Acute acalculous cholecystitis as a rare gastroenterological association of COVID-19: a case series and systematic review
Background and aim: Acute acalculous cholecystitis (AAC) is an acute inflammatory disease of the gallbladder in the absence of cholecystolithiasis. It is a serious clinicopathologic entity, with a high mortality rate of 30%–50%. A number of etiologies have been identified that can potentially trigger AAC. However, clinical evidence on its occurrence following COVID-19 remains scarce. We aim to evaluate the association between COVID-19 and AAC.
Methods: We report our clinical experience based on 3 patients who were diagnosed with AAC secondary to COVID-19. A systematic review of the MEDLINE, Google Scholar, Scopus, and Embase databases was conducted for English-only studies. The latest search date was December 20, 2022. Specific search terms were used regarding AAC and COVID-19, with all associated permutations. Articles that fulfilled the inclusion criteria were screened, and 23 studies were selected for a quantitative analysis.
Results: A total of 31 case reports (level of clinical evidence: IV) of AAC related to COVID-19 were included. The mean age of patients was 64.7 ± 14.8 years, with a male-to-female ratio of 2.1:1. Major clinical presentations included fever 18 (58.0%), abdominal pain 16 (51.6%), and cough 6 (19.3%). Hypertension 17 (54.8%), diabetes mellitus 5 (16.1%), and cardiac disease 5 (16.1%) were among the common underlying medical conditions. In our analysis of initial presentation patterns, COVID-19 pneumonia was encountered before, after, or concurrently with AAC in 17 (54.8%), 10 (32.2%), and 4 (12.9%) patients, respectively. Coagulopathy was noted in 9 (29.0%) patients. Imaging studies for AAC included CT scan and ultrasonography in 21 (67.7%) and 8 (25.8%) cases, respectively. Based on the Tokyo Guidelines 2018 criteria for severity, 22 (70.9%) had grade II and 9 (29.0%) patients had grade I cholecystitis. Treatment included surgical intervention in 17 (54.8%), conservative management alone in 8 (25.8%), and percutaneous transhepatic gallbladder drainage in 6 (19.3%) patients. Clinical recovery was achieved in 29 (93.5%) patients. Gallbladder perforation was encountered as a sequela in 4 (12.9%) patients. The mortality rate in patients with AAC following COVID-19 was 6.5%.
Conclusions: We report AAC as an uncommon but important gastroenterological complication following COVID-19. Clinicians should remain vigilant for COVID-19 as a possible trigger of AAC. Early diagnosis and appropriate treatment can potentially save patients from morbidity and mortality.
Relevance for Patients: AAC can occur in association with COVID-19. If left undiagnosed, it may adversely impact the clinical course and outcomes of patients. Therefore, it should be considered among the differential diagnoses of right upper abdominal pain in these patients. Gangrenous cholecystitis can often be encountered in this setting, necessitating an aggressive treatment approach. Our results point out the clinical importance of raising awareness about this biliary complication of COVID-19, which will aid in early diagnosis and appropriate clinical management.
[1] Duncan J. Femoral Hernia: Gangrene of the Gallbladder, Extravasation of Bile; Peritonitis; Death. North J Med 1844;2:151-3.
[2] Huffman JL, Schenker S. Acute Acalculous Cholecystitis: A Review. Clin Gastroenterol Hepatol 2010;8:15-22.
[3] Jones MW, Ferguson T. Acalculous Cholecystitis. Treasure Island: StatPearls Publishing; 2022.
[4] Waseem H, Inayat F, Abduraimova M, Kamholz S. Allopurinol-induced Drug Reaction with Eosinophilia and Systemic Symptoms Syndrome: A Cause of Acalculous Cholecystitis? Cureus 2017;9:e1569.
[5] Katabathina VS, Zafar AM, Suri R. Clinical Presentation, Imaging, and Management of Acute Cholecystitis. Tech Vasc Interv Radiol 2015;18:256-65.
[6] Indar AA, Beckingham IJ. Acute Cholecystitis. BMJ 2002;325:639-43.
[7] Sureka B. Gangrenous Cholecystitis. AJR Am J Roentgenol 2017;208:W58.
[8] World Health Organization. WHO Coronavirus (COVID-19) Dashboard. Available from: https://www. covid19.who.int [Last accessed on 2022 Dec 23].
[9] Bourgonje AR, Abdulle AE, Timens W, Hillebrands JL, Navis GJ, Gordijn SJ, et al. Angiotensin-Converting Enzyme 2 (ACE2), SARS-CoV-2 and the Pathophysiology of Coronavirus Disease 2019 (COVID-19). J Pathol 2020;251:228-48.
