Autoimmune hepatitis and primary biliary cholangitis overlap syndrome after COVID-19
Keywords:COVID-19, Hepatitis, Autoimmune, Liver Diseases, SARS-CoV-2
COVID-19 is commonly associated with high serum levels of pro-inflammatory cytokines, and the post-infection status can disturb self-tolerance and trigger autoimmune responses. We are reporting a 45-year-old male who was admitted with fatigue, jaundice, elevated liver enzymes (with cholestatic pattern), and acute kidney injury two weeks after recovering from a mild SARS-CoV-2 infection. Serologies for viral hepatitis and anti-mitochondrial antibody were negative, while anti-nuclear and anti-smooth muscle antibodies were positive. There were no signs of chronic liver disease, and a magnetic resonance cholangiography showed no dilatation of biliary ducts. Histologic evaluation of the liver evidenced numerous foci of lobular necrosis without ductopenia or portal biliary reaction. Considering the autoantibody profile and histologic changes, the medical team started oral prednisone, but there was a suboptimal biochemical response in the outpatient follow-up. Two months later, a second liver biopsy was performed and revealed non-suppurative destructive chronic cholangitis, extensive areas of confluent necrosis with hepatocytes regenerating into pseudorosettes, and numerous plasma cells. According to the Paris Criteria, the patient was then diagnosed with an autoimmune hepatitis-primary biliary cholangitis overlap syndrome (AIH-PBC-OS). After adding azathioprine and ursodeoxycholic acid to the treatment, there was a satisfactory response. This is the second worldwide report of an AIH-PBC-OS triggered by COVID-19, but the first case with a negative anti-mitochondrial antibody. In this setting, histologic evaluation of the liver by an experienced pathologist is a hallmark of achieving the diagnosis and correctly treat the patient.
Dotan A, David P, Arnheim D, Shoenfeld Y. The autonomic aspects of the post-COVID19 syndrome. Autoimmun Rev. 2022;21(5):103071. http://dx.doi.org/10.1016/j.autrev.2022.103071. PMid:35182777.
Liu Y, Sawalha AH, Lu Q. COVID-19 and autoimmune diseases. Curr Opin Rheumatol. 2021;33(2):155-62. http://dx.doi.org/10.1097/BOR.0000000000000776. PMid:33332890.
Kabaçam G, Wahlin S, Efe C. Autoimmune hepatitis triggered by COVID-19: a report of two cases. Liver Int. 2021;41(10):2527-8. http://dx.doi.org/10.1111/liv.15044. PMid:34478591.
Bartoli A, Cursaro C, Andreone P. Severe acute respiratory syndrome coronavirus-2-associated cholangiopathies. Curr Opin Gastroenterol. 2022;38(2):89-97. http://dx.doi.org/10.1097/MOG.0000000000000808. PMid:35098930.
Floreani A, De Martin S. COVID-19 and autoimmune liver diseases. J Clin Med. 2022;11(10):2681. http://dx.doi.org/10.3390/jcm11102681. PMid:35628807.
Erard D, Villeret F, Lavrut PM, Dumortier J. Autoimmune hepatitis developing after COVID 19 vaccine: presumed guilty? Clin Res Hepatol Gastroenterol. 2022;46(3):101841. http://dx.doi.org/10.1016/j.clinre.2021.101841. PMid:34920137.
Chazouillères O, Wendum D, Serfaty L, Montembault S, Rosmorduc O, Poupon R. Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: clinical features and response to therapy. Hepatology. 1998;28(2):296-301. http://dx.doi.org/10.1002/hep.510280203. PMid:9695990.
Vitrone M, Mele F, Durante-Mangoni E, Zampino R. Drugs and liver injury: a not to be overlooked binomial in COVID-19. J Chemother. 2022;34(4):207-20. http://dx.doi.org/10.1080/1120009X.2021.1988203. PMid:34644236.
National Institute of Diabetes and Digestive and Kidney Diseases. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Azithromycin [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2021. Available from: April 25, 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548434/
Martinez MA, Vuppalanchi R, Fontana RJ, et al. Clinical and histologic features of azithromycin-induced liver injury. Clin Gastroenterol Hepatol. 2015;13(2):369-76.e3. http://dx.doi.org/10.1016/j.cgh.2014.07.054. PMid:25111234.
Ellison CA, Blackwell SB. Acute hepatocellular injury associated with Azithromycin. J Pharm Pract. 2021;34(3):493-6. http://dx.doi.org/10.1177/0897190019894428. PMid:31928122.
