Hepatitis associated with severe respiratory syncytial virus-positive lower respiratory tract infection.

Abstract

Sir, Since the isolation of respiratory syncytial virus (RSV) from the liver tissue of a 7-month-old infant with bronchiolitis and extrahepatic biliary atresia (1) there have been no reports in the medical literature of hepatic involvement in RSV disease. To our knowledge this is the erst report of liver function tests in RSV-positive lower respiratory tract infection. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels of all children with respiratory secretions positive for RSV antigen admitted to a paediatric intensive care unit over a 2-y period were investigated retrospectively. Of 55 such admissions, 52 required mechanical ventilation. Case records were evaluated for risk factors for acute or chronic hepatocellular damage. The median age of children admitted with RSV disease was 2.7 months (interquartile range: 1.2‐6.0 months). Transaminase levels were elevated in 27 of 55 (49%) children. ALT levels for children with hepatic involvement and ALT above upper limit of normal for age (\36 IU:l) in relation to time from admission are shown in Fig. 1. This graph excludes 1 outlier in whom ALT levels peaked at 2903 IU:l and AST levels at 11,166 IU:l on the day after admission, after which the patient died of multiorgan failure. Coagulopathy (international normalized ratio 4.8) was associated in this case. In 7 cases AST levels were at least twice as high as ALT levels. In 3 of these cases only AST levels were above the upper limit of normal (\58 IU:l). However, in the majority of cases AST levels were lower than or not signiecantly different from ALT levels. There was no statistically signiecant (5% level; x 2 and Fisher’s exact test) difference between children with and without abnormal liver function tests, with regard to the following potentially confounding factors: previous neonatal intensive care unit admission; history of hypoxic event before admission; congenital heart disease; and medication added in ventilated children during admission. The duration of ventilation was signie cantly longer (pae0.02; 2-sample t-test for unequal variance) in patients with elevated transaminase levels (geometric mean 8.6 d; 95% CI 7.3‐9.9) compared to patients with normal transaminase levels (geometric mean 5.8 d; 95% CI 4.6‐7.0). Pre-existing liver disease was identieed in 2 infants with abnormal liver function tests. One infant with abnormal liver function tests was found to be infected with adenovirus in addition to RSV. His course was particularly stormy, requiring 2 weeks of extracorporeal membrane oxygenation. Hepatitis has been reported in 3 patients with severe bronchiolitis previously, and in each case double infection with RSV and adenovirus or CMV was present (2). Adenovirus and CMV are known causes of hepatitis. Among our ventilated children RSV disease accompanied by elevated transaminase levels appeared to be more severe, as judged by the duration of mechanical ventilation. The severe course of disease in our patients may have been due to infection with a second respiratory pathogen. Our RSV-positive patients were not systematically investigated for viral pathogens other than RSV. An alternative explanation for our endings may have been the presence of different RSV strains with greater virulence as well as the potential of causing hepatitis. For cases in which AST was predominantly elevated a myocardial origin of the enzyme levels was a possibility. Myocarditis has been associated with RSV infection (3). In our study group, hepatitis was commonly associated with RSV-positive bronchiolitis. Research into the incidence of double infection in patients with severe RSV-positive bronchiolitis could further elucidate the cause of the hepatitis (and possibly also myocarditis). Whether RSV alone can cause extrapulmonary manifestations remains to be clarieed.