Acalculous Cholecystitis as a Complication of Epstein-Barr Virus

Case Reports and Literature Review

Case Report

Acalculous Cholecystitis as a Complication of Epstein-Barr Virus: A Case Report

Ahmed Al-Muhsin1*, Hesham Eltomy1, and Antonio Privitera2
1Department of General Surgery, King Fahd Military Medical Complex, Kingdom of Saudi Arabia
2Department of General Surgery, Kin Fahad Specialist Hospital Dammam, Kingdom of Saudi Arabia
*Corresponding author: Dr. Ahmed Mohammed Al.Muhsin, Department of General Surgery, King Fahd Military Medical Complex, Dammam, Kingdom of Saudi Arabia, Tel: +966501589990; E-mail:
Received: February 18, 2018; Accepted: March 26, 2018; Published: March 31, 2018
Copyright: ©2018 Al-Muhsin A, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Citation: Al-Muhsin A, Eltomy H, Privitera A (2018) Acalculous Cholecystitis as a Complication of Epstein-Barr Virus: A Case Report. Case Rep Lit Rev 2(1): 100007.


Acute acalculous cholecystitis (AAC) is an uncommon disease mostly occurring in critically ill and immunosuppressed patients. Very few cases have been reported during the course of infectious diseases in particular Espstein-Barr virus (EBV). A wide range of complications have been reported in EBV infection including liver involvement that is usually self-limiting and characterized by mild elevation of liver enzymes. AAC during EBV infection can be the result of direct invasion of the virus or induced by cholestasis associated with infective hepatitis. Serological tests and ultrasound scan are the most common tools for diagnosis. Most cases resolve with antibiotic treatment. Very rarely a cholecystectomy is indicated. The authors present another case of the unusual association in a young female patient and review the literature.

Keywords: acute acalculous cholecystitis, epstein-barr virus, primary infection
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Acute Acalculous Cholecytitis (AAC) is a well-recognized disease characterized by inflammation of the gallbladder in the absence of stones. Most cases of AAC occur in immunosuppressed patients, following trauma, severe burns, long stay in the intensive care unit, and long-term total parenteral nutrition. Resuscitation from hemorrhagic shock, cardiac arrest, congestive heart failure, abdominal vasculitis has also been associated with the disease [1]. AAC has rarely been described in the course of systemic infections with secondary gallbladder involvement. Very few cases have been associated with the causative agents of Infectious Mononucleosis (IM), in particular Epstein Barr Virus (EBV) [2,3]. The authors report another case of this uncommon complication during EBV infection and review the literature.

Case Report


A 27-year-old female presented to the emergency department with a 7-day history of fever, epigastric pain, nausea and vomiting. Past medical history was unremarkable apart from self-administration of herbal medications for weight loss. There was no history of smoking or alcohol intake. On examination she had mild fever of 37.9°C. Abdominal examination showed tenderness in the right upper quadrant with positive Murphy’s sign. There was no lymphadenopathy or any signs of upper respiratory tract infections.

Laboratory tests showed an elevated WBC 16.4 (NR 4-11 × 109/L) with lymphocytosis 64.6% (NR 20-45%). Liver function tests were deranged: ALK 136 u/L (NR 50-136 u/L), ALT 289 u/L (NR 12-78 u/L), AST 237u/L (NR 15-37 u/L), total bilirubin 20 µmol/L (NR 3-17 µmol/L), direct bilirubin 16.2 µmol/L (0-3 µmol/L), albumin 30 g/L (NR 34-50 g/L). Amylase and lipase were normal. ESR was 67 mm/hr. EBV IgM was Positive, CMV IgM Positive. Hepatitis and HIV screen were negative.

During her admission the WBC raised and reached up to 26 with differential showing 74 % of lymphocytes.

An abdominal ultrasound scan revealed mild thickening of the gallbladder measuring 4.4 mm with no evidence of gallstones or dilatation of the biliary tree (Figure 1).

Figure 1

Figure 1: Abdominal ultrasound showing gallbladder wall thickening with absence of stones

A CT scan of the abdomen showed hyperenhancing gallbladder wall with mucosal edema and adjacent fat stranding. No stones were demonstrated. Subcentimetric paraortic, mesenteric and inguinal lymphnodes were noted.

An MRCP was carried out and this showed thickening and edema of the gallbladder with minimal peri-cholecystic fluid. The CBD was not dilated and had no filling defects.

A HIDA scan was performed revealing a homogeneous liver uptake while the gallbladder was not visualized suggesting acute acalculous cholecytitis.

The patient was treated conservatively with IV fluid and antibiotics (Ciprofloxacin). She made an uneventful recovery and was discharged on the 9th day post admission.