Chalasani N, Bonkovsky HL, Fontana R, et al. Features and outcomes of 899 patients with drug-induced liver injury: the DILIN prospective study. Gastroenterology. 2015;148(7):1340-1352.e7. http://dx.doi.org/10.1053/j.gastro.2015.03.006. PMid:25754159.
Björnsson ES, Andrade RJ. Long-term sequelae of drug-induced liver injury. J Hepatol. 2022;76(2):435-45. http://dx.doi.org/10.1016/j.jhep.2021.10.011. PMid:34688732.
Freedman BL, Danford CJ, Patwardhan V, Bonder A. Treatment of overlap syndromes in autoimmune liver disease: a systematic review and meta-analysis. J Clin Med. 2020;9(5):1449. http://dx.doi.org/10.3390/jcm9051449. PMid:32414025.
Couto CA, Terrabuio DRB, Cançado ELR, et al. Update of the brazilian society of hepatology recommendations for diagnosis and management of autoimmune diseases of the liver. Arq Gastroenterol. 2019;56(2):232-41. http://dx.doi.org/10.1590/s0004-2803.201900000-43. PMid:31460591.
Jiang Y, Xu BH, Rodgers B, Pyrsopoulos N. Characteristics and inpatient outcomes of primary biliary cholangitis and autoimmune hepatitis overlap syndrome. J Clin Transl Hepatol. 2021;9(3):392-8. http://dx.doi.org/10.14218/JCTH.2021.00008. PMid:34221925.
Tan XY, Miao Q, Chen XY. Clinicopathological analysis of anti-mitochondrial antibody negative primary biliary cholangitis-autoimmune hepatitis overlap syndrome. Zhonghua Gan Zang Bing Za Zhi. 2019;27(5):376-80. http://dx.doi.org/10.3760/cma.j.issn.1007-3418.2019.05.010. PMid:31177663.
Nardo AD, Schneeweiss-Gleixner M, Bakail M, Dixon ED, Lax SF, Trauner M. Pathophysiological mechanisms of liver injury in COVID-19. Liver Int. 2021;41(1):20-32. http://dx.doi.org/10.1111/liv.14730. PMid:33190346.
Bartoli A, Gitto S, Sighinolfi P, Cursaro C, Andreone P. Primary biliary cholangitis associated with SARS-CoV-2 infection. J Hepatol. 2021;74(5):1245-6. http://dx.doi.org/10.1016/j.jhep.2021.02.006. PMid:33610679.
Cesar Machado MC, Kalil R Fo, El Bacha IAH, et al. Post-COVID-19 secondary sclerosing cholangitis: a rare but severe condition with no treatment besides liver transplantation. Am J Case Rep. 2022;23:e936250. http://dx.doi.org/10.12659/AJCR.936250. PMid:35978523.
Roth NC, Kim A, Vitkovski T, et al. Post-COVID-19 cholangiopathy: a novel entity. Am J Gastroenterol. 2021;116(5):1077-82. http://dx.doi.org/10.14309/ajg.0000000000001154. PMid:33464757.
Andrés L, Badia E, Fernández C, et al. Autoimmune hepatitis. Another consequence of COVID-19? Gastroenterol Hepatol. 2023;46(2):135-6. http://dx.doi.org/10.1016/j.gastrohep.2022.05.001. PMid:35577224.
Izagirre A, Arzallus T, Garmendia M, Torrente S, Castiella A, Zapata EM. Autoimmune hepatitis following COVID-19 vaccination. J Autoimmun. 2022;132:102874. http://dx.doi.org/10.1016/j.jaut.2022.102874. PMid:35985054.
Singh B, Kaur P, Maroules M. Autoimmune hepatitis-primary biliary cholangitis overlap syndrome triggered by COVID-19. Eur J Case Rep Intern Med. 2021;8(3):002264. http://dx.doi.org/10.12890/2021_002264. PMid:33768072.
To U, Silveira M. Overlap syndrome of autoimmune hepatitis and primary biliary cholangitis. Clin Liver Dis. 2018;22(3):603-11. http://dx.doi.org/10.1016/j.cld.2018.03.010. PMid:30259856.
Silveira MG, Talwalkar JA, Angulo P, Lindor KD. Overlap of autoimmune hepatitis and primary biliary cirrhosis: long-term outcomes. Am J Gastroenterol. 2007;102(6):1244-50. http://dx.doi.org/10.1111/j.1572-0241.2007.01136.x. PMid:17319931.
Liu JM, Chi J. Is COVID-19-associated cytokine storm distinct from non-COVID-19 secondary hemophagocytic lymphohistiocytosis? Exp Biol Med (Maywood). 2022;247(4):330-7. http://dx.doi.org/10.1177/15353702211068840. PMid:35068219.
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