[10] Saleem S, Ishtiaq R, Inayat F, Aziz M, Bleibel W. Gastrointestinal and Liver Manifestations in COVID-19 Population. Middle East J Dig Dis 2021;13:281-6.
[11] Marasco G, Cremon C, Barbaro MR, Salvi D, Cacciari G, Kagramanova A, et al. Prevalence of Gastrointestinal Symptoms in Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Results of the Prospective Controlled Multinational GI-COVID-19 Study. Am J Gastroenterol 2022;117:147-57.
[12] Elshazli RM, Kline A, Elgaml A, Aboutaleb MH, Salim MM, Omar M, et al. Gastroenterology Manifestations and COVID-19 Outcomes: AMeta-analysis of 25,252 Cohorts among the First and Second Waves. J Med Virol 2021;93:2740-68.
[13] Inayat F, Hurairah A. Gastrointestinal and Hepatic Involvement in Hypereosinophilic Syndrome. Cureus 2016;8:e760.
[14] Inayat F, Jafar MS, Ali NS, Hussain Q, Hurairah A. Enigma of Extrapulmonary Tuberculosis: Where do We Stand? Cureus 2017;9:e1554.
[15] Yokoe M, Hata J, Takada T, Strasberg SM, Asbun HJ, Wakabayashi G, et al. Tokyo Guidelines 2018: Diagnostic Criteria and Severity Grading of Acute Cholecystitis (with Videos). J Hepatobiliary Pancreat Sci 2018;25:41-54.
[16] Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 2009;6:e1000097.
[17] Alhassan SM, Iqbal P, Fikrey L, Ibrahim MI, Qamar MS, Chaponda M, et al. Post COVID 19 Acute Acalculous Cholecystitis Raising the Possibility of Underlying Dysregulated Immune Response, a Case Report. Ann Med Surg (Lond) 2020;60:434-7.
[18] Asti E, Lovece A, Bonavina L. Gangrenous Cholecystitis during Hospitalization for SARS-CoV2 Infection. Updates Surg 2020;72:917-9.
[19] Balaphas A, Gkoufa K, Meyer J, Peloso A, Bornand A, McKee TA, et al. COVID-19 can Mimic Acute Cholecystitis and is Associated with the Presence of Viral RNA in the Gallbladder Wall. J Hepatol 2020;73:1566-8.
[20] Bruni A, Garofalo E, Zuccalà V, Currò G, Torti C, Navarra G, et al. Histopathological Findings in a COVID-19 Patient Affected by Ischemic Gangrenous Cholecystitis. World J Emerg Surg 2020;15:43.
[21] Cirillo B, Brachini G, Crocetti D, Sapienza P, Mingoli A. Acalcolous Hemorrhagic Cholecystitis and SARS-CoV-2 Infection. Br J Surg 2020;107:e524.
[22] Hassani AH, Beheshti A, Almasi F, Moghaddam PK, Azizi M, Shahrokh S. Unusual Gastrointestinal Manifestations of COVID-19: Two Case Reports. Gastroenterol Hepatol Bed Bench 2020;13:410-4.
[23] Lovece A, Asti E, Bruni B, Bonavina L. Subtotal Laparoscopic Cholecystectomy for Gangrenous Gallbladder during Recovery from COVID-19 Pneumonia. Int J Surg Case Rep 2020;72:335-8.
[24] Kabir T, Ngaserin S, Koh FH, Huang J, Ong BC, Chew MH. The COVID-19 Conundrum: SARS-CoV-2 is Not Present in Bile. Br J Surg 2020;107:e381.
[25] Mattone E, Sofia M, Schembari E, Palumbo V, Bonaccorso R, Randazzo V, et al. Acute Acalculous Cholecystitis on a COVID-19 Patient: A Case Report. Ann Med Surg (Lond) 2020;58:73-5.
[26] Palmieri A, Palmieri AM, Hernandez LA, Canchila E. Acute Acalculous Cholecystitis in a Patient with Covid-19. Adv Res Gastroenterol Hepatol 2020;16:555936.
[27] Singh R, Domenico C, Rao SD, Urgo K, Prenner SB, Wald JW, et al. Novel Coronavirus Disease 2019 in a Patient on Durable Left Ventricular Assist Device Support. J Card Fail 2020;26:438-9.
[28] Ying M, Lu B, Pan J, Lu G, Zhou S, Wang D, et al. COVID-19 with Acute Cholecystitis: A Case Report. BMC Infect Dis 2020;20:437.
[29] Wahid N, Bhardwaj T, Borinsky C, Tavakkoli M, Wan D, Wong T. Acute Acalculous Cholecystitis during Severe COVID-19 Hospitalizations. Am J Gastroenterol 2020;115:S794.