AAC accounts for 5 to 10 % of all cases of cholecystitis. Many factors have been implicated in the pathogenesis including gallbladder ischemia, bile stasis, infections, and release of proinflammatory mediators [1].

Ultrasound scan of the gallbladder is the most accurate tool for the diagnosis of AAC. A gallbladder wall thickening >3 mm, distention of the gallbladder, localized tenderness, and pericholecystic fluid are the main diagnostic findings. The presence of two or more of these findings is considered diagnostic [4,5]. CT and radionuclide scans are also useful diagnostic modalities [1]. Supportive therapy and antibiotic treatment together with percutaneous cholecystostomy in severe cases arethe mainstay of treatment. Cholecystectomy is rarely required [1].

The occurrence of AAC during IM is a rare event [1]. IM is a clinical entity characterized by the presence of fever, pharyngitis, and lymphadenopathy [2]. The most common causative agents are Epstein Barr Virus (EBV) and less commonly Cytomegalovirus (CMV). Toxoplasma gondii, viral hepatitis, and human herpes virus 6 can also rarely be involved [3]. The majority of cases of IM experience an uneventful recovery, although a wide range of complications have been reported including liver impairment that is usually mild and self-limiting [6,7].

The exact mechanism of gallbladder involvement during IM is still unclear. Taking into consideration that viral hepatitis induces cholestasis, this may be considered a predisposing factor to inflammation [8,9]. Also, direct invasion of the gallbladder wall mucosa by the virus is possible since viral antigens have been isolated from the gallbladder epithelial cells [10].

Only 17 cases of AAC during EBV infection have been reported in the literature (Table 1) [11-25]. All cases are females, apart from one case diagnosed in a 21-year-old male patient. This contrasts with the general higher incidence of AAC in males [25]. AAC can occur at any age group but most commonly observed in adults especially in the fourth and eight decades of life. Most of the cases reported were young, presumably due to the greater occurrence of EBV infections in young adults [24]. Diagnosis was made with thorough clinical history and examination, pathognomonic features in peripheral blood films, and serological tests. In the reported case CMV IgM was thought to be a false-positive due to crossreactivity [26]. As in our case, patients presented with gastrointestinal symptoms including RUQ tenderness. The classical presentation of EBV infection with pharyngitis and lymphadenopathy was not predominant, and most cases showed elevation of liver enzymes [24]. Patients were treated conservatively with antibiotics and monitoring of liver function, although there was no difference in the outcome of patients receiving antibiotics compared to those who did not receive any antibiotic therapy. Surgical intervention for AAC during the course of EBV is usually unnecessary [24]. Only one of the reviewed cases underwent laparoscopic cholecystectomy for severe septic cholecystitis [15].

Table 1: Reported cases in the literature of AAC during EBV infection
Age/Gender Lymphadenopathy Pharyngitis ALP (IU/L) AST (IU/L) ALT (IU/L) Wall thickness US/mm) Management Reference
53/F - - 1081 (40-120) - 339 10 Medical [11]
18/F Yes Yes 312 (38-148) 220 (5-45) 328 (5-45) 9 Medical [8]
19/F Yes Yes 710 (<280) 426 (<40) 584 (<40) 8 Medical [12]
20/F Yes Yes 727 171 299 - Medical [13]
22/F Yes Yes 2.2 µkat/L (0.5-2) 6.87 µkat/L (0-0.65) 12.79 µkat/L (0-0.8) 6 Medical [14]
22/F - - - - - 7 Surgical [15]
29/F Yes Yes 161 (53-151) 121 (10-35) 166 (10-35) 15 Medical [16]
18/F No No 146 118 - >10 Medical [17]
22/F No No - - 89 5 Medical [18]
22/F No - 239 329 464 14 Medical [19]
18/F Yes No 165 321 214 12 Medical [20]
20/F Yes No 131 453 494 16 Medical [20]
48/F Yes - 516 (90-260) 221 (5-35) 165 (5-40) Marked Medical [21]
34/F No Yes 429 (35-105) - 61 (10-45) 11.3 Medical [22]
21/M No No 179 (<140) 172 (<40) 232 (<40) 4.5 Medical [23]
30/F Yes No 376 (50-136) 233 (8-37) 220 (15-65) 7.4 Medical [24]
27/F No No 136 237 289 4.4 Medical Reported case (2017)


AAC may result as a complication of IM and a high index of suspicion is needed in patients developing GI symptoms during the course of the disease. Ultrasound scan represents the main diagnostic investigation. Most cases can be treated conservatively with antibiotic therapy, and surgical intervention is rarely needed.


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