hospital on April 27, 2020. He was treated with multiple antibiotics during his stay, the last ones were an association of imipenem, polymyxin B and amikacin for a New Delhi metallo-beta-lactamase (NDM) Pseudomonas aeruginosa infective endocarditis. He underwent an endoscopic retrograde cholangiopancreatography (ERCP), which found a choledochal cast, composed of microlithiasis in the pathology report. He also underwent a percutaneous transhepatic cholangiography, which showed sclerosing cholangitis associated with intrahepatic lithiasis. He was discharged on September 25, 2020 with liver transplantation referral. After a couple of weeks of the hospital discharge, he was readmitted with a new severe sepsis, and the family opted for palliative care, and died not long afterwards. We believe this might be the first case reported of this entity, with extensive workup, including ERCP and percutaneous transhepatic cholangiography (PTHC), showing the presence of casts and lithiasis in the intra and extra-hepatic biliary tract, which makes this case unique. As based in the article by Roth et al. (2), we have put together a table summarizing our data (Table 1).
Table 1
Clinical characteristics of patients with severe cholangiopathy during recovery from COVID-19 | Reported case data |
---|---|
Patient demographics | |
Age (years) | 63 |
Sex | Male |
Ethnicity/race | Caucasian |
Hypertension | No |
Diabetes mellitus | No |
Other pre-existing comorbidities | No |
Clinical characteristics of COVID-19 infection | |
Hospitalizations | Day 1–151 |
Acute rehabilitation | No |
Subacute rehabilitation | No |
Mechanical ventilation and tracheostomy | Yes |
Venovenous extracorporeal membrane oxygenation | No |
Vasopressor support | Yes |
Biventricular systolic heart failure | No |
Acute kidney injury | Yes → hemodialysis |
Renal replacement therapy | Yes |
Secondary infections | Pseudomonas aeruginosa endocarditis |
Other notable complications | Infection by Candida albicans |
Hydroxychloroquine | No |
Azithromycin | Yes |
Ivermectin | No |
Corticosteroids | Yes |
Tocilizumab | No |
Anakinra | No |
Convalescent plasma | Yes |
Remdesivir | No |
Antibiotics | Azithromycin, Ampicillin + Sulbactam, Imipenem, Levofloxacin, Meropenem, Piperacillin, Polymyxin B, Trimethoprim, Sulfamethoxazole and Vancomycin |
Liver chemistries (serum) on admission (day 1) | |
Antifungal medications | Fluconazole |
Alkaline phosphatase (U/L) | 202 |
Aspartate aminotransferase (U/L) | 111 |
Alanine aminotransferase (U/L) | 39 |
Total bilirubin (mg/dL) | 25.20 |
Peak liver chemistries (serum) | |
Alkaline phosphatase (U/L) | 936 (day 46) |
Aspartate aminotransferase (U/L) | 378 (day 46) |
Alanine aminotransferase (U/L) | 690 (day 46) |
Total bilirubin (mg/dL) | 31.9 (day 96) |
Last available liver chemistries (serum) | |
Days after initial admission | Day 173 |
Alkaline phosphatase (U/L) | 238 |
Aspartate aminotransferase (U/L) | 105 |
Alanine aminotransferase (U/L) | 78 |
Total bilirubin (mg/dL) | 30.9 |
Hepatobiliary imaging findings | |
Cirrhotic morphology | No |
Hepatomegaly | No |
Extrahepatic bile duct dilatation | Yes |
Intrahepatic bile ducts | Dilatation, stenosis and intrahepatic lithiasis in a transhepatic percutaneous cholangiography |
Endoscopic retrograde cholangiography (days after initial admission) | Choledochal casts, suggestive of microlithiasis in the pathology report |
Histologic parameters | |
Liver biopsy (days after initial admission) | Suggestive of drug-induced cholangitis |
Portal tract findings | |
Bile duct paucity (% of portal tracts with interlobular bile ducts) | Not identified |
Ductular reaction | Mild |
Cholangiocyte swelling (bile ducts, ductules) | Severe |
Cholangiocyte regenerative change (bile ducts) | No |
Portal tract inflammation (lymphoplasmacytic, with scattered neutrophils) | Mild |
Hepatic arteries | Without changes |
Portal veins | Without changes |
Terminal hepatic veins | Without changes |
Parenchyma | Without changes |
Immunohistochemistry | Not done |
Fibrosis | No |
COVID-19, coronavirus disease 2019.