[30] Abaleka FI, Nigussie B, Bedanie G, Mohammed A, Galiboglu S. Acute Acalculous Cholecystitis due to COVID-19, an Unusual Presentation. Cureus 2021;13:e15431.
[31] Alam W, Karam K. Gangrenous Cholecystitis as a Potential Complication of COVID-19: A Case Report. Clin Med Insights Case Rep 2021;14:11795476211042459.
[32] Rivera-Alonso D, Rivera-Alonso I, Burneo-Esteves M, Martínez-Ruíz C, Rojo-Abecia M, Moreno-Sanguino C. Acute Portal Vein Thrombosis in Mild Cholecystitis. A Consequence of Coronavirus Disease 2019 Infection? Cir Cir 2021;89:399-402.
[33] Futagami H, Sato H, Yoshida R, Yasui K, Yagi T, Fujiwara T. Acute Acalculous Cholecystitis Caused by SARS-CoV-2 Infection: A Case Report and Literature Review. Int J Surg Case Rep 2022;90:106731.
[34] Liapis SC, Stavrou A, Perivoliotis K, Christodoulou P, Kalodimos G, Kitsakis G, et al. Laparoscopic Cholecystectomy for Acalculous, Gangrenous Cholecystitis on an Outpatient COVID-19 Adult: A Case Report. J Surg Case Rep 2022;2022:rjac205.
[35] Hurtado FB, Arrabal EG, Delgado AB, Rodríguez AJ. SARS-CoV-2 Infection Presenting as Acute Acalculous Cholecystitis. Rev Esp Quimioter 2022;35:87-8.
[36] Puig G, Giménez-Milà M, Campistol E, Cano V, Valcarcel J, Colomina MJ. Development of Concomitant Diseases in COVID-19 Critically Ill Patients. Rev Esp Anestesiol Reanim (Engl Ed) 2021;68:37-40.
[37] Hajebi R, Habibi P, Maroufi SF, Bahreini M, Yazdi SA. COVID-19 Patients Presenting with Gangrenous Acalculous Cholecystitis: Report of Two Cases. Ann Med Surg (Lond) 2022;76:103534.
[38] D’Introno A, Gatti P, Manca G, D’Amuri A, Minniti S, Ciracì E. Acute Acalculous Cholecystitis as an Early Manifestation of COVID-19: Case Report and Literature Review. Acta Biomed 2022;93:e2022207.
[39] Franch-Llasat D, Sabaté-Ortigues R, Bellaubí-Pallarés N, Andrés-Castrillo F, Comí-Codina S, Roche-Campo F. The Incidence of Acute Acalculous Cholecystitis in Critically Ill COVID-19 Patients. Acute Crit Care 2022;37:678-80.
[40] Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, et al. A Familial Cluster of Pneumonia Associated with the 2019 Novel Coronavirus Indicating Person-to-person Transmission: A Study of a Family Cluster. Lancet 2020;395:514-23.
[41] Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med 2020;382:1708-20.
[42] Mao R, Qiu Y, He JS, Tan JY, Li XH, Liang J, et al. Manifestations and Prognosis of Gastrointestinal and Liver Involvement in Patients with COVID-19: A Systematic Review and Meta-analysis. Lancet Gastroenterol Hepatol 2020;5:667-78.
[43] Barie PS, Eachempati SR. Acute Acalculous Cholecystitis. Curr Gastroenterol Rep 2003;5:302-9.
[44] Campanile FC, Podda M, Arezzo A, Botteri E, Sartori A, Guerrieri M, et al. Acute Cholecystitis during COVID-19 Pandemic: A Multisocietary Position Statement. World J Emerg Surg 2020;15:38.
[45] Lei S, Jiang F, Su W, Chen C, Chen J, Mei W, et al. Clinical Characteristics and Outcomes of Patients Undergoing Surgeries during the Incubation Period of COVID-19 Infection. EClinicalMedicine 2020;21:100331.
[46] Mori Y, Itoi T, Baron TH, Takada T, Strasberg SM, Pitt HA, et al. Tokyo Guidelines 2018: Management Strategies for Gallbladder Drainage in Patients with Acute Cholecystitis (with Videos). J Hepatobiliary Pancreat Sci 2018;25:87-95.
[47] Saleem S, Weissman S, Gonzalez H, Rojas PG, Inayat F, Alshati A, et al. Post-Cholecystectomy Syndrome: A Retrospective Study Analysing the Associated Demographics, Aetiology, and Healthcare Utilization. Transl Gastroenterol Hepatol 2021;6:58.