Siblings With Cholecystitis, a Rare Complication of Hepatitis A Infection
Two siblings immigrated to the United States from Singapore after a 2-month visit to India, and neither sibling had received the hepatitis A vaccine. The boy, who was 7 years of age, was admitted to the hospital 3 weeks after arrival in the United States with a 1-week history of fever, malaise, anorexia, severe abdominal pain, and jaundice. On physical examination, he had icteric sclerae and significant tenderness in the right upper quadrant of the abdomen. Laboratory test results showed elevated liver enzymes, with an alanine aminotransferase (ALT) level of 1797 U/L, an aspartate aminotransferase (AST) level of 1601 U/L, a total bilirubin level of 5.2 mg/dL, and a direct bilirubin level of 4.7 mg/dL. In addition, serum was positive for immunoglobulin M (IgM) antibodies to hepatitis A virus.
Ultrasonography of the abdomen revealed a necrotic gallbladder with thickened wall, septations, and pericholecystic fluid. However, there were no stones, and the appearances of the liver and spleen were unremarkable (Figure 1). The boy was treated symptomatically with hydration, pain control with acetaminophen, and a vegetarian diet. He improved after several days in the hospital, and 2 weeks after discharge his liver enzyme and bilirubin levels were within reference ranges, and repeat ultrasonography results were unremarkable.
His 13-year-old sister developed nausea, anorexia, abdominal pain, and jaundice without fever about 2 weeks after her brother’s presentation. She had received the hepatitis A vaccine for an unimmunized household contact 2 weeks earlier. Her laboratory test results showed elevated liver enzymes (ALT, 2473 U/L; AST, 2107 U/L), a total bilirubin level of 6.3 mg/dL, a direct bilirubin level of 5.3 mg/dL, and positive results for serum IgM antibodies to hepatitis A virus. Her abdominal ultrasonography results were similar to those of her brother, and both were consistent with acalculous cholecystitis (Figure 2). The girl was managed symptomatically at home. Four weeks later, laboratory test results showed that her liver enzymes and bilirubin levels were unremarkable. Her repeat ultrasonography results were also unremarkable.
DISCUSSION
The siblings had been exposed to the hepatitis A virus during the same time period, and their exposure resulted from contaminated food or water while traveling in an endemic area. It is notable that the 13-year-old girl received a dose of hepatitis A vaccine when her brother had been hospitalized, which may have modified the course of her illness. The incubation period for hepatitis A ranges from 15 to 50 days.1 As a result of hepatitis A infection, the boy and the girl both developed the rare complication of acalculous cholecystitis. In one review,2 11 cases of acalculous cholecystitis occurred as a result of hepatitis A infection in children aged 2 to 16 years from 1992 to 2012 in countries where the disease is endemic. The highest number of cases was in India, where the siblings had spent 2 months. No cases were reported in the United States.
The siblings fulfilled most of the criteria for a diagnosis of acalculous cholecystitis, which include the following: gallbladder distention, thickening of the gallbladder wall (> 3.5 mm), no acoustic shadow or biliary sludge, perivesical liquid accumulation, and no dilatation of the intrahepatic and extrahepatic bile ducts.2 Gangrenous changes are the most serious manifestations of inflammation and can progress to perforation.3,4
The mechanism of acalculous cholecystitis associated with hepatitis A virus infection is not fully elucidated. Several hypotheses include direct viral invasion of the biliary epithelium, changes in the physical properties of bile secretions, or a cell-mediated immunologic response.4,5
TREATMENT
Not all cases of acalculous cholecystitis require surgical management. Supportive care remains the cornerstone of management for hepatitis A virus infections, including those complicated with acalculous cholecystitis, except in cases with perforation.3,4 In the cases of the siblings we treated, the boy and girl were safely managed with supportive care and watchful observation, and there was no progression to a surgical abdomen.
The hepatitis A vaccine is recommended for travelers to endemic countries. With proper vaccination practices, this potentially serious illness, and rare but serious complications such as acalculous cholecystitis, can be prevented.1 It is important for pediatric health care providers to have a high index of suspicion and recognize acalculous cholecystitis as a rare complication of hepatitis A virus infection in returning travelers.
Roberto P. Santos, MD, is an associate professor of pediatric infectious diseases at Albany Medical Center in New York.
Karamjit Chela, MD, is a recent graduate of the Albany Medical College in New York.
Nikki Allmendinger, MD, is an attending pediatric gastroenterologist at Albany Medical Center in New York.
Maria T. Boulos, MD, is an attending pediatric radiologist at Albany Medical Center in New York.
Christina Whyte, MD, is an attending pediatric surgeon at Albany Medical Center in New York.
Martha L. Lepow, MD, is an attending pediatric infectious diseases physician at Albany Medical Center in New York.
REFERENCES
1.Hepatitis A. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015:391-399.
2.Kaya S, Eskazan AE, Ay N, et al. Acute acalculous cholecystitis due to viral hepatitis A. Case Rep Infect Dis. 2013;2013:407182.
3.Black MM, Mann NP. Gangrenous cholecystitis due to hepatitis A infection. J Trop Med Hyg. 1992;95(1):73-74.
4. Prashanth GP, Angadi BH, Joshi SN, Bagalkot PS, Maralihalli MB. Unusual cause of abdominal pain in pediatric emergency medicine. Pediatr Emerg Care. 2012;28(6):560-561.
5.Souza LJ, Braga LC, Rocha NSM, Tavares RR. Acute acalculous cholecystitis in a teenager with hepatitis A virus infection: a case report. Braz J Infect Dis. 2009;13(1):74-76.