COVID-19 infection might cause liver injury, which is generally mild and transient. Although, in more severe cases, the patients might develop an entity entitled “post-COVID-19 cholangiopathy”. In 2021, two articles published in the American Journal of Gastroenterology discussed in total 15 cases of this disease (2,3). The case described had a cast removed in ERCP and we found one case similar to ours published in 2022 (4). It has been suggested that the diagnosis and management of this disease might demand an ERCP, especially if a dilated choledocus is identified in imaging studies (5,6). An actual cause is yet to be determined, but it is believed that it might be secondary to infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus or by drug-induced liver injury, since these patients sometimes use ketamine and carbapenems for long periods of time (7). Since we know so little of this entity, diagnosis and treatment for this condition are continuously revised as per available information. Symptoms, clinical signs, laboratorial manifestations, and imaging findings of the post-COVID-19 cholangiopathy do not differ from other etiological types. An adequate treatment is yet to be determined, but it seems that liver transplantation might have good results (8-11).
In conclusion, as the COVID-19 pandemic is now transforming into an endemic, we will have to manage the long-term consequences of this infection. Liver transplantation programs will require more data in this pathology, since it seems as of right now the only adequate readily available therapy in the long term (12).
Acknowledgments
Funding: None.
Footnote
Provenance and Peer Review: This article was commissioned by the editorial office, Digestive Medicine Research. The article has undergone external peer review.
Peer Review File: Available at https://dmr.amegroups.com/article/view/10.21037/dmr-22-83/prf
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dmr.amegroups.com/article/view/10.21037/dmr-22-83/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The family of the deceased patient has verbally agreed in the reporting of this case. All clinical procedures described in this article were performed in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). The family of the deceased patient has verbally agreed in the reporting of this article.
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References
- Graciolli AM, Bortoli BR, Gremelmier EMC, et al. Post-COVID-19 Cholangiopathy: a novel clinical entity. Rev AMRIGS 2021;65:69-73.
- Roth NC, Kim A, Vitkovski T, et al. Post-COVID-19 Cholangiopathy: A Novel Entity. Am J Gastroenterol 2021;116:1077-82. [Crossref] [PubMed]
- Faruqui S, Okoli FC, Olsen SK, et al. Cholangiopathy After Severe COVID-19: Clinical Features and Prognostic Implications. Am J Gastroenterol 2021;116:1414-25. [Crossref] [PubMed]
- Morão B, Revés JB, Nascimento C, et al. Secondary Sclerosing Cholangitis in a Critically Ill Patient with Severe SARS-CoV-2 Infection: A Possibly Emergent Entity during the Current Global Pandemic. GE Port J Gastroenterol 2022;27:1-6. [PubMed]
- Mayorquín-Aguilar JM, Lara-Reyes A, Revuelta-Rodríguez LA, et al. Secondary sclerosing cholangitis after critical COVID-19: Three case reports. World J Hepatol 2022;14:1678-86. [Crossref] [PubMed]
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- Wendel-Garcia PD, Erlebach R, Hofmaenner DA, et al. Long-term ketamine infusion-induced cholestatic liver injury in COVID-19-associated acute respiratory distress syndrome. Crit Care 2022;26:148. [Crossref] [PubMed]
- Durazo FA, Nicholas AA, Mahaffey JJ, et al. Post-Covid-19 Cholangiopathy-A New Indication for Liver Transplantation: A Case Report. Transplant Proc 2021;53:1132-7. [Crossref] [PubMed]
- Rojas M, Rodríguez Y, Zapata E, et al. Cholangiopathy as part of post-COVID syndrome. J Transl Autoimmun 2021;4:100116. [Crossref] [PubMed]
- Lee A, Wein AN, Doyle MBM, et al. Liver transplantation for post-COVID-19 sclerosing cholangitis. BMJ Case Rep 2021;14:e244168. [Crossref] [PubMed]
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- Bartoli A, Cursaro C, Andreone P. Severe acute respiratory syndrome coronavirus-2-associated cholangiopathies. Curr Opin Gastroenterol 2022;38:89-97. [Crossref] [PubMed]
Cite this article as: Graciolli AM, De Bortoli BR, Maslonek C, Gremelmier EMC, Henrich CF, Salgado K, Balbinot RA, Balbinot SS, Soldera J. Post-COVID-19 cholangiopathy. Dig Med Res 2023;6:29.