Adenoviral Hepatitis in an Immunocompetent Child

A 10-month-old previously healthy infant was brought to the emergency department with a runny nose and wet cough that had started a week earlier. He had a tactile fever and decreased oral intake for 2 to 3 days, and 3 to 4 episodes of nonprojectile, nonbilious, non-bloody vomiting for 1 day. His mother reported that he had been extremely fussy and irritable.

The infant had a temperature of 101.3 ^oF; heart rate, 138 beats/min; respiration rate, 40 breaths/min; blood pressure, 90/48 mm Hg; and O₂ saturation, 100% while breathing room air. He was crying inconsolably. The anterior fontanel was flat. He had copious nasal secretions with transmitted upper airway sounds. He had one episode of generalized tonic clonic seizure in the ED, which lasted for 20 seconds, with a brief postictal state. He received a loading dose of fosphenytoin and was admitted to PICU to rule out meningitis. A CSF analysis was also done and empiric antibiotic therapy was initiated.

Because viral meningitis was suspected, liver function tests (LFTs) were done. Results indicated elevated levels of ALT (4233 U/L) and AST (3603 U/L). However, PCR analysis of CSF for HSV yielded negative results. Antibiotics were discontinued. The patient’s respiratory distress gradually resolved. Additional testing revealed the cause of the elevated LFTs.

Diagnosis
Tests for liver function showed an ammonia level of 43 µmol/L and a normal coagulation profile. Abdominal ultrasonography showed an enlarged liver. A work up was done for probable causes of hepatitis. The serum acetaminophen level was normal, as were results of a hepatitis panel. ANA, anti-smooth muscle antibody, and anti-liver kidney microsomal antibody assays were negative; serum ceruloplasmin and alpha-fetoprotein levels were within normal limits. EBV and CMV panels were also negative. Results of an immunochromatography test for adenoviral antigen were positive.

The onset of hepatic injury in our patient appeared to occur concomitantly or just after respiratory tract infection. Therefore, an infectious cause of acute liver failure was highly possible. Lack of serologic evidence of causes of hepatitis and respiratory infection led us to search for adenovirus in the respiratory secretions.

Several methods are used to detect adenovirus infection depending on the site and severity of infection. Adenovirus infection can be shown by immunochromatography (as in our case) or characteristic pathologic changes -- including intranuclear inclusion bodies in biopsy material, isolation of virus by culture or PCR, or demonstration of an increase in antibody titers.¹

Our patient was given supportive care. Gradually, his LFTs returned to baseline.

Adenovirus: Take home points
Adenovirus accounts for 5% to 10% of upper and lower respiratory tract infections in infants and children.² Transmission is by respiratory and fecal oral routes. Approximately 50 serotypes of adenovirus are recognized. Serotypes 1, 2, 3, and 5 cause mainly respiratory illness, and serotypes 40 and 41 cause mainly gastroenteritis.³ In healthy children, adenoviral infection causes a benign, self-limited illness. Acute liver failure from adenovirus is rare, and is described especially in immunocompromised patients, in whom it is usually fatal. More virulent types (particularly type 7) can cause respiratory failure, shock and hepatitis in immunocompetent children.¹

The clinical course of adenovirus infection among healthy children is usually benign but can be complicated by severe or fatal pneumonia, myocarditis, and hepatitis.² We recommend that adenovirus infection be included in the differential diagnosis of fulminant hepatic failure seen in childhood.¹

References:

1. Ozbay HF, Canan O, Ozcay F, Bilezikci B. Adenovirus infection as possible cause of acute liver failure in a healthy child: a case report. Turk J Gastroenterol. 2008;19:281-283.
2. Shike H, Shimizu C, Kanegay, et al. Quantitation of adenovirus genome during acute infection in normal children. Pediatr Infect Dis J. 2005; 24: 29-33.
3.  Peled N, Nakar C, Huberma, H, et al. Adenovirus infection in hospitalized immunocompetent children. Clin Pediatr (Phila). 2004;43: 223-229.